- Email: [email protected]
Abstract of papers in this issue
Lymphoma
Hodgkin’s disease.
Sleep
Desaturation
Apnea
me-
Continued
Twenty-one postmenopausal women were monitored for sleep-disordered breathing and nocturnal oxygen desaturation to evaluate the contribution of progestational hormones to the occurrence of these sleep events. For approximately one month, 11 subjects received 30 mg medroxyprogesterone and 10 received placebo tablets in a randomized double-blind control study. Respiration, saturation and electroencephalography were monitored during one night of sleep before therapy and one night after therapy. Contrasted with the low incidence of disordered breathing and desatumtion in premenopausal women, 71 percent of the postmenopausal women had such events. In the placebo-treated group all measured variables of sleep and breathing were identical on the two nights, which suggested that a single night of sleep monitoring may represent other nights of sleep. Although several subjects appeared to show some improvement with medroxyprogesterone. only the maximum duration of apnea was significantly reduced the second night (p <0.03).
Block AJ. Wynne JW, Boysen PG, Lindsey S. Martin C, Cantor El: Menopause, droxyprogesterone and breathing during sleep. Am J Med 1981; 70: 506-510.
Menopause
Medroxyprogesterone
kin’s disease who entered into Stanford University Medical Center randomized trials comparing radiation therapy alone to radiation therapy plus six cycles of adjuvant chemotherapy were evaluated. Of these, 54 patients had extralymphatic lesions. There were five relapses among these patients (9 percent), not different from the 37 relapses among the 264 patients (14 percent) with Hodgkin’s disease confined to the lymphatic system. Actuarial survival and freedom from relapse were not significantly different for patients with or without extralymphatic disease. The survival of patients with extralymphatic disease was similar whether they were treated with radiation therapy alone or radiation therapy plus chemotherapy.
Three hundred eighteen patients with pathologic stage IA and IB, IIA and IIB, and IIIA Hodg-
Torti FM, Portlock CS, Rosenberg SA, Kaplan HS: Extralymphatic Prognosis and response to therapy. Am J Med 1981; 70: 487-492.
Extranodal
Chemotherapy
Hodgkin’s disease
Radiation therapy basement
Electron microscopy membrane
Papillary thyroid cancer
Radioiodine
therapy
on page A33
Data from 576 patients with papillary thyroid cancer were retrospectively analyzed. With a median follow-up of 10 years three months, there were six deaths from, and 84 recurrences of, thyroid cancer, 16 (19 percent) of which could not be eradicated. Death from thyroid cancer occurred only in those over 30 years of age at the time of diagnosis, and only when the primary tumor was larger than 1.5 cm. The prognosis of those with locally invasive tumor was poor. When cervical lymph node metastases were present, recurrence of, but not mortality from, cancer was higher than when the tumor was not locally metastatic. Treatment with total thyroidectomy, postoperative radioiodine and thyroid hormone resulted in the lowest recurrence and mortality rates except in those with small primary tumors (cl.5 cm) in whom less than total thyroidectomy and postoperative thyroid hormone alone were effective therapy. Simple excision of cervical lymph node metastases was as effective as more aggressive surgery. Externa! radiation used as initial adjunctive therapy adversely influenced outcome.
Mazzaferri EL, Young RL: Papillary thyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med 1981; 70: 511-518.
Total thyroidectomy
Thyroid cancer
Fifty-eight patlents with Alport’s syndrome were followed up in our department during the last 20 years. Age at diagnosis was less than six years in 74 percent of the cases. Clinical symptoms included microscopic hematuria (100 percent), gross hematuria (55 percent), proteinuria (88 percent). hearing loss (63 percent) and ocular abnormalities (3 1 percent). Evolution to terminal failure occurred in 34.5 percent of the patients. Ultrastructural study of renal biopsy specimens obtained in 20 children one to 17 years old showed two types of glomerular basement membrane changes: (1) in all cases, thickening and splitting of the glomerular basement membrane; (2) in 19 cases, thinning of the glomerular basement membrane which was the predominant feature in younger children.
Gubler M, Levy M, Broyer M, Naizot C, Gonzales G, Perrin D, Habib R: Alport’s syndrome. A report of 58 cases and a review of the literature. Am J Med 1981; 70: 493505.
Glomerular
Alport’s syndrome
Vaivuiar Sudden cardiac
death
Prekaiiikrein Factor Xii
factor
Radioimmunoassay Hageman
Nephrotic
syndrome
interstitial lavage
lung disease
Bronchoaiveoiar
pulmonary Gallium scintigraphy
idiopathic
fibrosis
Sarcoidosis
Continued
on page A36
The interstitial lung diseases are a Qroup of chronic disorders distinguished by the presence of both chronic alveolitis and fibrosis resulting in derangement of the alveolar structures. Bronchoalveolar lavage studies suggest that these diseases may be categorized on the basis of the cell type relevant to the specific pathologic process involved. The central pathogenetic mechanisms operative in these diseases appear to involve the local production of specific cellderived chemotactic factors that recruit inflammatory cells from the blood into the alveolar interstitium, thus maintaining the alveolitis. Although definitive therapy of the interstitial lung diseases awaits precise description of the initiating processes involved in the generation of the inflammatory response, corticosteroid and cytotoxic therapy, directed at the potentlally reversible alveolitis, promise more effective clinical control of these diseases when results can be monitored by bronchoalveolar IavaQe and s’ga!lium scanning in conjunction wi!h sonventional roentQenoQraphlc and physioloQfc studies. _.__._. _. .~
ibuprofen
Ibuprofen (Motrine) given either on a prophylactic regimen or on a therapeutic regimen, 400 mg four times a day, in a double-blind, cross-over trial was found highly effective in the treatment of primary dysmenorrhea. Ibuprofen therapy reduced menstrual prostaglandin release and relieved dysmenorrhea, but placebo therapy did not. Oral contraceptives decreased menstrual flow, reduced prostagiandin release and also alleviated dysmenorrhea. The two drugs suppress endometrial prostaglandin production through different mechanisms. Reduction of menstrual prostaglandin release leads to alleviation of dysmenorrhea. Thus, these findings support the hypothesis that primary dysmenorrhea is caused. at least in part, by a high level of menstrual prostagbndin release. ProstaQlandin synthetase inhibitors, such as ibuprofen, represent a specific therapy for this menstrual disorder.
inhibitors
Crystal RG, Gadek JE, Ferrans VJ, Fulmer JD, Line BR, Hunninghake GW: Interstitial lung disease: current concepts of pathogenesis, Staging and therapy. Am J Med 1981: 70: 542-568.
therapy
_.._
Chan WY, Dawood MY, Fuchs F: Prostaglandins in primary dysmenorrhea. Comparison of prophylactic and nonprophylactic treatment with ibuprofen and use of oral contraceptives. Am J Med 1981; 70: 535-541.
Dysmenorrhea
synthetase
Preatagiandin
Oral contraceptive
Proatagiandins
sclerotic plaque. Thus, radiation to the heart may produce a wide spectrum of functional and anatomic changes but particufarly damage to the pericardia and ths underlying epicardial coronary arteries.
Of the heart. Six of the 16 study patients and one of 10 control subjects had one or more major epicardial coronary arteries narrowed 76 to 100 percent in cross-sectional area by athero-
in the left side of the heart, presumably because of higher radiation doses to the anterior surface
The titers of plasma HaQeman factor (factor XII) were examined in 11 patients with the nephrotic syndrome by both functional and radioimmunoassays. All patients had decreased titers of the functional HaQeman factor, but essentially normal titers of immunoreactive Hegernan factor. Thus, the ratio of immunoreactive Hageman factor to functional Hageman factor was significantly higher than in control patients. No circulating anticoagulants against Hagernan factor were detected. Urinary excretion of Hageman factor was present in six patients, but did not appear to account for the reduced plasma tiageman factor activity. These studies indicate urinary excretion of HaQemafl factor and alterations in the functional sites of plasma Hagernan factor molecules in the nephrotic syndrome.
infarction
heart disease
Certain clinical and necropsy findings are described in 16 young (aged 15 to 33 years) patients who received >3,500 rad to the heart five to 144 months before death. All 16 had some radiation-induceddamage to the heart: 15 had thickened pericsrdia (five of whom had evidence of cardiac tsmponade); eight had increased interstitial myocerdial fibrosis, particularly in the right ventricle; 12 had fibrous thickening of the mural endocardium and 13 of the valvular endocsrdium. Except for valvuler thickening, the changes were more frequent in the right than
Myocardiai
Saito l-i, Goodnough LT, Makker SP, Kallen RJ: Urinary excretion of HaQeman factor (factor XII) and the presence of nonfunctional HaQeman factor in the nephrotic syndrome. Am J Med 1981; 70: 531-534.
heart dlsease
Brosius FC 111,Wailer SF, Roberts WC: Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med 1981; 70:519-530.
