Timing of completed suicides among residents of Olmsted County, Minnesota, 1951-1985

In man, GHRH has been shown to potentiate the TSH-releasing activity of TRH. To study the way by which GHRH affects TRH-stimulated TSH release, we examined the effect of GHRH (1-29)NH2 on basal and stimulated TSH secretion in intact male rats and superfused dispersed rat pituitary cells. In the intact rats, GHRH(1-29)NH2 potentiated TRH-stimulated TSH release in the evening, but potentiation was not observed in the morning and in dispersed pituitary cells. Basal TSH levels were not changed by GHRH(1-29)NH2. It is concluded that GHRH(1-29)NH2 potentiates the TSH-releasing activity of TRH in the evening in rats possibly through suprahypophyseal disinhibition.     

Strategies for designing a research utilization project with labor and delivery nurses

The background and development of the second National AWHONN Research Utilization Project on Second Stage Labor Management that was conducted in multiple sites within the United States and Canada are presented. On the basis of the results of the project, recommendations for designing other research utilization projects are discussed.     

Factors influencing outcome of prolonged norepinephrine therapy for shock in critical surgical illness

Immunocytochemistry for manganese-superoxide dismutase (Mn-SOD) was studied in 12 normal adenohypophyses and 38 various pituitary lesions. The proportions of cells with granular immunoreactivity for Mn-SOD in normal adenohypophysis ranged from 9.8% to 29.6% (mean +/- SD; 18.4+/-6.2%). Some positive cells tended to accumulate in clusters, distribution of which corresponded well with those immunopositive for mitochondrial protein and cytochrome oxidase. The number of Mn-SOD-positive cells increased in adjacent residual adenohypophysis in eight of nine recent infarcts, in two of five old infarcts, in all four cases of lymphocytic hypophysitis, in two of four abscess cases and in one of three metastatic tumour cases, whereas the immunoreactivities of mitochondrial protein- and cytochrome oxidase-positive cells either did not vary or decreased. The intensity of the histological inflammatory reactions showed a positive correlation with reactivity for Mn-SOD in these lesions. Of eight adenomas, the surrounding area of compressed adenohypophysis showed increased numbers of Mn-SOD- and mitochondrial protein-/cytochrome oxidase-positive cells in four and six cases respectively. It is suggested that positivity for Mn-SOD may be related to some functional activity of mitochondria. It is further suggested that adenohypophysial cells have a high potential to induce Mn-SOD by inflammatory and ischaemic stress and, in addition, by enhanced mitochondrial activity.     

Performance of a semiautomated Papanicolaou smear screening system: results of a population-based study conducted in Guanacaste, Costa Rica

Cardiovascular disease is one of the most common complications of dialysis and renal transplant patients, and high levels of AGE are present in end-stage renal failure. To address the potential involvement of AGE and growth factors in the pathophysiology of cardiovascular complications, we performed immunostaining using cardiac tissues from autopsy cases of patients on maintenance dialysis (10 cases), long-term surviving renal transplant patients with functioning grafts (8 cases), control subjects with normal renal function (7 cases) and non diabetic subjects with mild renal insufficiency (8 cases). We used two types of AGE-antibodies, 6D12 [monoclonal anti-AGE antibody, recognizing N epsilon-(carboxymethyl) lysine(CML)-modified AGE] (oxidative AGE) and non-CML-PA [polyclonal, not recognizing CML], and antibodies against PDGFs, PDGF receptors and TGF beta. Positive 6D12 staining was observed in the coronary arterial walls and in macrophages. The accumulation of 6D12-reactive AGE in the coronary arterial walls of maintenance dialysis patients was significantly greater than that of control subjects (p < 0.05). Renal transplantation significantly reduced this accumulation (p < 0.05). On the other hand non-CML-PA mainly detected AGE in intracardiac arterioles and neural tissues. There was little difference in the accumulation of non-CML-AGE among the four groups. PDGFs and PDGF receptors were mainly detected in vascular endothelial cells and infiltrating cells of cardiac tissues of renal transplant patients, but not of maintenance dialysis patients. TGF beta was not detected in cardiovascular tissue of transplant patients. Our results indicated that the accumulation of oxidative AGE (CML-AGE) in the cardiac vascular tissue is one of the factors for cardiovascular complications of maintenance dialysis patients, and also that renal transplantation has a reducing effect on CML-AGE accumulation. PDGFs may be involved in the cardiovascular complications after renal transplantation.     

Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer

PURPOSE: To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. PATIENTS AND METHODS: Thirty-five chemotherapy-naive patients with suboptimally debulked stage III (tumor masses > 3 cm) and stage IV ovarian cancer were entered onto this phase I trial in which paclitaxel was administered as a 3-hour intravenous (IV) infusion at dosages of 125 to 225 mg/m2 immediately followed by carboplatin over 30 minutes at dosages of 300 to 600 mg/m2. A total of six courses was planned, followed by a second-look laparoscopy/laparotomy. Patients with a response and/or minimal residual disease at second-look laparoscopy received three additional courses. Twenty-six patients participated in the pharmacokinetic part of the study. RESULTS: The most important hematologic toxicity encountered was neutropenia. Neutropenia was more pronounced for the higher dose levels (DLs) and was cumulative. Thrombocytopenia was mild in the first eight DLs, but increased during the treatment courses. Nonhematologic toxicities consisted mainly of vomiting, neuropathy, fatigue, rash, pruritus, myalgia, and arthralgia. Dose-limiting toxicities (DLTs) in this trial were neutropenic fever, thrombocytopenia that required platelet transfusions, and cumulative neuropathy. Of 33 patients assessable for response, 26 major responders (78%, 20 complete response [CR] and six partial response [PR]) were documented. The maximal concentration (Cmax) of paclitaxel and the area under the concentration-time curve (AUC) were not different from the historical data for paclitaxel as a single agent. Retrospective analysis using a modified Calvert formula showed that the measured carboplatin AUCs in plasma ultrafiltrate (pUF) were 30% +/- 3.4% less than the calculated carboplatin AUC. Neutropenia was more pronounced than could be expected on the basis of the historical times above a threshold concentration greater than 0.1 mumol/L (T > or = 0.1 mumol/L) or 0.05 mumol/L (T > or = 0.05 mumol/L), and thrombocytopenia was less than could be expected from historical sigmoidal Emax models. CONCLUSION: The combination of paclitaxel 200 mg/ m2 and carboplatin 550 mg/m2 every 4 weeks is a well-tolerated treatment modality. The paclitaxel-carboplatin combination is highly active in stage III (bulky) and stage IV ovarian cancer. No indications for a pharmacokinetic drug-drug interaction between carboplatin and paclitaxel were found.     

Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study

OBJECTIVE: The purpose of this study was to compare the side effect +profiles of clozapine and risperidone. METHOD: The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports. RESULTS: Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment. CONCLUSIONS: In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.     

Managed care contracts and negotiations

This article examines the key provisions which should be focused on when reviewing managed care contracts. It offers guidance on how gastroenterologists can negotiate more favorable terms and avoid common contracting pitfalls. The article also highlights specific issues applicable to capitated and other risk-sharing arrangements.     

Solution structure of human intestinal fatty acid binding protein: implications for ligand entry and exit

