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Biomedical subjects

S M Lang

Publications and source records attributed to S M Lang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Theophylline improves acute mountain sickness.

A randomized two-part study was conducted in order to determine the efficacy of theophylline in the treatment of acute mountain sickness during fast ascent to altitudes >2,500 m. Fourteen healthy male subjects participated in a randomized single-blind placebo-controlled crossover study carried out in a decompression chamber (simulated altitude 4,500 m). A second randomized single-blind, placebo-controlled study was conducted at a high-altitude research laboratory (3,454 m) and included 21 healthy male subjects. The study medication was either 375 mg oral slow-release theophylline (250 mg if <70 kg) or a matched placebo tablet taken twice daily. The acute mountain sickness score (AMSS) was assessed three times a day, beginning 18 h prior to altitude exposure and continuing for 18 h after altitude exposure. In addition, measurements of respiratory frequency, pulse rate, oxygen saturation and arterial blood gas levels were performed. Acute mountain sickness was significantly reduced by theophylline during the decompression chamber study (mean+/-SD 1.2+/-0.9) with placebo versus 3.6+/-0.8 with theophylline; p=0.03). During the high-altitude study, subjects with theophylline showed a significantly lower AMSS on arrival and after 18 h at altitude (0.6 versus 2.3, p=0.03). Oxygenation was improved in both parts of the study. In conclusion, oral slow-release theophylline improves acute mountain sickness.

Administration, Oral↗
PubMed1999

The acidic region and conserved putative protein kinase C phosphorylation site in Nef are important for SIV replication in rhesus macaques.

Variants of the pathogenic SIVmac239 clone with changes in Nef were analyzed to assess the functional relevance of two highly conserved regions in Nef in vitro and in vivo. Changes in a region with an acidic charge (Aci-Nef), or a potential protein kinase C phosphorylation site (PKC-Nef), impaired the ability of Nef to down-regulate CD4 and MHC class I surface expression and to alter CD3-initiated signal transduction in Jurkat T cells. The Aci-Nef, but not the PKC-Nef, associated with the previously described p65 phosphoprotein. SIV containing Aci-Nef, but not SIV containing PKC-Nef, showed reduced infectivity and replication in cell culture systems. One of two rhesus macaques infected with the PKC-Nef mutant virus showed rapid reversion and progressed to disease. In the second animal no reversions and nonprogressive infection was observed. In one of two macaques infected with the Aci-Nef variant, the mutations were stable during the first 40 weeks after infection. Thereafter, variants evolved in which up to six of the eight mutated positions in Nef were reverted and functional activity in vitro was partially restored. These changes occurred concomitantly with increasing viral load and disease progression. The second animal infected with the Aci-Nef variant showed no reversions and remained asymptomatic. Our study suggests that the acidic region and conserved PKC phosphorylation site in Nef are important for SIV replication in rhesus macaques and for several in vitro Nef functions. An almost wild-type activity in in vitro infectivity and replication assays seems insufficient to confer a full nef-positive phenotype in vivo.

Amino Acid Sequence↗
PubMed1999

[Pulmonary trichomoniasis: diagnosis based on identification of irritation in bronchoalveolar lavage].

Bronchopulmonary infections caused by trichomonads have been reported mainly in patients with pre-existing pulmonary or debilitating disease (e.g. bronchial carcinoma, lung abscess, bronchiectasis). Pulmonary trichomoniasis is most often due to infection with Trichomonas tenax, usually regarded as a harmless commensal of the human mouth, and may rarely be caused by other trichomonas species. A 45 year old female presented with a dry cough, exertional dyspnoea and malaise. These symptoms persisted for 6 months regardless of anti-inflammatory and anti-obstructive inhalative therapy. Sarcoidosis of the lungs, diagnosed 20 years prior, had been asymptomatic since and there was no coexistent disease. Laboratory data revealed increased ACE-levels (90 IE/ml) and lung function showed bronchial hyperreactivity on histamine challenge. No other abnormalities were found (chest x-ray, bronchoscopy, lung function test, blood count and serum calcium). The diagnosis was based on the cytological identification of numerous trophozoites of T. tenax in the bronchoalveolar lavage. Therapy with oral metronidazol for 40 days led to complete recovery from symptoms and normalisation of ACE serum levels. The patient has remained well for 12 months since. The pathogenicity of oral trichomonads in the non-immunocompromised host remains uncertain. Our patient had no known medical risk factors by comparison with published cases. The case illustrates the clinical relevance of pulmonary trichomoniasis in an otherwise healthy person.

