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Biomedical subjects

N Thompson

Publications and source records attributed to N Thompson.

At least 91 records · Page 5Linked to original sources

High prevalence and persistence of cytotoxin-positive Helicobacter pylori strains in a population with high prevalence of atrophic gastritis.

Helicobacter pylori is strongly associated with both chronic gastritis and duodenal ulcer. Certain strains of H. pylori produce a vacuolating cytotoxin in vitro. At New Orleans Charity Hospital, concentrated culture supernatants from 119 of 144 (83%) H. pylori strains isolated from 86 patients at high risk of developing gastric cancer, caused vacuolization in HeLa S3 cells. Cytotoxin activity was neutralized by acid (pH 4) and basic (pH 10) solutions and proteases, and was precipitable by (NH4)2SO4, which suggests that the cytotoxin is a protein. In 66 of 86 (76.7%) patients, the H. pylori strains isolated from single or multiple sequential gastric biopsies had a vacuolating cytotoxin. These cytotoxin-positive H. pylori strains were isolated from 69% of patients with diffuse antral gastritis and 89% of patients with chronic atrophic gastritis. The latter lesion is considered a precursor of gastric cancer. The cytotoxicity persisted in sequential biopsies over an interval of several months, indicating persistence of these strains in the gastric mucosa. Fifty-eight percent (7/12) of the sera from cytotoxin-positive H. pylori-infected patients neutralized cytotoxin activity, whereas 20% (1/5) of sera from patients with H. pylori cytotoxin-negative strains and none of five H. pylori-negative patients' sera neutralized cytotoxin activity. The relevance of this cytotoxin in the pathogenesis of H. pylori-induced gastritis requires further study.

Adult↗

Modification of biological responses to interleukin-1 by agents that perturb signal transduction pathways.

In this study we have examined the effect of agents known to perturb certain signal transduction pathways on the biological responses of target cells to stimulation with interleukin-1 (IL-1). In the murine thymoma cell line EL4, IL-1 stimulation results in the secretion of interleukin-2 (IL-2), which was subsequently measured by proliferation of an IL-2-dependent cell line. Agents that elevated intracellular cAMP blocked or partially blocked IL-1 induction of IL-2 secretion, whereas agents that activated protein kinase C (PKC) resulted in a synergistic enhancement. Both pertussis and cholera toxins also inhibited IL-1-induced IL-2 secretion, although probably by acting at different levels. IL-1 simulation of human and murine fibroblasts resulted in release of prostaglandin E2. This response was inhibitable by pertussis toxin but not by cholera toxin, whereas co-stimulation of the fibroblasts with IL-1 and phorbol ester resulted in a synergistic response. Murine fibroblasts could also be stimulated to proliferate by IL-1, and this response was also inhibitable by pertussis toxin. These findings are consistent with coupling of the IL-1 receptor to a signalling pathway via a pertussis toxin substrate.

1-Methyl-3-isobutylxanthine↗

Transhepatic portal vein catheterization for localization of insulinomas: a ten-year experience.

One of the most important factors in the management of insulinomas is the ability to localize the tumor accurately either before or during surgery. We prospectively carried out transhepatic portal venous sampling (THPVS) for tumor localization in 35 of 40 patients with organic hyperinsulinism during a 10-year period. In 32 patients who underwent THPVS and in whom a single tumor was subsequently identified surgically, the maximal insulin gradient was located in the vicinity of the tumor in 100% of cases. Specific regionalization of the tumor on the basis of the site of the maximal insulin gradient to one of three regions (the tail, the body/neck region, and the head/uncinate region) gave a sensitivity of 81% and a specificity of 91%. In contrast, the use of specific cutoff levels for the insulin gradient as a guide to the presence of a tumor in one of these three regions did not increase the accuracy, leading instead to a significant loss of sensitivity with no comparable increase in specificity. There were no major complications from the procedure in any patient. The initial use of computed tomographic/ultrasound scanning and selective angiography localized only 46% of tumors, whereas subsequent THPVS led to the accurate preoperative localization of 100% of all tumors submitted to surgery. Although the surgeon would have identified 81% of the tumors correctly at operation, in 19% (n = 6) he would have failed. Four tumors were in the uncinate and two were in the head. It seems that in patients with proved or established organic hyperinsulinism, THPVS may continue to be of value, if only to regionalize the tumor, especially those in the pancreatic head and uncinate process so as to preclude noncurative operations on the body and tail of the pancreas.

