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Biomedical subjects

R Saral

Publications and source records attributed to R Saral.

At least 109 records · Page 6Linked to original sources
PubMed1983

The Johns Hopkins Oncology Clinical Information System.

The Johns Hopkins Oncology Center has developed and maintains a clinical information system to support patient care, education, research, and administrative functions. It operates on a dedicated minicomputer (PDP-11) programmed in MUMPS. Clinical information collected includes patient medical status and laboratory values. Data are used daily in patient care and also in support of retrospective and prospective research. The use of the system to manage a large blood pheresis program and to study and treat infectious disease is described. Administrative functions include patient and personnel scheduling, program evaluation, and projects directed toward control of costs.

Blood Transfusion↗
PubMed1983

Ocular manifestations of graft-vs-host disease.

In patients who have graft-vs-host disease (GVHD) after bone marrow transplantation, ocular involvement occurs in approximately 60% of cases. Among 13 such GVHD patients, the most frequent ocular manifestations included keratoconjunctivitis sicca, cicatricial lagophthalmos, and sterile conjunctivitis and uveitis. The severe ocular complications of persistent corneal epithelial defects and both noninfected and infected stromal ulceration were related to the concomitant dry-eye condition and could be managed by conventional therapy including topical lubricants and antibiotics, punctal occlusion, bandage soft contact lenses, tarsorrhaphy, tissue adhesive, conjunctival flap, and conjunctival homograft. Postmortem and surgical tissues from four patients revealed conjunctival and corneal epithelial thinning and keratinization, lacrimal inspissation without inflammatory infiltration, and diffuse choroiditis. Keratoconjunctivitis sicca in GVHD patients might be a combined result of drug toxicity effects and GVHD. The frequent and potentially severe ocular problems in these patients suggest that close ophthalmic monitoring is mandatory in bone marrow transplant recipients.

Adolescent↗
PubMed1983

Colonization and infection with Trichosporon species in the immunosuppressed host.

Trichosporon beigelii and Trichosporon capitatum have recently been recognized as systemic pathogens in the immunosuppressed host. We studied the incidence of colonization and systemic infection with these organisms in 353 highly immunocompromised patients over a 37-month period. Thirteen patients (3.7%) had positive surveillance cultures for Trichosporon species in stool, skin, or urine. Three of the 13 patients developed systemic infections after having positive surveillance cultures. In two of these three patients, urine cultures were positive near the time of systemic infection. The route of entry appeared to have been enteric in two patients and cutaneous in one patient. Both colonizing and infecting organisms showed in vitro susceptibility to amphotericin B and nystatin. This study suggests that positive surveillance cultures for Trichosporon species may correlate with systemic infection in the severely immunocompromised patient and that repeated positive urine cultures may indicate dissemination.

Adolescent↗
PubMed1983

Effect of several antiviral agents on human lymphocyte functions and marrow progenitor cell proliferation.

Toxicity to hematopoiesis and lymphocytic function are major considerations in the clinical applicability of antiviral agents. We have examined the toxicities of five antiviral agents showing activity against herpesviruses: vidarabine, acyclovir, (E)-5-(2-bromovinyl)-2'-deoxyuridine, trifluorothymidine, and (S)-9-(2,3-dihydroxypropyl)adenine. The drugs were tested in vitro for inhibition of herpes simplex virus type 1 and human cytomegalovirus replication, effects on marrow progenitor cell growth, effects on lymphocyte responses to mitogen and alloantigen stimulation, and effects on several lymphocyte cytotoxic responses. In general, lymphocyte proliferative responses were inhibited by the various drugs at lower concentrations than were cytotoxic activities. Acyclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine were the least toxic drugs tested, with antiviral indices exceeding 10,000. Vidarabine and trifluorothymidine were more toxic, with antiviral indices generally between 10 and 100. (S)-9-(2,3-dihydroxypropyl)-adenine was the most toxic, with several antiviral indices between 1 and 10.

Antiviral Agents↗
PubMed1983

Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. A randomized, double-blind, placebo-controlled study.