The human intestinal fatty acid binding protein (I-FABP) is a small (131 amino acids) protein which binds dietary long-chain fatty acids in the cytosol of enterocytes. Recently, an alanine to threonine substitution at position 54 in I-FABP has been identified which affects fatty acid binding and transport, and is associated with the development of insulin resistance in several populations including Mexican-Americans and Pima Indians. To investigate the molecular basis of the binding properties of I-FABP, the 3D solution structure of the more common form of human I-FABP (Ala54) was studied by multidimensional NMR spectroscopy. Recombinant I-FABP was expressed from E. coli in the presence and absence of 15N-enriched media. The sequential assignments for non-delipidated I-FABP were completed by using 2D homonuclear spectra (COSY, TOCSY and NOESY) and 3D heteronuclear spectra (NOESY-HMQC and TOCSY-HMQC). The tertiary structure of human I-FABP was calculated by using the distance geometry program DIANA based on 2519 distance constraints obtained from the NMR data. Subsequent energy minimization was carried out by using the program SYBYL in the presence of distance constraints. The conformation of human I-FABP consists of 10 antiparallel beta-strands which form two nearly orthogonal beta-sheets of five strands each, and two short alpha-helices that connect the beta-strands A and B. The interior of the protein consists of a water-filled cavity between the two beta-sheets. The NMR solution structure of human I-FABP is similar to the crystal structure of rat I-FABP. The NMR results show significant conformational variability of certain backbone segments around the postulated portal region for the entry and exit of fatty acid ligand.     

Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery

OBJECTIVES: This study evaluated the prognostic value of abnormal test results with pharmacologic stress with regard to perioperative and long-term outcomes in a large population of candidates for vascular surgery. BACKGROUND: Although numerous studies have demonstrated the prognostic value of dipyridamole-thallium-201 myocardial perfusion and dobutamine echocardiography in vascular surgery candidates, a synopsis of predictive estimates is difficult because of individual study variability in pretest clinical risk, sample size and study design. METHODS: A systematic review of published reports on preoperative pharmacologic stress risk stratification from the MEDLINE data base (1985 to 1994) identified 10 reports on dipyridamole-thallium-201 myocardial perfusion (1,994 patients) and 5 on dobutamine stress echocardiography (446 patients). Random effects models were used to calculate summary odds ratios and 95% confidence intervals. RESULTS: Summary odds ratios for death or myocardial infarction and secondary cardiac end points were greater for dobutamine echocardiographic dyssynergy (14- to 27-fold) than for dipyridamole-thallium-201 redistribution (4-fold); wider confidence intervals were noted with dobutamine echocardiography. Pretest coronary disease probability was correlated with the positive predictive value of a reversible thallium-201 defect (r=0.70), increasing sixfold from low to high risk patient subsets. Cardiac event rates were low in patients without a history of coronary artery disease (1% in 176 patients) compared with patients with coronary disease and a normal or fixed-defect pattern (4.8% in 83 patients) and one or more thallium-201 redistribution abnormality (18.6% in 97 patients, p=0.0001). CONCLUSIONS: Meta-analysis of 15 studies demonstrated that the prognostic value of noninvasive stress imaging abnormalities for perioperative ischemic events is comparable between available techniques but that the accuracy varies with coronary artery disease prevalence.     

Recombinant bovine somatotropin and clinical mastitis: incidence, discarded milk following therapy, and culling

Holstein cows (n = 555) from four Michigan dairy farms were randomly assigned to receive bovine somatotropin (bST) or to serve as untreated controls. Bovine somatotropin (500 mg) was administered every 14 d beginning at 63 to 69 d of lactation and continuing until approximately 21 d prior to dry-off or until the cow was removed from the herd. Trial objectives were to determine the effect of bST on the incidence of clinical mastitis, number of days that milk was discarded because of therapy for clinical mastitis, and culling for mastitis. A total of 127 (22.9%) cases of clinical mastitis occurred during lactation. In the pretrial period (before 63 to 69 d of lactation), 42 (33.1%) cases occurred, and 85 (66.9%) cases occurred during the trial. Of the 42 pretrial cases, 57.1% occurred in control cows, and 42.9% occurred in treated cows. Of the 85 trial cases 47.1% occurred in control cows, and 52.9% occurred in treated cows. Using logistic regression, the odds ratio for the occurrence of clinical mastitis in treated cows was 1.06 (95% confidence interval = 0.62 to 1.81). The number of days that milk was discarded following therapy for clinical mastitis and the culling rate for mastitis did not differ between study groups.