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Biomedical subjects

S M Hammer

Publications and source records attributed to S M Hammer.

At least 91 records · Page 5Linked to original sources

Infectious complications with the use of cyclosporine versus azathioprine after cadaveric kidney transplantation.

Infectious complications within 1 year of cadaveric kidney transplantation were compared in 45 patients treated with azathioprine, prednisone, and antilymphocyte globulin and 38 patients treated with cyclosporine and prednisone. Although there was no difference in the 1 year patient or graft survival rate, cyclosporine-treated patients had significantly fewer wound infections, infection-related transplant nephrectomies, and infection-related graft failures than azathioprine-treated patients. The cyclosporine-treated diabetic recipients had more nonviral pneumonias and opportunistic infections but fewer cases of infection-related transplant nephrectomy than did the azathioprine-treated diabetic patients. Our data suggest cyclosporine is associated with reduced infectious morbidity after cadaveric kidney transplantation in nondiabetic patients.

Adult↗

Synergistic activity of granulocyte-macrophage colony-stimulating factor and 3'-azido-3'-deoxythymidine against human immunodeficiency virus in vitro.

The ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 3'-azido-3'-deoxythymidine (AZT) to inhibit human immunodeficiency virus (HIV) in the U-937 monocytic cell line was examined. Acutely HIV-infected U-937 cells were exposed to GM-CSF (0.03, 0.3, 3.0, or 30.0 U/ml) and AZT (0.1, 1.0, or 10.0 microM) alone and in combination for 14 to 17 days. Reverse transcriptase activity in the supernatant, the percentage of cells expressing viral antigens by indirect immunofluorescence, and the 50% tissue culture infectious dose per milliliter of supernatant were determined to assess the level of viral replication in treated and control cultures. By the fractional-product method of analysis, nearly all combinations of GM-CSF and AZT synergistically inhibited HIV replication by these three measurements. The most effective combinations were 30 U of GM-CSF per ml with 0.1, 1.0, or 10.0 microM AZT. These treatments resulted in no reverse transcriptase activity in the supernatants, less than 1% immunofluorescent positive cells, and less than 8 50% tissue culture infectious doses per ml in the absence of cytotoxicity. Despite this degree of suppression, productive viral replication returned in all cultures within 4 to 10 days after drug removal. Combined therapy with GM-CSF and AZT merits consideration in the approach to HIV-associated illnesses.

Antiviral Agents↗

Infusion phlebitis associated with a programmable syringe-pump system versus gravity-feed minibottles.

The occurrence of infusion phlebitis in patients receiving intravenous antibiotics via a gravity-feed minibottle system versus a new syringe-pump system was compared. Patients at least 18 years old who had indwelling intermittent injection sites inserted for medication administration were randomized to either the minibottle system or the syringe-pump system. Antibiotics in minibottles were diluted in 50-100 mL of 5% dextrose injection; in the syringe-pump group, aminoglycoside antibiotics were diluted in 0.9% sodium chloride injection and all other antibiotics were diluted in sterile water for injection. Antibiotics were not piggybacked into running primary infusions in any of the study patients, and no other medications except for 0.9% sodium chloride flushes were administered through the catheters. All catheters were inserted in peripheral veins and evaluated for phlebitis by i.v. nurse specialists using standardized criteria. Catheters were changed upon the occurrence of grade 1 phlebitis or after a period of three days without the development of phlebitis. Over an 18-week period, 85 catheter sites (53 syringe-pump group versus 32 minibottle group) were evaluated in 30 patients (14 syringe-pump group versus 16 minibottle group). The mean +/- S.D. catheter life in both groups was 50.6 +/- 20 hours. Phlebitis occurred in 62% of syringe-group sites versus 66% of minibottle-group sites; the incidence and severity of phlebitis were not significantly different between groups. The majority of catheter sites were infused with cefazolin sodium. The potential for phlebitis using the syringe-pump system in this study appears to be similar to that of the gravity-feed minibottle system when appropriate diluents, diluent volumes, and infusion rates are used.

Adult↗

In vitro modification of human immunodeficiency virus infection by granulocyte-macrophage colony-stimulating factor and gamma interferon.