Pericardiai
Coronary heart disease
THEO-DUIR: Enduring Action Anhydrous Theophylline Sustained
Action
Tablets
THEO-OUR Sustamed Actton Tablets contain anhydrous theophylline, with no color additives Actions: The pharmacologrc actrons of theophylhne are as a bronchodilator, pulmonary vasodilator and smooth muscle relaxant since the drug directly relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels. Theophylline also assesses other acttons typrcal of the xanthine derivatives: coronary vasodrlator, 8mretrc, cardiac stimulant, cerebral stimulant and skeletal muscle stimulant The actrons of theophylhne may be medrated throu h inhibition of phos hodiesterase and a resultant increase in intracellular cyc9IC AMP which coul 8 mediate smooth muscle relaxation. Indications: Symptomatic relief and/or preventron of asthma and reversible bronchospasm associated wrth chronic bronchitis and emphysema. Contraindlcatlons: THEO-DUR is contraindicated in mdividuals who have shown hypersensitivity to any of its components or xanthine derivatives. Warnin 8: Excessive theophyllrne doses may be associated with toxicity; serum theophylt me levels should be monitored to assure maximum benefit with mmimum risk. lncrdence of toxicity increases at serum levels greater than 20 mc /ml. High blood levels of theophylline resulting from conventional doses are corre9ated with clinical manifestations of toxicity in, patients with lowered body plasma clearances, patients with liver dysfunction or chronic obstructive lung disease, and patients who are older than 55 years of age, particularly males There are often no early signs of less serious theophyllme toxicity such as nausea and restlessness, which may a pear in up to 50% of patients prior to onset of convulsions. Ventricular arrhytP,mras OI serzures may be the frrst signs of toxicity. Many atients who have higher theophylline serum levels exhrbit a tachycardia. TheophylPine products may worsen pre-existing arrhythmias. Usage In Prs nancy: Sale use in pregnancy has not been established relative to possible adverse effects on fetal develo ment, but neither have adverse effects on fetal development been established f his IS. unfortunately, true for most anti-asthmatc medications Therefore, use of theophylline in pregnant women should be balanced against the risk of uncontrolled asthma. Precautions: THEODUR TABLETS SHOULD NOT BE CHEWED OR CRUSHED. Theophyllines should not be administered concurrently with other xanthine medications It should be used with caution in patients with severe cardrac disease, severe hypoxemia, hypertensron, hyperthyroidism. acute myocardial injury, car pulmonale, congestive heart failure, liver disease and in the elderly, particularly males, and in neonates Great caution should be used in grvmg theophyllme to patients in congestive heart failure since these patients show markedly prolonged theophylline blood level curves. Use theophylline cautious1 in patients with history of peplic ulcer Theophylhne may occasionally act as a Yocal irritant to G.I. tract although gastrointestinal symptoms are more commonly central and associated wtth high serum concentrations above 20 mcg/ml. Adverse Reactlons: The most consistent adverse reactions are usually due to overdose and are’ Gastromtestinal: Nausea, vomiting, epigastric pain, hematemesis, diarrhea. Central Nervous System: Headaches, irritabilit restlessness,, insomnia, reflex hyperexcitability, muscle twitching, clonic an(r, tonic generalized convulsions. Cardiovascular. Pal rtation, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, II.Pe threatening ventricular arrhythmias. Respiratory. Tachypnea. Renal. Albummuria, increased excretion of renal tubular cells and redblood cells; potentiation of diuresis. Others: Hyperglycemia and inappropriate ADH syndrome. How Supplied: THEO-DUR 100 mg. 200 mg and 300 mg Sustained Action Tablets are available in bottles of 100, 1000, and 5000, and in unit dose packages01 100 (20 x 5’s). Cautlon: FEDERAL LAW PROHIBITS DISPENSING WITHOUT A PRESCRIPTION. 0779 For full prescribing Information, see package insert Description:
ZERO-ORDER dc/dt=K’” (Constant rate absorption by GI infusion)
200 mg
100 mg
ii%tM*cmICAls INC. Miami, A36
Florida
33169
(&IA)
Diabetic
retinopathy
Photocoagulation
Epidemiology
Vitrectomy
diabetes
ratio
maiformation Estrioi
in pregnancy: have all the problems been solved? Am J
Fetal moottortng
Congenttal
Continued
The past decade has seen a remarkable improvement in the prognosis for pregnancy complicatedby diabetes meiiitus. Perinatal survival has become as common in these pregnancies as in normal gsetatifm. This improved outccme has been achiived through a better lnderstanding of matemai ~t&OliSm and the needs to regulate glycemia carefully in the pregnant subject as well as through reliable techniques for the surveillance of fetal well-being and advances in neonatal care. Significant perinatai morbidity still cccurs and congenital malformations. +he leading cause of perinatai mortality today, remain an unsolved problem.
Gabbe %I Diabetes mellitw Med 1981: 70: 613-618.
Lecithtn/sphfngomyelin
Gestational
Despite the fact that we still do not understand what causes the development of retinopathy in diabetic patients, major advances in its treatment have taken place. Photocoagulation clearly reduces the development of severe visual loss in eyes with proliferative diabetic retinopathy aithcugh how early treatment should be initiated has not been clearly defined. Vitrectcmy is capable of restoring vision in many already blind eyes but at some risk. We are inching closer to an w&Hand@ of the pathophyGt of retincpathy with development of retinal endotheliii and pericyte ceil culture techniques, studies of vascular permeability, flow and anglogenesis. Diabetic retlncpathy is more common early in the ccurse of diabetes than previously realized. This may allow for prospective intervention studies using the development of retinopathy as an endpoint. Diabetic retinopathy may be a reasonable index of short-term survival.
Rand LI: Recent advances in diabetic retinopathy. Am J Med 198 1; 70: 595-602.
Pathophysiologv
Diabetic
nephropathy
Pancreas
70:
membrane
transplantation basement
Am J Med 1981;
Giomeruiar
MW, Brown DM: The kidney in diabetes.
Dialysis
Mesangium
insuiin/giucagon
inhibiting factor
and diabetes. Am J Med 1981; 70: 619-626.
Islet ceil function
Growth hormone release
secretion
on page A45
Somatostatin is a tetradecapeptide originally isolated from the hypothalamus. Its ability to inhii pancreatic islet A and B cell function, and its location within pancreatic islet D cells suggest that lt may act as a local regulator of insulin and glucagon secretion. Recent studies have provided evidence that the peptide may modulate nutrient homeostssis not only by affecttng insulin and giucagon secretion but also by effects on gastrointestinal function. Alterations of islet D cell morphclcgy and secretion in experimentally-induced and spontaneous diabetes in laboratory animals suggest that abnormal somatostatin secretion may be involved in the pathophysloicgy of diabetes. Clinical studies with the peptide have provided insight into the physiologic roles of growth hormone and giucagon. and have indicated a therapeutic potential for the peptide in the treatment of diabetes in man.
Gerich JE: Somatostatin
Tetradecapeptide
Somatostatin
The kidney as a target organ for secondary microvascular complications of diabetes meilitus represents a heatth problem of enomlcus social cost. Recent studies strongly suppcrt the concept that the primary responsibility for diabetic nephropathy rests with the metabolic derangements of the diabetic state. Alterations in microvascular hemodynamics in diabetes probably contribute to giomeruiar pathology. These alterations may be based upon disturbed vasoactive control mechanisms regulating angiotensin and prostagiandin secretion and metabolism. The nature of glomeruiar basement membrane and mesangial thickening may be separable as mesangiai thickening is reversible by cure of the diabetic state in rats whereas glomerular basement membrane thidtening is not. Treatment for the diabetic patient with end-stage renal failure has recently improved. Presently, kidney transplants from living related donors appear best, cadaver transplants and long-term hemodialysis are reasonable optlons.
Mauer SM. Steffes 603-6 12.
Kidney transpiantatlon
Platelet
disease
aggregation
Diabetes meiiiius
infections
Surgical ‘infections
Nosocomiai care unit
and control in the severely traumatized
intensive
pa-
Continued
Among severely traumatized patients, infection is second only to head trauma as the leading cause of death. Few studies have defined the infections that occur, the risk factors involved, or the appropriate means of evaluating these patients. In this trauma unit, daily infection surveillance included clinical evaluation of every patient and all microbiologic data. In addition, prophylactic and therapeutic antibiotics were directly under control. Over a two year period 2,368 patients were admiied, most arriving directly from the scene by helicopter. The overall mortality was 20 percent. In thts setting, 639 nosocomial infections occurred in 381 patients of whom 14 percent died of their infection. Over-all 44 percent of the infections were bacteremic. Most infections were directly related to an invasive procedure.
Caplan ES, Hoyt N: Infection surveillance tient. Am J Med 1981: 70: 838-840.
infection
Trauma
The platelets of many patients with diabetes mellitus are abnormally sensitive to the effects of aggregatc+y agents in vitro. The effects of six weeks of treatment with the sulfonylurea agents gliclazide and glyburide on platelet aggregation have been investigated in 10 noninsulindependent diabetic patients. During treatment with diet alone, the platelets of these patients were abnormally sensitive to aggregation in response to 1 @I of ADP, as compared with those in normal controls. Treatment with both drugs normalized ADP-induced aggregation in these patients. Treatment with glyburide significantly reduced aggregation in response to 10 PM of epinephrine and collagen at 750 ug/ml. The alteration in platelet function did not correlate with the improvement in plasma glucose concentration, thus suggesting that this may be a drug effect. This alteration in platelet aggregatory function may be of importance in the prevention of vascular disease in diabetic subjects.
and platelet func-
Suifonyiureas
Klaff W, Kernoff L, Vinik Al, Jackson WPU, Jacobs P: Sulfonylureas tion. Am J Med 1981; 70: 827-830.
