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Biomedical subjects

H S Sacks

Publications and source records attributed to H S Sacks.

At least 37 records · Page 2Linked to original sources
PubMed1995

Early or deferred zidovudine therapy in HIV-infected patients without an AIDS-defining illness.

PURPOSE: To do a meta-analysis on the efficacy of early or deferred zidovudine monotherapy in patients with human immunodeficiency virus (HIV) infection but not the acquired immunodeficiency syndrome (AIDS). DATA SOURCES: Articles on zidovudine monotherapy published through May 1994. STUDY SELECTION: Double-blind, randomized, placebo-controlled trials addressing the efficacy of zidovudine monotherapy in HIV-infected persons without an AIDS-defining illness. DATA EXTRACTION: Progression to any primary trial end point; any clinical end point; and AIDS or death. Data were stratified according to disease stage at study entry and duration of follow-up (short-term, < 14 months; long-term, > 21 months). DATA SYNTHESIS: Early initiation of zidovudine therapy was of short-term benefit for all the end points evaluated (for example, the risk ratio for progression to any primary end point was 0.51; 95% CI, 0.41 to 0.64). Long-term trials showed a marginally significant trend of decreased progression to any primary end point (risk ratio, 0.73; CI, 0.52 to 1.03). The trend was not significant for other end points. With further stratification according to disease stage, progression to AIDS or death in the short term was significantly decreased for both symptomatic and asymptomatic patients with CD4 cell counts of less than 500 x 10(6)/L (risk ratios, 0.26 [CI, 0.13 to 0.56] and 0.43 [CI, 0.30 to 0.64], respectively). A regression analysis indicated a larger relative benefit in short-term trials and symptomatic patients than in long-term trials and asymptomatic patients. CONCLUSIONS: Early initiation of zidovudine therapy offers a benefit that decreases over time. Symptomatic patients experience a larger benefit than asymptomatic patients. The implications beyond 3 years of follow-up remain unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Opioid and tachykinin neuropeptides in prolactin-secreting human pituitary adenomas.

Two opioid neuropeptides, methionine enkephalin (ME) and beta-endorphin (BE), and one tachykinin neuropeptide, substance P (SP), were quantified in 10 prolactin (PRL)-secreting human pituitary adenomas and in 10 control human pituitaries. Immunohistochemical techniques provided appropriate staining for PRL. Reversed-phase high performance liquid chromatography (RP-HPLC) was used to purify these three neuropeptides before their analysis, radioimmunoassay (RIA) was used for the quantification of SP-like immunoreactivity (SP-LI), and liquid secondary-ion mass spectrometry (LSIMS) was used for the qualitative and quantitative analysis of ME and a tryptic peptide of BE. This study shows that, for 90% of the cases studied here (excluding one hypothyroidism case), the tachykinin A neuropeptide SP-LI level is decreased, the POMC peptide BE level is not altered, and the proenkephalin A neuropeptide ME level is increased in these PRL-secreting tumors.

Adenoma↗
PubMed1995

Stavudine in patients with AIDS and AIDS-related complex: AIDS clinical trials group 089.

In a phase I trial of stavudine in AIDS or AIDS-related complex (ARC), antiviral effects and safety were assessed in 41 patients treated with dosages of 0.5-12.0 mg/kg/day. Among evaluable patients, 10% increases in CD4 lymphocyte counts were sustained in 24 (60%) of 40 during treatment; an NAUC response (normalized area under the CD4 cell count-versus-time curve > 1.0) was observed in 31 (91%) of 34 at 10 weeks and in 20 (80%) of 25 at 24 weeks; 15 (83%) of 18 had decreases in p24 antigenemia; and 24 (60%) of 40 gained > or = 2.5 kg body weight. Median CD4 lymphocyte levels remained above baseline for 6 months in patients receiving > 0.5 mg/kg/day. Median serum p24 antigen levels remained below baseline for > or = 1 year in patients with p24 antigen responses. The principal toxicity was peripheral neuropathy, which generally resolved after drug discontinuation but limited the dosage to < or = 2.0 mg/kg/day. Additional trials assessing the effect of stavudine on overall morbidity and mortality are ongoing.

