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Biomedical subjects

J Levi

Publications and source records attributed to J Levi.

At least 37 records · Page 2Linked to original sources
PubMed1997

A randomized study of paclitaxel versus cyclophosphamide/methotrexate/5-fluorouracil/prednisone in previously untreated patients with advanced breast cancer: preliminary results. Taxol Investigational Trials Group, Australia/New Zealand.

When administered as a single agent to previously treated patients with advanced breast cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has good activity. This trial was undertaken to compare paclitaxel with standard chemotherapy as front-line treatment for this disease. Patients with measurable or evaluable metastatic breast cancer, no prior chemotherapy for metastatic disease, and Eastern Cooperative Oncology Group performance status of 0 to 2 were randomized to receive either paclitaxel 200 mg/m2 intravenously over 3 hours for eight cycles over 24 weeks or standard treatment with oral cyclophosphamide 100 mg/m2/d days 1 to 14, intravenous methotrexate 40 mg/m2 days 1 and 8, intravenous 5-fluorouracil 600 mg/m2 days 1 and 8, and oral prednisone 40 mg/m2 daily days 1 to 14 (CMFP) for six cycles over 24 weeks. Patients whose disease progressed or relapsed were recommended for second-line therapy with epirubicin. Accrual has been completed with 209 patients randomized, and an interim analysis of the first 100 patients is reported here. Analysis of quality of life, assessed by the linear analogue scale and overall quality of life indices, is ongoing. Objective response occurred in 31% (confidence interval, 19% to 45%) with paclitaxel and 35% (confidence interval, 22% to 51%) with CMFP, with stable disease in an additional 33% and 29%, respectively. Median time to progression was 5.5 months with paclitaxel and 6.4 months with CMFP, with a median survival of 17.3 months for patients treated with paclitaxel and 11.3 months for those given CMFP. Grades 3 and 4 neutropenia occurred in 64% of patients with paclitaxel and 63% with CMFP. However, febrile neutropenia was the primary reason for hospitalization in 1% of paclitaxel courses, compared with 8% with CMFP. Major infections (World Health Organization grade 4) were seen in 7% of patients treated with CMFP, but in none of those given paclitaxel. Moderate or severe mucositis occurred in 13% of paclitaxel and 27% of CMFP patients. Alopecia and peripheral neuropathy were more common with paclitaxel. Quality of life assessments in the first 100 patients suggest better overall results for those treated with paclitaxel compared with CMFP. Preliminary analyses suggest that single-agent paclitaxel is well tolerated and provides control of metastatic cancer comparable to that of CMFP combination therapy when used as front-line therapy in an outpatient setting.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Excretion of epidermal growth factor in human adult polycystic kidney disease.

In chronic renal failure, epidermal growth factor (EGF) excretion is decreased. In this study, asymptomatic adult polycystic kidney disease (APKD) patients with a relatively preserved glomerular filtration rate were examined. Excretion of EGF was studied in 6 patients with APKD (median age 42 years; serum creatinine [median] 95 [range-80-133] mumol/l) and compared with that of 28 healthy controls. EGF was determined in a spot morning urine by using a specific radioimmunoassay, and expressed in relation to creatinine excretion. Excretion of EGF in APKD was (median) 157 (range-13-359) and in the controls (median) 546 (range-238-1199) pmol/mmol creatinine (p < 0.001). Low excretion of EGF in APKD patients with preserved kidney function suggests a distal abnormality at an early stage of the disease, prior to the development of renal failure.

Adult↗
PubMed1995

Chlamydia pneumoniae: risk factors for seropositivity and association with coronary heart disease.

