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Biomedical subjects

M M Harris

Publications and source records attributed to M M Harris.

At least 19 recordsLinked to original sources

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: The best dynamic test for the assessment of the hypothalamic-pituitary-adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic-pituitary-adrenal axis. DESIGN: Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed. SETTING: Programmed Investigation Unit. SUBJECTS: Fifty-seven healthy volunteers and 166 patients. MAIN OUTCOME MEASURES: Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycemia (plasma glucose < 2 mmol/l) during an IST. RESULTS: From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean - 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission. CONCLUSIONS: Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

Adrenal Cortex Function Tests

Analysis of myocardial response to significant weight loss in obese rats.

We evaluated cardiac response to weight loss induced by a very-low-energy (VLE) diet similar to commercially available protein-sparing diets. Such diets have been implicated in sudden death, and whether organ and tissue responses to them are untoward is not known. Rapid weight loss was induced in rats with weights ranging from obese to normal, and cardiac mass and myocardial histomorphometry were assessed. Over 3 wk body weight dropped from 544 +/- 12 to 417 +/- 21 g (P < 0.001). Heart weight was less in the VLE group than in obese controls (1246 +/- 115 vs 1625 +/- 179 mg, P < 0.001), as were the weights of the left ventricle (805 +/- 81 vs 1061 +/- 134 mg, P < 0.001) and right ventricle (198 +/- 27 vs 265 +/- 40 mg, P < 0.002). Reduction in heart weight was commensurate with loss of body weight (r = 0.89). Myocyte cross-sectional area was reduced in the VLE group (452.6 +/- 108.6 to 331.8 +/- 41.5 microns 2, P < 0.05), with no structural abnormalities. We conclude that weight loss in the weight range studied is accompanied by proportional reduction in cardiac mass and myocyte size. Myocardial regression is not accompanied by myocyte dropout or edema, and likely represents a simple adaptation to reduced body size.

Animals

"Oh, no, not another hand-washing in-service!".

The need for in-service education is constant in the 1990s. To meet the mandates of federal and accreditation bodies, organizations must be prepared to conduct required education. In an environment where healthcare organizations are being asked to do more with less, education dollars are at a premium. There is also the need to be creative to heighten the interest of the staff in what might otherwise be considered a boring topic. Our annual in-service program on hand-washing and infection control was scheduled to present the required information, but this time we had fun and the participants paid attention. The message was received and the home health agency met its requirements and those imposed by outside regulatory and accrediting organizations.

Education, Nursing, Continuing

Hepatic response to a very-low-energy diet and refeeding in rats.

Hepatic effects of very-low-energy diets (VLEDs) and refeeding were studied in dietary obese rats. Rats weighing 490-530 g (ages 72-119 d) were randomly assigned to control (C) and VLED groups. Control animals consumed a complete diet ad libitum whereas VLED animals consumed 20% of the energy intake of C animals for 7, 14, or 21 d, and some VLED animals were refed the C diet for 7 d. Hepatic weights, lipid, DNA, and total protein decreased in VLED animals. Observed hepatocytic lipid was high in C and progressively decreased in VLED rats. Hepatocytes from VLED rats lost cytoplasmic organelles, contained myelin figures, and became smaller. Decreased protein-DNA ratios and lipids in these same animals is consistent with atrophy. Other biochemical findings included reductions in blood urea nitrogen, albumin, triglycerides, total protein, and glucose, all of which are synthesized or metabolized by the liver. These observations suggest that attenuation of hepatic function is likely.

Adipose Tissue

Use of the [14C]aminopyrine breath test to assess the hepatic response of dietary obese rats to a very-low-energy diet.