Animals↗
PubMed1999

Molecular screening of patients with long standing extensive ulcerative colitis: detection of p53 and Ki-ras mutations by single strand conformation polymorphism analysis and differential hybridisation in colonic lavage fluid.

BACKGROUND: In patients with long standing ulcerative colitis at risk of developing malignancy, mutations of the p53 and Ki-ras gene were investigated in lavage solution obtained at surveillance colonoscopy. METHODS: DNA was isolated from 31 consecutive patients with total or subtotal ulcerative colitis and a disease duration of between seven and 26 years. Twenty seven control patients showed no macroscopic or microscopic inflammation on colonoscopy. Exons 5-8 of the p53 gene and exon 1 of the Ki-ras gene were amplified by polymerase chain reaction. Mutations of the p53 gene were detected by single strand conformation polymorphism analysis. Point mutations of the Ki-ras gene were hybridised on dot blots with oligonucleotides marked with digoxigenin. RESULTS: In all cases of ulcerative colitis and in all of the 27 control patients, wild type p53 and wild type Ki-ras could be detected. In four patients with ulcerative colitis, a mutation in exon 5 to 7 of the p53 gene was found, and two patients had a mutation of the Ki-ras gene (Gly to Asp-12, Gly to Val-12). None of these patients had dysplasia in serial biopsy specimens, and all but one had had the disease for more than 10 years. One control patient had a mutation. CONCLUSIONS: Mutations were more frequent in patients with long standing ulcerative colitis (19%) than in control patients (3%, p = 0.07). The technique may be useful for screening for early malignancy in ulcerative colitis.

Adult↗
PubMed1999

[Membranectomy with intestinal-plasty for the treatment of duodenal and upper jejunal constrictive abnormalities].

OBJECTIVE: To sum up the experience of diagnosis and treatment of intrinsic upper gastro-intestinal membrane, 13 cases in children were studied retrospectively. METHODS: There were 10 boys and 3 girls, the major symptoms were vomiting and epigastric distension. Eleven cases were treated by membranectomy with intestinal plasty, and 2 cases were treated by retrocolic side to end duodenojejunostomy. RESULTS: All cases had good results without severe complications. CONCLUSION: The children who have typical symptom of upper digestive tract should be considered duodental and upper jejunal membrane, and should be proved by contrast radiology. The membranectomy with intestinal plasty is the better operative method.

Child, Preschool↗
PubMed1998

Dissociation between high anti-PR3 titers (c-ANCA) and the clinical course of disease in a case of Wegener granulomatosis.

In May 1984 a 58-year-old woman presented with a broad spectrum of clinical symptoms including malaise, arthralgia, hemoptysis and dyspnea, proteinuria and hematuria and a vasculitic necrotizing rash. Bronchial biopsies revealed subglottic granulomatous lesions and renal biopsies showed necrosis, extracapillary proliferation and crest formation, confirming the diagnosis of Wegener granulomatosis. Positive c-ANCA and anti-proteinase 3 subfraction (anti-PR3) titers were first analysed in 1991. Clinical remission was achieved by standard immunosuppressive therapy and renal function was stabilised. Several minor relapses were treated with pulsed intravenous cyclophosphamide but the symptoms could not be completely controlled. Eight years after the onset of disease, a dramatic increase in anti-PR3 titers was observed (34438 U/ml, normal range < 10, ELISA), followed 3 months later by a clinically apparent relapse. Immunosuppressive therapy was reinstituted without clinical improvement. At this point plasmapheresis resulted in an amelioration of clinical symptoms as well as a reduction in anti-PR3 titers. Concomitant immunosuppressive therapy was administered with oral corticosteroids. Forty days later anti-PR3 titers increased, reaching 75000 U/ml twelve months later, however this time without associated clinical symptoms. During the following months the patient had a further transient deterioration of pulmonary and renal function due to secondary bacterial infection which was successfully treated with antibiotics. A nephritic sediment was not present during these episodes. Curiously, the anti-PR3 titers have remained excessively elevated for the last three years.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1998

Human vertebral body apparent and hard tissue stiffness.

