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Biomedical subjects

M Horowitz

Publications and source records attributed to M Horowitz.

At least 307 records · Page 17Linked to original sources

A retrospective study of the effects of pelvic irradiation for carcinoma of the cervix on gastrointestinal function.

PURPOSE: To evaluate the prevalence of disordered gastrointestinal function following therapeutic irradiation. METHODS AND MATERIALS: Gastrointestinal function was evaluated in 30 randomly selected patients who had received pelvic irradiation for treatment of carcinoma of the cervix between 1 and 6 years previously. Each patient underwent evaluations of (a) gastrointestinal symptoms (b) absorption of bile acid, vitamin B12, lactose and fat (c) gastrointestinal transit: gastric emptying, small intestinal transit and whole gut transit and (d) intestinal permeability. Results were compared with those obtained in 18 normal volunteers. RESULTS: Stool frequency was above the control range in five patients and had increased (p < 0.001) since radiotherapy treatment. Bile acid (p < 0.001) vitamin B12 (p < 0.01) and lactose (p < 0.01) absorption were less in the patients when compared with the control subjects. Bile acid absorption was below the control range in 14 of the 30 patients. Dietary calcium intake was lower (p < 0.05) in those patients with lactose malabsorption. Gastric emptying (p < 0.01) and small intestinal transit (p < 0.01) were more rapid in the patients. Both small intestinal (r = -0.39, p < 0.05) and whole gut (r = -0.45) transit were inversely related to stool frequency. Either bowel frequency, bile acid absorption, vitamin B12 absorption was outside the control range in 19 of the 30 patients. CONCLUSION: Abnormal gastrointestinal function is essentially an inevitable long-term sequel of pelvic irradiation.

Adult↗

Mice transgenic for HTLV-I LTR-tax exhibit tax expression in bone, skeletal alterations, and high bone turnover.

HTLV-I infection can result in adult T cell leukemia with accompanying hypercalcemia and increased bone resorption. A viral etiology has also been invoked for Paget's disease, a disease of high bone turnover. Delineation of pathogenetic mechanisms of viral-associated bone diseases has been impeded by the complexity of viral and host factors. In order to consider the relationship of HTLV-I infection to skeletal changes we have evaluated the role of a single viral gene in mice transgenic for HTLV-I tax under the control of the viral promoter. Tax mice exhibited severe skeletal abnormalities characterized by high bone turnover, increases in osteoblast and osteoclast numbers and activity, and myelofibrosis. These changes were apparent as early as two months of age. Tax mRNA and protein were highly expressed in bone but not in bone marrow nor in any other tissues except, as previously reported, salivary gland and neurofibromas when they did develop. Within bone, tax protein was detected in only two cell types, mature osteoclasts and spindle-shaped cells within the endosteal myelofibrosis. These observations suggest that local expression of the tax gene, which encodes a viral regulatory protein known to influence host gene expression, can induce within the bone environment marked changes in bone cell activity, resulting in profound skeletal alterations.

Animals↗

Central and peripheral contributions to control of heart rate during heat acclimation.

The contributions of the autonomic nervous system and the cardiac pacing cells in the development of heat-acclimation-induced bradycardia were analyzed, and the effect of heat acclimation on the chronotropic response of the heart to heat stress (40 degrees C) was studied. Rats were acclimated at 34 degrees C for 0, 5, 14, 30 and 60 days. Heart rate (HR) was measured in conscious animals, using chronic subcutaneous electrodes. Sympathetic and parasympathetic influences were studied by IP administration of 0.1 and 1 mg/100 g body weight atropine and propranolol respectively, while intrinsic HR (HRi) was measured following administration of both drugs simultaneously. The effects of carbamylcholine and norepinephrine on the beating rate of isolated rat atria were investigated to study pacemaker responsiveness to neutrotransmitters. Up to day 14 of heat acclimation, bradycardia was attained by tonic parasympathetic acceleration (18%) and temporal sympathetic withdrawal (0.8% on day 14), to compensate for the gradually augmented HRi (2.5% and 8% on days 5 and 14, respectively). Following long-term acclimation HRi declined below pre-acclimation rate. This was associated with resumed sympathetic activity (16% and 10% on days 30 and 60 respectively) while parasympathetic activity continued to be high (18%). Tachycardia, known to occur with severe uncontrolled body hyperthermia, was attenuated following heat acclimation by 42%. It was concluded that during the initial phase of heat acclimation bradycardia is achieved primarily by changes in autonomic influences, while following long-term acclimation, changes in the intrinsic properties of the pacing cells (HRi) and the autonomic system both play a role.

