Dynamic radio-ulnar convergence after the Darrach procedure

We reviewed 23 patients who had had 25 Darrach procedures for traumatic or post-traumatic disorders of the wrist at a mean follow-up of 75.5 months (36 to 121). The mean age at the time of operation was 61.1 years (34 to 82). All patients were reviewed in person. Assessment included a history, a questionnaire on patient satisfaction and a detailed physical examination. Standardised radiographs of both wrists were taken with the patient's hands in a resting position and during maximal grip. Convergence of the distal ulnar stump towards the distal radius during maximal grip (dynamic radio-ulnar convergence) was seen in 14 wrists including five with actual contact (dynamic radio-ulnar impingement), but this produced symptoms in only two cases. The presence of dynamic radio-ulnar convergence did not correlate with grip strength, pinch strength, range of movement or wrist score, but was associated with increased length of excision of the distal ulna. Nineteen of the 23 patients were satisfied with the procedure. Dynamic radio-ulnar convergence is common after the Darrach procedure, but is rarely symptomatic; resection of the distal ulna remains a reliable procedure in the older patient with pain and loss of movement. Excision of the lower end of the ulna should be restricted to the least required to restore full rotation.     

MR angiography of the head and neck

A review of the basic physics and techniques for acquiring and evaluating magnetic resonance angiograms is provided, including time-of-flight and phase contrast techniques. Magnetic resonance (MR) angiography is becoming a routine method of evaluating carotid bifurcation atherosclerotic disease in both a screening and diagnostic capacity. The expanding clinical utility of MR angiography in the detection of intracranial aneurysms, characterization of arteriovenous malformations, and evaluation of intracranial atherosclerotic disease are also reviewed. Furthermore, MR angiography allows for the noninvasive diagnosis of arterial dissection. Magnetic resonance venography also allows the confirmation of the previously elusive and likely underdiagnosed entity of cerebral venous thrombosis.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Analysis of a genomic DNA expression library of Mycobacterium tuberculosis using tuberculosis patient sera: evidence for modulation of host immune response

DNA obtained from a human sputum isolate of Mycobacterium tuberculosis, NTI-64719, which showed extensive dissemination in the guinea pig model resulting in a high score for virulence was used to construct an expression library in the lambda ZAP vector. The size of DNA inserts in the library ranged from 1 to 3 kb, and recombinants represented 60% of the total plaques obtained. When probed with pooled serum from chronically infected tuberculosis patients, the library yielded 176 recombinants with a range of signal intensities. Among these, 93 recombinants were classified into 12 groups on the basis of DNA hybridization experiments. The polypeptides synthesized by the recombinants were predominantly LacZ fusion proteins. Serum obtained from patients who were clinically diagnosed to be in the early phase of M. tuberculosis infection was used to probe the 176 recombinants obtained. Interestingly, some recombinants that gave very strong signals in the original screen did not react with early-phase serum; conversely, other whose signals were extremely weak in the original screen gave very intense signals with serum from recently infected patients. This indicates the differential nature of either the expression of these antigens or the immune response elicited by them as a function of disease progression.     

Renal transplantation in adults with thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome

BACKGROUND: Thrombotic thrombocytopenic purpura/haemolytic-uraemic syndrome (TTP/HUS) is a rare cause of renal failure in adults. There is little data concerning the outcome of adult patients who receive a renal transplant for TTP/HUS: METHODS: We have carried out a survey of 22 transplant centres in the USA to determine the outcome of patients who developed ESRD from TTP/HUS and latter received a renal transplant. RESULTS: Twelve of the 22 centres responded to our inquiry. Seven centres had not transplanted any patients with TTP/HUS, and five centres had transplanted a total of 24 grafts in 17 patients with TTP/HUS: Thirty-three per cent of patients demonstrated definite clinical and pathological evidence of recurrence of TTP/HUS: An additional 16% of patients demonstrated pathological evidence of possible recurrence of TTP/HUS in the absence of clinical manifestations. The overall 1-year graft survival rate was 42% and the 2-year graft survival rate was 35%. In our experience recurrence TTP/HUS was associated with universal graft failure. Although cyclosporin A does occasionally cause a thrombotic angiopathy in patients with no history of TTP/HUS, we found no evidence that it should be avoided in patients with a previous history of ESRD from TTP/HUS who subsequently receive a renal transplant. CONCLUSIONS: TTP/HUS frequently recurres in adults who receive a renal transplant, with a 2-year graft survival rate of 35%.     