BACKGROUND: Two studies have suggested that seropositivity for Chlamydia pneumoniae (C. pneumoniae) is a risk factor for coronary heart disease (CHD) but the association remains tenuous. Further data is required in other populations to consolidate this observation. AIMS: Initially to determine descriptive risk factors for C. pneumoniae seropositivity in a general population sample and subsequently to examine the relation of seropositivity for this organism to CHD for the first time in a British population. SETTING: A single general practice health screening clinic and a cardiology clinic involving patients predominantly residing in south London and Surrey. SUBJECTS: 210 consecutive caucasian men (62%) and women (38%) aged 18-79 including 67 men aged 45-65. This latter group acting as controls were then also compared with 103 consecutive males aged 45-65 with angiographically confirmed coronary heart disease. METHODS: A questionnaire was administered by a research nurse and serum was analysed for IgG and IgA against C. pneumoniae and other Chlamydiae by a microimmunofluorescence test. Serum was said to be low positive at a specific IgG antibody titre of 16-32, and high positive if 64 or greater. RESULTS: Amongst the general practice health screening clinic population 14 subjects (7%) were excluded due to possible cross-reactivity with other Chlamydia species (predominantly C. trachomatis). Of the remaining 196 subjects, 13 (6%) had high positive C. pneumoniae IgG titres, 68 (35%) had low titres and 125 had no detectable antibody. After adjustment for sex, age, smoking history, social class and family size only one risk factor for high positive titres in this group was identified, which was the number of children currently living in the home (OR 2.29 (1.09-4.80), P = 0.03). No factors were significantly related to low titres. 22/100 (22%) cases with coronary heart disease and 3/64 (4.7%) of controls had high positive IgG titres for C. pneumoniae. Similarly 21% of cases and 9.4% of controls had positive C. pneumoniae specific IgA serology. 45% of cases and 44% of controls had low C. pneumoniae IgG titres. The association of CHD with a C. pneumoniae IgG titre of 64 or above was independent of all risk factors (OR 7.4 (1.7-33.1), P < 0.01). CONCLUSION: Serological evidence of C. pneumoniae infection is common amongst healthy British subjects. Smoking and social class are not important confounding variables in this study. Reinfection from contact with infected children in the home may be important in inducing higher titres in some subjects. These higher titres are more prevalent in subjects with coronary heart disease in the U.K. as reported in Finland and the U.S.A., and provide further evidence that C. pneumoniae may be important in the pathogenesis of this condition in these populations.

Adolescent↗
PubMed1995

Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine: cross-over study.

The lack of comparative studies of nifedipine and felodipine using 24-h blood pressure (BP) monitoring in the same patients led to the present study evaluating the antihypertensive efficacy and side effects of treatment with slow-release (SR) nifedipine (20 mg twice daily) and extended-release (ER) felodipine (10 mg once daily). In the double-blind study, subjects were randomly assigned to one of two treatment groups: 6 weeks of nifedipine SR (20 mg twice daily) followed by 6 weeks of felodipine (ER) (10 mg once daily with evening matched placebo), or vice versa. Twenty-four-hour ambulatory BP monitoring showed no significant differences in systolic BP (SBP) during the day. There were no significant differences in diastolic BP (DBP) throughout the 24 h, although the frequency of DBP recordings > 90 mm Hg was greater during nifedipine (33.1%) than felodipine (27.75%) treatment. The most common side effects were flushing, palpitations, headaches, and ankle edema; there were no adverse effect on lipid profile or glucose level.

Adolescent↗
PubMed1995

Serology for Helicobacter pylori compared with symptom questionnaires in screening before direct access endoscopy.

