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Biomedical subjects

J Rosenthal

Publications and source records attributed to J Rosenthal.

At least 55 records · Page 3Linked to original sources
PubMed1997

Promoting clinical effective practice. Attitudes of fundholding general practitioners to the role of commissioning.

Aims to evaluate the acceptability of commissioning to improve clinical effectiveness in secondary care and explore the conditions under which fundholders would be willing to use commissioning in this way. Describes how fundholders in two contrasting districts in North Thames Region were interviewed in 1995-1996. Respondents were selected from a list of all fundholders in the district with few fundholding practices and from lists of fundholders holding contracts with specified hospitals in the district with many fundholders. Interviews were analysed using the constant comparison method of content analysis. All fundholders in the districts were eligible. The sample represented a broad range of fundholders, containing all fundholding waves and large and small practices. Managers and general practitioners from multifunds outside the districts were also interviewed to assess whether they faced different issues from single practice fundholders. Many respondents felt unable to use commissioning to improve clinically effectiveness despite their awareness of the policy. Reasons identified included the problem of agreeing complex commissioning arrangements to reflect clinical issues, and an unwillingness to use fundholding to challenge hospital practice. Respondents from early wave fundholding practices and those with training in critically appraising research literature expressed more readiness to review research evidence, but only a few early wave fundholders said they would consider evidence-based commissioning. Concludes that steps should be taken to educate fundholders in clinical effectiveness and provide appropriate information to them. Also, they must be persuaded that clinical effectiveness is not a politically-driven policy or they will resist it.

Attitude of Health Personnel↗
PubMed1997

Focus groups among public, military, and private sector mothers: insights to improve the immunization process.

The underimmunization of children younger than 2 years old is a major health problem in U.S. cities. Innovative methods to increase immunization rates are being researched and implemented. In 1993, six focus groups were conducted with 41 mothers (25 African Americans and 16 Caucasians) to discuss their views regarding immunizations and the services they received from health care providers in the public health (n = 27), military (n = 4), and private (n = 10) sectors. Participants viewed immunizations positively, but perceived many barriers to immunization. They suggested the following ways to improve the immunization process: enhancing knowledge acquisition, improving reminder and appointment systems, providing transportation and child care, decreasing waiting times, improving the clinic environment, and making the immunizations less traumatic. According to mothers in this study, obtaining an immunization on time is a complex task that requires planning and resources. The fewer resources that are available to mothers, the more difficult it is to succeeded. Health care providers must help mothers identify and remove barriers if immunization rates are to be increased.

Adult↗
PubMed1996

Neutrophils from patients after burn injury express a deficiency of the oxidase components p47-phox and p67-phox.

Infection is a major cause of morbidity and mortality in patients after thermal injury. This predisposition to infections is related, in part, to abnormal polymorphonuclear leukocyte (PMN) function and a diminished respiratory burst. To evaluate the biochemical basis for the defective respiratory burst after major burns, the status of the oxidase enzyme system and its components was investigated. PMNs were isolated from 24 patients with 12% to 62% burns. Oxidase activity of intact PMNs, measured as superoxide anion (O2-) generation or oxygen consumption, was decreased in burn compared with healthy controls. Subcellular fractions from patient PMNs generated less O2- in the sodium dodecyl sulfate cell-free system, and this was related to a diminished contribution by cytosol but not by plasma membrane. Subsequently, cytosol was separated with CM-Sepharose, yielding two fractions; one contained the p47-phox and p67-phox (47/67 mix) and the other contained the remaining cytosolic components (run through [RT]). Although the contribution to oxidase activity made by RT from patient cytosol was similar to that of control, the activity of p47/67 mix from PMNs of burn patients was deficient. Quantitative assays using an immunoautoradiographic technique showed a consistent, but significant decrease in both p47-phox and p67-phox. The addition of purified or human recombinant p47-phox but not p67-phox corrected the diminished oxidase activity of cytosol from burn patients. Thus, decreased respiratory burst activity found in PMNs from individuals with thermal injury was associated with a specific, quantitative deficiency of p47-phox.

