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Ototoxicity of netilmicin
CURRENT LITERATURE
The taps were able to produce the jaw jerk response and were followed by a period of inhibition; however, this SP varied considerably between individuals and within each individual (1.5 to 100 msec). Also, approximately half of the SPs were divided into two parts distinctly separated by a peak of EMG activity. Despite standard stimulus and instructions, SP durations were inconsistent. Many reasons were given for this phenomenon: The starting point and end point of the SP were often unclear; indirect inhibition contributed to SP; patients made small movements of the head and changes in background masseter muscle activity despite instructions to avoid them; and internal disturbances caused by anticipation or expectation of the tap occurred. When considering the possibility of less controlled conditions in a dental office while performing SP measurements, it was concluded that it is impossible to establish criteria for a healthy or pathologic SP duration. The use of a carefully obtained history and clinical examination should prove more reliable when attempting to establish a correct diagnosis.-DoucLAs W. WALLACE Reprint requests to Dr. G. Hellsing: Karolinska Institutet, Odontologiska Fakulteten, Odontologiska Klinikerna, Box 4064, 141 04 Huddinge, Sweden.
Treatment of Herpes Simplex Labialis with Topical Acyclovir in Polyethylene Glycol. Spruance SL, Schnipper LE, Overall JC Jr, et al. J Infect Dis 146:1982 Acyclovir (ACV) is an antiviral agent reported to be topically effective against herpes simplex virus (HSV) infection in animals. It is 150 times more potent than adenine arabinoside against HSV in vitro. A doubleblind study evaluated the clinical use of 5% ACV in polyethelene glycol (PEG) or a placebo of PEG alone in patients who experienced episodes of herpes simplex labialis. The authors studied 208 patients with histories of recurrent episodes of vesicular lesions on the external portion of the lip and perioral skin. Patients were instructed to place either ointment containing ACV with PEG or the placebo q.i.d. The lesions were evaluated according to size, number, painfulness, and stage and were sampled for identification and titration of the virus. No difference was observed clinically with respect to size, painfulness, and stage of the lesion between the two groups. Patients treated with ACV experienced a greater decrease in the medial titer of virus in lesions between the first and second clinic visit than did those treated with the placebo. The antiviral effect of ACV was seen only in those patients who entered the study O-8 hours after the onset of a lesion. No difference was noted in the patients entering the study 9-25 hours after onset of a lesion. There was no statistically significant difference between the ACV and control groups. The efficacy of skin penetration of topically applied ACV and the response of lesions of different ages to ACV should be studied.-STEVE ARAGON Reprint requests to Dr. S. L. Spruance: Div. of Infectious Diseases, Dept. of Medicine, University of Utah Medical Ctr., 50 North Medical, Salt Lake City, UT 84132.
Direct Sagittal Computed Tomography of the Temporomandibular Joint. Mangione JV, Seltzer SE, Katzberg RW, et al: Roentgenology 140:165, 1983 Temporomandibular joint arthrography has been used to demonstrate intraarticular abnormalities involving the TMJ meniscus. Disadvantages of arthrography are that it
479
is invasive and at times painful. A noninvasive technique has been developed by the authors utilizing direct sagittal computed tomography. The technique uses the Siemans Somatom 2@’scanner with the patient lying supine on a stretcher that has been placed parallel to the gantry and perpendicular to the scanner trolley. The TMJ is scanned from the lateral plane to the medial plane using contiguous sections 2 mm thick with the mouth both opened and closed. A case report compares the direct sagittal CT examination with multidirectional tomography and arthrotomography. The CT examination shows a well-defined density anterior to the condyle that represents the displaced meniscus. With the CT image set to optimize bone detail, it was noted there was flattening of the condyle and hypertrophic bone formation. This also correlated well with the conventional tomogram. The close correlation of the CT with arthrographic findings and plain tomograms illustrates that the direct sagittal CT scan has the potential to provide a noninvasive evaluation of the meniscus as well as bony abnormalities of the TMJ.-GREGORY R. ERENA Reprint requests to Dr. Mangione: Dept. of Radiology, Harvard Medical School, Brigham & Women’s Hospital, 75 Francis St., Boston. MA 02115.