Vascular
Prophylactic hosts
antibiotics
Protected
isolation
Nosocomlai infections
Prevention
intensive
care units
Nosocomiai infection
on page A52
Conversion of an ICU from an open unit to isolation rooms permitted study of patient care practices, colonization and infection in both settings. Air sampling and observation of patient care practices included 99 of 410 open unit patients and 68 of 1,022 isolation room patients matched on the basis of risk factors for infection and staff contact. Number and type of interactions between staff and patients, and frequency of handwashing and its relationship to patient-staff interactions were recorded. All ICU patients were monitored daily for signs of and selected risk factors for infection, and material for culture for six surveillance organisms was obtained every four days. Over-all rates of infection in the open unit and isolation rooms were 15.0 and 13.4, respectively. The isolation rooms did not appear to reduce nosocomial acquisition of the six surveillance organisms. We conclude that many patient-staff interactions in an ICU are not followed by handwashing, and that the new unit design had no apparent effect upon the frequency of handwashing or over-all incidence of colonization and infection in the ICU.
Preston GA, Larson EL, Stamm WE: The effect of private isolation rooms on patient care practices, colonization and infection in an intensive care unit. Am J Med 1981; 70: 641-645.
isolation
Since infection is a major cause of death in the immunocompromised patient, considerable attention has been focused on developing methods for preventing infection. This has primarily been directed at suppressing or eliminating the host’s endogenous microbial burden and in decreasing the acquisition of new organisms. The prevention techniques employed vary in complexity from single-room isolation to elaborate systems utilizing air filtration and decontamination. The most sophisticated of these regimens is the total protected environment (TPE) consisting of a high-efficiency-particulate-air (HEPA)-filtered laminar air flow room which is surface disinfected and in which the patient is fully decontaminated with oral nonabsorbable antibiotics, cutaneous antisepsis, orificial antibiotics and a semisterile diet. Cumulative data to date show that the TPE affords a significant reduction in the incidence of serious infections. Nonetheless, the TPE is also elaborate, cumbersome and expensive, and its utilization depends og the success of the therapy available for the patient’s underlying disorder.
Pizzo PA: The value of protective isolation in preventing nosocomial infections in high risk patients. Am J Med 1981; 70: 631-637.
Compromised
1
When diet alone fails in maturity-onset diabetes and an oral agent is indicated...
DIABINESE” (chlorpropamide) 100 mg and 250 mg Tablets BRIEF SUMYARV DIABINESE’ Wkqupamlde)Thbta
+‘P3GLYCEM 4 IF ITCCClJRS MAY BE PRO_OUGEC Mnrw mlonm: Usuallv dose relatm and pe”erallY
am
LABORATORIES DIVISION CFIZCR IHC
Leaders in Oral Diabetic Therapy A52
Nosocomial
infection
Urinary tract infection Hospital epidemiology
Urethral catheter
Am
bacilli
Bacterlal
gram-negative
Interference
Pneumonia
Am J
infections
rod pneumonias: an overview.
Nosocomial
infections
marcescens
Urine measuring containers
Serratla
Urinometers
infections syncytial virus
Influenza
Viral respiratory
Parainfluenza
infections
viruses
Pediatrics
The frequency and importance of nosocomial infections of the respiratory tract in pediatrics have generally been underestimated. In part this has resulted from the emphasis on bacterial infections which occur primarily in select at-risk populations. Most respiratory infections in pediatric patients are viral, and all patients are potentially susceptible. The epkfemiologic patterns of these viral respiratory agents on the ward mirror those seen in the community in terms of frequency, season, age affected and severity of illness. Hence, the most frequent nosocomial agents are the epidemic respiratory viruses-respiratory syncytial virus (RSV), which causes the greatest morbidii and mortality; influenza, and the parainfluenza viruses. Their import results from (1) the severity of disease produced in young children; (2) the abundant and prolonged viral shedding; (3) the potential susceptibility of all patients and staff; and (4) the difficulty in conboIling nosocomial spread.
Hall CB: Nosocomial viral respiratory infections: perennial weeds on pediatric wards. Am J Med 1981: 70: 870-676.
Respiratory
Nosocomial
An outbreak of nosocomial infections of the urinary tract due to a multiply drug-resistant strain of Serratia marcesoens occurred at a community hospital. Acquisition of the epidemic strain was associated with (1) exposure to the intensive care unit, (2) presence of an indwelling bladder catheter, (3) treatment witi antibiotics, and (4) exposure to devices used for measurements of specific gravity and urine volume. An extensive microbiologic evaluation of the hospital environment failed to reveal the epidemic strain from any site other than urinometers and urine volume measuring containers. The resistant organism was also recovered from one of three pooled handwashings taken from nursing personnel. Thus, ‘the urinometer and urine measuring container may have served as inanimate reservoirs for the resistant S. marcescens which was subsequently inoculated onto ths hands of medical personnel or directly to a catheterized patient. Following institution of routine disinfection of the inanimate reservoir, no additional cases of multiply drug-resistant S. marcescens urinary tract infections have been observed.
Rutala WA, Kennedy VA, Loflin HB, Sarubbi FA Jr: Serratia marcescens nosocomial infectioris of the urinary tract associated with urine measuring containers and urinometers. Am J Med 1981; 70: 859-663.
Urinary tract infections
Nosocomial
Continued on page A58
Because of a high incidence and case fatality rate, nosocomial infections of the lower respiratory tract due to aerobic gram-negative t%ds are important, particularly in patients bedded in intensive care units. Risk factors include severity of illness, antimicrobial therapy and respiratory tract instrumentation. Respiratory tract colonization seems to be a general characteristic of patients with severe illness, whereas in normal subjects oral defenses clear gram-negative bacteria very efficiently. Pneumonia follows afler failure of pulmonary antibacterial defenses to cope with aspirated inoculums. Attempts to block colonization with local antimicrobials result not only in a transient decrease in colonization and pneumonia but also in the appearance of resistant organisms. Attempts to enhance human lung antibacterial defenses by bacterial interference or immunization have not been well studied. The general outlook for immediate control of these infections is not encouraging.
LaForce FM: Hospital+zquired Med 1981; 70: 864-869.
Colonization
Gram-negative
TO evaluate the efficacy of daily cleansing of the urethral meatus-catheter junction in preventing bacteriuria during closed urinary drainage, randomized, controlled trials of two widely recommended regimens for rneafal care were completed. In 32 of 200 patients given twice daily applications of a povidone-iodine solution and ointment bacteriuria was acquired, as compared with 24 of 194 patients who did not receive this treatment. In 28 of 229 patients given once daily meatal cleansing with a nonantlseptic solution of green soap arid water bacteriuia was acquired, as compared with 18 of 223 patients not given special meatal care. There was no evidence in either trial of a beneficial effect of meatal care. Moreover, each of four different statistical methods indicated that the rates of bacteriuria were higher in the treated groups than in the untreated groups. Current methods of meatal care appear to bs hazardous, as well as expensive, and cannot be recommended as measures to control infection.
eter-associated urinary tract infections. Efficacy of daily meatal care regimens. J Med 1981; 70: 855-658.
Burke JP, Garibaldi RA, Britt Ml?, Jacobson JA, Conti M, Ailing DW: Prevention of cath-
Povidone-iodine
Bacteriuria
-
LIMRltROL@TABLETS@ Tranqulllrer-AntIdepressant
Befun pnecrlbl please consult complete product Infarmotlon, a summary at wh“pch fallows: Indlcallon,: Relief of moderate to severe depression ossoclated with moderate
to severs anxiety Contralndfcatlont: Known hypersensitivity to bsnzodtazepines or tricychc antidepressants. Do not use with monoamine oxidase (MAO) Inhibitors or within 14 days following discontmuatlon of MAO Inhibitors since hyperpyretlc crises, severe convulsions and deaths have occurred with concomitant use; then initiate cautiously, gradually increasing dosoge until optimal response IS achieved Contraindicated during acute recovery phase following myocardiol infarction
Wamlnge: Use with great care In patients with history of urinary retentionor angle-closure glaucoma. Severeconstipation may occur in pahents taklng
tricyclic antldepressonts and onticholinergic-type drugs Closely supervise cardiovascular patients. (Arrhythmias. sinus tachycardlo and prolongahon of conduction time reported with use of iricychc antidepressants, especially high doses. Myocardlal inforctlon and stroke reported with use of this class of druas.) Caution ootients about possible combmed effects with alcohol and oth& 6NS dep&ants and agdinst hozardous occupotlons requlnng complete mental alertness (e.0.. mochinerv. drivina) . -. operatina . Ueo#o In mnoncy: Use di rnbtor tniIqulllro?i during the Mel trlmeetor should almaet alwe bo avoldrd bocauee of increaeed rlelf ot congonltol maltormatlane 01 euggoeted In eeveml Hudlee.
