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Biomedical subjects

J D Connor

Publications and source records attributed to J D Connor.

At least 91 records · Page 5Linked to original sources
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

Treatment of cytomegalovirus pneumonia with high-dose acyclovir.

Cytomegalovirus pneumonia is a serious complication of marrow transplantation, with a 90 percent fatality rate. Acyclovir, a new antiviral agent with variable in vitro activity against cytomegalovirus, was administered to eight marrow transplant patients with biopsy-proven cytomegalovirus pneumonia; one patient survived. Doses were between 400 and 1200 mg/m2 and peak plasma levels between 47 and 316 microM were attained. Possible marrow toxicity occurred in three patients, and mild neurotoxicity occurred in one. High-dose acyclovir had mild toxicity but was not effective as treatment for cytomegalovirus pneumonia after marrow transplantation.

Acyclovir↗
PubMed1982

Treatment of herpes virus infections in immunocompromised patients with acyclovir by continuous intravenous infusion.

Sixteen immunocompromised patients with herpes virus infections were treated for three to five days with continuously administered intravenous acyclovir. Patients received initial acyclovir infusions over 5 minutes in dosages ranging from 1.5 to 5.0 mg/kg followed by continuously infused acyclovir at 7.2, 14.4, 21.6, 28.8, 36.0, or 43.2 mg/kg per day. The mean serum plateau levels of acyclovir determined by radioimmunoassay ranged from 4.1 microM for the 7.2 mg/kg per day dosage to 36.6 microM for the 43.2 mg/kg per day dose. A mean of 75 percent of acyclovir administered was recovered in the urine of patients treated. Eleven of 13 patients with varicella-zoster virus (VZV) infections had no new vesicle formation after three days of acyclovir treatment and all patients ceased to have new vesicles after five days of therapy. For the nine patients from whom complete viral cultures were available, six ceased to shed virus at three days, and viral shedding ceased by five days in all patients treated with acyclovir. No clinical or laboratory adverse reactions were associated with acyclovir therapy. These data suggest that acyclovir given by continuous intravenous infusion may be useful in the treatment of herpes virus infections in immunocompromised patients.

Acyclovir↗
PubMed1982

Double-blind controlled trial of topical acyclovir in genital herpes simplex virus infections.

Sixty-nine patients with first episodes and 111 with recurrent episodes of genital herpes simplex virus (HSV) infection were enrolled in a double-blind trial comparing a 5 percent topical acyclovir ointment versus placebo, polyethylene glycol (PEG). Among acyclovir recipients with first episodes of genital herpes, the mean duration of viral shedding from genital lesions, 2.0 days, mean duration of local pain or itching, 3.6 days, and mean time to healing of lesions, 11.2 days, were less than in placebo recipients 4.6, 6.7, and 15.8 days, respectively (p less than 0.05 for each comparison). Among patients with recurrent genital herpes, the mean duration of viral shedding from genital lesions was 0.8 days in acyclovir recipients compared with 1.7 days in placebo recipients (p less than 0.001). Among men with recurrent genital herpes, the mean time to crusting and healing of lesions was 3.5 and 7.5 days in acyclovir recipients compared with 5.0 and 9.7 days in placebo recipients, p = 0.03 and 0.07, respectively. No significant differences in the duration of symptoms or healing times were noted between acyclovir- and placebo-treated women with recurrent genital herpes. Acyclovir therapy was not associated with a decrease in frequency of clinical recurrences or an increase in the time of the next recurrence in patients with either first or recurrent genital herpes. Topical acyclovir appears effective in shortening some of the clinical manifestations of genital HSV infections.

Acyclovir↗
PubMed1982

Controlled trial of oral acyclovir in the therapy of recurrent herpes simplex genitalis. A preliminary report.

A randomized, placebo-controlled, double-blind study was performed to evaluate the efficacy and toxicity of orally administered acyclovir in the treatment of patients with recurrent herpes simplex genitalis (HSG). A total of 107 patients from centers in Burlington, Vermont, and San Diego, California, were entered into the study within 48 hours of the onset of lesions. Patients who received acyclovir shed virus for 1.8 +/- 0.6 days (mean +/- SEM) compared with 2.8 +/- 1.2 days for those who received placebo. The duration of shedding from genital lesions of patients in the acyclovir-treated group was significantly less than from lesions of patients who received placebo (p = 0.016 by a logrank test). An analysis of the toxicity of the drug was performed in 52 of the study participants. Acyclovir was well-tolerated and no alterations were observed in measurements of bone marrow, liver, or kidney function. Orally administered acyclovir is a promising antiviral compound for the treatment of recurrent HSG.

