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Biomedical subjects

O L Laskin

Publications and source records attributed to O L Laskin.

At least 37 records · Page 2Linked to original sources
PubMed1986

Herpes zoster and zosteriform herpes simplex virus infections in immunocompetent adults.

Among 111 immunocompetent patients referred to a general hospital setting with the clinical diagnosis of herpes zoster, viral cultures were obtained from 47 patients. Six of these patients (13 percent) had herpes simplex virus isolated, with four of the six infections involving the facial distribution, and the other two involving the T4 (breast) distribution. Excluding those in whom herpes simplex virus was isolated, the mean age (+/- SD) of the remaining 105 patients was 50 +/- 19 years. Thirty-two percent of the patients were at least 65 years old; however, 39 percent were younger than 40 years of age. Thus, herpes zoster frequently occurs in young, immunocompetent adults. Also, since zosteriform rashes may be caused by herpes simplex virus, viral cultures of lesions are useful to differentiate infections caused by herpes simplex virus from those due to varicella-zoster virus. The need to distinguish between these two viruses may be important with the advent of antiviral drugs and for use of the proper epidemiologic isolation procedures.

Adolescent↗
PubMed1986

Antiviral therapy with ganciclovir for cytomegalovirus retinitis and bilateral exudative retinal detachments in an immunocompromised child.

A child with bilateral cytomegalovirus (CMV) retinitis, vitritis, and exudative retinal detachments, who was in remission from stage IV neuroblastoma and status post-chemotherapy and autologous bone marrow transplantation, was treated with ganciclovir. The drug is a new acyclic nucleoside antiviral drug with potent antiCMV activity. There was bilateral retinal reattachment, clearing of vitritis and regression of retinal exudates and hemorrhages, with concomitant resolution of viral shedding in urine and blood, on ganciclovir 7.5 mg/kg per day. There was recurrence of exudative detachments, vitritis and retinitis when the dose was reduced to 2.5 mg/kg per day, and regression of these findings when the dose was again increased to 7.5 mg/kg per day. Despite continued therapy at this dose, a relapse occurred. When the dose of drug was doubled to 15 mg/kg per day, there initially was a partial therapeutic response, followed by a subsequent relapse. No further response was seen when the dose was increased to 19.5 mg/kg per day. This patient was treated with ganciclovir for a total of 192 days. No adverse reactions to ganciclovir were seen. On the last day of drug administration, there were persistent bilateral exudative retinal detachments and progressive optic nerve head involvement with optic disc pallor, despite quiescence of the retinitis.

Acyclovir↗
PubMed1986

Pentamidine-induced hypoglycemia in patients with the acquired immune deficiency syndrome.

We conducted an analysis of 37 patients with the acquired immune deficiency syndrome (AIDS) who received pentamidine for the treatment of Pneumocystis carinii pneumonia to quantitate the incidence and severity of pentamidine-induced hypoglycemia. Ten of these patients (27%), nine of whom were symptomatic, developed hypoglycemia during or shortly after pentamidine therapy. The mean nadir blood glucose concentration in those who developed hypoglycemia during or shortly after pentamidine therapy was 38 mg/dl (range 20 to 55 mg/dl). The hypoglycemia frequently persisted after the end of pentamidine therapy. The incidence of nephrotoxicity in patients who developed hypoglycemia was 100%, as compared with 38% in the group who remained euglycemic (P less than 0.01). The overall incidence of pentamidine-induced hypoglycemia with AIDS is several-fold higher than previously reported for patients with other immunocompromising diseases who receive pentamidine. We conclude that pentamidine-induced hypoglycemia is a frequent adverse reaction in patients with AIDS and is potentially life-threatening if not recognized.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Acyclovir. Pharmacology and clinical experience.

Acyclovir is a selective antiherpes agent. Its selective activity is by exploitation of differences between the herpes-specific and host cell enzymes. The major route of elimination of acyclovir is via the kidney by glomerular filtration and renal tubular secretion. In immunocompromised patients, acyclovir is effective for the prophylaxis and therapy of herpes simplex virus infections and for the treatment of herpes zoster and varicella. In nonimmunocompromised patients, acyclovir is beneficial in the therapy of herpes keratoconjunctivitis and in the therapy of genital herpes, with maximal benefit seen in those patients who have primary genital herpes. There is some benefit from acyclovir administration in patients with herpes zoster who are otherwise normal. The toxic reactions to acyclovir consist of phlebitis, local irritation, and occasionally, reversible renal dysfunction. Dose reduction is recommended in patients with impaired renal function.