Coneldor poeelblllty of pmgnancy when lnetltutln~ thtmpy; advise patlenb to diecur, therapy If they Intend to or do become prognanf.
Since physical ond psychological dependence to chlordiazepoxide have been reported rarely, use caution m administering Limbitrol to addlction-prone indrvlduals or those who might increase dosoge; withdrmval symptoms following discontinuation of either component alone have been reported (nouse!, heodoche ond malaise for omitriptyline, symptoms [Including convulslons] similar to those of barbilurate withdrawal for chlordlozepoxide) Procautlone: Use with caution in patients with a history af seizures, in hyperthyroid patients or those on thyroid medlcotion, and in potlents with impaired renal or hepotlc tunction. Because of the possibility of suicide m depressed patients, da not permit easy access to Iar e quantities in these potlents. Periodic IivBr function tests and blood coun ?s are recommended during prolonged treatment. Amitriptyline component may block octlon of guonethidrne or similar antihypertensives. Concomitant use with other psychotroplc drugs has not been emluated: sedative effects may be odditive Discontinue several doys before surgery Limit concomitant admmistrahon of ECT to essential treatment See Warnings for precautions about pregnancy. Limbitrol should not be taken during the nursing period Not recommended in children under 12. In the elderly and debilitated, limit to smallest effective dosage to preclude atoxia, avarsedotion, confusion or anhcholinergic effects Advene Reactlone: Most frequently reported ore those (IssocIafed with either component alone: drowsiness, dry mouth, constipation, blurred vision, dizziness and bloohng. LSSSfrequently occurnng moctions include vivid dmoms, impotence, tremor, confusion and nasal congestion. Many depressive symptoms including anorexia, fatigue, weokness, restlessness and lethargy have been reported as side effecis of both Limbitrol and omltnptylme Granulocytopenio, jaundice and hepatic dysfunction have been observedrarely The following list includes adverse reactions not reported with Llmbltrol but requiring consideration because they hove been reported with one or both components or closely related drugs Cardiovnscu/oc Hypotension. hypertension, tachycardia. polpltotions. mvocordial infarction, arrhvlhmias, heart block, stroke P&fi/r?!fic: Euphona, apprehension, poor concentrahon, delusions, hallucinations, hypomanio and increased or decmased hbldo. Mumlogic: Incoordination, ataxia, numbness, tingling and porestheslos of the extremities, extropyramidol symptoms, syncope, changes in EEG patterns. Antlcholinergic: Disturbance of accommodation, parolytlc ileus, urinary retention, dilatation of urinary tract Allergic: Skin rash, urticaria, photosensitization, edema of face ond tongue, prurltus. Hemafologic: Bone morrow depresslon including ogranulocytosls. eosinophilio, purpuro, thrombocytopenia. Gostroinfestinot Nausea, epigastnc drsfress. vomiting, anorexra, stomatrtis. oeculiar taste, diarrhea, block tongue. kndocrins. Teshculor swelling and-gynecomostia In the mole, breast enlargement, galactanhea and minor menstrual irregularities in me female and eletiion ond lowering of blood sugar levels. Other: Headache, weight gain or loss, increased persplrolion, urmory frequency, mydriasis, jaundice, alopema, parohd swelling Ovordoeogo: Immediately hospitalize patient suspected of having token on overdose. Tmotment is symptomatic and supportive. I.V. administratIon of 1 to 3 mg physostigmine salicylate has been reported to reverse the symptoms of am~lriptyline poisoning. See complefe product information for manifestation and treatment. Doeafle: lndividuolize according to symptom severity and patient response Reduce to smallest effective dosage when satisfactory response is obtained. Larger portion of daily dose may be taken at bedtime Single h.s dose may suffice for some patients. Lower dosages am recommended for the elderly Limbitrol 10-25, initial dosage of three to tour tablets daily in divided doses, increased to six tablets or decreased to two tablets daily OS aquired Llmbitrol 5-12.5, initial dosage ot three to four tablets daily in divided doses, for patients who do not tolerate higher doses. 10 mg chlordiozHow Bepplled: White, titm-cooted tablets, each containin epoxide ond 25 m omltriptyline (as the hydrochloride soB1) and blue, filmYl ” coated tablets, eoc contammg 5 mg chlord~azepoxlde and 12.5 mg amitriptVline (as the hydrochloride salt)-botttes of 100 ond 500; Tel-E-Dose* packages at 100, woilable in trays ot 4 mverse-numbered boxes of 25, and in boxes containing 10 strips ot 10; Prescription Puks ot 50. RDCHE PRODUCTS INC. Manati, Puerto Rico 00701
infections
septicemia
infections
and meningitis in neonates.
Nosocomial
Am J Med 1981; 70:
Control measures
disease
Nosocomial
Legionnaires’
legionellosis
disease
Pneumonia Legionnaires’
in the
As of April 30. 1980.83 nosocomial cases of sporadic legionellosis had been reported to the Centers for Disease Control (CDC). All 83 patients had pneumonia: their median age was 56.5 years. All but one were hospitalized at the time of onset. Of 7 1 patients for whom outcome is known, 22 (3 1 percent) died of causes directly attributed to their infection. Eleven patients had end-stage renal disease, 28 were receiving systemic immunosuppressive medications, 17 had cancer, 12 had chronic bronchitis or emphysema, 29 were smokers, and four had diabetes mellll. Risks of acquiring nosocomial sporadic legionellosis for patients with these conditions relative to the general United States population = 340, 26, 11, 3.7, 1.9 and 1.3, respectively. These risk factors are similar to those identified for sporadic community-acquired legionellosis and for epidemic nosocomial legionellosis. Methods for preventing nosocomial legionellosis are not known, but comparing Legionella to other water-associated organisms which have been spread from medical devices to cause pneumonia may be fruitful.
England AC, Ill, Fraser DW: Sporadic and epidemic nosocomial legionellosis United States. Epidemiologic features. Am J Med 1981; 70: 707-711.
Nosocomial
Legionellosls
The past decade brought with it both highly sophisticated neonatal intensive care with improved perinatal mortality rates and increased risk for nosocomial septicemia and meningitis among survivors. Although most of these infections were caused by multiple antibiotic-resistant gram-negative enteric bacteria, Staph. aureus “outbreaks” appeared sporadically. Risk for nosocomial infection was related primarily to factors which enhance infant contact with these bacteria in combination with those poorly defined determinants of bacterial virulence and host defense. Control measures for the prevention or reduction of these infections are aimed at decreasing the neonate’s contact with the “outbreak” strains. Future efforts should be directed toward better definition of bacterial virulence, host susceptibility, and preventive measures.
Baker CJ: Nosocomial 696-701.
Neonatal
therapy
Steel needles
Intravenous
Septicemia Teflon catheters
Preservation of host defenses, antisepsis and asepsis are the three major avenues by which control over infection has been increased. Despite major successes. infection remains the major limitor of surgical horizons. Asepsis has probably been developed to nearly its greatest capacity. Antisepsis, including preventive antibiotics, is also reaching its zenith. Resistant organisms, toxicity and cost, limit further applications. A “social contract” among surgeons is needed to limit, by defined rules, the choice of agent, the total dose and the indications for use. Controlled studies of the effects of “preventive antibiotics” on hospital ecology and infection are also needed. Preservation and enhancement of host defenses is the oldest but the most neglected of these ideas. It appears to be me most exploitable now. Enhancement by nutrition, maintenance of tissue perfusion, oxygenation and immune stimulation appear to have contributed to reduction of infection rates. More success in this area seems distinctly possible.
Am J Med 1981; 70: 712-718.
Antisepsis Immune maintenance
Host resistance
Hunt TK: Surgical wound infections: an overview.
Wound Infection
Asepsis
Complications of intravenous therapy with steel needles and small-bore Teflon catheters were compared in a randomized study of 954 cannula insertions. Cannulas were inserted and cared for by an intravenous team following a standard protocol. There were no cases of cannula-related septicemia and only one case of local infection. There was a low incidence of positive semiquantitative cannula cultures in both treatment groups The risk of phlebitis was significantly greater with Teflon catheters whereas steel needles were significantly associated with infiltration. The over-all rate of complications was significantly greater for the group in which steel needles were used principally due to the increased risk of infiltration. Analysis of the per-day risk of infiltration and phlebitis revealed that these relationships were present for each day cannulas remained in place. It was concluded that steel needles and small-bore Teflon catheters can both be used with low risk of infection and that Teflon catheters more frequently cause phlebitis, whereas steel needles infiltrate more readily.
Tully JL, Friedland GH, Baldini LM, Goldmann DA: Complications of intravenous therapy with steel needles and Teflon Catheters. A comparative study. Am J Med 1981; 70: 702-706.
Infections
Infusions, parenteral Nosocomial
Hodgkin’s disease.
