Primary gastric non-Hodgkin's lymphoma in a population-based registry.

BACKGROUND. The incidence of primary gastric non-Hodgkin's lymphoma (NHL) appears to have increased worldwide in recent years, and this seems to be confirmed by large-sample population studies. METHODS AND RESULTS. We derived our data from the Lombardy Cancer Registry, which provides the incidence of cancer in the province of Varese, Northern Italy. From 1978 to 1987 we identified 3261 cases of gastric neoplasms, 119 of which were gastric NHL: 32 (1.87%) from 1978 to 1982, and 87 (5.32%) from 1983 to 1987. The difference in the age and sex standardized incidence trend between these two time periods was statistically significant (p < 0.001). The overall survival rate of the 112 evaluable patients was 54% at 5 years and 45% at 10 years. A multivariate analysis was performed. Age (p < 0.0005), clinical stage (p < 0.04) and therapy (p < 0.0005) were found to be significant prognostic factors for survival. CONCLUSIONS. This study stresses the utility of prospective randomized clinical trials that could indicate the optimal management of patients with primary gastric lymphoma.     

Rehabilitation: the Cinderella of neurological research? A bibliometric study

Rehabilitation is under-represented in the neurological literature on disabling diseases. A Medline search was conducted to retrieve the articles published between January 1991 and June 1994 under the main headings of Stroke, Parkinson's disease, Multiple sclerosis, Brain injury, Ataxia and Dementia. These were then combined with the sub-heading Rehabilitation. The former search yielded 27724 articles, the latter 1272 (4.6%). In 1992, the Journal of Citation Reports (JCR) assigned to Journals publishing rehabilitation papers an average Impact Factor (IF) of 0.7–2.8 (median 1.8): that is, 31–90% (depending on the various main headings, median 68%) of the average IF given to Journals publishing non-rehabilitation papers. In the present study, the weight of the literature was defined as the product of the number of articles multiplied by the IF of the corresponding Journal (IF=0 for non-JCR Journals). Across the various neurologic conditions, the weight of the Rehab literature was 0.1–7% (median 2%) of the weight of the non-Rehab literature. The results suggest that neurology is still reluctant to face the disability challenge.

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Sommario La riabilitazione è scarsamente rappresentata nella letteratura neurologica sulle patologie che causano disabilità. Gli Autori hanno interrogato la banca-dati Medline nella ricerca degli articoli pubblicati fra il Gennaio 1991 ed il Giugno 1994 sotto le parole-chiave Stroke, Parkinson's disease, Multiple Sclerosis, Brain injury, Ataxia e Dementia. È stato poi eseguito un incrocio con la parola-chiave secondaria Riabilitazione.La prima ricerca ha prodotto 27724 articoli mentre la seconda ne ha prodotti 1272 (4.6%). Nel 1992 il Journal of Citation Reports (JCR) ha attribuito alle Riviste che hanno pubblicato articoli con tema riabilitativo un Impact Factor (IF) medio di 0.7–2.8 (mediana 1.8), pari al 31–90% (a seconda della parola-chiave principale: mediana delle percentuali 68%) dell'IF medio attribuito alle Riviste che hanno pubblicato soltanto articoli su temi non riabilitativi. In questo studio è stato definito come peso della letteratura il prodotto del numero di articoli per l'IF delle rispettive Riviste (IF=0 per le Riviste non censite dal JCR). A seconda delle diverse patologie neurologiche, il peso della letteratura riabilitativa variava fra 0.1 e 7% (mediana 2%) del peso della letteratura non riabilitativa.I risultati suggeriscono che la Neurologia sia ancora riluttante ad affrontare la sfida che le pone la disabilità.

     

Road traffic noise around schools: a risk for pupil's performance?

