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Biomedical subjects

S Holt

Publications and source records attributed to S Holt.

At least 127 records · Page 7Linked to original sources

Brain 12-HETE formation in different species, brain regions, and in brain microvessels.

We used gas chromatography/mass spectrometry to measure brain 12-HETE (12-Hydroxy-5,8,10,14-eicosatetraenoic acid) formation from endogenous arachidonic acid in different species and different brain regions and in isolated brain microvessels. When blood-free brain slices were incubated for 20 minutes we found that the rabbit and cat brain incubates contained little 12-HETE when compared to rat and mouse brain incubates. Further in vitro studies of various rat brain regions showed a generally even distribution of 12-HETE. When isolated rat or rabbit microvessels were incubated and analyzed, we found 1 and 0.25 micrograms, respectively, of 12-HETE/mg of microvessel protein. Also, rabbit brain had limited or no capacity to actively metabolize tritiated 12-HETE. In summary, these studies show substantial species variation with respect to brain formation of 12-HETE and indicate that the vasculature is a potentially significant contributor to the 12-HETE found in whole brain tissue.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Gastric enzymes as a screening test for gastric cancer.

Levels of lactic dehydrogenase and beta-glucuronidase were measured in gastric wash samples obtained from 445 patients over 40 years old attending a routine diagnostic endoscopy clinic. An index was derived from the two levels and used as a test for the presence of gastric cancer. Of the 24 patients with an endoscopic diagnosis of gastric cancer, 21 (91.3%) proved positive on this test, including all four cases of early gastric cancer, which were found at repeat endoscopy. The specificity of the test for gastric cancer was 81.3%. Among those patients with false positive results who had endoscopic biopsy were four out of the five cases of severe dysplasia, and four out of the 13 cases of type 2B intestinal metaplasia. Atrophic gastritis alone or with intestinal metaplasia was found in 95.9% of the false positives who were biopsied.

Gastroscopy↗

Clinical versus laboratory detection of alcohol abuse: the alcohol clinical index.

To determine reliable indicators of alcohol abuse a comprehensive set of clinical and laboratory information was acquired from three groups of subjects with a wide range of drinking histories: 131 outpatients with alcohol problems, 131 social drinkers, and 52 patients from family practice. Findings from clinical examination provided greater diagnostic accuracy than laboratory tests for detecting alcohol abuse. Logistic regression analysis produced an overall accuracy of 85-91% for clinical signs, 84-88% for items from the medical history, and 71-83% for laboratory tests in differentiating the three groups. Further analyses showed 17 clinical signs and 13 medical history items that formed a highly diagnostic instrument (alcohol clinical index) that could be used in clinical practice. A probability of alcohol abuse exceeding 0.90 was found if four or more clinical signs or four or more medical history items from the index were present. Despite recent emphasis on the laboratory diagnosis of alcohol abuse simple clinical measures seem to provide better diagnostic accuracy.

Adult↗

Is gastric emptying abnormal in duodenal ulcer?

To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.

Achlorhydria↗

Measurement of gastric emptying rate in humans by real-time ultrasound.

Simultaneous studies of gastric emptying by ultrasound and scintigraphy were performed in 14 subjects to assess the use of ultrasound for the measurement of gastric emptying rate. The presence of air in the stomach prevented the acquisition of gastric emptying data by ultrasound in 3 of the 14 subjects. In the remaining 11 subjects there was no significant difference between values for the half-time (t1/2) of gastric emptying obtained by scintigraphy [for anterior imaging, mean t1/2 = 20.9 +/- 9.9 min (+/- SD); for anterior and posterior imaging, geometric mean t1/2 = 21.1 +/- 10.5 min (+/- SD)] compared with those derived by ultrasound [mean t1/2 = 20.2 +/- 10.0 min (+/- SD), p greater than 0.05 for each comparison]. A significant correlation between the t1/2 of gastric emptying derived by scintigraphy (anterior scanning and geometric mean of counts obtained by anterior and posterior scanning) and the t1/2 measured by ultrasound was obtained (r2 = 0.7, 0.69, respectively). These results imply that ultrasound can be used for the valid assessment of the gastric emptying rate in humans.

Adult↗

Myocardial tissue iron delocalization and evidence for lipid peroxidation after two hours of ischemia.