Cancellous bone apparent stiffness and strength are dependent upon material properties at the tissue level and trabecular architecture. Microstructurally accurate, large-scale finite element (LS-FE) models were used to predict the experimental apparent stiffness of human vertebral cancellous bone and to estimate the trabecular hard tissue stiffness. Twenty-eight LS-FE models of cylindrical human vertebral cancellous bone specimens (8 mm in diameter, 9.5 mm in height, one each from twenty-eight individuals) were generated directly from microcomputed tomography images and solved by a special purpose iterative finite element program. The experimental apparent stiffness and strength of the specimens were determined by mechanical testing to failure in the infero superior direction. Morphometric measurements including bone volume fraction (BV/TV), three eigenvalues of the fabric tensor and average P(L) were also calculated. The finite element estimate of apparent stiffness explained much of the variance in both experimental apparent stiffness (r2=0.89) and experimental apparent strength (r2=0.87). Stepwise linear regression analysis demonstrated that the LS-FE estimated apparent stiffness was the only significant predictor of experimental apparent stiffness and strength when it was included with all measured morphometric values. Hard tissue stiffness was quite variable between individuals (mean, 5.7 GPa; S.D. 1.6 GPa), but was not significantly related to age, sex, race, weight or morphometric measures for this sample.

Adult↗
PubMed1997

Hypertension induced by recombinant human erythropoietin (rHU-EPO) can be prevented by indomethacin. Pathogenetic role of cytosolic calcium.

Hypertension complicating the therapy of renal anemia with rHU-EPO is characterized by an increase in total peripheral vascular resistance, but the mechanisms underlying arteriolar vasoconstriction remain unclear. To assess the role of altered cellular calcium metabolism, resting platelet cytosolic calcium was measured in 12 previously normotensive patients with end-stage renal disease before and after 12 weeks of EPO-therapy, after 12 weeks of combined antihypertensive pharmacotherapy of EPO-induced hypertension, and after 12 weeks of concurrent administration of EPO and indomethacin. Patients with EPO-induced hypertension showed a significant raise in platelet calcium by comparison with calcium levels prior to EPO (179 +/- 15 vs 120 +/- 8 nmol/l), and there was a positive correlation between their blood pressure and platelet calcium levels (r = 0.9, p < 0.001). Antihypertensive therapy of EPO-induced hypertension resulted in a reduction of blood pressure and a reduction of platelet calcium to near normal levels (128 +/- 6 nmol/l). The non-steroidal antiinflammatory drug indomethacin prevented EPO-induced hypertension and EPO-associated alterations in platelet calcium. The results of the present study suggest that EPO-induced hypertension might be related to altered cellular calcium homeostasis. If EPO therapy induces alterations in calcium metabolism not only in platelets but also in vascular smooth muscle cells, these changes in calcium influx may contribute to arteriolar vasoconstriction during EPO therapy.

Anemia↗
PubMed1997

Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques.

The nef gene of simian immunodeficiency virus (SIV) is essential for high viral load and induction of AIDS in rhesus monkeys. A mutant form of the SIVmac239 Nef, which contains changes in a putative SH3-binding domain (amino acids 104 and 107 have been changed from PxxP to AxxA), does not associate with cellular serine/threonine kinases, but is fully active in CD4 downregulation and associates with the cellular tyrosine kinase Src. Infection of two rhesus macaques with SIVmac239 containing the mutant AxxA-Nef caused AIDS and rapid death in both animals. No reversions were observed in the majority of nef sequences analyzed from different time points during infection and from lymphatic tissues at the time of death. Our findings indicate that the putative SH3-ligand domain in SIVmac Nef and the association with cellular serine/threonine kinases are not important for efficient replication and pathogenicity of SIVmac in rhesus macaques.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Noradrenergic blood pressure dysregulation and cytosolic calcium in primary hyperparathyroidism.

The purpose of this study was to characterize the changes in noradrenergic blood pressure regulation and the causes of this dysregulation in patients with histologically proven primary hyperparathyroidism before and after parathyroidectomy. In untreated hypertensive patients with primary hyperparathyroidism slightly higher plasma levels of norepinephrine, enhanced cardiovascular reactivity to norepinephrine (p<0.05) and increased cytosolic free calcium concentration in platelets (p<0.05) were found. Parathyroidectomy resulted in the correction of noradrenergic blood pressure dysregulation and in the reduction of cytosolic free calcium and led to normotension. In vitro incubation of platelets from normal subjects with heterologous plasma ultrafiltrates from either hypertensive patients with primary hyperparathyroidism or normotensive uremic patients with secondary hyperparathyroidism led to raised platelet calcium in primary hyperparathyroidism but not in secondary hyperparathyroidism, although in both conditions intact parathormone levels were elevated equally. Furthermore, when platelets of normotensive subjects were preincubated with commercially available parathormone, no effect on resting platelet cytosolic calcium was observed. Our results suggest that hypertension in primary hyperparathyroidism may be caused in part by noradrenergic blood pressure dysregulation and seems to be causally linked to the secretion of a parathyroid hypertensive factor, which increases cytosolic calcium and alters vascular tone and reactivity.

Adult↗