Summary Noise levels around educational centres can negatively affect the performance of both teachers and pupils. Two public schools in Valencia, Spain, were selected for study. One of these schools was exposed to excessively high road traffic noise levels while the other was located in a relatively quiet area. The socioeconomic level of those attending the schools was very similar. A set of external and internal noise measurements were carried out, along with two different attention tests among the children. Test results were consistently better (both for tests and for children from different classrooms in each school) in the quiet school. Exposure to high traffic noise levels in the noisy school over the whole school year is a plausible determinant of these results.     

Protein kinase C activation reduces the function of the Na(+):K(+):2Cl(-) cotransporter in Xenopus laevis oocytes

BACKGROUND: The basolateral isoform of the Na(+):K(+):2Cl(-) cotransporter is expressed in several epithelial and non-epithelial cells, in which it is involved in ion secretion processes and in cell volume regulation. In humans, this cotransporter has been implicated in the development of primary hypertension. The major goal of the present study was to characterize the effect of protein kinase C activation on the function of the Na(+):K(+):2Cl(-) cotransporter isoform present in Xenopus laevis oocytes. METHODS: Oocytes were surgically harvested from adult female Xenopus laevis frogs, defolliculated by incubation in frog ringer containing collagenase B (2 mg/mL) under vigorous shaking, and by hand under the microscope. Only stage V-VI oocytes were used in the study. After overnight incubation in regular frog Ringer, oocytes were switched to a Cl(-)-free ringer for at least 12 h before beginning uptake experiments. The function of the Na(+):K(+):2Cl(-) cotransporter was determined by assessing tracer 22Na(+) uptake in the control group as well as under several experimental conditions, such as changes in extracellular osmolarity, absence of one of the cotransported ions, or the presence of drugs such as the specific cotransporter inhibitor bumetanide, phorbol esters (TPA, PDBu, or 4alphaPDD), and the PKC inhibitor bisindolylmaleimide I. At the end of the uptake period, tracer Na(+) uptake was counted by liquid scintillation of each individual oocyte previously dissolved in SDS. RESULTS: Xenopus oocytes exhibited a bumetanide-sensitive Na(+):K(+):2Cl(-) cotransporter in the plasma membrane activated by hypertonicity and inhibited by hypotonicity. The bumetanide-sensitive fraction of Na(+) uptake was significantly reduced by the addition of phorbol esters TPA or PDBu to the uptake media. This inhibitory effect of PKC activators was dose- and time-dependent. Phorbol ester 4alphaPDD, which cannot activate PKC, exhibited no effect on Na(+):K(+):2Cl(-) cotransporter function. In addition, pretreatment of oocytes with the PKC inhibitor bisindolylmaleimide I partially abolished TPA-induced reduction in the cotransporter function. CONCLUSION: In defolliculated Xenopus laevis oocytes, phorbol esters reduce the function of the Na(+):K(+):2Cl(-) cotransporter by a mechanism that includes the activation of an endogenous PKC.     

Effect of sulfonylurea agents on pyruvate dehydrogenase activity in circulating lymphocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM)

In circulating lymphocytes from patients with non-insulin-dependent diabetes mellitus (NIDDM) subnormal pyruvate dehydrogenase (PDH) activity returns to normal following patient treatment with sulfonylurea (gliclazide^*, 80 mg twice daily/5 weeks). Moreover, in vitro in cells from diabetic patients exposed to insulin at 50 μU/mL PDH activation also occurs; in cells of controls the same happens for insulin at 5 μU/mL, whereas at 50 μU/mL inhibition takes place. Therefore, the low PDH activity in cells of NIDDM patients might be caused by defective insulin control on the enzyme and its recovery in gliclazide-treated patients by drug-mediated removal of the defect. The validity of the hypothesis was verified in this study where cells of NIDDM patients before and after gliclazide treatment were exposed, in vitro, to insulin at 5 and 50 μU/mL and then tested for PDH activity. In such conditions, the profile of PDH behavior in treated patients was no longer comparable to that in untreated patients but closer to that in euglycemic controls, thus supporting the view that the recovery of PDH activity in NIDDM patients following gliclazide treatment might be the expression of an additional effect that the drug would have in these patients, aimed to renew cell responsiveness to insulin.     