Twenty-nine adult patients with acute leukemia receiving timed sequential chemotherapy participated in a randomized, double-blind, placebo-controlled trial of acyclovir prophylaxis against reactivated herpes simplex virus infection. Patients with pretreatment antibody titers of 1:16 or greater received acyclovir or placebo starting 4 days after their initial chemotherapy. Treatment was given either for 32 days or until the patients were discharged from the hospital or until a culture-positive herpes simplex virus infection was found. Culture-positive herpes simplex virus infection developed in 11 of 15 patients who received placebo. No infection appeared in 14 patients who received acyclovir (p less than 0.00005). No obvious acute drug toxicity was seen. Recurrent infection was seen in 6 of 14 patients after cessation of acyclovir when retreated with chemotherapy, suggesting no effect on viral latency in these 6 patients. Acyclovir provided highly effective prophylaxis against reactivated herpes simplex virus infections in adult patients with acute leukemia receiving timed sequential chemotherapy.

Acute Disease↗
PubMed1983

Renal transplantation in a patient with multiple myeloma and light chain nephropathy.

A case of multiple myeloma in a 41-year-old white man that resulted in chronic renal failure is discussed. During the period of hemodialysis treatment, remission of the patient's myeloma was induced by chemotherapy. Thereafter a transplanted cadaver kidney functioned well for 3.5 years despite episodes of sepsis, administration of nephrotoxic chemotherapeutic agents, and recurrence of the myeloma with intermittent excretion of Bence Jones protein in the urine. The results of this fully documented case, as well as two other cases we have previously reported, support the strategy of offering cadaver renal transplantation to carefully selected individuals who require long-term dialysis and whose myeloma is in remission after chemotherapy.

Adult↗
PubMed1982

Acyclovir in mouse cytomegalovirus infections.

A virus-specified thymidine kinase appears to be a general requirement for herpes virus susceptibility to the antiviral effect of acyclovir. Surprisingly, mouse cytomegalovirus (MCMV), which does not encode for a thymidine kinase, is exquisitely sensitive to the drug both in vitro and in vivo. The drug is active against the virus in the absence of a cellular thymidine kinase and the antiviral activity is not diminished in the presence of excess thymidine or a variety of nucleosides and deoxynucleosides. Thus, a thymidine phosphorylation pathway is not required for the drug's activation of this infection. The enzyme system responsible for phosphorylation of the drug has not been identified. Mouse cytomegalovirus mutants resistant to the drug have been isolated, indicating that the antiMCMV effect results from selective inhibition of viral replication rather than indirectly through toxicity to the host cell. Eight resistant mutants appear to be in the same complementation group and seven of the mutants demonstrate coresistance to phosphonoacetic acid, a marker for the DNA polymerase locus of herpes viruses. The evidence to date indicates that the MCMV DNA polymerases is the final site of action of the drug. Investigations of the antiMCMV activity of acyclovir should provide insights into the antiviral effects of this drug and other nucleoside analogs in other herpes virus infections in which the virus does not code for a thymidine kinase (for example, human cytomegalovirus and Epstein-Barr virus).

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

Multicenter collaborative trial of intravenous acyclovir for treatment of mucocutaneous herpes simplex virus infection in the immunocompromised host.

Intravenous acyclovir was evaluated in the treatment of 97 immunocompromised patients with mucocutaneous herpes simplex virus infection in a randomized, double-blind, placebo-controlled trial. Acyclovir recipients had significantly shorter periods of virus shedding (p less than 0.0002) and lesion pain (p less than 0.01), and more rapid lesion scabbing (p less than 0.004) and lesion healing (p less than 0.04). The most common adverse reaction was a low incidence of peripheral vein irritation; no serious toxicity could be definitely attributed to acyclovir treatment even in these seriously ill patients. Intravenous acyclovir offers both safe and effective treatment for mucocutaneous herpes simplex virus infection in the immunocompromised host.

Acyclovir↗
PubMed1982

Cytotoxic t cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients.