Ischemic tissue injury has been proposed to be in part due to oxygen-radical-mediated lipid peroxidation. In vitro studies of such reactions show that they are thermodynamically unfavorable unless catalyzed by transitional metals such as iron in low molecular weight species (LMWS iron), ie, the iron-ADP complex. This study tests for iron delocalization into a LMWS pool during myocardial ischemia and for increased tissue malondialdehyde (MDA), a product of lipid peroxidation. Anesthesia was induced in eight dogs (weighing 20 to 30 kg) with ketamine and maintained by ventilation with 1% halothane. The left anterior descending coronary artery was ligated in four animals, and the circumflex coronary artery was ligated in the other four. Two hours after ligation, the animals were sacrificed by a central venous injection of KCl. Tissue samples were immediately taken from the ischemic zone and from the corresponding nonischemic zone. MDA was determined by the thiobarbituric acid assay. LMWS iron was determined on a tissue ultrafiltrate by the o-phenanthroline assay. Statistical data analysis used the matched-pair two-tailed t test. LMWS iron was 18.3 nM/100 mg in ischemic tissue versus 13.1 nM/100 mg in nonischemic tissue (t = 4.14; P less than .01). MDA was 0.91 nM/100 mg in ischemic tissue versus 0.83 nM/100 mg in nonischemic tissue (t = 7.27; P less than .005). We conclude that there is a significant increase in tissue LMWS iron and in MDA after two hours of regional myocardial ischemia. This iron might be the catalyst for maturation of tissue injury during reperfusion as observed by other investigators.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Rat testicular dolichols: distribution and accumulation with age.

Dolichols, linear isoprenoids essential in the biosynthesis of N-glycosylated glycoproteins, are abundant in testicular tissue. This study investigated the distribution of dolichols among testicular cell and subcellular fractions. In addition, the accumulation of dolichol within the rat testis as a function of age was investigated. Dolichol content expressed either as total dolichol/testicle or as dolichol/mg protein exhibited a marked and continuous increase between 14 and 60 days of age. The 4-, 6-, 9-, and 12-mo-old animals exhibited only minor increases in testicular dolichol content. Mean value for retired breeders was 279 ng dolichol/mg protein. Although previous studies have suggested that dolichol synthesis occurs primarily within the spermatogenic cell, elutriation-purified spermatogenic cell fractions showed very low concentrations of dolichol. Pachytene spermatocyte and round spermatid fractions contained 25.8 and 36.5 ng dolichol/mg protein, respectively. Washed epididymal sperm also had a very low dolichol content (18.8 ng dolichol/mg protein). Recovery studies during elutriation purification of spermatogenic cells showed that the majority of dolichol was contained within the Sertoli-rich tubular fragments. Microsomal fractions isolated from whole testis exhibited a small enrichment (1.6-fold) in dolichol content, whereas Golgi apparatus fractions exhibited a large (12-fold) enrichment over that of the initial homogenate. These studies suggest that, although dolichols may be synthesized within the spermatogenic cell, they accumulate within the Sertoli cell.

Aging↗

Muscular dystrophy in girls with X;autosome translocations.

Twenty known cases of X;autosome translocations with breakpoints at Xp21 associated with Duchenne or Becker muscular dystrophy in girls are reviewed. The variable severity described for different persons may reflect differences in X inactivation or in the nature of the genomic target disrupted. High resolution cytogenetic studies on 12 cases indicate breakpoints on the X chromosome at Xp21.1 or Xp21.2. Translocation chromosomes from several of these cases have been isolated in human/mouse somatic cell hybrids. Molecular heterogeneity in the breakpoint positions has been established by probing DNA from these hybrids with a range of cloned sequences known to be located within, or closely linked to, the Duchenne region. The minimum separation between the most distal and the most proximal breakpoints is 176 kb suggesting that, if a single gene is involved, it must be large. Alternatively, the translocations may affect different genes, or confer alterations to regulatory sequences which operate at a distance.

Chromosome Banding↗

In vitro thymidine labelling index in primary operable breast cancer.