Acclimatization↗

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at--2, 2,5,10,15,30,45,60,75,90,105,120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3 +/- 0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r = -0.55, p < 0.05) and directly related to the retention in the distal stomach at 120 min (r = 0.72, p < 0.01). Peak plasma glucose was related to the amount emptied at 5 min (r = 0.58, p < 0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r = 0.58, p < 0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r = -0.56, p < 0.05) and plasma insulin at 30 min (r = -0.53, p < 0.05). Plasma insulin at 120 min was inversely related (r = -0.65, p < 0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r = 0.53, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of pelvic irradiation on gastrointestinal function: a prospective longitudinal study.

PURPOSE: Although radiation enteritis is a well-recognized sequel of therapeutic irradiation, the effects of abdominal and/or pelvic irradiation on gastrointestinal function are poorly defined and treatment is often unsuccessful. To determine both the short- and long-term effects of therapeutic irradiation on gastrointestinal function, we performed a prospective study. PATIENTS AND METHODS: Various aspects of gastrointestinal function were evaluated in 27 patients with potentially curable malignant disease (23 female, 4 male) before the commencement of, during, and 6 to 8 weeks, 12 to 16 weeks, and 1 to 2 years following completion of radiation therapy. Seventeen patients received pelvic irradiation alone and 10 patients received both abdominal and pelvic irradiation. Gastrointestinal symptoms, absorption of bile acid, vitamin B12, lactose, and fat, gastric emptying, small-intestinal and whole-gut transit, stool weight, and intestinal permeability were measured. Results were compared with those obtained in 18 normal volunteers. RESULTS: All 27 patients completed at least 2 series of measurements and 18 patients completed all 5 series of experiments. During radiation treatment, increased stool frequency (p < 0.001) was associated with decreased bile acid and vitamin B12 absorption (p < 0.001 for both), increased fecal fat excretion (p < 0.05), an increased prevalence of lactose malabsorption (p < 0.01), and more rapid small-intestinal (p < 0.01) and whole-gut (p < 0.05) transit. Although there was improvement in most of these changes with time, at 1 to 2 years after the completion of irradiation, the frequency of bowel actions was greater (p < 0.001), bile acid absorption was less (p < 0.05), and small-intestinal transit was more rapid (p < 0.01) when compared with that of baseline and the normal subjects. At this time, at least 1 parameter of gastrointestinal function was abnormal in 16 of the 18 patients. Stool weight was greater (p < 0.05) and whole-gut transit faster (p < 0.01) in patients who received both pelvic and abdominal irradiation, when compared with those who received pelvic irradiation alone. Stool frequency (p < 0.001) and fecal fat excretion (p < 0.05) were greater in those patients who had surgery before radiation therapy. CONCLUSION: Pelvic irradiation is usually associated with widespread, persistent effects on gastrointestinal function.

Abdominal Neoplasms↗

The effect of posture on gastric emptying and intragastric distribution of oil and aqueous meal components and appetite.