This prospective study aimed to compare serology for Helicobacter pylori with two, symptom questionnaires in screening patients before direct access endoscopy. Methods were compared in terms of the number of endoscopies saved and pathology missed in 315 patients referred to a gastroenterology unit by 65 local GPs. The serology used was based on an acid glycine extract of H pylori. One in-house questionnaire was based on the Glasgow dyspepsia (GLADYS) system and the other questionnaire was that reported by Holdstock et al. A cut off point of 6.3 U/ml for H pylori serology was selected for screening patients (97% sensitive and 75% specific). Serology was combined with a history of NSAID usage in determining who should have endoscopy. For the in-house questionnaire, a cut off score of more than 8 out of a possible maximum of 18 was chosen, after prior evaluation in 118 patients referred for direct access endoscopy (the sensitivity for detection of peptic ulcer was 88%, specificity 61%). A cut off score of more than 412 was used for the Holdstock questionnaire. In patients under 45 years, serology detected more peptic ulcers than the in-house questionnaire and the Holdstock questionnaire (27/28 v 24/28, NS and v 20/28, p < 0.05 respectively). The Holdstock questionnaire saved significantly more endoscopies than the other two methods (76/149 v 57/149 for the in-house questionnaire, p = 0.05 and 59/149 for serology, p = 0.05). In all age groups combined, serology was significantly better than the in-house and Holdstock questionnaires at detecting peptic ulcers and gastric cancer (61/63, 52/63, p<0.02, and 50/63, p<0.01 respectively). But serology saved significantly fewer endoscopies (89/315, 135/315, p<0.005, and 119/315, p<0.05 respectively). Serology was inferior to the Holdstock questionnaire at detecting severe oesophagitis. It is concluded that serology is the method of choice in screening before direct access upper gastrointestinal endoscopy in those under 45 years. It best combines a high sensitivity for peptic ulcer disease with a large reduction in unnecessary negative endoscopies.

Adolescent↗
PubMed1995

Effect of nifedipine on the renal functional reserve in cyclosporine-treated renal-transplant recipients.

Cyclosporine decreases renal perfusion and impairs the renal hemodynamic response to a protein load. High-dose nifedipine has been shown to elevate renal plasma flow (RPF). We measured the renal functional reserve of 6 cyclosporine-treated renal-transplant recipients following intravenous administration of an amino acid solution, before and 2 weeks after therapy with high-dose nifedipine (up to 120 mg/day). Pretreatment renal functional reserve was nil Following administration of nifedipine, RPF increased by 22% (p < 0.01), filtration fraction decreased by 14% (p < 0.005) and renal vascular resistance declined by 39% (p < 0.005). Renal functional reserve remained unchanged. High-dose nifedipine increases renal perfusion but does not restore renal functional reserve in cyclosporine-treated renal-transplant recipients.

Adult↗
PubMed1995

Adenocarcinoma at ureterosigmoidostomy junction in a renal transplant recipient 15 years after conversion to ileal conduit.

In recent years, adenocarcinoma of the colon mucosa has become a recognized complication of ureterosigmoidostomy and in most cases the tumor arises at the site of ureterocolonic anastomosis. We report a case of a 29-year-old renal transplant recipient who developed two colonic carcinomas at the site of ureterosigmoidostomy 25 years after the urinary diversion and 15 years after conversion to an ileal conduit. This case emphasizes the need for a careful life-long follow-up of all patients who undergo ureterosigmoidostomy.

Adenocarcinoma↗
PubMed1994

Resuscitation in cancer. Comparison of patient and health staff preferences.

One hundred oncology patients from a major teaching hospital and their treating health staff were studied in the second phase of research examining attitudes towards cardiopulmonary resuscitation (CPR). A descriptive approach was used incorporating semistructured interviews of patients and established questionnaire measures, examining knowledge of and attitude towards disease and treatment, psychological functioning, and current and projected attitude toward resuscitation. Health staff also participated in a semistructured interview. This phase of the project focused particularly on a direct comparison of patient and staff assessments. In current circumstances, 10% of patients refused resuscitation. This was associated with disease of good prognosis. In a future hypothetical deteriorated scenario presented to patients, 39% declined resuscitation. This was associated with a past history of suicidal behavior. In current circumstances, health staff designated 14% of patients "Do-Not-Resuscitate" (DNR)--this was associated with a number of variables considered to predict poor outcome in resuscitation. In the future scenario, staff designated 54% of patients DNR--this was associated again with poor resuscitation outcome variables, but also independently, with a past psychiatric history. Comparison of patient and health staff preferences for resuscitation showed moderate yet significant concordance in current circumstances but not in the future scenario. The findings indicate firstly the feasibility of discussing resuscitation preferences with seriously ill patients and secondly an urgent need to improve patient and staff discussions regarding resuscitation, as staff and patients' attitudes to resuscitation differ.