Adult↗
PubMed1996

Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease.

To reduce the morbidity and mortality associated with unrelated donor bone marrow (BM) transplantation and potentially extend the pool of suitable donors, cryopreserved unrelated donor umbilical cord blood was considered as an alternate source of hematopoietic stem cells for transplantation. Patients with leukemia, BM failure syndrome, or inborn error of metabolism were eligible for a phase I clinical trial designed to estimate the risk of graft failure and severe acute graft-versus-host disease after transplantation of umbilical cord blood from unrelated donors. As of December 21, 1995, unrelated donor umbilical cord blood was used to reconstitute hematopoiesis in eighteen patients aged 0.1 to 21.3 years weighing 3.3 to 78.8 kg with acquired or congenital lympho-hematopoietic disorders or metabolic disease. Patients received either HLA-matched (n = 7) or HLA-1 to 3 antigen disparate (n = 11) grafts collected and evaluated by the New York Blood Center (New York, NY). The probability of engraftment after unrelated donor umbilical cord blood transplantation was 100% with no patient having late graft failure to date. The probability of grade III-IV acute graft-versus-host disease at 100 days was 11%. With a median follow-up of 6 months (range, 1.6 to 17 months); the probability of survival at 6 months is 65% in this high risk patient population. We conclude that cryopreserved umbilical cord blood from HLA-matched and mismatched unrelated donors is a sufficient source of transplantable hematopoietic stem cells with high probability of donor derived engraftment and low risk of refractory severe acute graft-versus-host disease. Limitations with regard to recipient size and degree of donor HLA disparity remain to be determined.

Actuarial Analysis↗
PubMed1996

Adrenocortical activation by herpes virus: involvement of IL-1 beta and central noradrenergic system.

We investigated the involvement of brain cytokines and central monoamines in mediating the effect of the neurotropic herpes simplex virus-1 (HSV-1) on adrenocortical activity in rats. Corneal inoculation with a neurovirulent HSV-1 strain, but not with an avirulent strain, induced interleukin-1 beta (IL-1 beta) gene expression mainly in the pons and hypothalamus, and caused an elevation in serum corticosterone levels. Infectious virus was isolated in low titres only from the trigeminal ganglia and pons. Viral DNA was detected by PCR in these tissues and in other brain regions. Virus-induced adrenocortical activation was abolished in rats in which hypothalamic norepinephrine (NE) was depleted by 6-hydroxydopamine. Depletion of hypothalamic serotonin by 5,7-dihydroxytryptamine did not prevent adrenocortical activation. These results suggest that central IL-1 and NE are involved in HSV-1 induced adrenocortical activation.

5,7-Dihydroxytryptamine↗
PubMed1996

Effect of acidic phospholipids on sphingosine kinase.

Sphingosine-1-phosphate (SPP) is a unique sphingolipid metabolite involved in cell growth regulation and signal transduction. SPP is formed from sphingosine in cells by the action of sphingosine kinase, an enzyme whose activity can be stimulated by growth factors. Little is known of the mechanisms by which sphingosine kinase is regulated. We found that acidic phospholipids, particularly phosphatidylserine, induced a dose-dependent increase in sphingosine kinase activity due to an increase in the apparent Vmax of the enzyme. Other acidic phospholipids, such as phosphatidylinositol, phosphatidic acid, phosphatidylinositol bisphosphate, and cardiolipin stimulated sphingosine kinase activity to a lesser extent than phosphatidylserine, whereas neutral phospholipids had no effect. Diacylglycerol, a structurally similar molecule which differs from phosphatidic acid in the absence of the phosphate group, failed to induce any changes in sphingosine kinase activity. Our results suggest that the presence of negative charges on the lipid molecules is important for the potentiation of sphingosine kinase activity, but the effect does not directly correlate with the number of negative charges. These results also support the notion that the polar group confers specificity in the stimulation of sphingosine kinase by acidic glycerophospholipids. The presence of a fatty acid chain in position 2 of the glycerol backbone was not critical since lysophosphatidylserine also stimulated sphingosine kinase, although it was somewhat less potent. Dioleoylphosphatidylserine was the most potent species, including a fourfold stimulation, whereas distearoyl phosphatidylserine was completely inactive. Thus, the degree of saturation of the fatty acid chain of the phospholipids may also play a role in the activation of sphingosine kinase.