BACKGROUND: It is uncertain whether gastric emptying of fat is determined mainly by its physical characteristics or chemical composition. In particular, the intragastric distribution of extracellular fat and the importance of that distribution to gastric emptying of fat is controversial. The effects of posture on gastric emptying, intragastric distribution, and appetite after ingestion of a meal containing oil and aqueous phases was evaluated. METHODS: Eleven volunteers consumed 60 mL 99mTc-(V)-thiocyanate-labeled olive oil and 290 mL 113mIn-labeled soup while sitting and while lying in the left lateral decubitus position. Hunger before and after the meal was recorded. RESULTS: In the sitting position, oil emptied from the stomach more slowly (P < 0.01) whereas in the decubitus position oil emptied faster (P < 0.01) than the aqueous phase. Oil was preferentially retained in the proximal stomach when sitting (P < 0.01), and more oil was retained in the distal stomach in the decubitus position (P < 0.05). The amount of oil that emptied in the first 180 minutes was not different between the two postures. The aqueous phase emptied much more slowly (P < 0.01) in the decubitus position. At 120 minutes and 180 minutes, subjects were less hungry (P < 0.05) in the decubitus position. In the decubitus position, hunger at 120 minutes and 180 minutes was related to the retention of oil (r > or = 0.79; P < 0.01) in the stomach. CONCLUSIONS: These results indicate that (1) gravity has a major effect on the intragastric distribution and relatively little effect on total stomach emptying of oil, and (2) postprandial hunger is affected by posture and, in the decubitus position, is inversely related to the amount of oil that has entered the small intestine.

Adolescent↗

Secondary carcinoma of kidney from parotid gland tumor.

Secondary tumors of the kidney are rarely diagnosed during life. However they should be suspected in a patient with a primary malignancy of nonrenal origin and a renal mass. A case of parotid cancer metastatic to the kidney is presented. This case is unique because of its rarity, clinical presentation, and pathologic findings.

Adult↗

Untreated hypernephroma of thirty-three years.

The literature cites long-term (> 10 years) survivals after surgical treatment for renal cell carcinoma compared with few untreated cases with similar survival. We report the longest survival between time of diagnosis and documented distant metastases from an untreated renal cell cancer.

Aged↗

Pathological grief: an intensive case study.

Pathological mourning is such an excessive, blocked, or distorted process that psychiatric signs and symptoms develop. Explanation of how and why these signs and symptoms form could deepen an understanding of both normal and pathological mourning. Because many variables are involved in such explanations, intensive case study is a desirable methodology because it permits a detailed look at how various factors interact (Brewer and Hunter 1989; Luborsky and Mintz 1972; Luborsky and Spence 1971; Nessleroade and Ford 1985). While a patient may complain of symptoms as experiences that endure or occur episodically over days and weeks, a clinician observes psychiatric signs in the here-and-now seconds and minutes of an interview. Relating signs and symptoms to each other and to other variables in order to form a theoretical model of their formation requires exploration of data across long and short time frames. It is important to understand how the here-and-now phenomena combine to form patterns across longer periods of the individual's life. Hence, we developed a combined macro- and microanalytic approach to intensive case studies.

Adaptation, Psychological↗

Effects of skin thickness, age, body fat, and sunlight on serum 25-hydroxyvitamin D.

We tested the hypothesis that the age-related decline in skin thickness may contribute to the age-related decline in serum 25-hydroxyvitamin D [25(OH)D]. We measured skinfold thickness on the back of the hand, serum 25(OH)D, height, and weight in 433 normal postmenopausal women. We also noted the average daily hours of sunlight in the month in which the observations were made and in the preceding 2 mo. Serum 25(OH)D was positively related to hours of sunlight (with a time lag of 2 mo) and to skin thickness, and negatively to body mass index (wt/ht2). Serum 25(OH)D fell significantly after age 69 y. Seasonal variation of serum 25(OH)D was greater in lean than in fat subjects, which we attributed to the larger fat mass and consequent larger pool size in the latter group. The results suggest that the tendency for serum 25(OH)D to fall with age is due in part to the age-related decline in skin thickness.

Adipose Tissue↗

The nature and significance of the relationship between urinary sodium and urinary calcium in women.