Sleep
Desaturation
Apnea
me-
Continued
Twenty-one postmenopausal women were monitored for sleep-disordered breathing and nocturnal oxygen desaturation to evaluate the contribution of progestational hormones to the occurrence of these sleep events. For approximately one month, 11 subjects received 30 mg medroxyprogesterone and 10 received placebo tablets in a randomized double-blind control study. Respiration, saturation and electroencephalography were monitored during one night of sleep before therapy and one night after therapy. Contrasted with the low incidence of disordered breathing and desatumtion in premenopausal women, 71 percent of the postmenopausal women had such events. In the placebo-treated group all measured variables of sleep and breathing were identical on the two nights, which suggested that a single night of sleep monitoring may represent other nights of sleep. Although several subjects appeared to show some improvement with medroxyprogesterone. only the maximum duration of apnea was significantly reduced the second night (p <0.03).
Block AJ. Wynne JW, Boysen PG, Lindsey S. Martin C, Cantor El: Menopause, droxyprogesterone and breathing during sleep. Am J Med 1981; 70: 506-510.
Menopause
Medroxyprogesterone
kin’s disease who entered into Stanford University Medical Center randomized trials comparing radiation therapy alone to radiation therapy plus six cycles of adjuvant chemotherapy were evaluated. Of these, 54 patients had extralymphatic lesions. There were five relapses among these patients (9 percent), not different from the 37 relapses among the 264 patients (14 percent) with Hodgkin’s disease confined to the lymphatic system. Actuarial survival and freedom from relapse were not significantly different for patients with or without extralymphatic disease. The survival of patients with extralymphatic disease was similar whether they were treated with radiation therapy alone or radiation therapy plus chemotherapy.
Three hundred eighteen patients with pathologic stage IA and IB, IIA and IIB, and IIIA Hodg-
Torti FM, Portlock CS, Rosenberg SA, Kaplan HS: Extralymphatic Prognosis and response to therapy. Am J Med 1981; 70: 487-492.
Extranodal
Chemotherapy
Hodgkin’s disease
Radiation therapy basement
Electron microscopy membrane
Papillary thyroid cancer
Radioiodine
therapy
on page A33
Data from 576 patients with papillary thyroid cancer were retrospectively analyzed. With a median follow-up of 10 years three months, there were six deaths from, and 84 recurrences of, thyroid cancer, 16 (19 percent) of which could not be eradicated. Death from thyroid cancer occurred only in those over 30 years of age at the time of diagnosis, and only when the primary tumor was larger than 1.5 cm. The prognosis of those with locally invasive tumor was poor. When cervical lymph node metastases were present, recurrence of, but not mortality from, cancer was higher than when the tumor was not locally metastatic. Treatment with total thyroidectomy, postoperative radioiodine and thyroid hormone resulted in the lowest recurrence and mortality rates except in those with small primary tumors (cl.5 cm) in whom less than total thyroidectomy and postoperative thyroid hormone alone were effective therapy. Simple excision of cervical lymph node metastases was as effective as more aggressive surgery. Externa! radiation used as initial adjunctive therapy adversely influenced outcome.
Mazzaferri EL, Young RL: Papillary thyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med 1981; 70: 511-518.
Total thyroidectomy
Thyroid cancer
Fifty-eight patlents with Alport’s syndrome were followed up in our department during the last 20 years. Age at diagnosis was less than six years in 74 percent of the cases. Clinical symptoms included microscopic hematuria (100 percent), gross hematuria (55 percent), proteinuria (88 percent). hearing loss (63 percent) and ocular abnormalities (3 1 percent). Evolution to terminal failure occurred in 34.5 percent of the patients. Ultrastructural study of renal biopsy specimens obtained in 20 children one to 17 years old showed two types of glomerular basement membrane changes: (1) in all cases, thickening and splitting of the glomerular basement membrane; (2) in 19 cases, thinning of the glomerular basement membrane which was the predominant feature in younger children.
Gubler M, Levy M, Broyer M, Naizot C, Gonzales G, Perrin D, Habib R: Alport’s syndrome. A report of 58 cases and a review of the literature. Am J Med 1981; 70: 493505.
Glomerular
Alport’s syndrome
Vaivuiar Sudden cardiac
death
Prekaiiikrein Factor Xii
factor
Radioimmunoassay Hageman
Nephrotic
syndrome
interstitial lavage
lung disease
Bronchoaiveoiar
pulmonary Gallium scintigraphy
idiopathic
fibrosis
Sarcoidosis
Continued
on page A36
The interstitial lung diseases are a Qroup of chronic disorders distinguished by the presence of both chronic alveolitis and fibrosis resulting in derangement of the alveolar structures. Bronchoalveolar lavage studies suggest that these diseases may be categorized on the basis of the cell type relevant to the specific pathologic process involved. The central pathogenetic mechanisms operative in these diseases appear to involve the local production of specific cellderived chemotactic factors that recruit inflammatory cells from the blood into the alveolar interstitium, thus maintaining the alveolitis. Although definitive therapy of the interstitial lung diseases awaits precise description of the initiating processes involved in the generation of the inflammatory response, corticosteroid and cytotoxic therapy, directed at the potentlally reversible alveolitis, promise more effective clinical control of these diseases when results can be monitored by bronchoalveolar IavaQe and s’ga!lium scanning in conjunction wi!h sonventional roentQenoQraphlc and physioloQfc studies. _.__._. _. .~
ibuprofen
Ibuprofen (Motrine) given either on a prophylactic regimen or on a therapeutic regimen, 400 mg four times a day, in a double-blind, cross-over trial was found highly effective in the treatment of primary dysmenorrhea. Ibuprofen therapy reduced menstrual prostaglandin release and relieved dysmenorrhea, but placebo therapy did not. Oral contraceptives decreased menstrual flow, reduced prostagiandin release and also alleviated dysmenorrhea. The two drugs suppress endometrial prostaglandin production through different mechanisms. Reduction of menstrual prostaglandin release leads to alleviation of dysmenorrhea. Thus, these findings support the hypothesis that primary dysmenorrhea is caused. at least in part, by a high level of menstrual prostagbndin release. ProstaQlandin synthetase inhibitors, such as ibuprofen, represent a specific therapy for this menstrual disorder.
inhibitors
Crystal RG, Gadek JE, Ferrans VJ, Fulmer JD, Line BR, Hunninghake GW: Interstitial lung disease: current concepts of pathogenesis, Staging and therapy. Am J Med 1981: 70: 542-568.
therapy
_.._
Chan WY, Dawood MY, Fuchs F: Prostaglandins in primary dysmenorrhea. Comparison of prophylactic and nonprophylactic treatment with ibuprofen and use of oral contraceptives. Am J Med 1981; 70: 535-541.
Dysmenorrhea
synthetase
Preatagiandin
Oral contraceptive
Proatagiandins
sclerotic plaque. Thus, radiation to the heart may produce a wide spectrum of functional and anatomic changes but particufarly damage to the pericardia and ths underlying epicardial coronary arteries.
Of the heart. Six of the 16 study patients and one of 10 control subjects had one or more major epicardial coronary arteries narrowed 76 to 100 percent in cross-sectional area by athero-
in the left side of the heart, presumably because of higher radiation doses to the anterior surface
The titers of plasma HaQeman factor (factor XII) were examined in 11 patients with the nephrotic syndrome by both functional and radioimmunoassays. All patients had decreased titers of the functional HaQeman factor, but essentially normal titers of immunoreactive Hegernan factor. Thus, the ratio of immunoreactive Hageman factor to functional Hageman factor was significantly higher than in control patients. No circulating anticoagulants against Hagernan factor were detected. Urinary excretion of Hageman factor was present in six patients, but did not appear to account for the reduced plasma tiageman factor activity. These studies indicate urinary excretion of HaQemafl factor and alterations in the functional sites of plasma Hagernan factor molecules in the nephrotic syndrome.
infarction
heart disease
Certain clinical and necropsy findings are described in 16 young (aged 15 to 33 years) patients who received >3,500 rad to the heart five to 144 months before death. All 16 had some radiation-induceddamage to the heart: 15 had thickened pericsrdia (five of whom had evidence of cardiac tsmponade); eight had increased interstitial myocerdial fibrosis, particularly in the right ventricle; 12 had fibrous thickening of the mural endocardium and 13 of the valvular endocsrdium. Except for valvuler thickening, the changes were more frequent in the right than
Myocardiai
Saito l-i, Goodnough LT, Makker SP, Kallen RJ: Urinary excretion of HaQeman factor (factor XII) and the presence of nonfunctional HaQeman factor in the nephrotic syndrome. Am J Med 1981; 70: 531-534.
heart dlsease
Brosius FC 111,Wailer SF, Roberts WC: Radiation heart disease. Analysis of 16 young (aged 15 to 33 years) necropsy patients who received over 3,500 rads to the heart. Am J Med 1981; 70:519-530.