The ability of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and gamma interferon (IFN-gamma) to modify human immunodeficiency virus (HIV; also called HTLV-III/LAV) infection in the monocytic cell line U-937 was examined. When added to persistently infected cell cultures, GM-CSF at 30-300 units per ml produced maximal reductions in reverse transcriptase activity of 37-55% 10-14 days after its addition, whereas IFN-gamma produced reductions of 64-68% 10-17 days after addition. When used prior to acute HIV infection and maintained in the cell culture system, these cytokines reduced reverse transcriptase activity 90-100% and nearly eliminated viral antigen expression but did not prevent return of productive infection after their removal. These results indicate that, in a monocyte model of HIV infection, GM-CSF and IFN-gamma substantially restrict HIV expression and that these cytokines deserve further evaluation as therapeutic alternatives in HIV-related disorders.

Cells, Cultured↗

Pulmonary complications of orthotopic liver transplantation.

Pulmonary complications following orthotopic liver transplantation (OLT) were prospectively evaluated in 18 individuals transplanted at the New England Deaconess Hospital. Of sixteen patients who survived the immediate postoperative period, 12 (75%) sustained a pulmonary complication. Of these complications, 64% were noninfectious--whereas 22% were infectious, and 14% probably infectious. Six of eight documented infections were caused by viruses of the herpes group. In four cases of viral pneumonitis other pulmonary pathogens were isolated (fungi-3, protozoan-1, bacteria-1). Unlike noninfectious complications, pulmonary infections were associated with a fatal outcome in five of six patients who died after OLT. Pulmonary complications are frequent and serious occurrences after OLT, and contribute to both the morbidity and mortality of this procedure. Compared with pulmonary complications seen after transplantation of other organs, OLT was associated with a higher proportion of noninfectious complications but a similar spectrum of pulmonary infections.

Adult↗

Human T-lymphotropic virus type III infection in previously immunocompromised hosts.

The human T-lymphotropic virus type III (HTLV-III) is the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). HTLV-III infection in patients with prior underlying immune deficiency states such as cancer has not yet been studied. We report on the occurrence of clinically atypical opportunistic infections in previously immunocompromised patients that resulted from transfusion-acquired HTLV-III infection. Development of unusual infectious diseases in patients with neoplasms and other underlying immune deficiency disorders should lead to consideration of HTLV-III infection. Surveillance data should be obtained on these patients to accurately define the scope of HTLV-III infection.

Acquired Immunodeficiency Syndrome↗

Effects of recombinant interleukin-2 on resting human T lymphocytes.

The effects of recombinant interleukin-2 on resting T lymphocytes were examined in vitro. T cell enriched populations were isolated from the peripheral venous blood of three normal individuals by Ficoll-Hypaque gradient separation and standard sheep erythrocyte rosetting techniques. Interleukin-2 at concentrations of 100 and 1,000 U/ml stimulated tritiated thymidine incorporation, Tac antigen expression, interferon production, and blast transformation in T cell cultures. These changes were observed in the absence of cell proliferation. The effects of interleukin-2 at a concentration of 100 U/ml were substantially blocked by the addition of a 1:1,000 dilution of anti-Tac antibody to the culture medium indicating that the effects observed were mediated by the Tac receptor. These results indicate that recombinant interleukin-2 can have demonstrable functional and morphologic effects on unstimulated human T cells.

Adult↗

Staphylococcus epidermidis infections.

Staphylococcus epidermidis, an organism routinely found on the skin and in the hospital environment, has become a primary pathogen in infections associated with prosthetic devices. Because these infections are indolent and often clinically silent, diagnosis and therapy are often difficult. Pathogens are often misidentified as contaminants. Their variable, often resistant antibiotic susceptibility pattern and the uncertain correlation of in-vitro beta-lactam sensitivity testing with therapeutic efficacy make selection of an effective antibiotic regimen difficult. Vancomycin combined with rifampin, gentamicin, or both, is recommended for empiric therapy of these infections. Usually, removal of the prosthetic device is also necessary and may contribute equally to a successful therapeutic outcome.

Anti-Bacterial Agents↗

Methylation of the viral genome in an in vitro model of herpes simplex virus latency.