Acyclovir↗
PubMed1982

Vidarabine therapy of varicella in immunosuppressed patients.

In order to assess further the clinical usefulness of vidarabine therapy of chicken pox, a double-blind, placebo-controlled trial was performed in immunocompromised patients. Thirty-four patients entered the trial; 19 received vidarabine and 15 the placebo. All patients had disease less than or equal to 72 hours in duration and 23 had lymphoproliferative malignancies. Both patient populations were balanced for underlying disease, preceding chemotherapy, and duration of chicken pox. No patient received zoster immune globulin. Drug therapy accelerated cessation of new vesicle formation (P = 0.015) and decreased median daily lesion counts (P = 0.06 on days 2 and 3). Fever (greater than or equal to 37.8 degrees C orally) resolved more rapidly in the drug-treated group. By day five, 70% of drug-treated subjects were afebrile in contrast to 35% of placebo recipients (P = 0.066). One drug recipient developed mild pneumonitis during the study which resolved with therapy, whereas eight placebo recipients developed varicella-related complications which led to death in two patients (P less than 0.01). These results were achieved with minimal evidence of laboratory or clinical toxicity related to drug administration. The findings indicate that vidarabine has a good therapeutic index (efficacy/toxicity) for treatment of chicken pox in immunocompromised patients when given early in the course of the infection.

Aspartate Aminotransferases↗
PubMed1982

Intraventricular cerebrospinal fluid antibiotic concentrations in patients with intraventricular infections.

The antibiotic concentration of the fluid from either lateral ventricle was determined 104 times in 37 patients through direct ventricular puncture, external ventricular drainage (EVD), or cerebrospinal fluid shunt sampling. The patients were 1 month to 12 years old. When the patients were receiving maximal intravenous antibiotic therapy alone, the concentrations for the most part were below 5 microgram/ml, whereas patients receiving an antibiotic through direct ventricular puncture, EVD, or a shunt reservoir usually had concentrations over 5 microgram/ml. However, wide variations from patient to patient were found with all forms of treatment despite similar dosages. Clustering of the concentration tended to occur in each individual patient. The authors conclude that, to obtain a high concentration of an antibiotic in the ventricular fluid, one should administer it directly into the ventricle.

Amikacin↗
PubMed1981

The management of cerebrospinal fluid shunt infections: a clinical experience.

Fifty patients with infected cerebrospinal fluid shunts were treated by one of three forms of treatment: a) Twenty-two patients had shunt removal, systemic antibiotic treatment, and either external ventricular drainage or intermittent ventricular taps for decompression and antibiotic administration. b) Seventeen patients had removal and immediate replacement of the shunt with intrashunt and systemic antibiotics. c) Eleven patients received intrashunt and systemic antibiotics without shunt removal. In the first group, antibiotics were given for a period of one week; in the second and third groups, intravenous antibiotics were administered for a minimum period of three weeks, and intraventricular antibiotics twice daily for two weeks. In all patients ventricular CSF was obtained and cultured 48 hours after cessation of antibiotic therapy, and cultures were repeated within four months after completion of therapy. Twenty-one of 22 patients in the first group as well as 11 of 13 of the second group, were successfully treated. In the third group only four of the 11 patients responded to treatment.

Anti-Bacterial Agents↗
PubMed1981

Disposition of intravenous radioactive acyclovir.

The kinetic and metabolic disposition of (8-14C)acyclovir (ACV) was investigated in five subjects with advanced malignancy. The drug was administered by 1-hr intravenous infusion at doses of 0.5 and 2.5 mg/kg. Plasma and blood radioactivity-time, and plasma concentration-time data were defined by a two-compartment open kinetic model. There was nearly equivalent distribution of radioactivity in blood and plasma. The overall mean plasma half-life and total body clearance +/- SD of ACV were 2.1 +/- 0.5 hr and 297 +/- 53 ml/min/1.73 m2. Binding of ACV to plasma proteins was 15.4 +/- 4.4%. Most of the radioactive dose excreted was recovered in the urine (71% to 99%) with less than 2% excretion in the feces and only trace amounts in the expired Co2. Analyses by reverse-phase high-performance liquid chromatography indicated that 9-(carboxymethoxymethyl)guanine was the only significant urinary metabolite of ACV, accounting for 8.5% to 14.1% of the dose. A minor metabolite (less than 0.2% of dose) had the retention time of 8-hydroxy-9-[(2-hydroxyethoxy)methyl]guanine. Unchanged urinary ACV ranged from 62% to 91% of the dose. There was no indication of ACV cleavage to guanine. Renal clearance of ACV was approximately three times the corresponding creatinine clearances.