Acyclovir↗
PubMed1984

Acyclovir.

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Acyclovir↗
PubMed1983

Acyclovir halts progression of herpes zoster in immunocompromised patients.

We conducted a placebo-controlled, double-blind study of acyclovir therapy for acute herpes zoster in immunocompromised patients. Of the 94 patients enrolled in the study, 52 had localized skin lesions at entry, and 42 had disseminated cutaneous zoster. A one-week course of intravenous acyclovir (1500 mg per square meter of body-surface area per day) halted progression of zoster in both groups, as determined by development or progression of cutaneous dissemination, development of visceral zoster, or proportion of cases deemed treatment failures. Significantly fewer patients treated with acyclovir within the first three days after the onset of exanthem had complications of zoster, as compared with patients treated with placebo (P = 0.02 by Fisher's exact test), but acyclovir also stopped progression of zoster in patients treated after three days of rash (P = 0.05 by Fisher's exact test). Acyclovir recipients with disseminated cutaneous zoster had a significantly accelerated rate of clearance of virus from vesicles, as compared with placebo recipients (P = 0.05 by the Breslow test).

Acyclovir↗
PubMed1983

Prospective randomized double-blind comparison of moxalactam and tobramycin in treatment of urinary tract infections.

In a prospective, randomized, double-blind trial, a regimen of 250 mg of moxalactam every 12 hours was compared with 1.0 mg/kg of tobramycin every eight hours in the treatment of urinary tract infections. One hundred and eleven patients were entered into the study; results in 63 (18 men and 45 women) were evaluable for both efficacy and toxicity. Thirty evaluable patients received moxalactam, and 33 received tobramycin. The mean duration of therapy in each group was seven days. There were six treatment failures in the moxalactam group and 10 failures in the tobramycin group (p greater than 0.4). Nephrotoxicity, defined as an increase in serum creatinine levels to 0.5 mg/dl or more, did not occur in either group. Thirteen patients in the moxalactam group and one in the tobramycin group had enterococci isolated from a urine culture specimen during or after therapy. It is concluded that use of the moxalactam regimen is as effective and safe as use of the tobramycin regimen in the treatment of urinary tract infections. The clinical significance of the enterococcal isolates associated with moxalactam therapy is yet to be determined.

Adult↗
PubMed1983

Netilmicin and gentamicin multidose kinetics in normal subjects.

Multidose netilmicin and gentamicin kinetics were studied in 20 healthy subjects who received 1.7 mg/kg gentamicin (n = 10) or netilmicin (n = 10) as a 20-min infusion every 8 hr for 10 days (28 doses) during a randomized, double-blind comparative trial designed to study adverse effects and kinetics of netilmicin and gentamicin. Multidose kinetics were of the same order for gentamicin and netilmicin with the exception of the terminal plasma t 1/2 (94 and 156 hr) and the volume of distribution at steady state (450 and 1072 ml/kg). Mean peak plasma concentrations of netilmicin were slightly lower than gentamicin. Percentage of the dose eliminated in urine did not differ for the two aminoglycosides. Aminoglycoside was detectable in plasma and continued to be eliminated in urine for at least 6 days after the final dose. The plasma concentration-time profiles for both netilmicin and gentamicin were well fitted with the sum of three exponential terms; urinary excretion rates-time plots showed biexponential decay. None of the subjects had any auditory, vestibular, or renal toxicity. Although the data confirm a deep tissue compartment, they suggest that the kinetic processes involved may be more complex than previously supposed.

Adult↗
PubMed1982

Influence of hemodialysis on acyclovir pharmacokinetics in patients with chronic renal failure.

The pharmacokinetic disposition of acyclovir was studied in six patients with chronic renal failure (CRF) and anuria. At the end of a one-hour intravenous infusion (2.5 mg/kg), the mean peak acyclovir plasma level (+/- SD), determined by radioimmunoassay, was 37.5 +/- 24.2 microM (8.4 +/- 5.4 microgram/ml), twice the level found at this dose in patients with normal renal function (NRF). In the CRF volunteers, significant plasma levels (3.0 +/- 1.4 microM) persisted at 47 hours after drug administration (before hemodialysis) whereas in the NRF patients levels dropped to less than 1 microM by 11 hours. Hemodialysis was started 47 hours after infusion and was continued for six hours. The pre-dialysis plasma drug level was reduced by 61.5 percent at 0.25 to 1.5 hours after the end of dialysis. The mean plasma t 1/2 during dialysis of 5.4 hours, the extraction ratio of 0.44, and the dialysis clearance for plasma of 113 ml/min indicate that acyclovir is efficiently removed by hemodialysis. One-half the suggested intravenous dose for a particular indication can be given every 24 hours and a similar replacement dose should be given after each dialysis.

