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Biomedical subjects

S A Berkman

Publications and source records attributed to S A Berkman.

14 recordsLinked to original sources
PubMed1997

Adenovirus-mediated suicide gene therapy for experimental bladder cancer.

OBJECTIVES: To determine the feasibility, safety, and efficacy of suicide gene therapy using adenoviral-mediated herpes simplex virus thymidine kinase gene (HSV-tk) and the prodrug ganciclovir (GCV) in a murine model of human transitional cell carcinoma. METHODS: We used a replication-defective adenoviral construct containing the beta-galactosidase gene (ADV/Rous sarcoma virus [RSV]-beta-gal) as a control or ADV/RSV-tk as the therapeutic vector under the transcriptional control of the RSV long-terminal repeat promoter. Transduction efficiency was assessed in vitro by infection of MBT-2 cells with ADV/RSV-beta-gal at various multiplicities of infection (MOI) utilizing 5-bromo-4-chlor-3-indolyl-beta-D-galactoside (X-gal) staining. Sensitivity of MBT-2 cells to the therapeutic vector was determined after infection with ADV/RSV-tk with or without GCV. Subcutaneous tumors were established in syngeneic C3H/He female mice with 5 x 10(5) MBT-2 cells. Optimal dosing of ADV/RSV-tk was determined by direct percutaneous tumor injection with increasing viral doses and treatment with GCV. Treatment efficacy, long-term survival, and toxicity were determined in separate, similar, controlled experiments. RESULTS: In vitro studies indicated greater than 95% transduction 96 hours after inoculation at an MOI of 3000 and a greater than 95% cell death rate with RSV-tk + GCV at an MOI of 61 or greater. In vivo experiments demonstrated an optimal viral dose of 3 x 10(8) plaque-forming units (pfu) and a greater than fourfold reduction in tumor growth for the animals treated with ADV/RSV-tk compared with control animals (P = 0.0013). Toxicity was limited to histologic evidence of hepatitis with ADV/RSV-tk doses greater than 3 x 10(8) pfu + GCV. Long-term survival of treatment animals was significantly increased over that of control animals (59%, P = 0.0001). CONCLUSIONS: ADV/RSV-tk with GCV treatment results in efficient gene transfer in vitro and provides effective therapy in experimental murine bladder cancer by significantly inhibiting tumor growth and improving host survival.

Adenoviridae↗
PubMed1992

Current concepts in anticoagulation.

Anticoagulation therapy continues to evolve as more precise indications for its use are recognized. With adoption of the international normalized ratio, safer and more effective application is in the offing. Newer uses are discussed.

Anticoagulants↗
PubMed1990

Clinical uses of intravenous immunoglobulins.

PURPOSE: To ascertain the activity of intravenous immunoglobulin in a wide range of diseases. DATA IDENTIFICATION: English-language literature search using MEDLINE (1982 to 89), review of meeting reports, and extensive hand searching of bibliographies of identified articles. STUDY SELECTION: All identified articles. DATA EXTRACTION: Study quality and specific descriptive information concerning population, intervention, and outcome measurements were assessed. RESULTS OF DATA SYNTHESIS: There have been few controlled, randomized trials of intravenous immunoglobulin. Available data suggest efficacy in persons with primary immune deficiency, premature infants at risk for group B streptococcus infection, patients with Kawasaki disease, transplant recipients at risk for cytomegalovirus infection, patients with idiopathic thrombocytopenic purpura, and selected patients with chronic lymphocytic leukemia. Data are also favorable concerning the use of intravenous immunoglobulin in some other autoimmune disorders, but randomized trials are needed. Interesting areas for future study include the acquired immunodeficiency syndrome (AIDS), multiple myeloma, and lymphomas. Risks of intravenous immunoglobulin are minimal. CONCLUSION: Intravenous immunoglobulin is safe and effective in treating several human diseases. Additional randomized trials are needed.

Bacterial Infections↗
PubMed1989

Hematologic aspects of renal insufficiency.

