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Biomedical subjects

S Nicholson

Publications and source records attributed to S Nicholson.

At least 109 records · Page 6Linked to original sources

Fatal placental hemorrhage in pregnant CD-1 mice following one oral dose of T-2 toxin.

Forty-eight hours after oral administration of a single dose (3.0 mg/kg BW) of T-2 toxin to mice on days 7, 8, 10, 11 and 12 of pregnancy, 17% maternal mortality following vaginal hemorrhage was encountered. Necropsy examination of the dead females revealed that massive hemorrhages originating from the placental regions had occurred into the reproductive tract. This observation supports the studies in which hemorrhagic disease has been described as characteristic for intoxications with T-2 toxin. The results suggest that fatal hemorrhage during pregnancy can occur in hemochorial and hemoendotheliochorial placental mammals as a result of T-2 toxin administration.

Administration, Oral↗

Pathology of acute 3-acetyldeoxynivalenol toxicity in mice.

Mice were killed 2, 4, 6, 12, 24, 48 and 96 hours after intragastrical administration of 0, 5, 10, 20, or 40 mg/kg body weight of 3-acetyldeoxynivalenol. The animals became clinically ill after 12 hours and some animals in the highest dose group died. Histological examination of duodenal crypts, thymus and spleen revealed, in all dose groups, presence of the characteristic lesions that are known to be produced by trichothecenes, but the intensity of lesions in the 40 mg group corresponded to lesions known to be caused by 4 mg/kg of T-2 toxin. A rabbit skin bioassay with 3-acetyldeoxynivalenol gave negative results on one occasion and a mild reaction to 100 to 500 micrograms/mL on another. It is concluded that 3-acetyldeoxynivalenol is considerably less toxic than T-2 toxin, but causes acute effects in the dividing cells of the body in a manner characteristic of trichothecenes.

Animals↗

In utero evaluation of fetal cardiac structure: a preliminary report.

Fetal echocardiography as a tool for the prenatal diagnosis of cardiac structural abnormalities was utilized in 27 consecutive patients who were referred for evaluation. Four abnormalities were recognized prenatally and confirmed postnatally. A fifth was identified postnatally. The sensitivity and specificity of this diagnostic test were 80% and 100%, respectively. The utilization of this tool in a tertiary care setting by an adequately trained team has proved to be helpful and is recommended.

Echocardiography↗

Autoantibodies against human insulin.

Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only human insulin displaced the remaining five, porcine and bovine insulins having little or no effect in concentrations up to 1000 U/1. These observations point to the existence of autoantibodies specifically against human insulin in some subjects with established autoimmunity.

Adult↗

Recovery of the hypothalamo-pituitary-adrenocortical axis in the rat after long-term dexamethasone treatment.

Male rats were treated for 14 days with dexamethasone (2.6 mumol/l in the drinking water) and killed at various times after withdrawal of the drug. Some animals were subjected to stress (ether or sham adrenalectomy) just before killing. The recovery of responsiveness of the components of the hypothalamo-pituitary-adrenocortical axis was assessed by measuring plasma and tissue concentrations of hormones, and the response of the tissue in vitro to appropriate stimuli. In vitro, bioactive corticotrophin-releasing factor (CRF) release in response to acetylcholine and adrenal corticosterone release in response to adrenocorticotrophin (ACTH) were significantly suppressed until 3 days after withdrawal. However, release of immunoreactive or bioactive ACTH in response to ovine CRF or hypothalamic extract did not return to normal until day 5. This was correlated with a reduction in pituitary immunoreactive ACTH content and bioactive plasma ACTH, which were suppressed until days 5 and 4, respectively. No change in hypothalamic immunoreactive CRF content could be detected after treatment, or after stress (ether or sham adrenalectomy) in either treated or control animals. Stress (ether) had no effect on the subsequent response of the anterior pituitary gland in vitro to ovine CRF. The large rises in plasma ACTH and adrenal corticosterone measured after stress (ether) in control animals were completely abolished after dexamethasone treatment and did not return to control values until 5 days after withdrawal. Therefore, it appears that after cessation of chronic dexamethasone treatment in the rat, the responsiveness of the hypothalamus and adrenal gland return to normal before that of the pituitary gland.

