Intestinal intussusception as an unusual complication of oral anticoagulation therapy

Hyponatremia is a common neuromedical problem seen in survivors of central nervous system injury. The etiology of this hyponatremia is often diagnosed as syndrome of inappropriate diuretic hormone (SIADH). Fluid restriction is usually the first line of treatment. However, this can exacerbate vasospasm and produce resultant ischemia. Cerebral salt wasting is a syndrome of renal sodium loss that may occur commonly after central nervous system injury, yet remains unrecognized. Treatment of cerebral salt wasting consists of hydration and salt replacement. This article uses a case report to discuss the importance of recognition of this syndrome, and treatment concerns are reviewed.     

Hair analysis does not support hypothesized arsenic and chromium exposure from drinking water in Woburn, Massachusetts

We hypothesized that residents of Woburn, Massachusetts, had been exposed to as much as 70 microg/l of arsenic (As) and 240 microg/l of chromium (Cr) in drinking water from municipal supply wells G and H. To test this hypothesis, we measured the concentrations of As and Cr in 82 hair samples donated by 56 Woburn residents. Thirty-six samples were cut between 1964 and 1979, the period during which wells G and H were in operation. The remainder were cut either before 1964 (1938-1963; n = 26) or after 1979 (1982-1994; n = 20). Washed hair samples were analyzed by instrumental neutron activation. Exposure to the well water--measured as access--was estimated using well pumping records and a model of the Woburn water distribution system. Our results show that access to wells G and H water was not significantly correlated (95% confidence interval) with As and Cr concentrations measured in the hair of Woburn residents, but As concentrations have declined significantly over the last half century. Linear regression of As concentrations (micrograms per gram) upon year of hair cut and access to wells G and H water yielded a standard coefficient for year of -0. 0074 +/- 0.0017 (standard error; p = 2.5 -multiple- 10(-5)) and -0.12 +/- 0.10 (p = 0.22) for access. The r2 value for the model was 0.19. The geometric mean concentrations (geometric standard deviation) of As and Cr in the hair of residents who had access (i.e., relative access estimate >0) to wells G and H water (n = 27) were 0.14 (2.6) and 2.29 (1.8) microg/g, respectively; the geometric mean concentrations of As and Cr in all of the hair samples from residents who did not have access (1938-1994; n = 55) were 0.13 (3.0) and 2.19 (2.0) microg/g, respectively.     

Control of the mutagenicity of arylamines by protein kinases and phosphatases: II. Lack of response of rat liver N-acetyl transferases to phosphorylation modulators

OBJECTIVES: Endoscopic sphincterotomy has become a generally accepted method for extracting common bile duct stones in high risk or cholecystectomized patients. However, stone extraction is impossible by the usual methods in 5 to 10% of cases. The purpose of this study was to evaluate the effect of a recently developed solvent system in patients with large bile duct stones. METHODS: Forty four patients (15 men and 29 women, median age of years) underwent contact dissolution after unsuccessful Dormia extraction. Solvents were administered via a nasobiliary catheter in 41 patients following papillotomy and through a T-tube in 3 patients. Solvent mixtures (26 mM ethylene diamine tetraacetic acid, 40 mM sodium deoxycholate and 30% dimethyl sulfoxide in an alkaline aqueous solution; and a 70/30 dimethyl sulfoxide/methyl tert-butyl ether mixture) were infused continuously and alternatively for 2 hours. RESULTS: Bile duct stones disappeared in 13-24 hours of infusion in 11 patients. In 29 patients, a clear reduction in stone volume occurred, allowing complete endoscopic extraction of the fragments. In 4 patients, the size of the stone did not change. Only mild and transient side-effects including abdominal pain (68%), nausea (72%), vomiting (52%), diarrhea and sleepiness (50%) were observed. CONCLUSION: Direct dissolution therapy could be an effective method for the non-surgical management of large bile duct stones in selected patients when intra- or extracorporeal lithotripsy is unsuccessful.     

Serum antibodies against Helicobacter pylori proteins VacA and CagA are associated with increased risk for gastric adenocarcinoma

Infection with Helicobacter pylori is associated with the development of gastric cancer. To study whether the infection with H. pylori strains expressing the vacuolating cytotoxin (VacA) and/or the cytotoxin-associated protein (CagA) is associated with an increased risk of developing gastric adenocarcinoma, sera of 90 patients with gastric cancer and 90 matched controls with cardiovascular diseases were investigated for the presence of antibodies to VacA and CagA by immunoblot. Although no significant difference in the overall H. pylori seropositivity was found between cancer patients and controls, antibodies against VacA or CagA were significantly more frequent in cancer patients than in control subjects. Seventy-five (97.4%) of 77 H. pylori-positive patients in the cancer group, but only 60 (84.5%) of 71 H pylori-positive control patients had antibodies against either VacA or CagA (chi 2 = 6.63; relative risk, 2.00; 95% confidence interval, 1.18-3.39; P = 0.01). The presence of antibodies against VacA or CagA alone was also associated with an increased cancer risk (92.2% vs 80.3%; chi 2 = 5.30; relative risk, 1.74; 95% confidence interval, 1.08-2.78; P = 0.021, for VacA; and 87.0% vs 74.6%; chi 2 = 4.90; relative risk, 1.61; 95% confidence interval, 1.06-2.45; P = 0.037, for CagA). The relative risk for gastric cancer was mainly elevated in patients under 65 years, but not in patients at or over 65 years. There is evidence that infection with VacA- or CagA-producing H. pylori strains increases the risk of developing gastric cancer, especially in younger patients.     