Clotting alterations in primary systemic amyloidosis

BACKGROUND AND OBJECTIVE: The bleeding manifestations frequently observed in patients with immunoglobulin light chain amyloidosis (AL) have been attributed to different pathogenetic factors: amyloid deposits in several organs and systems leading to failures of these latter, the affinity of amyloid for some clotting factors, and the presence of plasma components interfering with fibrin formation could all induce alterations of clotting tests. This investigation was aimed at defining the prevalence of clotting abnormalities and their clinical manifestations in patients with AL. DESIGN AND METHODS: Thirty-six consecutive patients with biopsy proven amyloidosis and documented monoclonal gammapathy were enrolled within one year. The following clotting tests were considered in the study: activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), reptilase time (RT), Russell's viper venom time (RVTT), fibrinogen, factor X and alpha-2 antiplasmin. RESULTS: Hemorrhagic manifestations were mild to moderate in nine patients, but severe and untractable in one. The most frequent clotting anomaly was defective fibrinogen conversion to fibrin, as demonstrated by prolongation of both TT (85% of cases) and RT (90% of cases). Low levels of factor X activity were observed in about 1 out of 4 samples, while fibrinogen and alpha2 antiplasmin levels were distributed over a wide range of values. PT was prolonged in 8 and aPTT in 25 patients. The search for lupus anticoagulant was negative in samples showing a prolongation of aPTT and/or RVVT. INTERPRETATION AND CONCLUSIONS: The prolongation of TT and RT is not dependent on either the presence of a heparin-like substance in the plasma or on fibrinogen levels; furthermore, the prolongation of RVVT is not related to factor X level. The hypothesized presence in the plasma of an inhibitor of fibrin formation could also affect factor X activation by Russell viper venom. The prolongation of TT and RT represents a peculiar feature of amyloidosis. The variability in the behavior of the other clotting times and hemostatic factors studied is mirrored in the heterogeneity of the clinical features observed in this disease.     

Deferment of objective assessment of deep vein thrombosis and pulmonary embolism without increased risk of thrombosis: a practical approach based on the pretest clinical model, D-dimer testing, and the use of low-molecular-weight heparins

BACKGROUND: Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined. METHODS: Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulant administration. However, all patients were scheduled to undergo objective tests for DVT or PE within 72 hours. Standard antithrombotic therapy was administered when deferred diagnostic tests confirmed venous thromboembolism. RESULTS: In total, 409 consecutive patients with suspected DVT and 124 with suspected PE were included in this study. A total of 23.8% (95% confidence interval [CI], 20.3%-27.3%) of patients had confirmed venous thromboembolism. At the short-term follow-up (72 hours), only a single thromboembolic event (0.2%; upper 95% CI, 0.6%) had occurred, whereas at the 3-month follow-up, 5 events (1.2%; 95% CI, 0.2%-2.1%) had occurred in patients in whom diagnosis of DVT or PE had previously been ruled out. None of the patients had major bleeding events. Ninety percent of patients were treated as outpatients. CONCLUSION: Our study demonstrates that this approach allows the safe deferral of diagnostic procedures for DVT and PE for up to 72 hours.     

Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy

Summary Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p<0.001), fibronectin (p<0.001) and fibrinogen (p<0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p<0.05 at shear-rate of 450 and 225 s⁻¹; p<0.01 at 90 s⁻¹; p<0.001 at 4.5 and 2.25 s⁻¹), plasma viscosity (p<0.001) and lower erythrocyte filtrability (p<0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p<0.01) and nephropathy (p<0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus. This study was presented in part at the 23rd Annual Meeting of the European Association for the Study of Diabetes, Leipzig (GDR), 15–19 September 1987.