Adrenalectomy↗

Investigation of acephalus.

We report twins, one of whom was diagnosed as grossly abnormal by ultrasound at 28 weeks' gestation. Postmortem angiographic investigation of this acardiac twin and of the inter-fetal placental anastomoses are reported. The acardiac fetus had a 45,X chromosome constitution, while the other twin had apparently normal chromosomes (46,XX). The association of chromosome anomaly with holoacardius acephalus is discussed.

Abnormalities, Multiple↗

Antibiotic sensitivity of bacteria from urine.

Bacteria isolated from the urine of 400 hospital inpatients and 483 outpatients were identified and the in vitro sensitivity of these organisms against 12 antibacterial agents currently used in the treatment of urinary tract infections was determined. There was little difference in the distribution of organisms between the two groups. Escherichia coli was predominant, accounting for 58% of the inpatients and 66% of the outpatients. Klebsiella was present in 15% of the inpatients as against 7% in the outpatients. Proteus mirabilis 9% inpatients and 8% outpatients and Enterococcus, 7% inpatients and 5% outpatients made up most of the remainder. The different organisms showed varying sensitivity patterns to the antibiotics tested. The commonly used antibiotics with the broadest spectrum were cephalexin and cotrimoxazole.

Anti-Bacterial Agents↗

Health insurance and the homeless.

There is very little known about health care utilization among the homeless or about the role of health insurance on utilization patterns. Many health care reform proposals advocate expanding health insurance coverage for various segments of society, including the homeless. Although homeless people who lack health insurance face strong financial barriers to health services, providing them with health insurance may not appreciably increase their demand for health care if they also face important non-financial barriers. We investigate the relationship between insurance and utilization for this group based on estimates from an empirical model of medical care use and insurance coverage. Using our estimates, we simulate potential effects of policy changes on various types of utilization, including use of mental health services and treatment for alcohol or other drug abuse.

Adult↗

Atrial and brain natriuretic peptide response to exercise in patients with ischaemic heart disease.

1. The response of venous plasma natriuretic peptides (atrial natriuretic peptide, ANP, and brain natriuretic peptide, BNP) plasma cyclic guanosine monophosphate (cGMP) and vasoactive hormones to dynamic exercise has been studied in 16 subjects undergoing diagnostic exercise tolerance for ischaemic heart disease (IHD), and in five healthy control subjects. 2. In patients with IHD, plasma ANP increased 3-fold (mean 16 +/- 2.5 pmol/L pre-exercise, 51 +/- 11 pmol/L after exercise, P < 0.01). Increase in plasma BNP (10.5 +/- 1.6 pmol/L pre-exercise, 13 +/- 2 pmol/L after exercise, P < 0.01) was proportionately much less than ANP but more sustained. In exercising normal subjects, plasma ANP levels doubled (P < 0.01) but there was no significant change in plasma BNP levels. 3. In patients with IHD, there was a significant correlation between levels of plasma ANP and BNP before exercise (r = 0.97, P < 0.001) as well as during exercise (r = 0.79, P < 0.001). 4. Hormone responses in patients with positive exercise tests did not differ significantly from those with negative tests. 5. Although resting levels of plasma ANP and BNP in IHD are correlated, the findings indicate different mechanisms of secretion. The low BNP/ANP ratio in response to acute dynamic exercise presumably reflects the predominance of ANP in pre-secretory atrial stores.

Aged↗

Use of infrared attenuated total reflectance spectroscopy for the in vivo measurement of hydration level and silicone distribution in the stratum corneum following skin coverage by polymeric dressings.

The ability of wound dressings to hydrate the stratum corneum has been tested experimentally using attenuated total reflectance (ATR) infrared spectroscopy. A silicone gel dressing was able to hydrate the stratum corneum to the extent that its water content within the sampled volume was >60% after 5 h of contact compared with about 15% of normal exposed skin and about 30% for a highly permeable hydrophilic polyurethane dressing. An ATR method was devised to determine the presence and depth of penetration of silicone in the stratum corneum as a result of skin coverage by the polymeric dressing.

Algorithms↗

Immunoglobulin Inhibiting Reagent: evaluation of a new method for eliminating spurious elevations in CA125 caused by HAMA.