Acyclovir↗
PubMed1982

Metabolic fate of radioactive acyclovir in humans.

The metabolic fate and the kinetics of elimination of [8-14C]acyclovir in plasma and blood was investigated in five cancer patients. Doses of 0.5 and 2.5 mg/kg were administered by one-hour intravenous infusion. Radioactivity was distributed nearly equally in blood and plasma. The plasma and blood concentration-time data were defined by a two-compartment open pharmacokinetic model. The overall mean acyclovir plasma half-life and total body clearance +/- SD were 2.1 +/- 0.5 hours and 297 +/- 53 ml/min/1.73 m2. Binding of acyclovir to plasma proteins was 15.4 +/- 4.4 percent. The radioactive dose was excreted predominantly in the urine (71 to 99 percent) with less than 2 percent excretion in the feces and only trace amounts of radioactivity in the expired air. Reverse-phase high-performance liquid chromatography indicated that 9-carboxymethoxymethylguanine was the only significant urinary metabolite of acyclovir accounting for 8.5 to 14.1 percent of the dose. A minor metabolite (less than 0.2 percent of dose) had the retention time of 8-hydroxy-9-(2-hydroxyethoxymethyl)guanine. Unchanged urinary acyclovir ranged from 62 to 91 percent of the dose. There was no indication of acyclovir cleavage to guanine. The renal clearances of acyclovir were three times higher than the corresponding creatinine clearances.

Acyclovir↗
PubMed1982

Acyclovir concentrations and tolerance during repetitive administration for 18 days.

Acyclovir, a new antiherpetic agent, was administered for 18 days to 10 recipients of bone marrow transplants as a part of a double-blind, randomized, placebo-controlled trial assessing its prophylactic efficacy and safety. Renal glomerular function diminished over the time of the study in the 10 acyclovir-treated and 10 placebo-treated patients. The decline in glomerular filtration rate (GFR) did not differ significantly between the two groups and is unlikely to be associated with acyclovir. The pharmacokinetics of acyclovir is expected to be altered by a change in GFR since glomerular filtration is probably the major process involved with the excretion of acyclovir. Such an alteration was seen as an increase over time of both peak (one hour after the end of an infusion) and trough (immediately before a dose) plasma acyclovir concentrations. Although peak and trough acyclovir concentrations rose from 8.5 to 15.8 microM and from 1.7 to 4.1 microM, respectively, these rises are fully attributable to the decreases in GFR seen in both drug- and placebo-treated groups. The placebo-controlled and blinded nature of this trial allows an assessment of the effects of acyclovir on a battery of hematologic, renal, and hepatic tests. The only adverse effects observed that statistically differed in the acyclovir-treated group compared with controls were the rises in SGOT (53.2 +/- (SEM) 19.9 versus 3.1 +/- 12.2) and SGPT (59.7 +/- 15.3 versus 12.3 +/- 13.8).

Acyclovir↗
PubMed1982

Isolation and characterisation of resistant Herpes simplex virus after acyclovir therapy.

Sensitivity of herpes simplex virus isolates to acyclovir became reduced in two bone-marrow transplant patients treated for established mucocutaneous infections. These isolates were thymidine-kinase-deficient mutants and were isolated within a week of discontinuation of a 1 week course of acyclovir therapy. The herpetic lesions in both patients continued to heal despite continued shedding of these viruses. Further studies and experience with this new class of antiviral agents are needed to determine the extent to which emergence of less sensitive virus will present clinical difficulties and to formulate treatment regimens that will minimise the emergence of such mutants.

Acyclovir↗
PubMed1982

Acyclovir kinetics in end-stage renal disease.

Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t1/2) of 2 to 3 hr in subjects with normal renal function. To determine the drug's kinetics and tolerance in patients with severe renal failure, six anuric subjects on long-term hemodialysis were studied. Each received a 1-hr infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a two-compartment open model. ACV terminal plasma t 1/2 and the total body clearance were 19.5 +/- 5.9 hr (mean +/- SD) and 28.6 +/- 9.5 ml/min/1.73 m2. Peak (end of infusion) and 8- and 24-hr plasma ACV concentrations were 37.5 +/- 23.3, 10.3 +/- 2.9, and 6.4 +/- 2.4 microM. Approximately 48 hr after the start of the infusion the subjects were hemodialyzed for 6 hr. The pre- and posthemodialysis ACV plasma levels were 2.74 +/- 1.38 and 1.11 +/- 0.60 microM. The terminal ACV t1/2 during hemodialysis was 5.7 +/- 0.85 hr. During hemodialysis paired arterial and venous samples showed that ACV was readily dialyzed, with a mean coefficient of extraction of 0.45 +/- 0.12. The dialysis clearance of acyclovir was 81.8 +/- 12.6 ml/min. None of the patients had any ACV-related adverse effects. Since ACV elimination is markedly reduced in end-stage renal failure and because ACV is readily hemodialyzible, dosage modification are needed to avoid cumulation and to replace dialyzed drug.

Acyclovir↗
PubMed1982

Pharmacokinetics and tolerance of acyclovir, a new anti-herpesvirus agent, in humans.

The pharmacokinetics and tolerance of acyclovir administered intravenously in single doses of 2.5, 5.0, 10.0, and 15.0 mg/kg were studied in 13 volunteers. The mean concentrations (+/- standard deviations) at the end of infusion as measured by radioimmunoassay were 4.52 +/0 0.31, 8.28 +/- 2.61, 14.6 +/- 2.30, and 22.7 +/- 10.4 microgram/ml, respectively. Drug elimination during and after the infusion of acyclovir was well described by a two-compartment open model. The mean terminal plasma half-life for each of the groups was 2.85, 2.80, 3.30, and 2.38 h, respectively. Within 72 h after the start of the infusion, 70% of the administered drug was recovered in the urine as unchanged acyclovir. The renal clearance of acyclovir accounted for about 77% of the total clearance and was about threefold greater than the creatinine clearance. This confirms that acyclovir is eliminated predominantly by the kidneys in patients with normal renal function and suggests that renal secretion and glomerular filtration may both be involved. The only adverse effect found by clinical and laboratory monitoring was irritation at he intravenous site after extravasation (in two cases), which resolved without significant sequelae.

Acyclovir↗
PubMed1982

Effects of probenecid on the pharmacokinetics and elimination of acyclovir in humans.

The effects of probenecid on the pharmacokinetics and renal clearance of acyclovir were studied in humans. Acyclovir (5 mg/kg) was given as a 1-h infusion to three volunteers with normal renal function both before and after oral administration of probenecid (1 g). The kinetics were well described by a two-compartment open model with zero-order infusion. The mean acyclovir concentrations at all time points after 1.0 h from the end of acyclovir infusion following probenecid administration were statistically higher than the corresponding mean acyclovir concentrations following the acyclovir infusion without probenecid administration. In the absence of probenecid, the renal clearance (248 +/- 80 ml/min per 1.73 m2) accounted for 83% of the total clearance (300 +/- 69 ml/min per 1.73 m2) and was almost threefold greater than the estimated creatinine clearance (90 +/- 48 ml/min per 1.73 m2). After probenecid administration, there was a 32% decline in renal clearance (248 to 168 ml/min per 1.73 m2; P less than or equal to 0.05), a 40% increase in the area under the curve (91.3 to 127.6 nmol.h/ml; P less than 0.05), and an 18% increase in the terminal plasma half-life (2.3 to 2.7 h; P less than 0.01). Although statistically significant, these effects due to the influence of probenecid probably have only limited clinical importance. In this study we confirmed that acyclovir is eliminated predominantly by renal clearance, both by glomerular filtration and tubular secretion; our results suggested that at least part of the tubular secretion is inhibited by probenecid.

Acyclovir↗
PubMed1981

Acyclovir prophylaxis of herpes-simplex-virus infections.

We conducted a double-blind, placebo-controlled study of acyclovir prophylaxis against infection with herpes simplex virus (HSV) in 20 seropositive recipients of bone-marrow transplants. Acyclovir or placebo was administered for 18 days, starting three days before transplantation. Culture-positive HSV lesions developed during the study in seven of the 10 patients who received placebo. In contrast, no such lesions appeared in the 10 patients who received acyclovir (P congruent to 0.003). None of the patients had evidence of drug toxicity. Five of the patients treated with acyclovir had mild culture-positive HSV infections after cessation of the drug, and two additional patients shed virus without having lesions. Acyclovir appears to be a potent inhibitor of HSV replication. Although acyclovir does no appear to eradicate latent infection, it can provide effective prophylaxis against reactivated infections.

Acyclovir↗