Orally or parenterally administered sodium is known to increase urinary calcium in experimental animals and humans, and there is well-documented correlation between urinary sodium and calcium in 24-h urine collections from normal subjects and renal stone formers. The correlation between urinary sodium and calcium is generally sodium driven, i.e., it is the sodium load that influences urinary calcium rather than vice versa, but the converse may also occur, as after an oral calcium load or in hypercalcemia. When sodium is the determinant, 100 mmol of sodium takes out approximately 1 mmol of calcium in the urine. When calcium load is the determinant, each millimole of calcium appearing in the urine is associated with an extra 10-20 mmol of sodium. Sodium-dependent calcium loss may continue indefinitely, but calcium-dependent natriuresis is self-limiting. There is a significant correlation between calcium and sodium in fasting urine from both pre- and postmenopausal women, but there is more calcium relative to sodium in postmenopausal women than in premenopausal women. In postmenopausal but not premenopausal women, urinary hydroxyproline is also related to obligatory sodium and calcium output, and restriction of salt intake lowers not only urinary sodium but also calcium and hydroxyproline. There is not only an increase in obligatory calcium excretion at the menopause, but also an increase in the fasting urinary sodium, which in turn accounts for some of the increase in calcium output. This rise in fasting urinary sodium represents a delay in sodium excretion that may have a significant effect on calcium homeostasis.

Adult↗

Abnormal neutrophil chemotaxis in Gaucher disease.

The tendency towards infection described in Gaucher disease patients has been attributed to their post-splenectomy state. We noticed that certain patients with intact spleen have also suffered from recurrent pyogenic infections, thus an attempt to study their neutrophil function has been made. Nine of 29 patients studied expressed significant decrease in neutrophil chemotaxis directed towards zymosan activated serum or N-formyl-methionyl-leucyl-phenylalanine. Random migration was significantly impaired in five of those nine patients. Adherence of neutrophils to nylon fibres and O2- production were intact. The patients with impaired chemotaxis were significantly afflicted by their disease (early onset of symptoms and severity score index > 10) and most of them had genotypes associated with severe disease (1448/1448 and 1226/84GG). No correlation was found with the spleen status. Three of the patients with impaired chemotaxis, and none of the patients with normal neutrophil function, suffered from recurrent pyogenic infections. It is suggested that the described neutrophil migration impairment may contribute to the tendency towards infection in certain patients with advanced Gaucher disease.

Adolescent↗

Effects of norethisterone on bone related biochemical variables and forearm bone mineral in post-menopausal osteoporosis.

OBJECTIVE: Progestogens may be a useful therapeutic alternative to oestrogen in the treatment of post-menopausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patients with post-menopausal osteoporosis. DESIGN/PATIENTS: The effects of treatment with norethisterone (5 mg/day) on bone related biochemical variables was determined in 44 women with post-menopausal osteoporosis. The effects of norethisterone on forearm bone mineral content (FMC) were evaluated by serial measurements in 39 of these women. MEASUREMENTS: We measured forearm mineral content, forearm mineral density, forearm fat content and fat-corrected forearm mineral density. Biochemical measurements included plasma calcium and plasma calcium fractions (ionized, protein bound, complexed and ultrafiltrable), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid hormone, osteocalcin and 1,25-dihydroxyvitamin D, radiocalcium (45Ca) absorption and fasting urinary calcium/creatinine, sodium/creatinine, phosphate/creatinine and hydroxyproline/creatinine molar ratios. RESULTS: After 4 months of treatment norethisterone produced a fall in plasma calcium (mean +/- SEM from 2.40 +/- 0.14 to 2.32 +/- 0.13 mmol/l, P < 0.001), primarily in the non-ionized calcium, due to a decrease in plasma bicarbonate (from 29 +/- 0.28 to 27 +/- 0.28 mmol/l, P < 0.001). There were decreases in urinary calcium/creatinine (from 0.41 +/- 0.03 to 0.19 +/- 0.02, P < 0.01) and sodium/creatinine (from 15 +/- 1.1 to 10 +/- 0.93, P < 0.001) molar ratios and a rise in the renal tubular maximum for calcium reabsorption (TmCa) (from 2.36 +/- 0.041 to 2.55 +/- 0.059 mmol/l of glomerular filtrate, P < 0.001). Plasma phosphate, urinary phosphate/creatinine and tubular maximum for phosphate reabsorption (TMP) all fell (P < 0.01). Both the urinary hydroxyproline/creatinine (P < 0.001) and plasma alkaline phosphatase (P < 0.001) fell. Serum parathyroid hormone rose from 4.1 +/- 0.36 to 5.5 +/- 0.51 pmol/l (P < 0.02) and radiocalcium absorption increased from 0.67 +/- 0.08 to 0.81 +/- 0.10 fx/h (P < 0.01). There was no change in serum 1,25-dihydroxy vitamin D. After treatment with norethisterone for 4 months there was an increase in forearm bone mineral content (P < 0.05) and a decrease in forearm fat content (P < 0.02). After two years treatment with norethisterone fat-corrected forearm bone mineral content rose (mean change 17.0 +/- 5.5 mg/cm, P < 0.01). CONCLUSIONS: These results suggest that norethisterone prevents bone loss in post-menopausal osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on intestinal calcium absorption, and increases serum parathyroid hormone levels.