3T3 Cells↗
PubMed1996

Pranidipine, a novel calcium antagonist, once daily, for the treatment of hypertension: a multicenter, double-blind, placebo-controlled dose-finding study.

The antihypertensive effects and tolerance of once-daily (od), pranidipine, a novel dihydropyridine derivative with a long duration of action, were evaluated in a double-blind, placebo-controlled, parallel-group dose-finding study. A total of 199 patients, with a diastolic blood pressure (BP) of 95-115 mmHg, were included in the trial. After 4 weeks on placebo, patients were randomly assigned to either placebo or pranidipine at 1, 2, 4, or 8 mg od for a further 4 weeks. A dose response was seen in the reduction (delta) of diastolic BP: placebo, delta 1.7 mm Hg; 1 mg, delta 6.4 mmHg; 2 mg, delta 7.5 mmHg, p < 0.01; 4 mg, delta 11.5 mmHg, p < 0.01; and 8 mg, delta 10.6 mmHg, p < 0.01. There were no meaningful changes in heart rate. The number of responders (decrease of diastolic blood pressure to < 90 mmHg and by 10 mmHg or more from baseline value) in each group also revealed a dose-response relationship: placebo = 9%; 1 mg = 25%, n.s.; 2 mg = 27%, n.s.; 4 mg = 41.5%, p < 0.01; and 8 mg = 41%, p < 0.01 (compared with placebo). Plasma concentrations of pranidipine also demonstrated linear dose-response relationships. An increase in adverse events was observed within the 8 mg group. The degree of reduction in BP and the number of responders were not greater in the 8 mg group compared with the 4 mg group, although the plasma concentration (mean values, ng/dl) of pranidine in the 8 mg group was higher (2.2 on day 42; 2.3 on day 56) compared with the 4 mg group (1.4 on day 42; 1.6 on day 56). In conclusion, pranidipine is a well-tolerated and 24-hour effective novel calcium antagonist that reduces BP in a dose-related manner up to 4 mg od.

Adult↗
PubMed1996

Follow-up assessment of medication-treated dysthymia.

1. The objective was to assess long-term efficacy of antidepressant medications in dysthymia. 2. In a naturalistic study, patients with DSMIII-R dysthymia who had participated in previous antidepressant trials with fluoxetine and trazodone were evaluated at a mean of 40.0 weeks of follow-up to assess whether medication response persisted over time. A multivariate analysis was performed for patients on vs. off medication. Relapse rates (with relapse defined as HDRS score > 13) were also compared for these two groups. 3. Of 40 patients, the 24 still on medication showed significantly lower scores on most rating scales (HDRS, Cornell Dysthymia Rating Scale, and CGI, but not on the SCL-58) than the heterogeneous group of 16 patients not taking medication. Relapse was low (17.4%) among patients remaining on medication. 4. These preliminary findings suggest that dysthymia patients who remain on medication maintain improvement over time.

Adult↗
PubMed1996

A two-year follow-up of neonates with presumed sepsis treated with recombinant human granulocyte colony-stimulating factor during the first week of life.

We have previously reported that recombinant human granulocyte colony-stimulating factor was well tolerated and resulted in sustained neutrophilia and improvement of neutrophil functions in newborn infants with presumed sepsis. We now report a 2-year follow-up on 21 of the initial cohort of 28 patients. Treatment with recombinant human granulocyte colony-stimulating factor in neonates with presumed sepsis was not associated with any long-term adverse hematologic, immunologic, or developmental effects.