We studied 58 recipients of bone-marrow transplants to evaluate immune responses to cytomegalovirus infection. Such infection developed in 43 patients; it was fatal in 12, nonfatal in 23, and present at death from other causes in eight. All patients had low or absent cytomegalovirus-specific cytotoxic lymphocyte activity before the onset of infection. Cytomegalovirus-specific cytotoxic responses developed in all survivors, whereas only two patients with fatal infection had even low-level cytomegalovirus-specific cytotoxic responses. Natural and antibody-dependent killer-cell activities were depressed both before and during infection in patients with fatal infections, but not in those who survived. The outcome of the infection did not correlate with the nature of the underlying disease, the type of transplant received, the pretransplantation cytomegalovirus-antibody status, or lymphocyte-proliferation responses to cytomegalovirus antigens or concanavalin A. The correlation between effective virus-specific cytotoxic response and recovery from infection indicates that these effector cells probably mediate recovery from cytomegalovirus infection.

Antibodies, Viral↗
PubMed1982

Infectious gastroenteritis in bone-marrow-transplant recipients.

We prospectively evaluated infections with several gastrointestinal pathogens in patients undergoing bone-marrow transplantation, in an attempt to correlate infection with morbidity and mortality. Thirty-one of 78 patients (40 per cent) were infected with one or more of the following enteric pathogens during the study: adenovirus (12 infections), rotavirus (nine), coxsackievirus (four), or Clostridium difficile (12). Several patients were infected with more than one pathogen. Infection correlated with the occurrence of diarrhea and abdominal cramps. The mortality rate among the infected patients was 55 per cent--significantly higher than the rate (13 per cent) among the noninfected patients (P less than 0.001). This study indicates that enteric pathogens that often cause mild diarrhea in normal populations can cause serious infections in marrow-transplant recipients. Measures aimed at preventing or treating such infections might reduce the morbidity and mortality associated with marrow transplantation.

Adult↗
PubMed1982

Outbreak of Coxsackie A1 gastroenteritis: a complication of bone-marrow transplantation.

In a three-week period 7 of 14 transplant recipients were infected with coxsackie A1 virus. Diarrhoea and mortality were significantly associated with infection (7 of 7 infected compared with 0 of 7 non-infected, and 6 of 7 infected compared with 1 of 7 non-infected, respectively). Early in the outbreak, the diarrhoea was presumed to be due to acute graft-versus-host disease (AGVHD). However, the distribution of AGVHD among infected and non-infected patients was nearly equal, and at necropsy 3 of 6 infected patients who had had diarrhoea showed no evidence of gastrointestinal involvement with AGVHD. Infection with viral enteric pathogens may be an important factor in the clinical course of transplant recipients.

Antigens, Viral↗
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

Epibulbar IgA plasmacytoma occurring in multiple myeloma.

The ophthalmic manifestations of a 51-year-old man with multiple myeloma included exudative retinal detachments and multiple epibulbar plasmacytomas. The retinal changes resolved with treatment for systemic effects, and the IgA-producing plasmacytomas rapidly resolved with local irradiation. The young age of onset (37 years), the prolonged course (14 years), and the IgA M protein and epibulbar involvement were, collectively, unusual findings in multiple myeloma. The presence of epibulbar, gastrointestinal tract, and prostate involvement suggested a homing mechanism of IgA-committed cells to mucosal surfaces.

Adult↗
PubMed1982

Prevention of cyclophosphamide-induced hemorrhagic cystitis.

The occurrence of hemorrhagic cystitis with the use of high-dose cyclophosphamide is thought to be a toxic effect of cyclophosphamide metabolites directly on the bladder mucosa. To decrease both the concentration of metabolites in contact with the bladder mucosa and the time of such contact, a regimen of diuresis and frequent voiding or catheter drainage was instituted in patients at risk for the development of hemorrhage. Prior to institution of this regimen, 8 of 97 patients experienced massive clot-producing hemorrhage, three-quarters of whom died as a direct result of such hemorrhage. Subsequent to use of this regimen, only 1 of 198 patients experienced this degree of hemorrhage. Although this is only a phase II study, the dramatic decrease in the incidence of hemorrhage strongly suggests the efficacy of this regimen in decreasing the potential morbidity associated with cyclophosphamide-induced hemorrhagic cystitis.

Cyclophosphamide↗
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↗