Treatment of the Acutely Atrophic Mandible with a Combined Subperiosteal Implant and Bone Graft. Golec TS, Cutri AA. J Oral Implantology 10(3):371, 1982 A technique that uses a combination of modalities for treatment of the atrophic mandible is described. In this technique, a subperiosteal implant is inserted in the usual manner, and cancellous bone from the iliac crest is packed over and under the implant. The major advantage is lessened postoperative ridge resorption. The authors claim that, unlike other grafting procedures, a vestibuloplasty is not needed. This technique is indicated when posterior mandibular bone height is less than 1 cm. It is stated that, given good oral hygiene and proper construction of the prostheses, this procedure is successful and has minimal postoperative complications-JEFFREY B. DEMBO Reprint requests to Dr. Golec: 7060 Clairmont Mesa Blvd., San Diego, CA 92111.
Ototoxicity of Netilmicin. Tjemstom 0, Denneberg T, Harris S, et al. Acta Otolaryngol 94:421, 1982 Netilmicin sulfate is a new semisynthetic aminoglycoside, a derivative of gentamicin CIA, which has an antimicrobial action comparable to that of gentamicin, sisomicin, tobramycin, and amikacin. This investigation studied the clinical efficacy and the ototoxic incidence of netilmicin when used in patients with severe infections. Seventy-six consecutive patients (44 females and 32 males) were included in the study. The median age was 59 years. The indication for treatment was moderate to severe infection with gram-negative bacilli or Sluphyfococcus aureaus. Many patients had other serious illnesses: six had diabetes mellitus; seven were chronic alcoholics, three had malignant diseases; seven had extensive burns; and 19 had reduced renal function. Netilmicin was given intramuscularly in a dose of 1.5 mg/kg two to three times daily. In patients with reduced renal function dosage was modified by increasing the dose intervals. Serum concentrations of netilmicin were assayed every second or third day by microbiologic agar well diffusion
480
CURRENT LITERATURE
method. Renal function was monitored with tests for serum creatinine concentrations at least three times a week. Audiologic and vestibular examinations were performed on four different occasions: the day of treatment; 7-10 days after treatment; one week after treatment, and two to three months after completion of therapy. Hearing function was tested with a pure-tone audiometer and vestibular function was tested for spontaneous gage and positional nystagmus followed by caloric stimulation with 30°C and 44°C water irrigation. Results with netilmicin alone or in combination with other antibiotics were considered efficacious in 70 out of 74 patients. Of the 77 bacterial specimens cultured, 51 were gram-negative bacilli, 13 were S. UWPUS, and 13 were various strains of streptococci. Elevated serum creatinine concentrations were seen in 17 patients. Six of these patients had underlying renal disease, but in the other 11, netilmicin could have been the cause of impaired renal function. Vestibular findings were abnormal in 12 patients after therapy. Audiologic findings showed that 27 patients had a hearing impairment, but 18 of these had prior impairment before treatment. In none of these 18 patients could any further deterioration of the hearing be found after treatment. In conclusion, the efficacy of netilmicin alone or in combination with other antibiotics was found to be clinically highly effective in a wide range of serious infections with a variety of gram-negative bacteria. The incidence of nephrotoxicity in this study was low, and the rise in serum creatinine was usually slight and in most cases reversible. Ototoxicity was related to the accumulation and the very slow clearance of the drug from inner ear fluids. The absence of sufficiently low trough levels for adequate periods may thus be an important factor of ototoxicity. The study found only one case of netilmicinrelated ototoxicity, and this was a reversible vestibular dysfunction.-ROBERT C. HOBBS Reprint requests to Dr. TjemstrBm: Department of Otolaryngology, Malmb General Hospital, S-21401, Malmii. Sweden. The pharmacokinetics of alfentanil (R39209): opioid analgesic. Bovill JG, et al. Anesthesiology 1982