Pericardiai
Coronary heart disease
THEO-DUIR: Enduring Action Anhydrous Theophylline Sustained
Action
Tablets
THEO-OUR Sustamed Actton Tablets contain anhydrous theophylline, with no color additives Actions: The pharmacologrc actrons of theophylhne are as a bronchodilator, pulmonary vasodilator and smooth muscle relaxant since the drug directly relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels. Theophylline also assesses other acttons typrcal of the xanthine derivatives: coronary vasodrlator, 8mretrc, cardiac stimulant, cerebral stimulant and skeletal muscle stimulant The actrons of theophylhne may be medrated throu h inhibition of phos hodiesterase and a resultant increase in intracellular cyc9IC AMP which coul 8 mediate smooth muscle relaxation. Indications: Symptomatic relief and/or preventron of asthma and reversible bronchospasm associated wrth chronic bronchitis and emphysema. Contraindlcatlons: THEO-DUR is contraindicated in mdividuals who have shown hypersensitivity to any of its components or xanthine derivatives. Warnin 8: Excessive theophyllrne doses may be associated with toxicity; serum theophylt me levels should be monitored to assure maximum benefit with mmimum risk. lncrdence of toxicity increases at serum levels greater than 20 mc /ml. High blood levels of theophylline resulting from conventional doses are corre9ated with clinical manifestations of toxicity in, patients with lowered body plasma clearances, patients with liver dysfunction or chronic obstructive lung disease, and patients who are older than 55 years of age, particularly males There are often no early signs of less serious theophyllme toxicity such as nausea and restlessness, which may a pear in up to 50% of patients prior to onset of convulsions. Ventricular arrhytP,mras OI serzures may be the frrst signs of toxicity. Many atients who have higher theophylline serum levels exhrbit a tachycardia. TheophylPine products may worsen pre-existing arrhythmias. Usage In Prs nancy: Sale use in pregnancy has not been established relative to possible adverse effects on fetal develo ment, but neither have adverse effects on fetal development been established f his IS. unfortunately, true for most anti-asthmatc medications Therefore, use of theophylline in pregnant women should be balanced against the risk of uncontrolled asthma. Precautions: THEODUR TABLETS SHOULD NOT BE CHEWED OR CRUSHED. Theophyllines should not be administered concurrently with other xanthine medications It should be used with caution in patients with severe cardrac disease, severe hypoxemia, hypertensron, hyperthyroidism. acute myocardial injury, car pulmonale, congestive heart failure, liver disease and in the elderly, particularly males, and in neonates Great caution should be used in grvmg theophyllme to patients in congestive heart failure since these patients show markedly prolonged theophylline blood level curves. Use theophylline cautious1 in patients with history of peplic ulcer Theophylhne may occasionally act as a Yocal irritant to G.I. tract although gastrointestinal symptoms are more commonly central and associated wtth high serum concentrations above 20 mcg/ml. Adverse Reactlons: The most consistent adverse reactions are usually due to overdose and are’ Gastromtestinal: Nausea, vomiting, epigastric pain, hematemesis, diarrhea. Central Nervous System: Headaches, irritabilit restlessness,, insomnia, reflex hyperexcitability, muscle twitching, clonic an(r, tonic generalized convulsions. Cardiovascular. Pal rtation, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, II.Pe threatening ventricular arrhythmias. Respiratory. Tachypnea. Renal. Albummuria, increased excretion of renal tubular cells and redblood cells; potentiation of diuresis. Others: Hyperglycemia and inappropriate ADH syndrome. How Supplied: THEO-DUR 100 mg. 200 mg and 300 mg Sustained Action Tablets are available in bottles of 100, 1000, and 5000, and in unit dose packages01 100 (20 x 5’s). Cautlon: FEDERAL LAW PROHIBITS DISPENSING WITHOUT A PRESCRIPTION. 0779 For full prescribing Information, see package insert Description:
ZERO-ORDER dc/dt=K’” (Constant rate absorption by GI infusion)
200 mg
100 mg
ii%tM*cmICAls INC. Miami, A36
Florida
33169
(&IA)
Diabetic
retinopathy
Photocoagulation
Epidemiology
Vitrectomy
diabetes
ratio
maiformation Estrioi
in pregnancy: have all the problems been solved? Am J
Fetal moottortng
Congenttal
Continued
The past decade has seen a remarkable improvement in the prognosis for pregnancy complicatedby diabetes meiiitus. Perinatal survival has become as common in these pregnancies as in normal gsetatifm. This improved outccme has been achiived through a better lnderstanding of matemai ~t&OliSm and the needs to regulate glycemia carefully in the pregnant subject as well as through reliable techniques for the surveillance of fetal well-being and advances in neonatal care. Significant perinatai morbidity still cccurs and congenital malformations. +he leading cause of perinatai mortality today, remain an unsolved problem.
Gabbe %I Diabetes mellitw Med 1981: 70: 613-618.
Lecithtn/sphfngomyelin
Gestational
Despite the fact that we still do not understand what causes the development of retinopathy in diabetic patients, major advances in its treatment have taken place. Photocoagulation clearly reduces the development of severe visual loss in eyes with proliferative diabetic retinopathy aithcugh how early treatment should be initiated has not been clearly defined. Vitrectcmy is capable of restoring vision in many already blind eyes but at some risk. We are inching closer to an w&Hand@ of the pathophyGt of retincpathy with development of retinal endotheliii and pericyte ceil culture techniques, studies of vascular permeability, flow and anglogenesis. Diabetic retlncpathy is more common early in the ccurse of diabetes than previously realized. This may allow for prospective intervention studies using the development of retinopathy as an endpoint. Diabetic retinopathy may be a reasonable index of short-term survival.
Rand LI: Recent advances in diabetic retinopathy. Am J Med 198 1; 70: 595-602.
Pathophysiologv
Diabetic
nephropathy
Pancreas
70:
membrane
transplantation basement
Am J Med 1981;
Giomeruiar
MW, Brown DM: The kidney in diabetes.
Dialysis
Mesangium
insuiin/giucagon
inhibiting factor
and diabetes. Am J Med 1981; 70: 619-626.
Islet ceil function
Growth hormone release
secretion
on page A45
Somatostatin is a tetradecapeptide originally isolated from the hypothalamus. Its ability to inhii pancreatic islet A and B cell function, and its location within pancreatic islet D cells suggest that lt may act as a local regulator of insulin and glucagon secretion. Recent studies have provided evidence that the peptide may modulate nutrient homeostssis not only by affecttng insulin and giucagon secretion but also by effects on gastrointestinal function. Alterations of islet D cell morphclcgy and secretion in experimentally-induced and spontaneous diabetes in laboratory animals suggest that abnormal somatostatin secretion may be involved in the pathophysloicgy of diabetes. Clinical studies with the peptide have provided insight into the physiologic roles of growth hormone and giucagon. and have indicated a therapeutic potential for the peptide in the treatment of diabetes in man.
Gerich JE: Somatostatin
Tetradecapeptide
Somatostatin
The kidney as a target organ for secondary microvascular complications of diabetes meilitus represents a heatth problem of enomlcus social cost. Recent studies strongly suppcrt the concept that the primary responsibility for diabetic nephropathy rests with the metabolic derangements of the diabetic state. Alterations in microvascular hemodynamics in diabetes probably contribute to giomeruiar pathology. These alterations may be based upon disturbed vasoactive control mechanisms regulating angiotensin and prostagiandin secretion and metabolism. The nature of glomeruiar basement membrane and mesangial thickening may be separable as mesangiai thickening is reversible by cure of the diabetic state in rats whereas glomerular basement membrane thidtening is not. Treatment for the diabetic patient with end-stage renal failure has recently improved. Presently, kidney transplants from living related donors appear best, cadaver transplants and long-term hemodialysis are reasonable optlons.
Mauer SM. Steffes 603-6 12.
Kidney transpiantatlon
Platelet
disease
aggregation
Diabetes meiiiius
infections
Surgical ‘infections
Nosocomiai care unit
and control in the severely traumatized
intensive
pa-
Continued
Among severely traumatized patients, infection is second only to head trauma as the leading cause of death. Few studies have defined the infections that occur, the risk factors involved, or the appropriate means of evaluating these patients. In this trauma unit, daily infection surveillance included clinical evaluation of every patient and all microbiologic data. In addition, prophylactic and therapeutic antibiotics were directly under control. Over a two year period 2,368 patients were admiied, most arriving directly from the scene by helicopter. The overall mortality was 20 percent. In thts setting, 639 nosocomial infections occurred in 381 patients of whom 14 percent died of their infection. Over-all 44 percent of the infections were bacteremic. Most infections were directly related to an invasive procedure.
Caplan ES, Hoyt N: Infection surveillance tient. Am J Med 1981: 70: 838-840.
infection
Trauma
The platelets of many patients with diabetes mellitus are abnormally sensitive to the effects of aggregatc+y agents in vitro. The effects of six weeks of treatment with the sulfonylurea agents gliclazide and glyburide on platelet aggregation have been investigated in 10 noninsulindependent diabetic patients. During treatment with diet alone, the platelets of these patients were abnormally sensitive to aggregation in response to 1 @I of ADP, as compared with those in normal controls. Treatment with both drugs normalized ADP-induced aggregation in these patients. Treatment with glyburide significantly reduced aggregation in response to 10 PM of epinephrine and collagen at 750 ug/ml. The alteration in platelet function did not correlate with the improvement in plasma glucose concentration, thus suggesting that this may be a drug effect. This alteration in platelet aggregatory function may be of importance in the prevention of vascular disease in diabetic subjects.
and platelet func-
Suifonyiureas
Klaff W, Kernoff L, Vinik Al, Jackson WPU, Jacobs P: Sulfonylureas tion. Am J Med 1981; 70: 827-830.