Effect of exercise intensity on glucose and insulin metabolism in obese individuals and obese NIDDM patients

OBJECTIVE: The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge. RESEARCH DESIGN AND METHODS: Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and VO2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% VO2peak for 70 min or 70% VO2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast. RESULTS: The average caloric expenditure did not differ between exercise at 50 and 70% VO2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (77 +/- 5 vs. 68 +/- 6 g) and obese NIDDM subjects (70 +/- 4 vs. 58 +/- 6 g). Muscle glycogen utilization was also higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (59 +/- 9 vs. 30 +/- 7 g) and in obese NIDDM subjects (48 +/- 5 vs. 24 +/- 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% VO2peak. Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% VO2peak. However, plasma insulin response area was reduced (P < 0.05) after 7 days of exercise at 70% VO2peak (9,644 +/- 1,783 vs 7,538 +/- 1,522 microU.ml-1.180 min-1). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% VO2peak. CONCLUSIONS: It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% VO2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% VO2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.     

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.     

Thyroid hormone export regulates cellular hormone content and response

Actions of thyroid hormones (THs) are determined by intracellular free hormone concentration. Here we report that enhanced TH extrusion via a saturable, cold-sensitive mechanism lowers intracellular TH and causes TH resistance in hepatoma cells. Since these cells overexpress multidrug resistance P-glycoproteins and TH extrusion and resistance are blunted by verapamil, P-glycoproteins may mediate this resistance. Verapamil-inhibitable TH efflux was also found in primary hepatocytes, cardiocytes, and fibroblasts. These findings demonstrate that TH extrusion can modulate TH availability and action in mammalian cells.     

Transformation of Rat-1 fibroblasts with the v-src oncogene increases the tyrosine phosphorylation state and activity of the alpha subunit of Gq/G11

Two major intermediaries in signal transduction pathways are pp60v-sre family tyrosine kinases and heterotrimeric guanine nucleotide-binding proteins. In Rat-1 fibroblasts transformed by the v-src oncogene, endothelin-1 (ET-1)-induced inositol 1,4,5-trisphosphate accumulation is increased 6-fold, without any increases in the numbers of ET-1 receptors or in the response to another agonist, thrombin. This ET-1 hyperresponse can be inhibited by an antibody directed against the carboxyl terminus of the Gq/G11 alpha subunit, suggesting that the Gq/G11 protein couples ET-1 receptors to phospholipase C (PLC). While v-src transformation did not increase the expression of the Gq/G11 alpha subunit, immunoblotting with anti-phosphotyrosine antibodies and phosphoamino acid analysis demonstrated that the Gq/G11 alpha subunit becomes phosphorylated on tyrosine residues in v-src-transformed cells. Moreover, when the Gq/G11 protein was extracted from control and transformed cell lines and reconstituted with exogenous PLC, AIF*4-stimulated Gq/G11 activity was markedly increased in extracts from v-src-transformed cells. Our results demonstrate that the process of v-src transformation can increase the tyrosine phosphorylation state of the Gq/G11 alpha-subunit in intact cells and that the process causes an increase in the Gq/G11 alpha-subunit's ability to stimulate PLC following activation with AIF-4.     

A comparison of in vivo and in vitro methods for determining availability of iron from meals

A comparison is made between in vitro and human and rat in vivo methods for estimating food iron availability. Complex meals formulated to replicate meals used by Cook and Monsen (Am J Clin Nutr 1976;29:859) in human iron availability trials were used in the comparison. The meals were prepared by substituting pork, fish, cheese, egg, liver, or chicken for beef in two basic test meals and were evaluated for iron availability using in vitro and rat in vivo methods. When the criterion for comparison was the ability to show statistically significant differences between iron availability in the various meals, there was substantial agreement between the in vitro and human in vivo methods. There was less agreement between the human in vivo and the rat in vivo and between the in vivo and the rat in vivo and between the in vitro and the rat in vivo methods. Correlation analysis indicated significant agreement between in vitro and human in vivo methods. Correlation between the rat in vivo and human in vivo methods were also significant but correlations between the in vitro and rat in vivo methods were less significant and, in some cases, not significant. The comparison supports the contention that the in vitro method allows a rapid, inexpensive, and accurate estimation of nonheme iron availability in complex meals.