A new 57:439,
Alfentanil hydrochloride is a new, short-acting opioid analgesic, chemically related to fentanyl, that is undergoing clinical testing. This study discusses the pharmacokinetic properties of alfentanil in humans. Six patients were given 50 p_g/kg. All underwent a variety of surgical procedures. Maintenance fluids were used, and blood loss in excess of 300 ml was replaced. Blood samples were drawn, and alfentanil concentrations were determined by radioimmunoassay. Ninety per cent of the administered dose had left the plasma within 30 minutes. The pharmacokinetics can be described by a three compartment model, with the plasma concentrations after intravenous bolus injection declining triexponentially in a manner similar to fentanyl. The terminal elimination half-life is considerable shorter than that of fentanyl. A continuous analgesic infusion is possible due to its short duration of action.-JOSEPH
E. VAN SICKELS
Reprint requests to Dr. Bovill: Department of Anaesthesia, Academic Hospital, University of Amsterdam, Eerste Helmersstraat 104, 1054 EG Amsterdam, Netherlands.
Role of Platelets and Fibrin in the Healing Knighton DR. Ann Surg 196(4):379, 1982
Sequence.
An orderly progression of healing follows the presence of activated platelets and fibrin at the site of tissue damage. In vivo studies (in rabbit corneas) demonstrated the ability of thrombin-activated platelets to stimulate angiogenesis and increase collagen synthesis. In addition, these experiments showed that fibrin and its degradation products were chemotactic for leukocytes, which subsequently produced neovascularization. Activated platelets produce and release a mitogen, platelet-derived growth factor (PDGF), for fibroblasts and smooth muscle cells. It may be assumed from these findings that in those patients with thrombocytopenia, leukopenia, or clotting disorders, nonhealing wounds might be due to the absence of these mitogenic and chemotactic factors. Transfusion of these blood products to a patient who was deficient in them resulted in wound healing.-VICTOR F. SZYMELA Reprint requests to Dr. Knighton. University of California, San Francisco 839 HSE. San Francisco. CA 94143.
Rhinometry: Measurement of Nasal Patency. JT. Ann Allergy 49(4):--, 1982
Connell
Rhinometry is the measurement of nasal airflow and therefore provides an assessment of nasal patency. The authors describe a method of rhinometry using simple devices applied externally to the nostrils. Transducers placed in one nostril measure the pressure, while those in the other measure the air speed. The nasal patency (resistance) is obtained by dividing the change in pressure (API, measured in centimeters of HzO, by volume (V’), measured in liters per second. This method is less expensive and less complex than other methods. It can be applied clinically to patient assessment in the clinician’s office before and after surgery. Other methods of measurement are discussed along with their disadvantages.VICTOR R. SZYMELA Reprint requests to Dr. Connell: Nasal Diseases Study Center, Holy Name Hospital, Teaneck, NJ 07666.
Influence of Oral Atropine or Hyoscine on the Absorption of Oral Diazepam. Gregoretti SM, Uges DRA. Br J Anesth 54(11):1231, 1982 This article studied the influence of oral atropine on the absorption of oral diazepam. Both drugs were administered at the same time to eight volunteers. Using a threeway crossover randomized double-blind design, the effects of combining anticholinergic premeditation with oral diazepam were assessed. No difference was found in the timing or the amount of sedation between diazepam used alone or in combination with atropine. The serum diazepam concentrations were not significantly different after any of the three test regimens. It is concluded from this study that when the use of an anticholinergic in premedication is desirable, atropine can be administered orally with diazepam without a delay or reduction in its effect.-CHARLES L. RINCGOLD Reprint requests to Drs. Gregoretti and Uges: Department of Anaesthesia, St. Radbound-Ziekenhuis, Catholic University, 6500 H B Nijmegen, The Netherlands.