Adult↗

Effects of steroid implants on the prepubertal increase in circulating gonadotropins and sexual receptivity in the female rabbit.

The pubertal increase in gonadotropins in the female rabbit was inhibited 14-42-fold with Silastic implants of progesterone (P4) testosterone propionate (TP), estradiol benzoate (EB) or P4/EB placed subcutaneously on Day 24 of life. Rabbits with empty implants showed the normal prepubertal increase in circulating gonadotropins. By contrast, rabbits with implants of P4 only, had a 2-fold decrease in LH secretion when peak areas were compared. However, FSH secretion though slightly depressed was not significantly different from controls. The prepubertal increase in circulating gonadotropins was completely suppressed by implants of EB, TP and combined P4/EB. At 115-days-of-age, sexual receptivity and mating were absent in EB-treated animals and significantly suppressed in P4-treated ones when compared to controls, all of which mated. Mating was not completely inhibited in TP and combined P4/EB animals. Corpora lutea were found in all rabbits that mated. In the sexually non-receptive does, vaginal stimulation induced an LH surge in 2 of 15 animals. Ovarian weights and follicular development were significantly suppressed in rabbits with EB implants. Ovarian estradiol content was significantly increased in P4- and TP-treated rabbits. Maximum specific binding for [3H]naloxone was suppressed in the hypothalami of P4-treated rabbits. These results suggest that the prepubertal increase in circulating gonadotropins may have an essential role in the control of sexual maturation in the female rabbit.

Animals↗

Transhepatic portal vein catheterization for localization of sporadic and MEN gastrinomas: a ten-year experience.

We review here the 10-year experience at the University of Michigan with 35 patients with gastrin hypersecretion who underwent transhepatic venous sampling (THVS) for tumor localization. Since 1978 THVS has been done routinely in all patients with gastrinoma syndrome considered for operation. Thirty-one patients had proved gastrinomas--21 benign sporadic tumors and 10 tumors associated with multiple endocrine neoplasia type-I (MEN I) syndrome. The correlation between the site of the maximal gradient and location of a sporadic tumor was poor. Overall sensitivity was only 35%, specificity 89%, and negative predictive value 89%. If gradients were regionalized to three areas--body and tail, gastrinoma triangle, and hepatic lobes--then sensitivity was 94%, positive predictive value 94%, and specificity 97%, with a negative predictive value of 97%. The maximal gastrin gradient above the mean for other values gave the greatest sensitivity and specificity. In MEN I syndrome, only four of eight patients with macroadenomas had their tumors correctly localized, a sensitivity of 50% and specificity and negative predictive value of 75%. In 19 patients who had operative localization of sporadic gastrinoma, computed tomography had a sensitivity of 31%, specificity of 66%, positive predictive value of 83%, and negative predictive value of 15%. Selective angiography was better, with a sensitivity of 29%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. Regionalization to the triangle proved valuable for detection of microgastrinomas, as was measurement of hepatic vein gastrins for identification of intrahepatic tumors. In MEN I syndrome, if regionalization was achieved (50%), tumor resection appeared to offer hope of "cure." We conclude that THVS is the best tool for tumor regionalization to the pancreatic tail and body, gastrinoma triangle, and hepatic lobes. It has allowed us to achieve surgical cure in 19 of 21 patients with sporadic gastrinomas and improvement in four of eight patients with MEN I syndrome.

Adolescent↗

Cyclosporin in juvenile dermatomyositis.

Juvenile dermatomyositis in fourteen children who had not responded fully to steroids and other immunosuppressants and who had had chronic active disease for an average of 3 years was successfully treated with cyclosporin. Twelve patients had serious complications of the disease or of previous treatment. The response to cyclosporin included recovery of muscle strength and function and resolution of complications. It was possible to stop steroids or to reduce the steroid dose, which had previously been difficult, in all fourteen patients. In general, a low dose of cyclosporin (2.5-7.5 mg/kg daily) was sufficient and no serious side-effects were seen.