Adult↗

The effect of chlorothiazide on bone-related biochemical variables in normal post-menopausal women.

OBJECTIVE: To evaluate the effects of short-term administration of chlorothiazide on fasting urinary hydroxyproline, an index of bone resorption, and other bone-related biochemical parameters in normal post-menopausal women. DESIGN: Subjects served as their own control before and after chlorothiazide treatment. SETTING: Subjects were recruited by advertisement. PARTICIPANTS: Thirteen healthy post-menopausal women with a mean age of 65 years. INTERVENTION: Each subject was given chlorothiazide 500 mg bd po for 7 days. Fasting blood and urine samples were obtained immediately before the commencement of chlorothiazide (day 1) and 2 and 7 days after starting chlorothiazide. RESULTS: Chlorothiazide decreased the urinary calcium/creatinine (mean value day 1, 0.267; day 2, 0.143; day 7, 0.135; P < 0.001) and hydroxyproline/creatinine (day 1, 0.0192; day 2, 0.0145; day 7, 0.0139; P < 0.02) molar ratios. CONCLUSION: Chlorothiazide decreases fasting urinary hydroxyproline, a marker of bone resorption in post-menopausal women. This observation supports a potential role for thiazide diuretics in the prevention of osteoporosis. The observed fall in urinary hydroxyproline is of the same order as that seen after treatment with estrogen or calcium supplements.

Acid-Base Equilibrium↗

The effects of thiazide diuretics on calcium metabolism in the aged.

OBJECTIVE: To determine the effects of long-term use of the thiazide diuretic chlorthalidone on serum bone-related biochemical variables in older persons. DESIGN: Cross-sectional comparison. SETTING: Community-dwelling subjects who had participated in the Systolic Hypertension in the Elderly (SHEP) program. PARTICIPANTS: Sixty-six Caucasians (36 male and 30 female), age range 70 to 89 years, of whom 23 were taking a thiazide diuretic. MEASUREMENTS: 25-hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, calcitonin, and serum bioavailable testosterone. RESULTS: In both groups, there was a high prevalence of low 25 (OHD) levels (30%). Log 25OHD showed a significant inverse relationship to parathyroid hormone (r = .33, P < 0.05). Thiazide users had lower levels of osteocalcin (P < 0.05) and parathyroid hormone levels (P < 0.05) compared with non-thiazide users. Male thiazide users had decreased bioavailable testosterone levels compared with non-thiazide users (P < 0.05). Serum osteocalcin was significantly related to bioavailable testosterone in men not on thiazide (r = .43, P < 0.05). CONCLUSIONS: Hypovitaminosis D is a common finding in older individuals with associated elevations in parathyroid hormone. Parathyroid hormone and testosterone concentration (in men) are correlated with serum osteocalcin, a measure of osteoblastic activity. Long-term thiazide use alters these relationships and produces a biochemical profile suggestive of decreased bone formation. Reduced bioavailable testosterone may also play a role in these biochemical changes.

