PubMed Health⌕ Search

Biomedical subjects

S Pack

Publications and source records attributed to S Pack.

53 records · Page 3Linked to original sources
PubMed1998

A double blind placebo controlled study to determine the effects of intermittent cyclical etidronate on bone mineral density in patients on long-term oral corticosteroid treatment.

BACKGROUND: A double blind, placebo controlled study was undertaken to determine the effects of 104 weeks of intermittent cyclical etidronate therapy on bone mineral density (BMD) in patients undergoing long-term oral corticosteroid therapy. METHODS: Forty nine patients of mean age 59 years on long-term (> 6 months) corticosteroid treatment were randomised to receive either 400 mg/day etidronate or placebo for 14 days followed in both groups by calcium (equivalent to 97 mg elemental Ca/day) with vitamin D (400 IU) for 76 days. The cycle was repeated a total of eight times over a period of two years. Dual energy x ray absorptiometry (DEXA) measurements of the lumbar spine and hip BMD and biochemical bone marker analyses were performed at baseline and every six months. RESULTS: Twenty six patients (10 men) received cyclical etidronate and 23 (nine men) received placebo. The mean (SD) dose of corticosteroid (prednisone or equivalent) at baseline in the etidronate group was 8 (4) mg/day and in the placebo group was 7 (4) mg/day. Most of the patients (43%) suffered from asthma. Forty one patients completed the study (22 in the etidronate group and 19 in the placebo group). All had a low BMD at entry and with treatment a significant difference was observed between groups in the mean (SE) percentage change from baseline in lumbar spine BMD at week 104 of 4.5 (1.65)% (p = 0.007) with a 95% confidence interval (CI) of 1.12 to 7.87%. No clinically or statistically significant treatment differences were observed at the hip or with bone markers. The incidence of adverse events was similar in the two groups. CONCLUSIONS: The results show that intermittent cyclical etidronate therapy with calcium and vitamin D supplementation significantly increases lumbar spine BMD in patients with osteoporosis resulting from long-term treatment with corticosteroids.

Aged↗
PubMed1998

Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3.

Aldosterone synthase (AS) is encoded by the CYP11B2 gene, a candidate for familial hypertension. CYP11B2 was previously mapped to chromosome 8q but its precise localization is necessary for genetic studies of hypertension. The present study reports the genetic mapping of the human CYP11B2 gene by radiation hybrid (RH) analysis, the isolation of a bacterial artificial chromosome (BAC) containing this gene and its physical mapping by fluorescent in situ hybridization (FISH). The CYP11B2 locus is on the most distal segment of the long arm of chromosome 8, proximal to the microsatellite polymorphic marker D8S1704. This location, which was confirmed by FISH, is approximately 60cM telomeric to the currently listed human gene locus (chromosome 8q21-22) and corresponds to cytogenetic band 8q24.3. The BACs containing the gene and a high-resolution map of the CYP11B2 locus are useful for genetic studies of hypertension and other endocrine disorders.

Chromosome Mapping↗
PubMed1998

11q13 allelic loss in pituitary tumors in patients with multiple endocrine neoplasia syndrome type 1.

Pituitary adenomas may develop sporadically or as part of the multiple endocrine neoplasia type 1 (MEN 1) syndrome. The gene responsible for MEN 1 syndrome was recently identified and cloned. Low rates of MEN 1 gene mutations and deletions have been reported in sporadic pituitary adenomas. To elucidate the role of the MEN 1 gene in the pathogenesis of MEN 1-associated pituitary tumors, we examined pituitary adenomas from 11 MEN 1 patients for the presence of 11q13 allelic loss. Ten of the 11 pituitary tumors were informative by PCR-based loss of heterozygosity analysis. Using a combination of family pedigree analysis and restriction analysis directed at the mutated allele in 8 of the 10 informative cases, it was demonstrated in all 8 cases that it is the wild-type allele that undergoes deletion. All 11 tumors, 4 of which were growth hormone secreting, were additionally analyzed for mutation in the Gs alpha subunit (gsp) gene. None of the tumors (0 of 11 tumors) revealed a gsp gene mutation. Therefore, genetic alterations of the MEN 1 gene seem to play a dominant role in MEN 1-associated pituitary tumorigenesis, whereas gsp gene mutations do not seem to be a frequent event in either growth hormone-secreting or other types of MEN 1-associated pituitary tumors. These results suggest that MEN 1-associated pituitary tumors develop via genetic pathways that differ from those of most sporadic pituitary tumors.

Adenoma↗
PubMed1998

Loss of heterozygosity and microsatellite instability in non-neoplastic mucosa from patients with chronic ulcerative colitis.