AIDS-Related Complex↗
PubMed1995

Dose-related activity of stavudine in patients infected with human immunodeficiency virus.

In a multicenter, randomized, open-label, dose-ranging study to determine the relative effects of three dose levels of stavudine on CD4 lymphocyte count, weight gain, and hematologic variables in patients infected with human immunodeficiency virus (HIV), 152 patients with CD4 lymphocyte counts < or = 600/mm3 received stavudine at 0.1 mg/kg/day (n = 51), 0.5 mg/kg/day (n = 53), or 2.0 mg/kg/day (n = 48). The study was designed to evaluate the activity of stavudine after 10 weeks of therapy and permitted extended dosing and follow-up for long-term safety. A significant dose effect on increases in CD4 lymphocyte counts and declines in HIV titer in peripheral blood mononuclear cells was observed. Stavudine was well-tolerated; the only dose-related, dose-limiting adverse event was peripheral neuropathy, which usually was reversible. In this trial, the most favorable therapeutic index was seen at 0.5 mg/kg/day.

Adult↗
PubMed1995

Octreotide enhances positive calcium balance in Duchenne muscular dystrophy.

Although receptors for somatostatin are found in bone cells, the effect of somatostatin analogs on calcium metabolism is unknown. The authors studied, in a metabolic ward, the effect of octreotide (a long-acting somatostatin analog) and a placebo in two 6-day calcium balance periods in 8 children with Duchenne muscular dystrophy. As expected, octreotide (2 micrograms/kg, subcutaneously, every 8 hours) reduced serum growth hormone and somatomedin (IGF-1) to levels found in growth hormone deficiency. Octreotide enhanced calcium retention by 30% (96 mg daily [P < 0.04]) in 7 boys for whom complete data (diet, urine, and fecal calcium) were available. In 6 children with urinary calcium excretion (Uca) greater than 50 mg daily, octreotide markedly lowered Uca, from 114 +/- 23 mg daily to 61 +/- 9 mg daily (P < 0.03). Calcium retention occurred in patients with or without initial hypercalciuria, but the higher the basal Uca, the greater was the inhibition by octreotide (r = 0.79; P < 0.03). Inactive, nonambulatory patients had a more pronounced response of Uca to octreotide (P < 0.02). Octreotide caused a mild, nonsignificant reduction in fecal calcium, with no major changes in serum calcium, phosphorus, parathyroid hormone, urinary excretion of sodium and potassium, or in creatinine clearance. Based on the current observations and the presence of receptors for somatostatin in bone cells, this hormone may have, at least on a short-term basis, an anabolic effect on calcium, perhaps favoring its deposition in bone.

Adolescent↗
PubMed1994

Drug treatment of hypertension in the elderly: a meta-analysis.

PURPOSE: A meta-analysis of the effect of antihypertensive drug treatment on mortality and morbidity in elderly patients. DATA SOURCES: A literature search of published articles from January 1980 to February 1992. STUDY SELECTION: Randomized controlled trials of drug treatment of hypertension with end points for elderly patients reported separately. DATA EXTRACTION: Mortality or morbidity end points or both in patients older than 59 years were pooled by determination of typical odds ratio. A meta-regression was used to study heterogeneity. RESULTS: Nine major trials with 15,559 patients older than 59 years were identified. Death rates in the control group varied between 2.7% and 77.2%; stroke and coronary mortality increased with the severity-of-illness rank (P < 0.001). Overall, treated patients had an approximately 12% reduction in all-cause mortality (odds ratio, 0.88; 95% CI, 0.80 to 0.97; 953 events compared with 1069 events, P = 0.009). There was a 36% reduction in stroke mortality (odds ratio, 0.64; CI, 0.49 to 0.82; 94 events compared with 149 events, P < 0.001) and a 25% reduction in coronary heart disease mortality (odds ratio, 0.75; CI, 0.64 to 0.88; 263 events compared with 350 events, P < 0.001). Coronary morbidity was reduced 15% (odds ratio, 0.85; CI, 0.73 to 0.99; 325 events compared with 379 events, P = 0.036), and stroke morbidity was reduced 35% (odds ratio, 0.65; CI, 0.55 to 0.76; 247 events compared with 382 events, P < 0.001). CONCLUSION: Overall, treatment of hypertension in elderly patients produces a significant benefit in total mortality and cardiovascular morbidity and mortality. However, this benefit may be reduced in the oldest age groups.