Child↗

Effects of in-vivo administration of GnRH on the release of gonadotrophins in the female rabbit.

Developing female rabbits were studied weekly from Day 22 of life to Day 100. At all ages GnRH (1.5 micrograms/kg) induced a large increase in LH release 15 min later. By contrast, FSH was significantly increased only on Days 22, 29 and 72 and no significant increase was detected up to 2 h after GnRH administration at other ages. Functional corpora lutea were absent at the start of all treatments as indicated by circulating concentrations of progesterone less than 2 ng/ml. It is concluded that the immature rabbit pituitary is functionally capable of responding to GnRH with an increase in LH secretion, whereas the control of FSH secretion may be regulated by other factors.

Animals↗

Clinical features of carcinoid syndrome and the use of somatostatin analogue in its management.

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.

Humans↗

Effects of ovariectomy and estradiol replacement on naloxone induced LH secretion in the female rabbit.

The effects of an opioid antagonist, naloxone, on the secretion of gonadotrophins were investigated in the long term ovariectomized rabbit. In the intact and acutely ovariectomized rabbit (2 days p.o.) naloxone at 10 mg/kg induced an increase of 260-300% in LH secretion at 40 min post-injection. From days 33-66 post-surgery naloxone at 10 mg/kg caused significant elevations in LH release even when animals were treated with estradiol benzoate 24 h previously. By contrast, treatment with oestradiol benzoate 3 h before naloxone abolished the LH increase. An LH surge could be elicited in these rabbits with GnRH treatment. These studies indicated that long term ovariectomy in the female rabbit does not completely remove the opioid control of GnRH release and that the LH response to naloxone is influenced by circulating estradiol levels.

Animals↗

Opioidergic control of luteinizing hormone release in the female rabbit: influence of ovariectomy and steroid replacement on pulsatile secretion.

The influence of ovariectomy and steroid replacement on naloxone-induced changes in pulsatile secretion of luteinizing hormone (LH) in the female rabbit was examined. Blood samples were taken every 5 min through an indwelling catheter in the rabbit ear artery, and plasma was stored until assayed for LH by established radioimmunoassay procedures. In the intact animal, saline injection had no effect on LH secretion. Although naloxone (10 mg/kg) caused a 7-fold increase in mean LH pulse amplitude by 30 min after injection, this increase was not statistically significant because 5 of 11 animals did not respond. In animals ovariectomized 48 h previously, naloxone significantly increased LH concentration by 194% at 23 min after injection. When long-term ovariectomized rabbits were treated with estradiol benzoate and then were given naloxone, no significant increase in LH was observed, although many animals did respond. Treatment of long-term ovariectomized rabbits with 1 microgram estradiol benzoate and 100 micrograms progesterone or 1 mg testosterone propionate on Days 1 and 3 and naloxone on Day 4 resulted in a significant increase in LH 19-24 min later. Although there was an increase in pulse amplitude, no change was detected in pulse frequency after naloxone. These data suggest that the hypothesis of steroid-opioid coupling in the control of LH secretion is not applicable to the female rabbit.

Animals↗

Failure of hepatic adenomas (HCA) to regress after discontinuance of oral contraceptives. An association with focal nodular hyperplasia (FNH) and uterine leiomyoma.

Oral contraceptives have been implicated in the development of hepatic cellular adenomas (HCA) and associated in at least one report with focal nodular hyperplasia (FNH). Recurrence of lesions or progression while the patient is no longer receiving exogenous steroids is less well documented. Three cases are reported in which progression or recurrence of HCA after the discontinuance of steroids was documented. In addition, FNH and uterine leiomyomas with HCA were observed in all three cases. The mechanism of tumor formation secondary to the use of oral contraceptives remains undetermined. In two cases, liver tissues were tested for estrogen receptors; both were found to be negative. Although technique as well as the observed progression of these lesions or development of new lesions after the discontinuance of steroids may account for this negative finding, it suggests that induction of this process may be caused by means other than direct cellular stimulation by the exogenous hormones. Finally, these three cases call attention to a potential subgroup of patients having oral contraceptive-associated HCA who may have progression of their liver tumors when no longer receiving steroids and who require an aggressive treatment program and noninvasive follow-up examinations.

