For determination of the best basis on which to calculate dosages of gentamicin or tobramycin to be administered to obese patients, the pharmacokinetics of these drugs were studied in 13 obese subjects and 13 subjects of a normal weight following intravenous infusion of 1 mg/kg. Half-lives, elimination constants, and absolute and relative volumes of distribution were calculated. Concentrations of drug in serum were significantly higher and relative volumes of distribution were significantly lower in obese subjects as compared with controls. However, relative volumes of distribution based on lean body mass of obese subjects were significantly greater than those of normal-weight subjects. These results indicate that gentamicin and tobramycin are distributed less to adipose tissue than to other tissues, but partial distribution to adipose tissue does occur. The mean relative volume of distribution in obese subjects closely approximated that in normal subjects when normalized body mass plus 40% of the adipose mass was used as the total weight in obese subjects.
Microneurosurgical procedures on the trigeminal-nerve root are often followed by reactivation of herpes simplex virus infection, manifested by herpes labialis or oropharyngeal herpesvirus shedding or both. In a double-blind study of the ability of human leukocyte interferon to prevent this reactivation, patients with a history of herpes labialis were given 7 x 10(4) U of interferon per kilogram of body weight per day or placebo for five days beginning on the day before operation. In 18 patients treated with placebo, herpes labialis developed in 10, and virus shedding in the oropharynx in 15. In 19 patients treated with interferon, lesions developed in five, and shedding in eight. The frequency of reactivation as measured by lesions or positive throat cultures or both was significantly reduced by interferon (P less than 0.05). Of 127 daily throat-wash cultures in the placebo group, 42 per cent were positive for herpesvirus, but of 134 in the interferon group, only 9 per cent were positive (P less than 0.001). We conclude that interferon at a well-tolerated dosage reduces reactivation of latent herpes simplex virus infection after a potent operative stimulus.
Reactivation of herpes simplex virus was prospectively studied in patients after microneurosurgical decompression of the trigeminal sensory root, a new operation for trigeminal neuralgia in which the nerve is not sectioned. Reactivation was detected in 28 (50%) of 56 patients. Virus was cultured from oropharyngeal secretions in 25 patients, and 21 patients developed cutaneous herpetic lesions. Seven patients had positive throat-wash (TW) cultures but did not develop lesions, and the converse occurred in three patients. Eighteen patients had both positive TW cultures and herpetic lesions. In eight of nine instances in which a sequence was determinable, TW cultures were positive before lesions developed. A history of recurrent herpes labialis was associated with a higher risk of developing reactivation postoperatively (59.4% vs. 31.6%, P less than 0.05). These observations suggest that minimal stimulation or inapparent trauma to the trigeminal sensory root is sufficient to activate latent herpes simplex virus in humans. These patients provide unique opportunities to study immunologic responses and therapeutic measures.
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