Adult↗
PubMed1994

Anemia of uremia is associated with reduced in vitro cytokine secretion: immunopotentiating activity of red blood cells.

Many in vitro studies demonstrate various stimulatory effects of red blood cells (RBC) on T cell reactivity. Only a few suggest a role for RBC in vivo, such as decreased B and T cell function in iron deficiency anemia. Immune deficiency of uremia is only partially corrected by dialysis treatment. We postulated therefore that this anemia may contribute in part to the immune deficiency of uremia. The aim of our study was to evaluate this postulate and to investigate the role RBC may have in the immune system in vivo. The in vitro secretion of interleukin-2 (IL-2), gamma-interferon (gamma-IFN), tumor necrosis factor (TNF) and colony stimulating factor (CSF) by human peripheral blood mononuclear cells isolated from patients and controls was used as a measure of immune function. The following protocols were carried out: IL-2 secretion was measured in patients with end-stage renal disease (ESRD) and in controls. RBCs were transfused to patients with ESRD and secretion of cytokines was measured before, and 4 hours, 4, 7 and 14 days afterwards; patients with ESRD received recombinant human erythropoietin (rHuEpo) and secretion of cytokines was measured before treatment and two and four months later. Finally, the effect of phlebotomy and transfusion of the autologous blood on cytokine secretion in healthy subjects was measured. Secretion of IL-2 by patients with ESRD was substantially lower than that of healthy subjects. In each group, IL-2 secretion correlated positively with hemoglobin level, r = 0.73, P < 0.01 and r = 0.71, P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Uninephrectomy aggravates tubulointerstitial injury in rats with adriamycin nephrosis.

The effects of uninephrectomy on the function and structure of the remnant kidney were assessed in rats with Adriamycin-induced nephrosis, 12 weeks after the injection of Adriamycin. The kidney volume of Adriamycin-treated uninephrectomized rats (NX-AD) was 2.3 times that of sham-operated, Adriamycin-treated animals (SH-AD; p < 0.001). The marked renal enlargement in NX-AD animals was due to the development of large tubular cysts. Following uninephrectomy, the fractional volume of tubular lumen almost doubled (NX-AD, 0.33 +/- 0.02; SH-AD, 0.17 +/- 0.02; p < 0.001) and the absolute volume of tubular lumen increased more than fourfold (NX-AD, 0.51 +/- 0.08 ml; SH-AD, 0.12 +/- 0.02 ml; p < 0.001). The frequency of tubular lumen with a large cross-sectional area (> or = 40,000 microns 2) was 5.8 +/- 1.1% in NX-AD and 0.7 +/- 0.2% in SH-AD groups (p < 0.001). The fractional volume of interstitial fibrosis in NX-AD animals was larger than in SH-AD (0.09 +/- 0.02 versus 0.04 +/- 0.01%, p < 0.05). As opposed to the worsening of tubulointerstitial disease, single-kidney glomerular filtration rate, fractional protein clearance, glomerular volume and the extent of glomerular sclerosis did not differ significantly in NX-AD as compared to SH-AD groups. This study shows that uninephrectomy in rats with Adriamycin nephrosis worsens interstitial nephrosis and aggravates the formation of tubular cysts, leading to a macrocystic kidney disease. These changes are not associated with an increase in glomerular sclerosis.

Animals↗
PubMed1994

Effects of erythropoietin on glucose tolerance in hemodialysis patients.