The taps were able to produce the jaw jerk response and were followed by a period of inhibition; however, this SP varied considerably between individuals and within each individual (1.5 to 100 msec). Also, approximately half of the SPs were divided into two parts distinctly separated by a peak of EMG activity. Despite standard stimulus and instructions, SP durations were inconsistent. Many reasons were given for this phenomenon: The starting point and end point of the SP were often unclear; indirect inhibition contributed to SP; patients made small movements of the head and changes in background masseter muscle activity despite instructions to avoid them; and internal disturbances caused by anticipation or expectation of the tap occurred. When considering the possibility of less controlled conditions in a dental office while performing SP measurements, it was concluded that it is impossible to establish criteria for a healthy or pathologic SP duration. The use of a carefully obtained history and clinical examination should prove more reliable when attempting to establish a correct diagnosis.-DoucLAs W. WALLACE Reprint requests to Dr. G. Hellsing: Karolinska Institutet, Odontologiska Fakulteten, Odontologiska Klinikerna, Box 4064, 141 04 Huddinge, Sweden.
Treatment of Herpes Simplex Labialis with Topical Acyclovir in Polyethylene Glycol. Spruance SL, Schnipper LE, Overall JC Jr, et al. J Infect Dis 146:1982 Acyclovir (ACV) is an antiviral agent reported to be topically effective against herpes simplex virus (HSV) infection in animals. It is 150 times more potent than adenine arabinoside against HSV in vitro. A doubleblind study evaluated the clinical use of 5% ACV in polyethelene glycol (PEG) or a placebo of PEG alone in patients who experienced episodes of herpes simplex labialis. The authors studied 208 patients with histories of recurrent episodes of vesicular lesions on the external portion of the lip and perioral skin. Patients were instructed to place either ointment containing ACV with PEG or the placebo q.i.d. The lesions were evaluated according to size, number, painfulness, and stage and were sampled for identification and titration of the virus. No difference was observed clinically with respect to size, painfulness, and stage of the lesion between the two groups. Patients treated with ACV experienced a greater decrease in the medial titer of virus in lesions between the first and second clinic visit than did those treated with the placebo. The antiviral effect of ACV was seen only in those patients who entered the study O-8 hours after the onset of a lesion. No difference was noted in the patients entering the study 9-25 hours after onset of a lesion. There was no statistically significant difference between the ACV and control groups. The efficacy of skin penetration of topically applied ACV and the response of lesions of different ages to ACV should be studied.-STEVE ARAGON Reprint requests to Dr. S. L. Spruance: Div. of Infectious Diseases, Dept. of Medicine, University of Utah Medical Ctr., 50 North Medical, Salt Lake City, UT 84132.
Direct Sagittal Computed Tomography of the Temporomandibular Joint. Mangione JV, Seltzer SE, Katzberg RW, et al: Roentgenology 140:165, 1983 Temporomandibular joint arthrography has been used to demonstrate intraarticular abnormalities involving the TMJ meniscus. Disadvantages of arthrography are that it
479
is invasive and at times painful. A noninvasive technique has been developed by the authors utilizing direct sagittal computed tomography. The technique uses the Siemans Somatom 2@’scanner with the patient lying supine on a stretcher that has been placed parallel to the gantry and perpendicular to the scanner trolley. The TMJ is scanned from the lateral plane to the medial plane using contiguous sections 2 mm thick with the mouth both opened and closed. A case report compares the direct sagittal CT examination with multidirectional tomography and arthrotomography. The CT examination shows a well-defined density anterior to the condyle that represents the displaced meniscus. With the CT image set to optimize bone detail, it was noted there was flattening of the condyle and hypertrophic bone formation. This also correlated well with the conventional tomogram. The close correlation of the CT with arthrographic findings and plain tomograms illustrates that the direct sagittal CT scan has the potential to provide a noninvasive evaluation of the meniscus as well as bony abnormalities of the TMJ.-GREGORY R. ERENA Reprint requests to Dr. Mangione: Dept. of Radiology, Harvard Medical School, Brigham & Women’s Hospital, 75 Francis St., Boston. MA 02115.