Vascular
Prophylactic hosts
antibiotics
Protected
isolation
Nosocomlai infections
Prevention
intensive
care units
Nosocomiai infection
on page A52
Conversion of an ICU from an open unit to isolation rooms permitted study of patient care practices, colonization and infection in both settings. Air sampling and observation of patient care practices included 99 of 410 open unit patients and 68 of 1,022 isolation room patients matched on the basis of risk factors for infection and staff contact. Number and type of interactions between staff and patients, and frequency of handwashing and its relationship to patient-staff interactions were recorded. All ICU patients were monitored daily for signs of and selected risk factors for infection, and material for culture for six surveillance organisms was obtained every four days. Over-all rates of infection in the open unit and isolation rooms were 15.0 and 13.4, respectively. The isolation rooms did not appear to reduce nosocomial acquisition of the six surveillance organisms. We conclude that many patient-staff interactions in an ICU are not followed by handwashing, and that the new unit design had no apparent effect upon the frequency of handwashing or over-all incidence of colonization and infection in the ICU.
Preston GA, Larson EL, Stamm WE: The effect of private isolation rooms on patient care practices, colonization and infection in an intensive care unit. Am J Med 1981; 70: 641-645.
isolation
Since infection is a major cause of death in the immunocompromised patient, considerable attention has been focused on developing methods for preventing infection. This has primarily been directed at suppressing or eliminating the host’s endogenous microbial burden and in decreasing the acquisition of new organisms. The prevention techniques employed vary in complexity from single-room isolation to elaborate systems utilizing air filtration and decontamination. The most sophisticated of these regimens is the total protected environment (TPE) consisting of a high-efficiency-particulate-air (HEPA)-filtered laminar air flow room which is surface disinfected and in which the patient is fully decontaminated with oral nonabsorbable antibiotics, cutaneous antisepsis, orificial antibiotics and a semisterile diet. Cumulative data to date show that the TPE affords a significant reduction in the incidence of serious infections. Nonetheless, the TPE is also elaborate, cumbersome and expensive, and its utilization depends og the success of the therapy available for the patient’s underlying disorder.
Pizzo PA: The value of protective isolation in preventing nosocomial infections in high risk patients. Am J Med 1981; 70: 631-637.
Compromised
1
When diet alone fails in maturity-onset diabetes and an oral agent is indicated...
DIABINESE” (chlorpropamide) 100 mg and 250 mg Tablets BRIEF SUMYARV DIABINESE’ Wkqupamlde)Thbta
+‘P3GLYCEM 4 IF ITCCClJRS MAY BE PRO_OUGEC Mnrw mlonm: Usuallv dose relatm and pe”erallY
am
LABORATORIES DIVISION CFIZCR IHC
Leaders in Oral Diabetic Therapy A52
Nosocomial
infection
Urinary tract infection Hospital epidemiology
Urethral catheter
Am
bacilli
Bacterlal
gram-negative
Interference
Pneumonia
Am J
infections
rod pneumonias: an overview.
Nosocomial
infections
marcescens
Urine measuring containers
Serratla
Urinometers
infections syncytial virus
Influenza
Viral respiratory
Parainfluenza
infections
viruses
Pediatrics
The frequency and importance of nosocomial infections of the respiratory tract in pediatrics have generally been underestimated. In part this has resulted from the emphasis on bacterial infections which occur primarily in select at-risk populations. Most respiratory infections in pediatric patients are viral, and all patients are potentially susceptible. The epkfemiologic patterns of these viral respiratory agents on the ward mirror those seen in the community in terms of frequency, season, age affected and severity of illness. Hence, the most frequent nosocomial agents are the epidemic respiratory viruses-respiratory syncytial virus (RSV), which causes the greatest morbidii and mortality; influenza, and the parainfluenza viruses. Their import results from (1) the severity of disease produced in young children; (2) the abundant and prolonged viral shedding; (3) the potential susceptibility of all patients and staff; and (4) the difficulty in conboIling nosocomial spread.
Hall CB: Nosocomial viral respiratory infections: perennial weeds on pediatric wards. Am J Med 1981: 70: 870-676.
Respiratory
Nosocomial
An outbreak of nosocomial infections of the urinary tract due to a multiply drug-resistant strain of Serratia marcesoens occurred at a community hospital. Acquisition of the epidemic strain was associated with (1) exposure to the intensive care unit, (2) presence of an indwelling bladder catheter, (3) treatment witi antibiotics, and (4) exposure to devices used for measurements of specific gravity and urine volume. An extensive microbiologic evaluation of the hospital environment failed to reveal the epidemic strain from any site other than urinometers and urine volume measuring containers. The resistant organism was also recovered from one of three pooled handwashings taken from nursing personnel. Thus, ‘the urinometer and urine measuring container may have served as inanimate reservoirs for the resistant S. marcescens which was subsequently inoculated onto ths hands of medical personnel or directly to a catheterized patient. Following institution of routine disinfection of the inanimate reservoir, no additional cases of multiply drug-resistant S. marcescens urinary tract infections have been observed.
Rutala WA, Kennedy VA, Loflin HB, Sarubbi FA Jr: Serratia marcescens nosocomial infectioris of the urinary tract associated with urine measuring containers and urinometers. Am J Med 1981; 70: 859-663.
Urinary tract infections
Nosocomial
Continued on page A58
Because of a high incidence and case fatality rate, nosocomial infections of the lower respiratory tract due to aerobic gram-negative t%ds are important, particularly in patients bedded in intensive care units. Risk factors include severity of illness, antimicrobial therapy and respiratory tract instrumentation. Respiratory tract colonization seems to be a general characteristic of patients with severe illness, whereas in normal subjects oral defenses clear gram-negative bacteria very efficiently. Pneumonia follows afler failure of pulmonary antibacterial defenses to cope with aspirated inoculums. Attempts to block colonization with local antimicrobials result not only in a transient decrease in colonization and pneumonia but also in the appearance of resistant organisms. Attempts to enhance human lung antibacterial defenses by bacterial interference or immunization have not been well studied. The general outlook for immediate control of these infections is not encouraging.
LaForce FM: Hospital+zquired Med 1981; 70: 864-869.
Colonization
Gram-negative
TO evaluate the efficacy of daily cleansing of the urethral meatus-catheter junction in preventing bacteriuria during closed urinary drainage, randomized, controlled trials of two widely recommended regimens for rneafal care were completed. In 32 of 200 patients given twice daily applications of a povidone-iodine solution and ointment bacteriuria was acquired, as compared with 24 of 194 patients who did not receive this treatment. In 28 of 229 patients given once daily meatal cleansing with a nonantlseptic solution of green soap arid water bacteriuia was acquired, as compared with 18 of 223 patients not given special meatal care. There was no evidence in either trial of a beneficial effect of meatal care. Moreover, each of four different statistical methods indicated that the rates of bacteriuria were higher in the treated groups than in the untreated groups. Current methods of meatal care appear to bs hazardous, as well as expensive, and cannot be recommended as measures to control infection.
eter-associated urinary tract infections. Efficacy of daily meatal care regimens. J Med 1981; 70: 855-658.
Burke JP, Garibaldi RA, Britt Ml?, Jacobson JA, Conti M, Ailing DW: Prevention of cath-
Povidone-iodine
Bacteriuria
-
LIMRltROL@TABLETS@ Tranqulllrer-AntIdepressant
Befun pnecrlbl please consult complete product Infarmotlon, a summary at wh“pch fallows: Indlcallon,: Relief of moderate to severe depression ossoclated with moderate
to severs anxiety Contralndfcatlont: Known hypersensitivity to bsnzodtazepines or tricychc antidepressants. Do not use with monoamine oxidase (MAO) Inhibitors or within 14 days following discontmuatlon of MAO Inhibitors since hyperpyretlc crises, severe convulsions and deaths have occurred with concomitant use; then initiate cautiously, gradually increasing dosoge until optimal response IS achieved Contraindicated during acute recovery phase following myocardiol infarction
Wamlnge: Use with great care In patients with history of urinary retentionor angle-closure glaucoma. Severeconstipation may occur in pahents taklng
tricyclic antldepressonts and onticholinergic-type drugs Closely supervise cardiovascular patients. (Arrhythmias. sinus tachycardlo and prolongahon of conduction time reported with use of iricychc antidepressants, especially high doses. Myocardlal inforctlon and stroke reported with use of this class of druas.) Caution ootients about possible combmed effects with alcohol and oth& 6NS dep&ants and agdinst hozardous occupotlons requlnng complete mental alertness (e.0.. mochinerv. drivina) . -. operatina . Ueo#o In mnoncy: Use di rnbtor tniIqulllro?i during the Mel trlmeetor should almaet alwe bo avoldrd bocauee of increaeed rlelf ot congonltol maltormatlane 01 euggoeted In eeveml Hudlee.
