Honey for wounds, ulcers, and skin graft preservation

756

MINIMUM INHIBITORY CONCENTRATIONS

Hepatic toxicity of liposomal encapsulated

(1l9/mL)

doxorubicin SIR,-We read with interest Dr Hengge and colleagues’ (Feb 6, 383) report of fatal hepatotoxicity in a patient with AIDS-related disseminated Kaposi’s sarcoma (KS) treated with liposomal encapsulated doxorubicin (Doxil). We have now treated 27 patients

p

with this

drug with no clinically significant episodes of hepatotoxicity. The results of treatment of the first 15 of these patients (all male homosexuals, median age 39, range 24-61) covering 86 treatment cycles (38 cycles at 10 mg/m2 and 33 at 20 mg/mz) have been analysed. Most patients had fairly poor prognosis disease as assessed by the TIS system1 (only 3 patients were stage TIll SI); Karnofsky indices ranged from 30-100 (median 70). In most treatment cycles, there were no changes in liver enzymes (table) and where they occurred no patient had a rise of more than 2-5 x normal or a rise in prothrombin time of more than 1.25

x

normal. HEPATIC TOXICITY OF LIPOSOMAL ENCAPSULATED DOXORUBICIN (DOXIL)

strains of S aureus that had been isolated from different patients in a hospital in Tokyo in 1991 were tested for susceptibility to triclosan. S aureus RN2677 was used as an antiseptic-sensitive strain and as the recipient in plamid-transfer experiments.3 Strains N4901 and N522 were resistant to triclosan while being sensitive to other antiseptics (table). The coagulases of strains N4901 and N522 were of types VII and III, respectively. Both

strains were sensitive to methicillin. Resistance to triclosan was not transfered from stains N4901 and N522 to S aureus RN2677 by the filter-mating method. The triclosan-resistant determinant is a new antiseptic-resistance determinant on the chromosome of S aureus. Triclosan-resistant strains may appear among methicillin-resistant strains of S aureus that are resistant to multiple antibiotics and multiple antiseptics.

Department of Microbiology, Tokyo College of Pharmacy, Tokyo 192 03, Japan Total 86 cycles, 3 not assessable *Cnteria from National Cancer Institute, Bethesda, USA.

London W2 1NY, UK

R. J. COKER N. D. JAMES J. S. W. STEWART

Wernz JC, for the AID S Clinical Trials Oncology Committee. acquired immunodeficiency syndrome: a proposal for uniform evaluation, response and staging criteria Clin Oncol 1989, 7: 1201-07. 2. Gregoriades G, ed. Liposomes as drug carriers. New York: Wiley, 1988. 3. Papahadjopoulos D, Allen TM, Gabizon A, et al. Sterically stabilised liposomes: improvements in pharmacokinetics and antitumour therapeutic efficacy. Proc Natl Acad Sci USA 1991; 88: 11460-64. 1. Krown SE, Metroka C,

Kaposi’s

sarcoma

Lyman FL, Furia T. Toxicology of 2,4,4’-trichloro-2’-hydroxy-diphenyl ether. Indust Med 1969; 38: 64-71. 2. Bartzokas CA, Paton JH, Gibson MF, Graham R, McLoughlin GA, Croton RS. Control and eradication of methicillin-resistant Staphylococcus aureus on a surgical unit. N Engl J Med 1984; 311: 1422-25. 3. Sasatsu M, Shibata Y, Tamura S, Kono M. Drug-resistant plasmids in multiply drug-resistant Staphylococcus aureus L20A. Microbiol Lett 1990; 43: 105-12. 4. Sasatsu M, Shibata Y, Noguchi N, Kono M. High-level resistance to ethidium bromide and antiseptics in Staphylococcus aureus. FEMS Microbiol Lett 1992; 93: 1.

Conventional liposomes are rapidly removed from the circulation by the reticuloendothelial system (RES) limiting their use as drug delivery systems,Z especially for hepatotoxic drugs such as doxorubicin. The liposomes used in the formulation of Doxil have been sterically stabilised by modification with polyethylene glycol, decreasing uptake by the RES, reducing hepatotoxicity and increasing circulation time five-fold.3 Evidence of hepatotoxicity from liposomal encapsulated doxorubicin in the patients treated at our institution is limited; indeed the toxicity of the treatment has been impressively low. Although Hengge and co-workers state that hepatitis B was not reactivated, they subsequently present polymerase chain reaction data showing that replication of the hepatitis B virus did indeed occur and correctly state that there are few data on viral load in patients with endstage HIV infection. Thus the case reported probably represents at worst an idiosyncratic reaction to doxorubicin, augmented by replication of the hepatitis B virus rather than a major toxicity of liposomal encapsulated doxorubicin Departments of Genitourinary Medicine and Communicable Diseases, and Oncology, St Mary’s Hospital,

MASANORI SASATSU KEIICHI SHIMIZU NORIHISA NOGUCHI MEGUMI KONO

in the

Triclosan-resistant Staphylococcus aureus SiR,—Triclosan is a bis-phenol disinfectant, with a bacteriostatic action against gram-positive and most gram-negative organisms,! and it is used in surgical scrubs, soaps, and deodorants at 0.5-2%. For washing and bathing, triclosan was effective in the control of infection due to methicillin-resistant Staphylococcus aureus in a surgical unit.2 The ebr gene in S aureus mediates resistance to DNA-intercalating dyes and quaternary ammonium-type antiseptics.3,4 However, strains with ebr gene are also sensitive to triclosan. We have found triclosan-resistant strains of S aureus. Minimum inhibitory concentrations were estimated by the two-fold dilution method on Mueller-Hinton agar plates.’ 50

109-14. 5.