Signed rank statistics for coherent predictions

A generalization of Wilcoxon's signed rank test is proposed for testing a dose-response relationship with one or more outcomes. The test is useful in matched observational studies or in nonrandomized experiments that use dose-response relationships and predictions about multiple outcomes in an effort to distinguish actual treatment effects from hidden biases. A sensitivity analysis indicating whether a dose-response relationship or multiple predictions are confirmed with sufficient strength to reduce sensitivity to hidden bias is performed. Together, the test and the sensitivity analysis help to quantify the degree to which a coherent pattern of associations is present or absent, and the degree to which this strengthens or fails to strengthen evidence of cause and effect. Formal properties of tests of this kind are examined. The form of the optimal test is determined, though this test is not usable because it depends upon the values of the unknown parameters under study. Also examined are the conditions under which the proposed test resembles the optimal test, as well as the impact of various violations of those conditions on power. An example involving matched pairs exposed to varying doses of cadmium is considered in detail.     

Site-directed mutagenesis of the yeast V-ATPase A subunit

To investigate the function of residues at the catalytic nucleotide binding site of the V-ATPase, we have carried out site-directed mutagenesis of the VMA1 gene encoding the A subunit of the V-ATPase in yeast. Of the three cysteine residues that are conserved in all A subunits sequenced thus far, two (Cys284 and Cys539) appear essential for correct folding or stability of the A subunit. Mutation of the third cysteine (Cys261), located in the glycine-rich loop, to valine, generated an enzyme that was fully active but resistant to inhibition by N-ethylmalemide, 7-chloro-4-nitrobenz-2-oxa-1,3-diazole, and oxidation. To test the role of disulfide bond formation in regulation of vacuolar acidification in vivo, we have also determined the effect of the C261V mutant on targeting and processing of the soluble vacuolar protein carboxypeptidase Y. No difference in carboxypeptidase Y targeting or processing is observed between the wild type and C261V mutant, suggesting that disulfide bond formation in the V-ATPase A subunit is not essential for controlling vacuolar acidification in the Golgi. In addition, fluid phase endocytosis of Lucifer Yellow, quinacrine staining of acidic intracellular compartments and cell growth are indistinguishable in the C261V and wild type cells. Mutation of G250D in the glycine-rich loop also resulted in destabilization of the A subunit, whereas mutation of the lysine residue in this region (K263Q) gave a V-ATPase complex which showed normal levels of A subunit on the vacuolar membrane but was unstable to detergent solubilization and isolation and was totally lacking in V-ATPase activity. By contrast, mutation of the acidic residue, which has been postulated to play a direct catalytic role in the homologous F-ATPases (E286Q), had no effect on stability or assembly of the V-ATPase complex, but also led to complete loss of V-ATPase activity. The E286Q mutant showed labeling by 2-azido-[32P]ATP that was approximately 60% of that observed for wild type, suggesting that mutation of this glutamic acid residue affected primarily ATP hydrolysis rather than nucleotide binding.     

Evaluation of the dizzy patient

This discussion has focused primarily on the history and physical examination of the patient with dizziness which, in fact, are the two most important elements in the evaluation process. To perform the examination expeditiously and completely, a broad differential diagnosis of dizziness must be kept in mind. The clinician should also keep in mind two basic objectives: first, to identify serious pathology (e.g., central nervous system lesion, brainstem ischemia, cardiac arrhythmia); and second, to recognize diseases that can be specifically treated, such as an endocrine abnormality, middle ear infection, Meniere's disease, or a drug reaction. Reassurance and/or vestibular rehabilitation are the mainstays of therapy for the patients not falling into the above two categories.     

Diagnosis and therapy of lymphoid tumors of the orbits

Injuries of the laryngotracheal axis caused by prolonged intubation in critically ill patients raise the issue of the timing of tracheotomy in intubated patients. In 1992 a prospective study was begun in intensive care patients with intubation lasting more than 48 hours. Eight months later, post-mortem data on the laryngotracheal axis of deceased patients was added to our prospective study protocol. The study was closed with 125 cases (52 deceased). The clinical data of 73 surviving patients was compared with that of 18 post-mortem cases. The macroscopic results of the post-mortem study are summarized by grading the lesions according to a personal modification of the Lindholm classification. All cases had laryngotracheal injuries. Only 15% of the lesions were located in the tracheal region. Five cases were classified as grade 2, with an average orotracheal intubation of 9 days, 9 cases as grade 3 with 15 days intubation, and 4 cases as grade 4 with 21 days intubation. We concluded that the severity of laryngotracheal injuries in the early post-mortem exploration was related with the duration of intubation.