Age Factors↗

A preliminary report of vitamin D and calcium metabolism in older African Americans.

OBJECTIVE: To determine normal serum bone-related biochemical variables in older African-Americans. DESIGN: A convenience sample of older African-Americans who had a health screening and blood testing for calciotropic hormones was compared with white Americans who were recruited at the end of the Systolic Hypertension in the Elderly Program (SHEP) study and were not on a thiazide diuretic. SETTING: Community-dwelling African-Americans who participated in SHEP or who attended one of two mass health screenings. PARTICIPANTS: Thirty-two African-Americans aged 68-93 years and 43 white Americans aged 70-89 years. MEASUREMENTS: Twenty-five hydroxyvitamin D (25OHD), parathyroid hormone, osteocalcin, and calcitonin. RESULTS: Serum 25OHD levels in 38% of the African-American men and 38% of African-American women were less than 8 ng/mL compared with 22% of Caucasian men and 40% of Caucasian women. Serum parathyroid hormone (PTH) was above the normal range in 25% of men and 33% of women of African-American descent and 14% of Caucasian men and 30% of Caucasian women. Serum 25OHD was lower (P < 0.05) in individuals with a previous history of fracture. Serum albumin (P < 0.05), calcitonin (P < 0.05), and osteocalcin (P < 0.05), but not 25OHD, were lower in African-Americans (men and women) when compared with Caucasians (P < 0.05). Serum calcium corrected for albumin was higher in the African-Americans than in the Caucasians (P < 0.05). As previously reported in Caucasians, PTH was inversely related to log 25OHD in African-Americans. Serum osteocalcin was positively correlated to PTH in African-Americans, as previously reported in Caucasians. Log 25OHD correlated inversely with osteocalcin in African-Americans, but this was not seen in Caucasians. CONCLUSIONS: In this limited sample, hypovitaminosis D (as assessed by 25OHD level) with secondary hyperparathyroidism occurred frequently in elderly African-Americans. Osteocalcin, a measure of osteoblast activity, correlated with 25OHD and parathyroid hormone. Osteocalcin serum levels were lower in African-Americans than Caucasians, but serum calcium corrected for albumin was higher in the former compared to the latter.

Aged↗

Cholecystokinin octapeptide stimulates phasic and tonic pyloric motility in healthy humans.

Stimulation of localised pyloric contractions may be an important mechanism in the slowing of gastric emptying by cholecystokinin infusion. The effect of cholecystokinin octapeptide on fasting pyloric motility was investigated in 14 healthy volunteers. Antral, pyloric, and duodenal pressure responses to normal saline and graded injections of cholecystokinin octapeptide (5, 10, and 20 ng/kg) were measured. Injections were given double blind and in randomised order. All doses of cholecystokinin octapeptide initially stimulated (p < 0.05 cf saline) phasic pressure waves localised to the pylorus--the median number of pyloric pressure waves in the 5 minutes after injection being 0, 3.5, 6, and 7 for the saline and the 5, 10, 20 ng/kg cholecystokinin octapeptide injections respectively. The phasic pyloric motor response to 20 ng/kg cholecystokinin octapeptide injection was greater than that to 5 ng/kg (p < 0.05). Basal pyloric pressure increased after 20 ng/kg (1.0 v 0.2 mm Hg, p < 0.05 cf saline). Antral and duodenal pressure waves were suppressed initially by all doses of cholecystokinin (p < 0.05 cf saline). Subsequently, 20 of the 42 cholecystokinin octapeptide, injections but none of the saline injections, were followed by antropyloric pressure waves. Atropine, 15 micrograms/kg iv as a bolus, and then 4 micrograms/kg/hour iv as an infusion, had no effect on the stimulation of localised phasic pyloric pressure waves by cholecystokinin octapeptide 10 ng/kg. It is concluded that stimulation of pyloric contractions and suppression of antral and proximal duodenal motility may contribute to the slowing of gastric emptying produced by cholecystokinin.

Adolescent↗