Japan Society of Chemotherapy. Method of MIC determination. Chemotherapy 1981; 29: 76-79.

Honey for wounds, ulcers, and skin graft preservation SIR,-With respect to your recent discussions (Jan 2, p 63, Jan 9, p 90) about the use of honey we draw your attention to the following. For 4000 years the wound healing properties of honey have been cleansing, absorption of oedema, antimicrobial activity, deodorisation, promotion of granulation, tissue formation, and epithelialisation, and improvement of nutrition. These factors are probably also important for preservation of skin grafts. The antibacterial activity of honey is due mainly to an "inhibine" factor, which is hydrogen peroxide, an end product of the enzymatic reaction of glucose oxidase (from the bee) with glucose in diluted honey.2 Honey, however, can certainly not be regarded as sterile and often contains, apart from non-pathogenic Bacillus spp, clostridial spores. Honey can cause infant botulism.3 Exposure of patients to an additional risk of infection—eg, wound botulism or gangrene, is medically unacceptable.4 Like other natural products, the composition of honey is not constant and, moreover, it may contain residues of pesticides or drugs such as tetracycline that are used for treatment of bee diseases. In most countries honey for human consumption must be checked for residues; however, for medical use higher quality standards are needed. It seems advisable to use only honey derived from specified-pathogen-free (SPF) hives, which have not been treated with drugs, and are gathered in areas where no pesticides are used. We showed that the floral origin considerably affected the antibacterial activity of honey, but different batches of the same origin showed only minor variations. The bactericidal quality of honey was tested by an agar dilution method. We used not only Staphylococcus aureus (ATCC 29213), as recommended by White et al/ but also other reference strains: Streptococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), and Escherichia coli (ATCC 25922). Five honey concentrations (20%,16%,12%,8%, and 4%

w/w) were tested and the inhibine value was the number of

757

INHIBINE VALUES FOR LIME TREE HONEY (L), FRUIT TREE HONEY (F), ACACIA HONEY (A), AND COMMERCIAL CLOVER-LIME HONEY (CL)

*Inactivated honey 100°C

(for L, F, and A).

the plate with the lowest honey concentration that did not allow visible growth. For example, an inhibine value of 4 means no growth on the fourth plate (8% honey). Control plates without honey were always included. The sum of the inhibine values for the four test strains was used as an indication for the antibacterial activity of a particular honey (table). Antibacterial activity varied with concentration and floral origin. Lime tree honey seemed better than both fruit tree and acacia honey. A lime honey concentration of 8% was bactericidal for Staph aureus, P aeruginosa, and E coli, and 12% was bactericidal for Strep faecalis; similar results (8% and 12%, respectively) were obtained with a Clostridium botulinum (ATCC 19397) and a C perfringens (ATCC 13124) strain. Lime honey had a total inhibine value of 15 (of a maximum 20), and fruit tree and acacia honey had values of 5 and 11, respectively. Clover-lime honey bought in a supermarket had no antibacterial activity (table). The same results were obtained with Iso sensitest agar (Oxoid) and Brucella agar (Oxoid), with or without 5% sheep plasma. However, addition of 5% sheep blood (catalase) eliminated all antibacterial activity. The total value of our lime honey remained constant over more than a year and perhaps much longer if properly

stored.5 Two batches of lime honey were tested for bacterial contamination.3 One batch contained 520 colony-forming units (CFU) per 100 g of honey (40 CFU were identified as C perfringens, the others were Bacillus spp), whereas the second batch contained 4200 CFU bacillus spores per 100 g. Irradiation with 1.8x104 Gy rendered both batches of honey sterile without affecting the antibacterial activity. Honey intended for medical use should be sterile and free of residues, which might make the clinical use of honey more acceptable. For evaulation of the results of clinical trials, the antibacterial activity of the batch of honey used might be important. Department of Internal Medicine, Academic Hospital Maasstricht, NL-6200 MD Maastricht, Netherlands