The in vitro Thymidine Labelling Index (TLI) of 164 primary breast carcinoma was measured. The relationship of TLI to other established prognostic variables was examined, and the rates of of recurrence and survival of groups of women with high and low TLI tumours were compared. Poorly differentiated tumours had significantly greater TLI values but there were no significant associations with tumour size, axillary lymph node status, age and menopausal status or steroid receptor status. Although there were more recurrences and deaths in the group of women with high TLI tumours, these differences were not statistically significant. In vitro TLI may be a further expression of tumour differentiation, rather than cellular proliferation, and from this study does not provide any additional prognostic information.

Autoradiography↗

Measurement by radioimmunoassay of the mitochondrial uncoupling protein from brown adipose tissue of obese (ob/ob) mice and Zucker (fa/fa) rats at different ages.

The concentration of the 'uncoupling protein' in brown adipose tissue mitochondria has been measured in lean and obese (ob/ob) mice and Zucker (fa/fa) rats at different ages using a specific radioimmunoassay. During the suckling period the concentration of the protein was similar in normal and mutant animals of both types, despite the decrease in mitochondrial GDP binding observed in the obese. The concentration of uncoupling protein was, however, decreased in adult ob/ob mice and adult Zucker rats compared with their respective lean siblings, in parallel with the decrease in GDP binding. It is concluded that there is a 'masked', or inactive, form of uncoupling protein in young ob/ob mice and fa/fa rats.

Adaptation, Physiological↗

Gastric emptying after anterior lesser curve seromyotomy and posterior truncal vagotomy.

Anterior lesser curve seromyotomy with posterior truncal vagotomy (ASPTV) provides a simple, safe and expeditiously performed method of denervating the parietal cell mass, whilst preserving the pylorus. Dumping and diarrhoea are uncommon after this procedure. Gastric emptying has been assessed after ASPTV and other elective operations for duodenal ulcer. Liquid and solid phase gastric emptying studies were performed in control subjects (17), patients before and at least six months after ASPTV (14), vagotomy and pyloroplasty both without (8) and with (6) diarrhoea, vagotomy and gastroenterostomy (11), and Polya gastrectomy (7). There was no delay in emptying time for liquids or solids between ASPTV patients and controls. With the exception of an increase in the early emptying of liquids (P = 0.02) after ASPTV, gastric emptying was not different from normal. After truncal vagotomy and pyloroplasty in patients without diarrhoea the gastric emptying of solids, but not of liquids, was markedly increased (P = 0.00001), whereas in those with diarrhoea both liquid and solid phase emptying were markedly increased (P less than 0.001). When gastroenterostomy was used as the drainage procedure both phases of emptying were increased. After Polya gastrectomy, both early and late emptying of liquids and solids were increased (early phase P less than 0.05, overall emptying P less than 0.001).

Diarrhea↗

The detection of abscesses with diffusible tracers.

In six patients with suspected infection, scintigraphy with diffusible tracers outlined the margins and central portion of an abscess. An animal model was developed to study this process quantitatively. Small inflammatory lesions yielding volumes of pus of 0.1-0.2 mL were shown to have increased blood volume of 0.7 +/- 0.5 mL, increased blood flow by a factor of three and increased extracellular fluid volume of 10 +/- 6 mL. This supports the patient data and indicates that the pathophysiologic features characterising the clinical studies are hyperemia and oedema associated with an abscess. The slow, central area of tracer diffusion corresponded to the presence of pus. Scintigraphy with 99mTc-DTPA is a convenient way of detecting suspected inflammatory lesions and localising collections of pus.

Abscess↗

Melanin inclusions in the peripheral blood leukocytes of a patient with malignant melanoma.

Dark pigmented inclusions were found in the monocytes and polymorphonuclear leukocytes of a patient with widely metastatic malignant melanoma. Special stains demonstrated the granules were composed of melanin. The authors are not aware of any previous case report of patients with metastatic malignant melanoma that had leukocytic melanin inclusions. Prospective search for this phenomenon in malignant melanoma patients may allow such a finding to be used as a diagnostic tool.

Humans↗

Jejunal perforation secondary to metastatic bronchogenic carcinoma.

A case of peritonitis secondary to the perforation of a bronchogenic small bowel metastasis is reported. To our knowledge this is only the fourth case in which peritonitis was the presenting feature of a squamous cell carcinoma of the bronchus. The publications to date are reviewed and the need to biopsy every small bowel perforation found at laparotomy is stressed.

Aged↗