Acyclovir↗
PubMed1981

The effects of piperazine on rat sympathetic neurones.

1. The neuronal effects of the anthelmintic piperazine (Pip) on rat sympathetic ganglia were studied in vitro by means of intracellular and extracellular recording techniques. 2. Surface potential recordings indicated that Pip (0.1-10 mM as citrate, 1-30 mM as hexahydrate) produced a sustained depolarization (reversible on washing) of rat ganglia. gamma-Aminobutyric acid (GABA, 1-100 micro M) also evoked reversible depolarizations but, unlike Pip, responses to the higher doses of GABA declined during a 2 min exposure. Depolarizations produced by Pip or carbachol (but not GABA) were markedly depressed by hexamethonium but only slightly by bicuculline or picrotoxin. 3. Intracellular recordings revealed that Pip-induced depolarizations were accompanied by an increase in membrane conductance and a broadening and depression of the directly-evoked spike. 4. In the presence of hexamethonium (1 mM), the responses to Pip hexahydrate and to cholinoceptor agonists were abolished, but Pip citrate still changed the spike configuration and induced membrane hyperpolarization with a small conductance increase. These residual effects were mimicked by superfusing with Na citrate or Ca2+-free medium, suggesting that significant Ca2+ binding by the citrate anion of the Pip salt was probably responsible for the observed activity of Pip citrate in the presence of hexamethonium. 5. It is concluded that on rat ganglia Pip is a nicotinic agonist, with no detectable GABA-mimetic activity.

Animals↗
PubMed1981

Single-dose pharmacokinetics of acyclovir.

The pharmacokinetics of intravenously administered acyclovir were studied in 10 patients with advanced malignancies. After doses of 0.5 and 1.0 mg/kg, the slow disposition half-life values (t1/2beta) ranged from 2.2 to 3.1 h for the 1-h infusions and from 1.8 to 3.7 h for the 6-h infusions. Plasma levels, measured by radioimmunoassay, reached a maximum at the end of the 1-h infusions and approached steady state at 3 to 4 h into the 6-h infusions. Mean peak plasma concentrations obtained at 0.5 and 1.0 mg/kg administered over 1 h were 3.03 and 5.99 microM, respectively. Mean peak levels for the 6-h infusions were 1.07 microM at 0.5 mg/kg and 2.58 microM at 1.0 mg/kg. The mean urinary elimination of acyclovir was 44.7% of the administered doses. No clinical or laboratory abnormalities were noted in the 10 patients studied.

Acyclovir↗
PubMed1980

Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice.

The effects of bath-applied glutamate, aspartate (and some related amino acids) on neurones of the guinea pig olfactory cortex slice were recorded intracellularly. Neurones were activated either by intracellularly-applied current or orthodromically by stimulating the lateral olfactory tract. In response to orthodromic stimuli several neurones displayed a late hyperpolarizing potential (LHP) after the usual sequence of EPSP, spike and IPSP. Glutamate and aspartate evoked 3 types of response: (a) a depolarization with apparent increase in input conductance; (b) a depolarization with no detectable conductance change; and (c) a hyperpolarization with conductance increase. Some possible mechanisms by which these 3 response-types could be generated are discussed. Depolarizations evoked by the glutamate analogue, kainate, were usually irreversible. Our results emphasize that glutamate and aspartate can evoke a variety of neuronal responses from olfactory cortex neurones. Several of these responses were previously undetected in experiments based on extracellular recordings.

Animals↗
PubMed1980

Para-halogenated phenethylamines: similar serotonergic effects in rats by different mechanisms.