THEO POSTMES

Department of Medical University of Limburg

ANTONY E. VAN DEN BOGAARD MATHEW HAZEN

Microbiology,

healing properties of honey. Br J Surg 1988, 75: 679-81. 2. White JW, Subers MH, Shepartz AI. The identification of inhibine, the antibacterial factor in honey, as hydrogen peroxide and its origin in a honey glucosidase-oxidase system. Biochem Biophys Acta 1963; 73: 37-70. 3. Midura TF, Snowden S, Wood RM, Amon SS. Isolation of clostridium botulinum from honey. J Clin Microbiol 1979; 9: 282-83. 4. Mossel DAA. Honey for necrotic breast ulcers. Lancet 1980; ii: 1091. 5. White JW. Wiley led the way: a century of federal honey research J Assoc Off Anal Chem 1987; 70: 181-89. 1. Efem S. Clinical observations of the wound

Acute stump

appendicitis

SIR,-Inflammation of the appendiceal stump is rarely reported and is considered to result from a stump left too long. We report a patient with acute stump appendicitis. A 26-year-old male was admitted with abdominal pain radiating to the groin and a raised temperature of 36 hours duration. He had been seen in the emergency room 12 hours previously and had been discharged with antibiotic treatment for a suspected urinary tract infection. He returned to hospital because the pain increased. One year previously, he had had an appendicectomy for acute appendicitis in another hospital. On admission, he appeared ill with a fever of 39°C and a tachycardia of 120/min. His abdomen was diffusely tender with maximum guarding over the appendicectomy scar, rebound, and no bowel sounds. Urinalysis, as well as plain

abdominal Sims and ultrasonography, showed no pathology, but his white blood cell count was 12 x 109/L. At laparotomy for diffuse peritonitis, the terminal ileum and caecum were oedematous and covered with fibrous adhesions and pus, the mesentery was also oedematous, and the appendiceal stump could not be identified. The caecum and distal 30 cm of terminal ileum were resected and a primary ileocolostomy was performed. The patient was treated with broad spectrum parenteral antibiotics and recovered uneventfully. Pathological examination of the specimen showed acute inflammation and perforation of the appendiceal stump with acute peritonitis; the resected caecum and ileal segment showed an inflammatory process of the serosal surfaces with no intrinsic

pathology. We believe that the incidence of stump appendicitis is underestimated. The relapse of an inflammatory process in an appendiceal stump, with an interval of onset ranging from a few months to 20 years,l,2 is probably related to incomplete removal of the appendix leaving a remnant as long as 1-9 cm.3 The general practitioner, as well as the surgeon, faced with a patient with abdominal pain and a past appendicectomy, will justifiably consider other diagnoses leading to a delay in referral and treatment. With the recently introduced technique of laparoscopic appendicectomy, we may encounter many more cases of stump appendicitis. Where possible, stump resection alone for cases of acute stump appendicitis should be favoured. Department of Surgery, Hadassah University Hospital Mount Scopus, PO Box 24035, Jerusalem 91240, Israel

E. FEIGIN M. CARMON A. SZOLD D. SEROR

Baumgardner LO. Rupture of appendiceal stump three months after uneventful appendectomy with repair and recovery. Ohio State Med J 1949; 45: 476-77. 2. Siegel SA. Appendiceal stump abscess: a report of stump abscess twenty-three years post appendectomy. Am J Surg 1954; 63: 630-32. 3. Green JM, Pekler D, Schumer W, et al. Incomplete surgical removal of the appendix: its complications. J Int Coll Surg 1956; 26: 141-46. 1.

myelopathy in 43-year-old woman

HTLV-II associated

SIR,-Despite case reports of haematological and neurological disorders in HTLV-II infected patients,1-4 no disease associations have been proven. The Retrovirus Epidemiology in Blood Donor Study (REDS) includes cohorts of HTLV-I and HTLV-II infected blood donors and their sexual partners. Enrolment examination of 364 HTLV-11 infected subjects yielded 1 case of an illness undistinguishable from HTLV-I associated myelopathy (HAM). Our patient is a 43-year-old white woman married to a symptom-free, HTLV-II infected man with a remote history of intravenous drug use. The patient received intramuscular amphetamine injections with shared needles 14 years ago. She described an insidious onset of intermittent painless "giving way" of her knees while standing or walking. She developed urinary frequency, urgency, and nocturia over the past 1-2 years and has longstanding, intermittent low back pain without a spinal or nerve root lesion on lumbar magnetic resonance imaging (MRI). She denied any stiffness or slowness in walking, and had no other neurological symptoms. There was no history of neurological disease among her four sisters or parents. Her two children were bom by caesarean section and have not been tested for HTLV-II. The patient’s general physical and mental status, and cranial nerve examinations were normal. There was normal bulk in the arms and legs, and fasciculations were absent. Muscle tone was normal in the arms and spastic in the legs. Fast finger movements were normal. Foot tapping was slow bilaterally but had a normal rhythm. Muscle power was normal, including foot dorsiflexors. Reflexes were more hyperactive in the legs than the arms; percussion of the quadriceps tendon elicited five beats of clonus bilaterally. The jaw jerk was normoactive. Her gait was mildly spastic. Plantar responses were unreactive. Sensory examination was normal, with no sensory level. Laboratory studies showed normal blood counts, erythrocyte sedimentation rate, vitamin Blz, and thyroid function tests, and negative syphilis and HIV serology. MRI of the brain and spinal