Cancer therapy utilising radiolabelled murine monoclonal antibodies frequently leads to the production of Human Anti-Mouse Antibodies (HAMA) in the recipient. HAMA interferes with "sandwich" immunoassays, such as those for tumour markers, rendering results unreliable. Published methods for eliminating HAMA from serum are not suitable for use in a laboratory which is processing a large number of assays using an automated system. We report on the use of Immunoglobulin Inhibiting Reagent (IIR) in CA125 assays from recipients of intraperitoneal radioimmunotherapy who had spuriously elevated results due to HAMA. IIR was found to be comparable to the admixture of mouse serum as a way of eliminating the effect of HAMA. IIR is ideally suited to use with an automated assay process.

Animals↗

Measuring community benefits provided by for-profit and nonprofit hospitals.

Nonprofit hospitals are expected to provide benefits to their community in return for being exempt from most taxes. In this paper we develop a new method of identifying activities that should qualify as community benefits and of determining a benchmark for the amount of community benefits a nonprofit hospital should be expected to provide. We then compare estimates of nonprofits' current level of community benefits with our benchmark and show that actual provision appears to fall short. Either nonprofit hospitals as a group ought to provide more community benefits, or they are performing activities that cannot be measured. In either case, better measurement and accounting of community benefits would improve public policy.

Benchmarking↗

Radioimmunotherapy after chemotherapy compared to chemotherapy alone in the treatment of advanced ovarian cancer: a matched analysis.

Ovarian cancer has an overall five-year survival of around 30% in spite of complete remissions being obtained after optimal surgery and platinum-based chemotherapy. Previous studies have indicated a survival advantage for patients treated with radiolabelled monoclonal antibodies (radioimmunotherapy). We report here on the survival of patients who received single-dose intraperitoneal radioimmunotherapy after having achieved complete remission with standard management. Twenty-five patients with epithelial ovarian cancer, stages Ic-IV, received adjuvant intraperitoneal radioimmunotherapy following completion of conventional chemotherapy. On achieving complete remission they receive once 25 mg of HMFG1 labelled with 18 mCi/m2. Controls for cases were sought from the database of the North Thames ovary group (NTOG). Controls were selected on the basis of stage, histological grade and type, and age of patient at diagnosis. Kaplan-Meier survival plots were constructed for cases and controls and subjected to statistical analysis with the log-rank test. Additionally, using a database of 84 NTOG patients known to be disease-free at the end of chemotherapy, estimated survival curves were constructed using Cox's proportional hazards regression model. Close matches were found for 20 of the 25 patients. Median survival has not been reached at a median follow-up of 59 months for cases and 27 months for controls. Survival at five years is 80% for cases and 55% for controls (p=0.0035). The Cox model estimates long-term (10-year) survival of 70% for patients who received radioimmunotherapy, compared to 32% for those that did not (p=0.003). All patients developed serological evidence of human anti-mouse antibody (HAMA). This study shows a likely survival benefit for patients with ovarian cancer who receive intraperitoneal radioimmuno-therapy in the adjuvant setting.

Adult↗

Community benefits: how do for-profit and nonprofit hospitals measure up?

The rise of the for-profit hospital industry has opened a debate about the level of community benefits provided by non-profit hospitals. Do nonprofits provide enough community benefits to justify the community's commitment of resources to them, and the tax-exempt status they receive? If nonprofit hospitals convert to for-profit entities, would community benefits be lost in the transaction? This debate has highlighted the need to define and measure community benefits more clearly. In this Issue Brief, the authors develop a new method of identifying activities that qualify as community benefits, and propose a benchmark for the amount of benefit a nonprofit hospital should provide.

Benchmarking↗

The effects of Medicare payment subsidies to teaching hospitals.

The Medicare program is the nation's largest single source of funds for graduate medical education. The program pays teaching hospitals for the direct costs of their residency programs and, since 1983, has paid for some of the indirect costs of graduate medical education. The rationale for, and extent of, the payments for indirect costs have been debated for years; recently, Congress has reduced the payments as it attempts to rein in Medicare costs. This Issue Brief reviews the status and recent history behind indirect medical education (IME) payments, and summarizes research that investigates how hospitals have responded to the incentives created by these and other supplemental payments.

Diagnosis-Related Groups↗