Aged↗
PubMed1993

Cesarean section to reduce perinatal transmission of human immunodeficiency virus. A metaanalysis.

OBJECTIVE: Individual epidemiologic investigations into the association between type of delivery and perinatal HIV transmission have been suggestive but inconclusive. Metaanalysis was used in an attempt to establish if there is, at present, adequate evidence concerning the effectiveness of cesarean section in reducing vertical HIV transmission rates. METHODS: The MEDLINE data retrieval system and other sources were used to identify studies containing data on the relationship between type of delivery and vertical HIV transmission. No randomized control trials were located. Six cohort studies identified were included in the metaanalysis. Crude and, in the only study in which these were available, adjusted data were extracted and pooled. RESULTS: The overall weighted risk of perinatal HIV infection was 20.2% and 14.0% after vaginal and cesarean delivery, respectively. Pooling data of all studies showed a statistically significant difference of HIV perinatal transmission rates between cesarean and vaginal delivery (odds ratio 0.65; 95% CI, 0.43 to 0.99; P = 0.044) (Random effects model: DerSimonian and Laird method). Approximately 16 (95% CI, 76 to 9) HIV-infected women must deliver by cesarean in order to prevent 1 case of HIV perinatal infection. CONCLUSIONS: Results of this study show that performing elective cesarean section in HIV-infected women is potentially an effective procedure. However, the nonexperimental nature of the available studies leads us to conclude that randomized control trials are indicated before setting specific guidelines for mode of delivery in HIV-infected women.

Bias↗
PubMed1993

Mass spectrometric analysis of opioid and tachykinin neuropeptides in non-secreting and ACTH-secreting human pituitary adenomas.

In a study to test the hypothesis that defects in the metabolism of neuropeptides might be a contributing factor to human anterior pituitary tumor formation, the proenkephalin A, proopiomelanocortin (POMC), and tachykinin systems, which produce methionine enkephalin (ME), beta-endorphin (BE), and substance P (SP), respectively, were measured in patients who had a wide variety of pituitary tumors. Mass spectrometry was used to optimize the level of molecular specificity of the ME and BE analytical measurements, and radioimmunoassay was used to measure SP-like immunoreactivity (SP-li). Compared to data obtained from pituitaries from post-mortem controls, the non-secreting tumors contained a significantly lower amount of the POMC neuropeptide, BE. The lower ME level was not significant. However, two adrenocorticotrophic hormone (ACTH)-secreting tumors contained ME, BE, and SP-li amounts that were much higher than both the controls and nonsecreting tumors. These data suggest that a hypometabolism of the POMC precursor may be operating in non-secreting tumors, and that a hypermetabolism of the proenkephalin A, POMC, and tachykinin precursors may be operating in two ACTH-secreting tumors. These data demonstrate that mass spectrometry plays a critical role in the study of human pituitary tumors.

Adenoma↗
PubMed1993

Influenza and pneumococcal vaccination of HIV-infected patients: a policy analysis.