Treatment of the Acutely Atrophic Mandible with a Combined Subperiosteal Implant and Bone Graft. Golec TS, Cutri AA. J Oral Implantology 10(3):371, 1982 A technique that uses a combination of modalities for treatment of the atrophic mandible is described. In this technique, a subperiosteal implant is inserted in the usual manner, and cancellous bone from the iliac crest is packed over and under the implant. The major advantage is lessened postoperative ridge resorption. The authors claim that, unlike other grafting procedures, a vestibuloplasty is not needed. This technique is indicated when posterior mandibular bone height is less than 1 cm. It is stated that, given good oral hygiene and proper construction of the prostheses, this procedure is successful and has minimal postoperative complications-JEFFREY B. DEMBO Reprint requests to Dr. Golec: 7060 Clairmont Mesa Blvd., San Diego, CA 92111.
Ototoxicity of Netilmicin. Tjemstom 0, Denneberg T, Harris S, et al. Acta Otolaryngol 94:421, 1982 Netilmicin sulfate is a new semisynthetic aminoglycoside, a derivative of gentamicin CIA, which has an antimicrobial action comparable to that of gentamicin, sisomicin, tobramycin, and amikacin. This investigation studied the clinical efficacy and the ototoxic incidence of netilmicin when used in patients with severe infections. Seventy-six consecutive patients (44 females and 32 males) were included in the study. The median age was 59 years. The indication for treatment was moderate to severe infection with gram-negative bacilli or Sluphyfococcus aureaus. Many patients had other serious illnesses: six had diabetes mellitus; seven were chronic alcoholics, three had malignant diseases; seven had extensive burns; and 19 had reduced renal function. Netilmicin was given intramuscularly in a dose of 1.5 mg/kg two to three times daily. In patients with reduced renal function dosage was modified by increasing the dose intervals. Serum concentrations of netilmicin were assayed every second or third day by microbiologic agar well diffusion
480
CURRENT LITERATURE
method. Renal function was monitored with tests for serum creatinine concentrations at least three times a week. Audiologic and vestibular examinations were performed on four different occasions: the day of treatment; 7-10 days after treatment; one week after treatment, and two to three months after completion of therapy. Hearing function was tested with a pure-tone audiometer and vestibular function was tested for spontaneous gage and positional nystagmus followed by caloric stimulation with 30°C and 44°C water irrigation. Results with netilmicin alone or in combination with other antibiotics were considered efficacious in 70 out of 74 patients. Of the 77 bacterial specimens cultured, 51 were gram-negative bacilli, 13 were S. UWPUS, and 13 were various strains of streptococci. Elevated serum creatinine concentrations were seen in 17 patients. Six of these patients had underlying renal disease, but in the other 11, netilmicin could have been the cause of impaired renal function. Vestibular findings were abnormal in 12 patients after therapy. Audiologic findings showed that 27 patients had a hearing impairment, but 18 of these had prior impairment before treatment. In none of these 18 patients could any further deterioration of the hearing be found after treatment. In conclusion, the efficacy of netilmicin alone or in combination with other antibiotics was found to be clinically highly effective in a wide range of serious infections with a variety of gram-negative bacteria. The incidence of nephrotoxicity in this study was low, and the rise in serum creatinine was usually slight and in most cases reversible. Ototoxicity was related to the accumulation and the very slow clearance of the drug from inner ear fluids. The absence of sufficiently low trough levels for adequate periods may thus be an important factor of ototoxicity. The study found only one case of netilmicinrelated ototoxicity, and this was a reversible vestibular dysfunction.-ROBERT C. HOBBS Reprint requests to Dr. TjemstrBm: Department of Otolaryngology, Malmb General Hospital, S-21401, Malmii. Sweden. The pharmacokinetics of alfentanil (R39209): opioid analgesic. Bovill JG, et al. Anesthesiology 1982