The intake of a very-low-energy diet (VLED) complete in all essential nutrients decreases liver mass and total liver protein in dietary obese rats. To determine how these findings may affect hepatic drug metabolizing activity, the aminopyrine breath test was performed in nine male dietary obese Sprague-Dawley rats weighing 440-460 g. Animals were maintained on a VLED, and at 0, 14, and 21 d were injected with 9.25 k Bq (0.25 microCi) [dimethylamine-14C]aminopyrine and placed in airtight restraining cages; exhaled 14CO2 was collected for 120 min. VLED animals had an increased half-life of exhaled 14CO2 (P < 0.01) and a decreased rate constant of aminopyrine elimination (P < 0.01) consistent with decreased N-demethylation of aminopyrine. Decreased liver glutathione suggests reduced ability to detoxify drugs through this conjugation pathway. These studies suggest that animals on VLEDs have reduced capacity for demethylation of aminopyrine as measured by oxidative elimination of 14CO2, and may exhibit decreased metabolism of other drugs.

Aminopyrine

Prevention of postmenopausal osteoporosis. A comparative study of exercise, calcium supplementation, and hormone-replacement therapy.

BACKGROUND: Osteoporosis among older women is a major public health problem. We studied the effects of three approaches to the prevention of osteoporosis in women with low bone density. METHODS: One hundred twenty postmenopausal women (mean [+/- SD] age, 56 +/- 4) who were selected because they had low forearm bone density were enrolled in a double-blind, placebo-controlled, randomized study comparing the effects of an exercise regimen (exercise group, n = 41), exercise plus dietary calcium supplementation (exercise-calcium group, n = 39), and exercise plus continuous replacement of estrogen and progesterone (exercise-estrogen group, n = 40). Periodically during the two-year study period, we measured the women's bone density at three forearm sites, measured indexes of calcium metabolism, and recorded symptom scores. A comparison group of 42 women (mean age, 55.5 +/- 3.1) with normal bone density was also followed for two years. RESULTS: Significant bone loss in the distal forearm occurred in the group with normal bone density (control group) and the exercise group (change, -2.7 percent and -2.6 percent of the base-line value per year, respectively). Bone loss at the distal forearm site was significantly lower in the exercise-calcium group (-0.5 percent of the base-line value per year), and bone density increased at this site in the exercise-estrogen group (+2.7 percent of the base-line value per year). Bone loss at the median forearm site was significantly lower in the exercise-calcium group (-1.3 percent of the base-line value per year) than in the exercise group (-2.4 percent), and bone density at this site increased significantly in the exercise-estrogen group (+0.8 percent of the base-line value per year). Breast tenderness occurred in 47 percent of the women in the exercise-estrogen group but in only 20 percent in the other two treatment groups. Vaginal bleeding occurred at some time in 52 percent of the women who had not had a hysterectomy in the exercise-estrogen group, as compared with 11 percent and 12.5 percent, respectively, in the exercise and exercise-calcium groups. CONCLUSIONS: In postmenopausal women with low bone density, bone loss can be slowed or prevented by exercise plus calcium supplementation or estrogen-progesterone replacement. Although the exercise-estrogen regimen was more effective than exercise and calcium supplementation in increasing bone mass, it also caused more side effects.

Bone Density

Intrathecal morphine for postoperative analgesia in children after selective dorsal root rhizotomy.

The authors report their experience with low doses (0.007-0.015 mg/kg), moderate doses (0.016-0.025 mg/kg), and high doses (0.026-0.035 mg/kg) of intrathecal morphine for postoperative analgesia after selective dorsal root rhizotomy surgery in 50 children, aged 3 to 12 years. After closure of the dura, a single dose of preservative-free morphine was injected into the subarachnoid space, and patients were assessed for 48 hours for level of comfort and side effects. The three doses of morphine provided equivalent analgesia and similar side effects. The duration of postoperative analgesia ranged from 3 to 48 hours (mean, 12.2 +/- 9.5 h). Common side effects were limited to nausea and vomiting (42%) and mild facial pruritus. No patient experienced late respiratory depression or generalized pruritus. The authors conclude that low doses of intrathecal morphine is as effective as moderate or high doses of morphine for reducing pain in the immediate postoperative period. Intrathecal morphine provides excellent analgesia after selective dorsal rhizotomy.