The serotonin (5-HT) behavioral syndrome in rats served as a model to test for possible acute serotonergic effects of para-halogenated phenethylamines. p-Chloro-, p-chloro-beta-methyl-, p-fluoro-, p-bromo-, and p-iodophenethylamine produced the same 5-HT behavioral syndrome as did p-chloroamphetamine, but unlike the latter did not deplete brain 5-HT 3 days after injection. Pretreatment of rats with the 5-HT depletor p-chlorophenylalanine (pCPA)( prevented the serotonergic effects of both chloro-derivatives, and partially prevented the effects of bromo- and iodophenethylamine. 5-hydroxytryptophan restored the behavioral responses to these compounds in pCPA-pretreated rats. pCPA treatment did not prevent the behavioral effects of p-fluorophenethylamine. Similarly, zimelidine, a 5-HT uptake inhibitor, prevented the serotonergic behavioral effects of all compounds tested except p-fluorophenethylamine. Taken as a group, para-halogenated phenethylamines are short-acting serotonergic compounds which, unlike p-chloroamphetamine, do not produce long-lasting depletion of brain 5-HT. p-Chlorophenethylamine and its beta-methyl analog apparently activate central 5-HT receptors indirectly, i.e., by 5-HT release; p-fluorophenethylamine is a direct 5-HT agonist. The p-bromo- and p-iodo-derivatives apparently possess both properties.

5-Hydroxytryptophan↗
PubMed1980

Prospective randomized study of therapy in cerebrospinal fluid shunt infection.

Thirty patients who met the rigid criteria for a prospective randomized study of cerebrospinal fluid (CSF) shunt infections underwent therapy with the three currently advocated treatment modalities to determine the efficacy of each form of therapy. Ten patients (Group A) underwent shunt removal and, in addition to receiving systemic antibiotics, were treated by either external ventricular drainage or intermittent ventricular taps for decompression and antibiotic administration; 10 patients (Group B) were treated by removal and immediate replacement of the shunt and intrashunt antibiotic therapy; and 10 patients (Group C) received antibiotics without removal or replacement of the shunt. All patients were given intravenous and intraventricular antibiotics as follows: in Group A, antibiotics were given by both the intravenous and the intraventricular routes for a minimal period of 7 days; in Group B, intravenous antibiotics were administered for a minimal period of 3 weeks and twice daily intraventricular antibiotics were given for a minimal period of 2 weeks; in Group C, intravenous antibiotics were administered for a minimal period of 3 weeks and twice daily intraventricular antibiotics were given for a minimal period of 2 weeks. In all patients, CSF was obtained from the shunt and cultured 48 hours after the cessation of antibiotic therapy, and the cultures were repeated within 4 months of the completion of treatment. All patients in Group A and 9 of 10 patients in Group B were treated successfully. They were clinically asymptomatic, and cultures after treatment were sterile. However, only 3 patients in Group C responded to treatment. The remaining patients of Group C had persistent infections requiring additional therapy. The mean follow-up of the study group was 23 +/- 14 (SD) months. The mean hospitalization time for the study group was 33 +/- 21 days; the hospitalization time was 24.7 +/- 17 days for Group A alone, 32.7 +/- 8 days for Group B, and 47 +/- 37 days Group C.

Anti-Bacterial Agents↗
PubMed1980

Etiology of pertussis syndrome.

One hundred patients with clinical pertussis were studied to determine the etiology of pertussis syndrome. Forty-two (42%) of the patients had either Bordetella pertussis of Bordetella parapertussis isolated from the nasopharynx. In additional 36 (36%) patients, B pertussis was isolated from the nasopharynx of the associated index case or family contact case. Thus, Bordetella was isolated from 78 (78%) of the patients or from their immediate family group. Of the 22 culture-negative patients residing in culture-negative families, 12 had serologic evidence of Bordetella infection and another was from a family group in which two members were seropositive. Therefore, 91 patients (91%) had bacteriologic or serologic evidence of Bordetella infection themselves or within their families. Viral cultures were obtained on 75 of the patients. Adenoviruses were isolated from 33% of those with positive cultures for B pertussis and from 14% of those with negative cultures. In the group without direct or indirect, bacteriologic or serologic evidence of Bordetella infection, the adenoviral isolation rate (13%) was not significantly different from the adenoviral isolation rate (33%) in patients with a positive bacterial culture. These data do not support a role of adenovirus alone in causing pertussis syndrome.

Adenoviridae↗