Microsatellite instability and allelic deletions of tumor suppressor genes have been observed frequently in tumors. Molecular pathogenesis of the development of dysplasia and carcinoma in ulcerative colitis is still unclear. In order to detect microsatellite alterations in ulcerative colitis, we analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) on chromosomes 3, 6, 7, 12, and tumor suppressor gene loci, including p53, APC, and p16, of chronically inflamed, non-dysplastic epithelium after microdissection. Twelve of 13 (92%) cases showed LOH and/or MI at one or more loci. LOH at chromosome 3 and MI at chromosome 12 were observed in 50% and 62%, respectively. However, LOH at p53 and p16 was detected in only one case each. These results suggest that chronic inflammation may initiate microsatellite alteration, which subsequently transform ulcerative colitis to dysplasia or cancer. This finding provides information for the evaluation and treatment of patients with ulcerative colitis.

Journal Article↗
PubMed1997

Mutations of the MEN1 tumor suppressor gene in pituitary tumors.

Although pituitary adenomas are monoclonal proliferations, somatic mutations involving genes that govern cell proliferation or hormone production have been difficult to identify. The genetic etiology of most pituitary tumors, therefore, remains unknown. Pituitary adenomas can develop sporadically or as a part of multiple endocrine neoplasia type 1 (MEN1). Recently, the gene responsible for MEN1 was cloned. To elucidate the potential etiological role of the MEN1 gene in pituitary tumorigenesis, 39 sporadic pituitary adenomas from 38 patients and 1 pituitary adenoma from a familial MEN1 patient were examined for MEN1 gene mutations and allelic deletions. Four of 39 sporadic pituitary adenomas showed a deletion of one copy of the MEN1 gene, and a specific MEN1 gene mutation in the remaining gene copy was detected in 2 of these tumors. The corresponding germ-line sequence was normal in all sporadic cases. A specific MEN1 mutation was detected in a pituitary adenoma and corresponding germ-line DNA in a patient with familial MEN1. An allelic deletion of the remaining copy of the MEN1 gene was also found in the patient's tumor. Genetic alterations of the MEN1 gene represent a candidate pathogenetic mechanism of pituitary tumorigenesis. The data suggest that somatic MEN1 gene mutations and deletions play a causative role in the development of a subgroup of sporadic pituitary adenomas.

Adenoma↗
PubMed1997

Somatic mutations of the MEN1 tumor suppressor gene in sporadic gastrinomas and insulinomas.

Gastrinomas and insulinomas are frequent in multiple endocrine neoplasia type 1 (MEN1). The MEN1 tumor suppressor gene was recently identified. To elucidate the etiological role of the MEN1 gene in sporadic enteropancreatic endocrine tumorigenesis, we analyzed tumors (28 gastrinomas and 12 insulinomas) from 40 patients for MEN1 gene mutations and allelic deletions. One copy of the MEN1 gene was found to be deleted in 25 of 27 (93%) sporadic gastrinomas and in 6 of 12 (50%) sporadic insulinomas. MEN1 gene mutations were identified in 9 of 27 (33%) sporadic gastrinomas and 2 of 12 (17%) insulinomas and were not seen in corresponding germ-line DNA sequence. A specific MEN1 mutation was detected in one gastrinoma and in the corresponding germ-line DNA of a patient who had no family history of MEN1. Somatic MEN1 gene mutations and deletions play a critical role in the tumorigenesis of sporadic gastrinomas and may also contribute to the development of a subgroup of insulinomas.

Adolescent↗
PubMed1996

Intramuscular prochlorperazine versus metoclopramide as single-agent therapy for the treatment of acute migraine headache.

To compare the efficacy of intramuscular prochlorperazine and metoclopramide in the short-term treatment of migraine headache in the emergency department 86 eligible adult patients with moderate to severe migraine headache were evaluated prospectively at a university-affiliated community hospital. After randomization, each subject received a 2-mL intramuscular injection of sterile saline, prochlorperazine (10 mg), or metoclopramide (10 mg). No other analgesics were administered during the 60-minute study period; patient assessment of relief was followed using visual analog scales. Reduction in median headache scores was significantly better among those treated with prochlorperazine (67%) compared to metoclopramide (34%) or placebo (16%). Similarly, symptoms of nausea and vomiting were significantly relieved in the prochlorperazine group (chi 2 = 17.1, P < .001). However, rescue analgesic therapy was necessary in the majority of patients treated with prochlorperazine (16/28) and metoclopramide (23/29) after the 60-minute study period. Although intramuscular prochlorperazine appears to provides more effective relief than metoclopramide, these results do not recommend either drug as single-agent therapy for acute migraine headache.

Acute Disease↗
PubMed1993

The shorthand vertical mattress stitch: evaluation of a new suture technique.