Cerebral Palsy

Octreotide.

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Acromegaly

Gastrointestinal and cardiac response to refeeding after low-calorie semistarvation.

A recent development in the treatment of obesity is the widespread use of very-low-calorie diets. This study assessed the response to refeeding (RF) after semistarvation (SS) in a rat model. Male Sprague-Dawley rats (440 g) were semistarved for 21 d, receiving a nutritionally complete defined formula diet at 23% of calories of control (C) rats fed ad libitum, and subsequently refed over 21 d (SS----RF). Organ weight, contents of protein and DNA, and the protein-DNA ratio were determined for the liver, pancreas, small intestine, and heart. Compared with C animals, SS----RF animals showed variable repletion of tissue protein but not of tissue DNA. The higher protein-DNA ratio shown in these organ systems suggests a cellular hypertrophic adaptive response to refeeding. A persistent reduced number of cells in ratio to protein concentration is evident despite refeeding over 21 d. Very-low-calorie diets as well as refeeding influence nitrogen economy of selected organ systems.

Adaptation, Physiological

Structure of the androgen dependent SVS VI protein as derived from cDNA.

The 11S poly(A+)RNA from rat seminal vesicle was cloned. By hybrid selection of clones reacting to the low molecular weight region of the 11S peak, a clone containing a new seminal vesicle cDNA sequence called SVS VI was isolated. The DNA sequence of two overlapping cDNAs (pSV24 and pSV33) is presented. The sequence of SVS VI was compared to the previously isolated SVS IV and SVS V cDNAS. Dot hybridization showed that SVS VI is androgen responsive after giving testosterone to castrated rats. The hydrophilicity was analyzed using standard Bionet procedures. All three proteins are extremely variable, rich in alpha-helix and very water soluble. The computer predicted hydrophilicity is compared for SVS VI, V and IV. A small region in the 3'-non-coding area of SVS VI has high similarity to a region in SVS IV mRNA.

Amino Acid Sequence

Gastrointestinal and cardiac response to low-calorie semistarvation diets.

Effects of low-calorie semistarvation diets on gastrointestinal and cardiac organ systems were studied. Male Sprague Dawley rats were divided into two groups, Group I, control (C) and Group II, semistarvation (SS), and maintained on a diet designed after low-calorie modified-fasting regimens in popular use. C animals consumed this diet ad libitum; SS animals received 23% of the total calories of C but the same ratio of calories from protein, carbohydrate, and fat and the same quantity and quality of all essential nutrients. Final weights of total body, heart, liver, and small intestine were lower in SS than in C animals. Protein depletion in SS compared with C animals was evident for heart, pancreas, and intestinal mucosa. Unless aggressively supplemented, low-calorie SS diets may deplete protein stores of the gastrointestinal organs of digestion and absorption and contribute to decrease in body nitrogen stores, specifically cardiac muscle.

Animals

Mutagenicity of drinking water detected by the Tradescantia micronucleus test.

Spring Lake reservoir of Macomb, Illinois, is a typical model of the drinking water supply of some midwestern towns of the United States. Water samples collected periodically in 1980 and 1981 from this lake were tested for mutagenicity using the Tradescantia micronucleus (Trad-MCN) test, a highly sensitive mutagen-detecting bioassay. Water samples from 1981 were also analyzed chemically. The micronucleus (MCN) frequency peaked (12-14 MCN/100 tetrads) in mid-July in both years, as compared with the average frequency (5 MCN/100 tetrads) of the base-line control that was maintained in nutrient solution (prepared with distilled water and pure chemicals). Drinking water from the tap was tested in parallel with lake water, and its mutagenicity tended to fluctuate with the mutagenicity of the lake water.

Cell Nucleus