Blood Cell Count↗
PubMed1996

Double-blind, randomized study of primary hormonal treatment of stage D2 prostate carcinoma: flutamide versus diethylstilbestrol.

PURPOSE: Patients with stage D2 prostate carcinoma are often treated initially with hormones to decrease endogenous testosterone. Therapy with diethylstilbestrol (DES), leuprolide, or bilateral orchiectomy has been reported to be equivalent. DES is the cheapest preparation, but has the potential for serious cardiovascular or thromboembolic complications. Flutamide is a novel antiandrogen with fewer side effects. PATIENTS AND METHODS: The Eastern Cooperative Oncology Group (ECOG) conducted a double-blind, randomized study to compare the efficacy of flutamide (250 mg three times daily) to DES (1 mg three times daily) as the primary hormonal therapy for patients with stage D2 prostate cancer. Patients were stratified by performance status, disease sites, and history of cardiovascular disease at randomization. RESULTS: Forty-eight patients received DES and 44 flutamide. Patient characteristics were evenly distributed between the two treatments. The overall response rate was similar (DES, 62%; flutamide, 50%). Grade III or worse cardiovascular or thromboembolic toxicity developed in 33.3% of patients on DES and in 17.6% on flutamide (P = .051). Other toxicities were similar between the two treatment arms. However, DES produced significantly longer time to treatment failure (26.4 v 9.7 months, P = .016) and longer survival than flutamide (43.2 v 28.5 months, P = .040). CONCLUSION: As the primary hormonal therapy for stage D2 prostate cancer, DES caused more serious cardiovascular or thromboembolic complications than flutamide. Despite this, flutamide was not as active an initial agent as DES. However, the effectiveness of flutamide in conjunction with other agents compared with DES remains undetermined, and the optimal initial hormone therapy of stage D2 prostate cancer requires further studies.

Administration, Oral↗
PubMed1996

Rescue of HSV-1 neurovirulence is associated with induction of brain interleukin-1 expression, prostaglandin synthesis and neuroendocrine responses.

Several HSV-1 neurovirulence genes have been mapped but the mechanisms by which they affect host-virus interactions are not known. We have previously mapped HSV-1 neurovirulence to the UL53 gene region of the viral DNA by transfer of this gene from the neurovirulent R-19 strain to the non-neurovirulent R-15 strain in the generation of the p-71 recombinant, in which neurovirulence was rescued. In the present study we inoculated these strains into the paraventricular nucleus (PVN) of the hypothalamus of rats. We examined: (1) Clinical course of encephalitis. (2) Hypothalamic-pituitary-adrenocortical (HPA) axis function. (3) Brain cytokine gene mRNA expression and prostaglandin E2 (PGE2) production. (4) The relation of these parameters to viral replication and to cellular inflammation. In R-15 infected rats no signs of disease were observed. There was a temporary inflammatory reaction and IL-1 beta transcription in the PVN area. The function of the HPA axis was similar to control rats. Only slight increase in brain PGE2 production was found. In R-19 and p-71 infected rats, overt clinical signs of encephalitis and cellular inflammation in the PVN area were observed within 3 days post-infection (p.i). All rats died between 4-7 days p.i. These strains induced IL-1 beta transcription in the hypothalamus as well as in extra-hypothalamic brain regions in which no cellular inflammation was found. Basal serum ACTH and' CS were markedly elevated and hypothalamic CRF-41 content was significantly reduced as compared to R-15 infected rats. Both strains markedly increased brain PGE2 production. HSV-1 brain titers at 3 days p.i. were 100-fold lower than the inoculum titer although clinical signs of encephalitis were prominent. The results suggest that rescue of HSV-1 neurovirulence by the UL53 gene region of the viral genome is associated with enhancement of viral-induced brain IL-1 beta gene expression, increased brain PGE2 synthesis and hypersecretion of HPA axis hormones. Viral-induced brain derived cytokines and prostaglandins may contribute to the clinical syndrome of acute herpetic encephalitis in particular at early stages of the disease when virus load in the brain is low and cellular infiltrates are not widespread.