A new 57:439,
Alfentanil hydrochloride is a new, short-acting opioid analgesic, chemically related to fentanyl, that is undergoing clinical testing. This study discusses the pharmacokinetic properties of alfentanil in humans. Six patients were given 50 p_g/kg. All underwent a variety of surgical procedures. Maintenance fluids were used, and blood loss in excess of 300 ml was replaced. Blood samples were drawn, and alfentanil concentrations were determined by radioimmunoassay. Ninety per cent of the administered dose had left the plasma within 30 minutes. The pharmacokinetics can be described by a three compartment model, with the plasma concentrations after intravenous bolus injection declining triexponentially in a manner similar to fentanyl. The terminal elimination half-life is considerable shorter than that of fentanyl. A continuous analgesic infusion is possible due to its short duration of action.-JOSEPH
E. VAN SICKELS
Reprint requests to Dr. Bovill: Department of Anaesthesia, Academic Hospital, University of Amsterdam, Eerste Helmersstraat 104, 1054 EG Amsterdam, Netherlands.
Role of Platelets and Fibrin in the Healing Knighton DR. Ann Surg 196(4):379, 1982
Sequence.
An orderly progression of healing follows the presence of activated platelets and fibrin at the site of tissue damage. In vivo studies (in rabbit corneas) demonstrated the ability of thrombin-activated platelets to stimulate angiogenesis and increase collagen synthesis. In addition, these experiments showed that fibrin and its degradation products were chemotactic for leukocytes, which subsequently produced neovascularization. Activated platelets produce and release a mitogen, platelet-derived growth factor (PDGF), for fibroblasts and smooth muscle cells. It may be assumed from these findings that in those patients with thrombocytopenia, leukopenia, or clotting disorders, nonhealing wounds might be due to the absence of these mitogenic and chemotactic factors. Transfusion of these blood products to a patient who was deficient in them resulted in wound healing.-VICTOR F. SZYMELA Reprint requests to Dr. Knighton. University of California, San Francisco 839 HSE. San Francisco. CA 94143.
Rhinometry: Measurement of Nasal Patency. JT. Ann Allergy 49(4):--, 1982
Connell
Rhinometry is the measurement of nasal airflow and therefore provides an assessment of nasal patency. The authors describe a method of rhinometry using simple devices applied externally to the nostrils. Transducers placed in one nostril measure the pressure, while those in the other measure the air speed. The nasal patency (resistance) is obtained by dividing the change in pressure (API, measured in centimeters of HzO, by volume (V’), measured in liters per second. This method is less expensive and less complex than other methods. It can be applied clinically to patient assessment in the clinician’s office before and after surgery. Other methods of measurement are discussed along with their disadvantages.VICTOR R. SZYMELA Reprint requests to Dr. Connell: Nasal Diseases Study Center, Holy Name Hospital, Teaneck, NJ 07666.
Influence of Oral Atropine or Hyoscine on the Absorption of Oral Diazepam. Gregoretti SM, Uges DRA. Br J Anesth 54(11):1231, 1982 This article studied the influence of oral atropine on the absorption of oral diazepam. Both drugs were administered at the same time to eight volunteers. Using a threeway crossover randomized double-blind design, the effects of combining anticholinergic premeditation with oral diazepam were assessed. No difference was found in the timing or the amount of sedation between diazepam used alone or in combination with atropine. The serum diazepam concentrations were not significantly different after any of the three test regimens. It is concluded from this study that when the use of an anticholinergic in premedication is desirable, atropine can be administered orally with diazepam without a delay or reduction in its effect.-CHARLES L. RINCGOLD Reprint requests to Drs. Gregoretti and Uges: Department of Anaesthesia, St. Radbound-Ziekenhuis, Catholic University, 6500 H B Nijmegen, The Netherlands.