OBJECTIVE: To analyze the policy of vaccinating human immunodeficiency virus (HIV)-infected young adults against influenza and pneumococcal infections. METHODS: Transition state model of clinical immune deterioration of HIV infection, published data, and experts' estimates for the uncertain variables. Outcome measures are the number of influenza and pneumococcal infection hospitalizations and deaths prevented over 10 years and cost-effectiveness ratios. PATIENTS: Hypothetical cohort of HIV-infected 30-year-old patients. RESULTS: Although pneumococcal vaccine effectiveness diminishes with advanced HIV disease, the risks of pneumococcal infection rise substantially. Pneumococcal vaccination was therefore found to be a reasonable prevention strategy at all HIV disease stages: few vaccinations are needed to prevent hospitalizations and deaths, and the vaccination strategy is cost-effective. By contrast, influenza incidence is low among young adults, and HIV-related immunodeficiency increases influenza risks only minimally. Because the vaccine is administered yearly, many more vaccinations must be administered and fewer hospitalizations and deaths are prevented than with pneumococcal vaccination. The costs to extend life expectancy are high, and beyond the costs of other prevention strategies for persons with moderate to severe immunodeficiency. CONCLUSIONS: Pneumococcal vaccination is a reasonable prevention strategy for HIV-infected patients at all stages of immunodeficiency. Fewer hospitalizations and deaths are prevented by influenza vaccination, making it a far less cost-effective prevention strategy than pneumococcal vaccination.

AIDS-Related Opportunistic Infections↗
PubMed1993

Intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus.

We retrospectively reviewed the charts of 96 patients infected with human immunodeficiency virus (HIV) who received intramuscular pentamidine for the prevention of Pneumocystis carinii pneumonia (PCP). These patients, all of whom had either a history of PCP or a CD4 lymphocyte count of < or = 0.2 x 10(9)/L, were intolerant of sulfa drugs, neutropenic, or intolerant of aerosolized treatment. Intramuscular pentamidine was given monthly by the Z-track technique at a dosage of 300 mg (4 mg/kg if the patient weighed < 50 kg). During a total of 350 months of primary prophylaxis in 47 patients and 426 months of secondary prophylaxis in 49 patients, only three cases of PCP occurred. More than 73% of the patients were receiving zidovudine concomitantly. Adverse reactions to intramuscular pentamidine included two episodes of hypotension, three of sterile abscess, two of glucose intolerance, and one of asymptomatic hypoglycemia. The administration of intramuscular pentamidine by the Z-track technique for PCP prophylaxis appears to be highly effective and minimally toxic.

AIDS-Related Opportunistic Infections↗
PubMed1993

Meta-analysis of the effectiveness of current drug therapy of ulcerative colitis.

We have conducted a meta-analysis of 16 placebo-controlled trials of single drug therapy in ulcerative colitis (UC) for both induction (11 trials) and maintenance of remission (five trials). A total of 468 and 343 patients, respectively, was studied. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference. Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, single drug therapy for the induction of remission conferred a therapeutic advantage of 37-48% over placebo. In trials for maintenance of remission, the therapeutic advantage at 6 months was 21%, whereas at 12 months the therapeutic advantage rose to 46% because of a decline in placebo responders with time. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding therapeutic advantages, can help determine the relative value of newer agents in the therapy of UC.

Aminosalicylic Acids↗
PubMed1992

Renal aspergilloma: an unusual cause of infection in a patient with the acquired immunodeficiency syndrome.

The case of a 36-year-old man with the acquired immunodeficiency syndrome (AIDS) and a renal aspergilloma is reported. Aspergillus infections are uncommon in patients with AIDS. Isolated renal aspergillomas have rarely been reported in the non-AIDS population (14 cases) and have never been reported in a patient with AIDS. The patient we describe was clinically symptomatic and initially treated medically, but he did not respond to intravenous amphotericin and oral itraconazole. He eventually required nephrectomy; however, there was local recurrence of the aspergilloma postoperatively. We comment on some issues in the spectrum of Aspergillus infections in AIDS and review the literature on the manifestations and treatment of renal aspergillomas.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Using patient reports to assess hospital treatment of persons with AIDS: a pilot study.