Adrenocorticotropic Hormone↗
PubMed1996

Phase II trial of heparin prophylaxis for veno-occlusive disease of the liver in children undergoing bone marrow transplantation.

Veno-occlusive disease (VOD) of the liver is an early complication of bone marrow transplantation (BMT). The initial event has been hypothesized to be an injury to the endothelial cells eventually resulting in post-sinusoidal obstruction and hepatic failure. The role of anticoagulants for the prevention of VOD is controversial. Continuous infusion of heparin has been reported to be effective in preventing VOD in adults undergoing myeloablative therapy and BMT. An unblinded, historical controlled study was carried out to assess the safety and efficacy of continuous infusion of low-dose heparin in prevention of VOD in children undergoing BMT following myeloablative therapy. Fifty consecutively BMT-treated children (10 months to 18 years 7 months) were enrolled into the study group and received continuous heparin infusion (100 units/kg/day) from the first day of the preparative regimen to day +30 or until discharge, whichever occurred earlier. These were compared with a control group of 70 patients who received BMT for a variety of disorders. Patient groups were similar with respect to primary diagnosis, age, sex, and baseline organ functions. Heparin was well-tolerated, with only minor grade I-II hemorrhagic episodes occurring in 28 patients (56%), compared to 50 patients in the control group (71%) (P = 0.184). Bleeding was significantly less following autologous BMT compared to allogeneic BMT (P < 0.05). VOD was diagnosed in five patients (10%) compared to 18 of 70 in the control group (25.7%) (P < 0.05). Analysis of risk factors demonstrated a significantly higher incidence of VOD in patients undergoing allogeneic BMT (matched related, mismatched related and matched unrelated), patients older than 15 years of age, and patients with advanced disease (> or = 2 CR). In summary, this phase II trial has demonstrated that continuous heparin infusion can be safely used prophylactically in children undergoing myeloablative therapy and BMT. The incidence of moderate and serious VOD was significantly less compared to historical controls. A future randomized, double-blinded, placebo-controlled phase III trial is, however, required to determine the efficacy of heparin in preventing VOD in children undergoing myeloablative therapy and BMT.

Adolescent↗
PubMed1996

[Detection of nicotine in prehistorical skeletal remains of South China].

Human remains from excavation sites in southern China, dated from 100 to 10,000 years, were investigated for nicotine. The nicotine concentrations were measured by radioimmunoassay. Consequently, the values measured represent the sum of nicotine and its metabolites. Positive results were observed in 25.9% (mean values of all samples). The concentrations ranged from 11.8 to 474.2 ng/g sample. From the excavation sites with the highest number of individuals, Chongtong (18 individuals) were 38.9%, and from the site Leigund (21 individuals) were 28.6% from the samples nicotine positive. The highest level with 474.2 ng/g nicotine was found in a sample dated 100 years. It is possible, that this individual was smoker. In addition the samples were investigated also by gas chromatography/mass spectrometry. The GC/MS indicated the presence of nicotine and its primary metabolite, cotinine. The presence of cotinine points out the assumption that nicotine was used antemortem. The detection of unchanged nicotine indicates that nicotine remained present in bones up centuries.

Bone and Bones↗
PubMed1995

Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils.