Renal dysfunction gives rise to a variety of hematologic disturbances, including anemia, leukocyte dysfunction, and coagulopathy. The anemia of renal failure has been attributed to a relative deficiency of erythropoietin, but contributing factors include an absolute deficiency of iron or folate. Other contributing factors include heavy metal toxicity, blood loss, and hemolysis. The treatment of the anemia of renal disease has advanced with the development of recombinant human erythropoietin. At doses from 15-500 micrograms/kg triweekly in selected patients, normalization of hemoglobin is presently possible. Transfusion may still have a role in patients with renal disease, although more as preconditioning for renal transplantation. In non-HLA matched transplantation, donor-specific transfusion, as well as immunosuppressives, may exert some benefit in graft survival. The coagulopathy of renal disease consists of an acquired qualitative platelet defect best remedied by dialysis but also treated successfully by cryoprecipitate or DDAVP. Infectious complications of uremia include diminished leukocyte chemotaxis, phagocytosis, and bactericidal activity. Cell-mediated immune defects and hypogammaglobulinemia have also been described. The pathophysiology involved in the protean hematologic manifestations of uremia are discussed; additionally, we describe therapeutic recommendations to deal with anemia, bleeding and infectious complications of renal failure.

Anemia↗
PubMed1989

Venous thromboembolic disease after hip surgery. Risk factors, prophylaxis, and diagnosis.

Thromboembolism is a recognized complication of elective and emergency hip surgery. Because of the high incidence of venous thrombosis, prophylactic measures are necessary. Numerous modalities have been explored, and this review formulates strategies to prevent this potentially lethal complication. While minidose heparin and anti-platelet agents may provide effective thromboembolism protection for some patients, their effect in patients treated with hip surgery is limited. Dextran 40 is useful in younger patients treated with hip arthroplasty who are at risk for bleeding complications and who can tolerate volume overload. Heparin dihydroergotamine is an alternative to oral anticoagulants and may cause fewer bleeding complications than oral anticoagulants. Low molecular weight heparin and adjusted-dose heparin can also be used effectively in hip surgery. Warfarin is perhaps the most effective regimen when the prothrombin time is maintained at 1.2-1.5 times control. The risk of thrombosis for patients treated with either emergency or elective hip surgery is significant, and numerous additional factors can increase the likelihood of this complication. The best approach to this problem is prevention, which is effective, safe, and economical.

Anticoagulants↗
PubMed1988

Infectious complications of blood transfusion.

Numerous infectious diseases are transmissible by blood, with AIDS and hepatitis being the predominant concerns today. Less in the limelight, but nonetheless blood transmissible, are cytomegalovirus infection, malaria, babesiosis, and hepatitis B. A major controversy with respect to non-A non-B hepatitis relates to the use of 'surrogate' testing of donors for ALT and hepatitis B core antibody. Transfusion-associated AIDS has been markedly reduced as a risk, due to blood donor antibody screening implemented in March 1985. However, other retroviruses such as HTLV-1, HTLV-II and HIV-II pose additional concerns regarding the safety of the blood supply, and decisions will be forthcoming regarding testing of donated blood for antibody to these viruses.

Humans↗
PubMed1988

Clinical uses of intravenous immunoglobulins.

Immunoglobulins are an important component of host defense against infections. They also play a central role in immune regulation. A wide spectrum of human diseases is associated with decreased or abnormal regulation of immunoglobulin levels. Recently IV preparations of immunoglobulin have become available for clinical studies. There are already substantial data indicating a useful role for IV immunoglobulin in patients with primary hypogammaglobulinemia, neonates predisposed to group B streptococcal infections, individuals with ITP, children with Kawasaki disease, and bone marrow transplant patients predisposed to CMV infections. Promising data have been reported in burn patients and in individuals with CLL; these data require confirmation. Potential areas for future investigation include AIDS, autoimmune disorders, and viral disorders other than CMV.

Bacterial Infections↗
PubMed1986

Hypercoagulable states and venous thrombosis.

Many factors predispose patients to thromboembolic disease. A young person presenting with idiopathic deep venous thrombosis may never have its etiology elucidated, despite exhaustive testing. On the other hand, hypercoagulability is no mystery in an obese, bedridden, postoperative patient with a malignancy. Invasive or noninvasive testing should be performed in all suspicious cases. Patients with positive results should be treated promptly; those with negative findings should not be subjected to anticoagulation. The length of anticoagulation depends on the length of time the patient remains at risk of thrombosis and may vary from months to a lifetime. Patients over 40 should receive prophylactic minidose heparin for abdominal and thoracic surgery. Patients undergoing hip surgery require some form of anticoagulation--be it heparin, warfarin, aspirin, or dihydroergotamine-heparin. Because of lower morbidity and superior long-term efficacy, transvenous devices are favored over surgical techniques for inferior vena caval interruption.

Blood Coagulation Disorders↗