Thoracic outlet syndrome: evaluation with CT

Diagnosis of the thoracic outlet syndrome is often difficult, particularly in patients without osseous abnormalities on plain radiographs. The radiographic and computed tomographic (CT) findings were reviewed from 27 patients with thoracic outlet syndrome and 21 normal subjects. The plain radiographs and CT scans were assessed by two independent observers without awareness of the clinical history. Fifteen patients with thoracic outlet syndrome had osseous abnormalities (anomalous cervical ribs; abnormally long, drooping C-7 transverse processes) identifiable on plain radiographs. CT did not provide further diagnostic information in the patients with abnormal radiographs. Eight of 12 patients (66%) with normal plain radiographs had abnormal findings on CT scans, consisting of impingement of the C-7 transverse process on the scalene triangle or anteromedial aspect of the middle scalene muscle. Only two of 21 control patients (9.5%) displayed this CT abnormality (P less than .01). CT may be useful in patients with symptoms suggestive of thoracic outlet syndrome and no osseous abnormalities on plain radiographs.     

Tongue and oropharynx: findings on MR imaging

Ten healthy subjects and 44 patients with diseases of the tongue or oropharynx were studied with magnetic resonance (MR) imaging. Axial, coronal, and sagittal images with a thickness of 4 mm were obtained with a pixel size of 0.75 X 0.75 mm on a 256 matrix. Nineteen of the patients underwent computed tomography (CT). Nine of those patients later had surgery, and the specimens were obtained for organ sectioning. These three studies as well as clinical history and physical examination findings were correlated. MR imaging was equal to or better than CT in those patients having both examinations. However, neither CT nor MR allowed recognition of histologic features or detection of microscopic spread of disease. Direct coronal and sagittal imaging planes on MR imaging allowed visualization of intrinsic tongue musculature, not possible with CT; this was important in recognizing subtle tumor extension. For these reasons, MR is the imaging method of choice for studying diseases of the tongue and oropharynx.     

Loss of end‐differentiated β‐cell phenotype following pancreatic islet transplantation

Replacement of pancreatic β‐cells through deceased donor islet transplantation is a proven therapy for preventing recurrent life‐threatening hypoglycemia in type 1 diabetes. Although near‐normal glucose levels and insulin independence can be maintained for many years following successful islet transplantation, restoration of normal functional β‐cell mass has remained elusive. It has recently been proposed that dedifferentiation/plasticity towards other endocrine phenotypes may play an important role in stress‐induced β‐cell dysfunction in type 2 diabetes. Here we report loss of end‐differentiated β‐cell phenotype in 2 intraportal islet allotransplant recipients. Despite excellent graft function and sustained insulin independence, all examined insulin‐positive cells had lost expression of the end‐differentiation marker, urocortin‐3, or appeared to co‐express the α‐cell marker, glucagon. In contrast, no insulin⁺/urocortin‐3^? cells were seen in nondiabetic deceased donor control pancreatic islets. Loss of end‐differentiated phenotype may facilitate β‐cell survival during the stresses associated with islet isolation and culture, in addition to sustained hypoxia following engraftment. As further refinements in islet isolation and culture are made in parallel with exploration of alternative β‐cell sources, graft sites, and ultimately fully vascularized bioengineered insulin‐secreting microtissues, differentiation status immunostaining provides a novel tool to assess whether fully mature β‐cell phenotype has been maintained.     

Hypoxemic reperfusion after 120 mins of intestinal ischemia attenuates the histopathologic and inflammatory response

OBJECTIVE: It has been suggested that reactive oxygen species play a pivotal role in the initial organ-tissue injury during reperfusion, eliciting inflammatory reaction and multiple organ failure. It was investigated if hypoxemic reperfusion attenuates tissue injury and inflammatory response. DESIGN: Randomized animal study. SETTING: Medical school laboratory. SUBJECTS: Twenty-five male pigs weighing 25-28 kg. INTERVENTIONS: Pigs were subjected to 120 mins of intestinal ischemia by clamping the superior mesenteric artery. Upon declamping, the animals were randomly assigned to receive either hypoxemic reperfusion (HR group, n = 9) reperfused with a Pao2 = 30-35 or normoxemic reperfusion (control group, n = 16) reperfused with a Pao2 = 100 mm Hg for 120 mins. Fluids without inotropes were given to combat circulatory shock during reperfusion. MEASUREMENTS AND MAIN RESULTS: Portal blood and intestinal and lung biopsies were collected at baseline, end of ischemia, and end of reperfusion. Histopathologic changes were scored, and interleukin-1beta, qualitative Limulus amebocyte, lysate test, and Pao2/Fio2 were measured. Eight of 16 animals of the control group and seven of nine of the HR group survived (p = .22). At the end of reperfusion, the intestinal (p = .004) and lung (p = .028) pathologic scores were lower in the HR group compared with controls. The only significant difference in concentration of interleukin-1beta in the portal blood between the two animal groups occurred 120 mins after reperfusion (p = .006). The number of HR animals with a positive Limulus test was significantly smaller compared with controls at 60 (p = .041) and 120 (p = .07) mins of reperfusion. During the period of ischemia, the Pao2/Fio2 decreased similarly in the control and HR group, whereas after 120 mins of reperfusion the rate was significantly higher in the HR group. CONCLUSIONS: Hypoxemic reperfusion represents an intervention that may attenuate the triggering of multifactorial cascade and organ tissue injury.     

Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.     

Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n = 30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 micrograms (6 weeks), to 200 micrograms (6 weeks), to 400 micrograms (14 weeks). Fasting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red- cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p < or = 0.001) homocysteine lowering in the top (10.90 +/- 0.83 mumol/l) and middle (9.11 +/- 0.49 mumol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mumol/l, no significant response was observed. Of the three folic acid doses, 200 micrograms appeared to be as effective as 400 micrograms, while 100 micrograms was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 micrograms/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.      

Bleeding duodenal ulcer: comparison between Helicobacter pylori positive and Helicobacter pylori negative bleeders

BACKGROUND AND AIMS: To provide a direct comparison of Helicobacter pylori-positive subjects bleeding from duodenal ulcer with H. pylori-negative ones, in terms of severity of bleeding and outcome. PATIENTS AND METHODS: A case-control study was prospectively conducted in 105 H. pylori-negative duodenal ulcer bleeders and same number of sex- and age-matched H. pylori-positive ones. RESULTS: NSAID consumption was more common among H. pylori-negative subjects (81%) compared to their H. pylori-positive counterparts (58.1%, P < 0.001). H. pylori-negative bleeders were found to need more often haemostasis (55.2% versus 31.4%, P < 0.001) or surgical intervention (15.2% versus 4.8%, P = 0.011) and to have a greater proportion of rebleeding (32.4% versus 13.3%, P = 0.001), a more prolonged hospitalisation (11.6 +/- 4.1 versus 6.2 +/- 1.5 days, P < 0.001) and a higher rate of in-hospital mortality (15.2% versus 3.8%, P = 0.005). In the overall population (N = 210), H. pylori negativity, among other known risk factors, emerged as independent predictor (odds ratio: 3.2; 95% CI: 1.5, 11.2; P = 0.004) of an unfavourable outcome (surgery or death). CONCLUSIONS: Duodenal ulcer bleeding in H. pylori-negative subjects appears to be more severe, to have a higher rate of rebleeding, and to lead more often to surgery or fatality compared to the vast majority of H. pylori-positive duodenal ulcer bleeders.