Coneldor poeelblllty of pmgnancy when lnetltutln~ thtmpy; advise patlenb to diecur, therapy If they Intend to or do become prognanf.
Since physical ond psychological dependence to chlordiazepoxide have been reported rarely, use caution m administering Limbitrol to addlction-prone indrvlduals or those who might increase dosoge; withdrmval symptoms following discontinuation of either component alone have been reported (nouse!, heodoche ond malaise for omitriptyline, symptoms [Including convulslons] similar to those of barbilurate withdrawal for chlordlozepoxide) Procautlone: Use with caution in patients with a history af seizures, in hyperthyroid patients or those on thyroid medlcotion, and in potlents with impaired renal or hepotlc tunction. Because of the possibility of suicide m depressed patients, da not permit easy access to Iar e quantities in these potlents. Periodic IivBr function tests and blood coun ?s are recommended during prolonged treatment. Amitriptyline component may block octlon of guonethidrne or similar antihypertensives. Concomitant use with other psychotroplc drugs has not been emluated: sedative effects may be odditive Discontinue several doys before surgery Limit concomitant admmistrahon of ECT to essential treatment See Warnings for precautions about pregnancy. Limbitrol should not be taken during the nursing period Not recommended in children under 12. In the elderly and debilitated, limit to smallest effective dosage to preclude atoxia, avarsedotion, confusion or anhcholinergic effects Advene Reactlone: Most frequently reported ore those (IssocIafed with either component alone: drowsiness, dry mouth, constipation, blurred vision, dizziness and bloohng. LSSSfrequently occurnng moctions include vivid dmoms, impotence, tremor, confusion and nasal congestion. Many depressive symptoms including anorexia, fatigue, weokness, restlessness and lethargy have been reported as side effecis of both Limbitrol and omltnptylme Granulocytopenio, jaundice and hepatic dysfunction have been observedrarely The following list includes adverse reactions not reported with Llmbltrol but requiring consideration because they hove been reported with one or both components or closely related drugs Cardiovnscu/oc Hypotension. hypertension, tachycardia. polpltotions. mvocordial infarction, arrhvlhmias, heart block, stroke P&fi/r?!fic: Euphona, apprehension, poor concentrahon, delusions, hallucinations, hypomanio and increased or decmased hbldo. Mumlogic: Incoordination, ataxia, numbness, tingling and porestheslos of the extremities, extropyramidol symptoms, syncope, changes in EEG patterns. Antlcholinergic: Disturbance of accommodation, parolytlc ileus, urinary retention, dilatation of urinary tract Allergic: Skin rash, urticaria, photosensitization, edema of face ond tongue, prurltus. Hemafologic: Bone morrow depresslon including ogranulocytosls. eosinophilio, purpuro, thrombocytopenia. Gostroinfestinot Nausea, epigastnc drsfress. vomiting, anorexra, stomatrtis. oeculiar taste, diarrhea, block tongue. kndocrins. Teshculor swelling and-gynecomostia In the mole, breast enlargement, galactanhea and minor menstrual irregularities in me female and eletiion ond lowering of blood sugar levels. Other: Headache, weight gain or loss, increased persplrolion, urmory frequency, mydriasis, jaundice, alopema, parohd swelling Ovordoeogo: Immediately hospitalize patient suspected of having token on overdose. Tmotment is symptomatic and supportive. I.V. administratIon of 1 to 3 mg physostigmine salicylate has been reported to reverse the symptoms of am~lriptyline poisoning. See complefe product information for manifestation and treatment. Doeafle: lndividuolize according to symptom severity and patient response Reduce to smallest effective dosage when satisfactory response is obtained. Larger portion of daily dose may be taken at bedtime Single h.s dose may suffice for some patients. Lower dosages am recommended for the elderly Limbitrol 10-25, initial dosage of three to tour tablets daily in divided doses, increased to six tablets or decreased to two tablets daily OS aquired Llmbitrol 5-12.5, initial dosage ot three to four tablets daily in divided doses, for patients who do not tolerate higher doses. 10 mg chlordiozHow Bepplled: White, titm-cooted tablets, each containin epoxide ond 25 m omltriptyline (as the hydrochloride soB1) and blue, filmYl ” coated tablets, eoc contammg 5 mg chlord~azepoxlde and 12.5 mg amitriptVline (as the hydrochloride salt)-botttes of 100 ond 500; Tel-E-Dose* packages at 100, woilable in trays ot 4 mverse-numbered boxes of 25, and in boxes containing 10 strips ot 10; Prescription Puks ot 50. RDCHE PRODUCTS INC. Manati, Puerto Rico 00701
infections
septicemia
infections
and meningitis in neonates.
Nosocomial
Am J Med 1981; 70:
Control measures
disease
Nosocomial
Legionnaires’
legionellosis
disease
Pneumonia Legionnaires’
in the
As of April 30. 1980.83 nosocomial cases of sporadic legionellosis had been reported to the Centers for Disease Control (CDC). All 83 patients had pneumonia: their median age was 56.5 years. All but one were hospitalized at the time of onset. Of 7 1 patients for whom outcome is known, 22 (3 1 percent) died of causes directly attributed to their infection. Eleven patients had end-stage renal disease, 28 were receiving systemic immunosuppressive medications, 17 had cancer, 12 had chronic bronchitis or emphysema, 29 were smokers, and four had diabetes mellll. Risks of acquiring nosocomial sporadic legionellosis for patients with these conditions relative to the general United States population = 340, 26, 11, 3.7, 1.9 and 1.3, respectively. These risk factors are similar to those identified for sporadic community-acquired legionellosis and for epidemic nosocomial legionellosis. Methods for preventing nosocomial legionellosis are not known, but comparing Legionella to other water-associated organisms which have been spread from medical devices to cause pneumonia may be fruitful.
England AC, Ill, Fraser DW: Sporadic and epidemic nosocomial legionellosis United States. Epidemiologic features. Am J Med 1981; 70: 707-711.
Nosocomial
Legionellosls
The past decade brought with it both highly sophisticated neonatal intensive care with improved perinatal mortality rates and increased risk for nosocomial septicemia and meningitis among survivors. Although most of these infections were caused by multiple antibiotic-resistant gram-negative enteric bacteria, Staph. aureus “outbreaks” appeared sporadically. Risk for nosocomial infection was related primarily to factors which enhance infant contact with these bacteria in combination with those poorly defined determinants of bacterial virulence and host defense. Control measures for the prevention or reduction of these infections are aimed at decreasing the neonate’s contact with the “outbreak” strains. Future efforts should be directed toward better definition of bacterial virulence, host susceptibility, and preventive measures.
Baker CJ: Nosocomial 696-701.
Neonatal
therapy
Steel needles
Intravenous
Septicemia Teflon catheters
Preservation of host defenses, antisepsis and asepsis are the three major avenues by which control over infection has been increased. Despite major successes. infection remains the major limitor of surgical horizons. Asepsis has probably been developed to nearly its greatest capacity. Antisepsis, including preventive antibiotics, is also reaching its zenith. Resistant organisms, toxicity and cost, limit further applications. A “social contract” among surgeons is needed to limit, by defined rules, the choice of agent, the total dose and the indications for use. Controlled studies of the effects of “preventive antibiotics” on hospital ecology and infection are also needed. Preservation and enhancement of host defenses is the oldest but the most neglected of these ideas. It appears to be me most exploitable now. Enhancement by nutrition, maintenance of tissue perfusion, oxygenation and immune stimulation appear to have contributed to reduction of infection rates. More success in this area seems distinctly possible.
Am J Med 1981; 70: 712-718.
Antisepsis Immune maintenance
Host resistance
Hunt TK: Surgical wound infections: an overview.
Wound Infection
Asepsis
Complications of intravenous therapy with steel needles and small-bore Teflon catheters were compared in a randomized study of 954 cannula insertions. Cannulas were inserted and cared for by an intravenous team following a standard protocol. There were no cases of cannula-related septicemia and only one case of local infection. There was a low incidence of positive semiquantitative cannula cultures in both treatment groups The risk of phlebitis was significantly greater with Teflon catheters whereas steel needles were significantly associated with infiltration. The over-all rate of complications was significantly greater for the group in which steel needles were used principally due to the increased risk of infiltration. Analysis of the per-day risk of infiltration and phlebitis revealed that these relationships were present for each day cannulas remained in place. It was concluded that steel needles and small-bore Teflon catheters can both be used with low risk of infection and that Teflon catheters more frequently cause phlebitis, whereas steel needles infiltrate more readily.
Tully JL, Friedland GH, Baldini LM, Goldmann DA: Complications of intravenous therapy with steel needles and Teflon Catheters. A comparative study. Am J Med 1981; 70: 702-706.
Infections
Infusions, parenteral Nosocomial