The shorthand vertical mattress suture is a new suture technique that provides the same amount of wound eversion in less time than the classic method. A randomized, prospective clinical trial was designed to test this hypothesis in a University-affiliated community hospital. Thirty patients who presented to the emergency department with traumatic lacerations requiring primary closure were eligible for this study. Wounds involving the hands, feet, or face were excluded. Patients meeting inclusion criteria were allocated randomly to have either shorthand or classic vertical mattress sutures. Wound information was collected on data sheets and included physician training level, repair time, number of knots placed, and degree of wound-edge eversion for each suture technique. Subjects were then asked to return to the emergency department in 7 to 10 days for wound assessment and suture removal. Thirty-six lacerations to the scalp, trunk, and extremities were evaluated. Shorthand vertical mattress sutures were used on 20 wounds (56%) and classic mattress sutures were used on 16 (44%) wounds. The shorthand stitch provided the same amount of wound eversion in half the time as the classic technique. No infectious complications, delayed wound healing, or cosmetic problems were observed with the shorthand technique. The shorthand vertical mattress stitch described is an efficient, alternative method for laceration repair without compromising wound eversion or cosmetic results.

Adult↗
PubMed1988

Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity.

Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of bypass (r = 0.91, p less than 0.001). Serial measurement of octadeca-9, 11-dienoic acid, a non-peroxide marker of free radical activity, showed significant changes only in the plasma free fatty acid fraction, suggesting a direct relation to the action of heparin rather than to the bypass procedure as such. These studies support the hypothesis that neutrophil activation plays a central role in the organ dysfunction that may complicate cardiopulmonary bypass and suggest that elastase release rather than free radical generation may be the appropriate marker of the event.

Aged↗
PubMed1981

Evidence of diminished suppressor T cell activity in patients with atopy and SLE.

The T cell mitogen concanavalin A (Con A) was added to lymphocytes pre-cultured for 24 hours in vitro in tissue culture medium. Delayed addition of the mitogen resulted in an enhanced lymphocyte activation measured by incorporation of radioactive precursors of DNA. T cells isolated by rosetting with sheep erythrocytes also exhibited this enhancement. In a limited study, lymphocytes from both atopic patients and those with systemic lupus erythematosus (SLE) showed little or no enhanced responsiveness to Con A. The possibility that some patients with atopy and SLE possess defective suppressor T cells is discussed in the light of these data.

Adult↗
PubMed1980

Histamine suppression of lymphocyte activation.

Histamine suppresses lymphocyte transformation induced by the mitogen Con A. The effect is dose-related and is not blocked by H1 or H2 antagonists. High dose of H2 antagonists (10(-3) M) enhances the suppression induced by histamine. The proliferation of T cells alone cultured with histamine is suppressed indicating that histamine can exert its effect directly on T cell proliferation without the requirement for accessory cells. Atopic subjects are more sensitive to histamine-induced suppression than normals. The presence of histamine produced locally during a Type I response may provide a mechanism for preventing the proliferation of sensitized T cells which enter the site of antigen stimulation. In the atopic, who already has the immunological machinery to mount cell-mediated immune responses to pollens, this increased histamine sensitivity may be protective in suppressing unwanted delayed hypersensitivity reactions.

Adult↗
PubMedDate not supplied

Morbidly obese patients with pulmonary disease--a retrospective study of four cases: a brief report.

Morbid obesity is a common chronic condition that predisposes affected individuals to a decrease in functional status. The purpose of this case series is to highlight the benefit of institutional rehabilitation for this subgroup of patients. A 6-mo retrospective review of 117 consecutive admissions to the rehabilitation unit of a municipal hospital center was conducted. A total of four patients (3.4%) met the criteria for morbid obesity. We present the brief case histories of these four subjects. All showed significant functional improvement and were able to return home after a mean length of stay of 61 days. They each required specialized rehabilitation intervention and specialized equipment such as extra large beds and oversize walkers. All four subjects had obstructive pulmonary disease, accounting for their initial hospital admission. This study demonstrates that inpatient rehabilitation improves functional status in morbidly obese patients. Further research regarding physiatric intervention in the morbidly obese patient is needed.

Activities of Daily Living↗
PubMedDate not supplied

Immunogenetic studies of multiple sclerosis patients in Caithness County, Scotland.

The present report indicates that there is an increased frequency of HLA-B7 in multiple sclerosis patients compared to unrelated controls and unaffected siblings. HLA-A3 was not significantly increased. The increased frequency of certain HLA antigens was not reflected in increased titres of serum measles antibodies in this group. In contrast to our previous studies, there were only minimal differences in the cellular response to measles antigen in multiple sclerosis patients as compared to siblings and unrelated controls.

Adult↗