Neonates, especially those of very low birthweight (VLBW), have an increased risk of nosocomial infections secondary to deficiencies in development. We previously demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells. Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia, increased neutrophil production, and increased survival of pups during experimental Staphylococcus aureus sepsis. In the present study, we sought to determine the safety and biologic response of recombinant human (rhu) GM-CSF in VLBW neonates. Twenty VLBW neonates (500 to 1,500 g), aged < 72 hours, were randomized to receive either placebo (n = 5) or rhuGM-CSF at 5.0 micrograms/kg once per day (n = 5), 5.0 micrograms/kg twice per day (n = 5), or 10 micrograms/kg once per day (n = 5) given via 2-hour intravenous infusion for 7 days. Complete blood counts, differential, and platelet counts were obtained, and tibial bone marrow aspirate was performed on day 8. Neutrophil C3bi receptor expression was measured at 0 and 24 hours. GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2, 4, 6, 12, and 24 hours after the first dose of rhuGM-CSF. At all doses, rhuGM-CSF was well tolerated, and there was no evidence of grade III or IV toxicity. Within 48 hours of administration, there was a significant increase in the circulating absolute neutrophil count (ANC) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day, which continued for at least 24 hours after discontinuation of rhuGM-CSF. When the ANC was normalized for each patient's first ANC, there was a significant increase in the ANC on days 6 and 7 at each dose level. By day 7, all tested doses of rhuGM-CSF resulted in an increase in the absolute monocyte count (AMC) compared with placebo-treated neonates. In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day, there was additionally a significant increase in the day 7 and 8 platelet count. Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool (BM NSP) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day. Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day. The elimination half-life (T1/2) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Birth Weight↗
PubMed1995

The immunization of children enrolled in the Special Supplemental Food Program for Women, Infants, and Children (WIC). The impact of different strategies.

OBJECTIVE: To assess the impact of different interventions to increase measles vaccination coverage among preschool children enrolled in the Special Supplemental Food Program for Women, Infants, and Children (WIC). DESIGN: Public health intervention trial. SETTING: Six volunteer WIC sites in New York City. STUDY PARTICIPANTS: Children aged 12 to 59 months presenting for WIC certification between April 1 and September 30, 1991, who were eligible for measles vaccination. INTERVENTIONS: Two WIC sites were assigned at random to one of three immunization strategies: (1) escort: child was escorted to a nearby pediatric clinic for immunization; (2) voucher incentive: the family returned monthly, rather than every 2 months, to pick up WIC food vouchers until the child was immunized; or (3) referral: the family was passively referred for immunization. MAIN OUTCOME MEASURE: Proportion of eligible children receiving measles vaccination. RESULTS: Of children eligible for measles immunization, 74% (618/836) were immunized. Children at escort sites were 5.5 times (relative risk [RR] = 5.5; 95% confidence interval [CI], 3.7 to 8.1) and those at voucher incentive sites were 2.9 times (RR = 2.9; 95% CI, 1.9 to 4.5) more likely to be immunized than children at referral sites. Children were immunized more rapidly at escort sites (median, 14 days) and voucher incentive sites (median, 26 days) than at referral sites (median, 45 days; P < .001). CONCLUSIONS: Both escort and voucher incentive models resulted in more children being immunized more rapidly than passive referral. Because of ease of administration, voucher incentives may be a more suitable immunization intervention for use at WIC sites, with addition of escort where feasible.

Female↗
PubMed1995

Comparison of the positional cloning methods used to isolate the BRCA1 gene.

A critical step in positional cloning is the identification of candidate genes from a large, genetically defined region. Candidate gene isolation by hybrid selection, genomic sequencing, and direct cDNA library screening identified 45 candidate gene fragments (CGFs) from a 600 kb genomic region that contains the BRCA1 gene. These CGFs define a minimum of 15 genes, six of which are newly localized to the BRCA1 region. We present an analysis of the efficiency and the sequences generated for each of these methods. We also compare our CGF set to those reported for the BRCA1 region by three other groups, revealing a surprising lack of overlap among the sets.

Breast Neoplasms↗
PubMed1995

Delivery systems for vision care benefits.

The best way to provide a vision care benefit is with a managed care plan. With this type of design, there is cost containment without cost shifting, and quality assurance and member satisfaction are readily attainable at relatively inexpensive rates.

Fees and Charges↗