Erythropoietin (EPO) therapy is widely used to correct the anemia of end-stage renal disease. It has been reported that this treatment affects various hormonal systems. The aim of the present study was to evaluate the effects of EPO therapy on glucose tolerance. Anemia was corrected with EPO in 10 patients on chronic hemodialysis therapy. Oral glucose tolerance tests (OGTT) were performed before and after correction of anemia. The following measurements were made: the areas under the glucose curves (AUCglue), the areas over basal glucose values (OABVglue), the areas under the insulin curves (AUCins) and the areas over basal insulin values (AOBVins). Hemoglobin concentration increased from 70 +/- 1.4 milligrams to 111 +/- 1 milligram. Fasting plasma glucose, insulin and glucagon levels were were not affected by correction of the anemia. Following administration of EPO, AOBVglue increased by 19%, from 2101 +/- 243 to 2508 +/- 230 mmol.min/l (p < 0.02), while AOBVins remained unchanged. AUCins and AUCglue remained unchanged. These data show that correction of anemia with EPO in hemodialyzed patients causes an increase in the glycemic response to an oral glucose load while not affecting the insulin response.

Anemia↗
PubMed1994

Effect of enalapril on the microvascular albumin leakage in patients with diabetic microangiopathy and normal or mildly elevated blood pressure.

The transcapillary escape rate of albumin (TERalb) is often elevated in patients with diabetic microangiopathy. The objective of this study was to examine the effect of enalapril on the TERalb of diabetic patients with albuminuria and normal or mildly elevated blood pressure. Seventeen diabetic patients with diabetic retinopathy, albuminuria, a diastolic blood pressure below 100 mmHg and increased TERalb participated in the study. Blood pressure and TERalb were measured before and after 14 days of therapy with enalapril, 20 mg daily for 14 days. Systolic and diastolic blood pressure fell from 168 +/- 6 to 155 +/- 6 (p < 0.001) and from 87 +/- 2 to 81 +/- 2 mmHg (p < 0.005) respectively. Mean arterial pressure declined from 114 +/- 3 to 105 +/- 3 mmHg (p < 0.0001). The elevated TERalb decreased from 9.5 +/- 0.5 to 7.2 +/- 0.5%/hr (p < 0.005). In the hypertensive subset, systolic, diastolic and mean arterial pressure decreased significantly by 15, 7 and 10 mmHg (p < 0.005, p < 0.005 and p < 0.005 respectively); TERalb decreased from 9.5 +/- 0.6 to 7.3 +/- 0.6 (p < 0.03). In the normotensive subset, arterial pressure remained unchanged and TERalb decreased from 9.0 +/- 0.8 to 6.8 +/- 1.0%/hr (p < 0.03). Plasma fructosamine decreased from 373 +/- 23 to 347 +/- 20 (p < 0.05) in the hypertensive group and remained unchanged in the normotensive patients. No correlation could be demonstrated between variation in TERalb and changes in blood pressure. In conclusion, enalapril decreases microvascular albumin leakage in patients with diabetic microangiopathy and normal or mildly elevated blood pressure.

Blood Pressure↗
PubMed1993

DNA repair and recovery of RNA synthesis in uremic patients.

A high frequency of cancer appears among uremic patients. As depressed DNA repair ability is thought to be one of the causes for malignancy in cancer prone diseases, the present study was undertaken to examine DNA repair in uremic patients. Unscheduled DNA repair synthesis in peripheral lymphocytes was measured after both ultraviolet (UV) and gamma irradiations. In hemodialysis (HD) patients the repairs were normal, but in chronic renal failure (CRF) patients not yet on dialysis treatment, both UV- and gamma-induced DNA repair abilities were depressed to about 60% of the control. Recovery of RNA synthesis after UV irradiation followed the same pattern: it was reduced in CRF but normal in HD cells. When CRF lymphocytes were incubated in normal plasma, the UV-stimulated DNA repair improved to a nearly normal level, whereas incubation of normal cells in CRF plasma depressed their repair capacity to 70% of the initial level. These results suggest that a plasmatic substance such as the carcinogenic heterocyclic amines may be involved in the impairment of DNA repair in chronic renal failure.

Adult↗