An in vitro model of latency of herpes simplex virus type 1 (HSV-1) in a lymphoid cell line has been developed recently. CEM cells persistently infected with HSV-1 transiently ceased to produce virus for 24 days. This nonproductive state could either be reversed with phytohemagglutinin or maintained with concanavalin A. This system was used to study the relationship between DNA methylation and HSV-1 latency. DNA was probed for methylation by comparing the cleavage patterns generated by two pairs of restriction endonucleases (Sma I vs. Xma I and Hpa II vs. MspI); these enzymes show differential activity reflecting methylation of the recognition sequences. Viral DNA in the concanavalin A-treated cells (not producing virus) was found to be extensively methylated. By contrast, no methylated copies were detected in viral DNA from producer cells. About 800 days after the initial infection, the productive culture once again became nonproductive. Viral sequences in the latter cells were also methylated. Reconstitution experiments revealed 1-2 copies of viral DNA in cells from the latent stages and 40-80 copies in cells from productive stages. Most (if not all) of the viral genome is present in cells from various productive and latent stages. No differences in sequence arrangement were detected (although a terminal fragment of intracellular HSV-1 DNA appeared to be under-represented in latent cells). These results suggest a role for DNA methylation in the mechanism of HSV-1 latency in this system.

Cell Line↗

Alpha interferon and acyclovir treatment of herpes simplex virus in lymphoid cell cultures.

The T-lymphoblastoid cell line CEM, persistently infected with herpes simplex virus type 1, has been used to examine the antiviral efficacy of human alpha interferon and acyclovir, both alone and in combination. Acyclovir and interferon each produced dose-dependent decreases in virus titer at concentration ranges of 1 to 100 microM (approximately 0.225 to 22.5 micrograms/ml) and 10 to 10,000 U/Ml, respectively. Mean reductions in titer of 1.9 and 4.2 log10 PFU/ml were observed with 100 microM acyclovir and 10,000 U of interferon per ml, respectively, on day 10 of treatment. The combination of 100 microM acyclovir and 10,000 U of interferon per ml produced the most rapid fall in virus titer of all regimens examined and elimination of infections virus by day 7. Prolonged treatment (greater than 10 days) with acyclovir or alpha interferon was accompanied by a gradual return of virus titer to control levels despite the continuous presence of drug. Virus preparations isolated from such cultures were tested for antiviral agent sensitivity by a plaque reduction method. Acyclovir-exposed isolates were found to be acyclovir resistant, with 50% inhibitory doses of greater than 200 microM, and to be thymidine kinase deficient. Alpha interferon-exposed isolates were not interferon resistant. These results suggest that, in persistently herpes simplex virus-infected CEM cells: (i) combination treatment with 100 microM acyclovir and 10,000 U of alpha interferon per ml is more effective in reducing virus titer than either agent alone; (ii) prolonged exposure to drug may result in development of resistance by either the virus strain or the host cell system; and (iii) development of acyclovir resistance by herpes simplex virus in lymphoid cells is mediated by thymidine kinase.

Acyclovir↗

Herpes simplex virus infection of human T-cell subpopulations.

The ability of herpes simplex virus type 1 to productively infect human T-cell subpopulations was examined. Unstimulated helper/inducer (T4+) and cytotoxic/suppressor (T8+) lymphocytes limited herpes simplex virus replication as effectively as unseparated peripheral blood T cells (T3+). Phytohemagglutinin stimulation before infection resulted in equivalently productive herpes simplex virus infections in the three cell fractions.

Adult↗

Temporal cluster of herpes simplex encephalitis: investigation by restriction endonuclease cleavage of viral DNA.

Eight patients with brain biopsy-proven herpes simplex encephalitis were seen at the Massachusetts General Hospital, Boston, within a three-month period in the summer of 1977. The unusual temporal clustering of these cases engendered a formal epidemiologic investigation. No significant link among these patients was uncovered, and analysis of the cleavage products of seven of the eight viral isolates produced by the restriction endonucleases HsuI and HpaI showed that they were different. This cluster thus appears to have been a random event. Its occurrence, however, emphasizes that herpes encephalitis is not a rare disease in this country. In addition, the utility of restriction enzyme cleavage of DNA in clarifying the epidemiology of viral disease is underscored.

Adolescent↗

Treatment of Listeria monocytogenes infection with trimethoprim-sulfamethoxazole: case report and review of the literature.

A 55-year-old female recipient of an orthotopic liver transplant, who was receiving azathioprine, prednisone and cyclosporin, developed bacteremia due to Listeria monocytogenes. Because of a penicillin allergy, the patient was treated primarIly with trimethoprim-sulfamethoxazole, to which she responded well. The prior literature on use of trimethoprim-sulfamethoxazole in listeria infections is reviewed, and future recommendations are considered. On the basis of the experience described in this case report as well as a review of the literature, trimethoprim-sulfamethoxazole appears to be an effective treatment of listeria infections.

Drug Combinations↗