Providing efficacious, compassionate, and efficient medical care to persons with HIV infection is one of the greatest challenges that will face US hospitals this decade. Unfortunately, there have been almost no studies of how organizational arrangements are related to the quality of care. We developed an interview protocol and conducted a pilot study to evaluate the instrument's ability to detect differences in selected interpersonal aspects of care provided to persons with AIDS. We evaluated the care received in two different treatment models in a major teaching hospital: a designated AIDS unit and general medical beds. We assessed several areas of patient care that are clinically important and that patients can evaluate: communication between patients and providers, patient education, respect for patient preferences, emotional support, involvement of family and friends, trust and confidence, physical care, pain management, AIDS knowledge, perceived segregation, confidentiality, and financial information. Patients generally were very satisfied with their hospital care, but many reported problems with certain aspects of their care. The instrument used detected differences between the care reported by patients treated in general hospital beds and in a designated AIDS unit in several specific aspects of care.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Human immunodeficiency virus and hepatitis B virus infections in a New York City alcoholic population.

Alcoholics have previously been reported to have an increased susceptibility to hepatitis B virus (HBV) infection. Since human immunodeficiency virus (HIV) is transmitted in a similar fashion, we studied 143 consecutive in- and outpatient alcoholics residing in New York City for HIV and HBV prevalence and associated risk factors. Of these alcoholics, 19 (13%) individuals were HIV positive, 57 (40%) were hepatitis B seropositive. Intravenous drug use and sexual contact with an IV drug user were the most important risk behaviors for HIV acquisition, with large numbers of partners and anal heterosexual intercourse being lesser factors. The only significant risk behavior determined for hepatitis B infection was IV drug use. These high-risk behaviors did not appear to be related to episodes of alcoholic intoxication. However, it is conceivable that alcoholism may, in other ways, affect susceptibility to HIV infection.

Adult↗
PubMed1992

The inpatient AIDS unit: a preliminary empirical investigation of access, economic, and outcome issues.

An AIDS unit model ("cluster beds") and a general inpatient placement model ("scatter beds") in a major teaching hospital were compared to determine whether they differed on several dimensions of care. After controlling for severity of illness, (the major predictor of admission to the AIDS unit), length of stay, charges, and inpatient mortality rates did not differ between the two settings. Equal proportions of White, Hispanic, male, and privately insured patients were found in both settings. Nursing staff turnover rates were comparable to those of other sites. However, the data raise new issues regarding access to AIDS units for older, Black, and female patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

An open-label, dose-ranging trial of AL 721 in patients with persistent generalized lymphadenopathy and AIDS-related complex.

AL 721, a lipid mixture with reported in vitro activity against human immunodeficiency virus (HIV) via cell membrane or virion cholesterol depletion, was evaluated in a multicenter, open-label, dose-ranging trial. Forty men with persistent generalized lymphadenopathy or AIDS-related complex were treated with doses of 20, 30, 40, or 50 g orally twice daily for 8 weeks, and monitored for toxicity, disease progression, and with immunologic, virologic, and serum lipid profiles. The compound was found to be well tolerated over the broad range of doses examined; adverse reactions were confined to the gastrointestinal tract, of mild to moderate severity, and self-limited in duration. Modest weight gains observed on treatment were reversed within 4 weeks following cessation of therapy. While disease progression was not observed in this short-term study, we could find no indication of an immunorestorative or antiviral effect of AL 721, as determined by T-lymphocyte subset quantitation or HIV culture. All three patients who were HIV p24 antigenemic at entry retained positive antigen levels throughout treatment. As a consequence of therapy, however, significant increases in serum lipids were observed, including elevations in both triglyceride and total cholesterol levels. In conclusion, our experience on the largest group of HIV-infected patients treated with the highest doses of AL 721 provides no support for the use of this compound as an antiretroviral agent.

AIDS-Related Complex↗
PubMed1990

Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations.

OBJECTIVE: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.

Acquired Immunodeficiency Syndrome↗