Adult↗

Opioidergic control of luteinizing hormone secretion in the female rabbit: influence of age on the response to naloxone.

To examine the role of opioid neurons on luteinizing hormone (LH) secretion in the female rabbit, we determined LH release at timed intervals after naloxone administration to rabbits aged 25-150 days. The LH response to naloxone (10 mg/kg) was not significantly elevated until day 43 when LH rose 76-113% above basal levels at 40-80 min. In 56-day-old females the corresponding increase was 160% at 15 min and in 65- to 67-day-olds it was 154%. From 70 to 80 days of age the LH response was blunted and no significant elevations could be elicited. By contrast, naloxone-induced LH increases were again evident when rabbits were older than 100 days. At all ages no significant change in FSH concentrations was observed. In the adult females, naloxone at 2.5, 5, and 10 mg/kg caused increases in LH secretion which occasionally were high enough to induce ovulation as exemplified by elevated serum progesterone 4 days later. These data suggest that opioid peptides may be involved in the prepubertal rise in LH and in the normal inhibition of adult secretion in the female rabbit.

Aging↗

High school football injuries: evaluation.

An epidemiologic survey of the literature on high school football injuries revealed methodologic problems. These numerator-denominator inconsistencies and other confounding factors are discussed. The authors suggest a more reliable system of reporting these parameters to further reduce the risk of high school football injuries.

Adolescent↗

High school football injuries: identifying the risk factors.

This epidemiologic survey of the literature on the factors contributing to the high number of high school football injuries consolidates the current information on the characteristics and risk factors associated with these injuries. To reduce the incidence of knee sprains and strains, the most common injuries to this population, the following preventive recommendations are presented: 1) optimum maintenance of playing fields; 2) use of the soccer-style shoe; 3) noncontact and controlled activities in practice sessions; and 4) increased vigilance over technique during injury-prone preseason practices. The authors conclude that more research into factors such as exposure time and activity at injury will further reduce the risk to the high school football player.

Adolescent↗

Calcium homeostasis after parathyroidectomy in normal and shocked states.

The natural history of parathyroidectomy was studied for 75 weeks in two dogs. After parathyroidectomy, the dogs required intravenous and intramuscular calcium supplementation for 1 week. Despite calcium supplementation, in 2 weeks the ionized calcium (Ca++) level fell from 4.67 mg/dl to 2.39 mg/dl. The Ca++ level rose to 4.25 mg/dl by 7 weeks after which the intramuscular calcium supplement was gradually weaned so that no calcium was given after 20 weeks. The Ca++ level stabilized at 3.15 to 3.25 mg/dl after 20 weeks. Postoperative parathormone (PTH) levels remained low. The response to hemorrhagic shock in these two calcium-independent dogs was compared with that seen in two calcium-dependent dogs 4 weeks after parathyroidectomy and to that seen in two euparathyroid dogs. Shock caused a sharp decrease in Ca++ in all animals that had parathyroid ectomy. Prostaglandin E2 (PGE2) was elevated preoperatively in these dogs and fell markedly during shock. Ca++ remained normal and PGE2 increased slightly after shock in the euparathyroid dogs. Cardiac output rose with resuscitation in the euparathyroid dogs but remained constant in the calcium-dependent dogs and increased slightly in the calcium independent parathyroidectomized animals. PTH levels were low in the parathyroidectomy groups and did not react to shock. PTH increased markedly after resuscitation in the euparathyroid dogs, suggesting its role as an acute-phase hormone. All levels returned to baseline levels within 3 days after shock. Adaptation to hypocalcemia occurs in parathyroidectomized dogs and involves PGE2 as well as other factors. Hemorrhagic shock exceeds this compensatory response which in euparathyroid dogs involves active PTH release in response to hypocalcemia.

Animals↗