Acute renal failure in an alcoholic during therapeutic acetaminophen ingestion

Acute renal failure characteristic of acute tubular necrosis developed in an alcoholic man after therapeutic acetaminophen ingestion, without the development of hepatic failure. This case illustrates the need to obtain an adequate drug history of over-the-counter medication in evaluating acute renal failure in an alcoholic patient.     

Segmental heterogeneity of the rat colon in the response to activators of secretion on the cAMP-, the cGMP- and the Ca(2+)-pathway.

The electrolyte transport was compared in proximal and distal segments of the rat colon under control conditions and after induction of secretion on the cAMP-, the cGMP- and the Ca(2+)-pathway. Baseline short-circuit current was decreased by indomethacin and tetrodotoxin in the distal colon, indicating a spontaneous production of neuronally acting prostaglandins. In contrast, baseline short-circuit current in the proximal colon was decreased only by indomethacin, but not by tetrodotoxin. Unidirectional flux measurements revealed that in the distal colon sodium and chloride were absorbed, while the proximal colon secreted chloride. A morphological comparison between the distal and proximal epithelium revealed that the zonulae occludentes and the microvilli were longer in the distal colon. The size of the Golgi apparatus was several times larger in the crypt than in the surface region without differences between proximal and distal colon. Distal segments were more sensitive to an activator of the Ca(2+)-pathway, carbachol, or activators of the cAMP-pathway such as forskolin and a cAMP-analogue. In contrast, the activation of the cGMP-pathway by a cGMP-analogue or by the heat-stable enterotoxin of E. coli (STa) was more effective in the proximal colon. The results give evidence for a segmental specificity with regard to the intracellular pathways responsible for the activation of secretion.     

Strontium transport in the rat colon

Summary Concentration dependence of strontium (Sr) fluxes across the colon ascendens and descendens of the rat were measured in a modified Ussing-chamber. Mucosa (m) to serosa (s) and s to m Sr fluxes across both colonic segments were linearly related to the Sr concentration from 0.125 mmol/l to 10 mmol/l. In the colon ascendens m to s Sr fluxes were slightly higher than the fluxes in the opposite direction, resulting in net Sr absorption. In the colon descendens s to m fluxes were higher than the ms fluxes, resulting in net Sr secretion. Neither Sr nor calcium (Ca) showed a concentration dependent interaction with respect to their unidirectional fluxes in both parts of the colon. Only in the colon ascendens Sr at the highest concentration (10 mmol/l) inhibited m to s calcium transport.Experiments, in which the voltage dependence of the unidirectional Sr fluxes was measured confirmed the results obtained from the concentration dependence: (1) The unidirectional fluxes of Sr across the colon ascendens and descendens were totally voltage dependent, i.e. diffusive. (2) In the colon descendens the voltage dependence of the s to m flux was steeper than the flux from m to s. It is hypothesized that this prevalence is caused by an anomalous solvent drag effect. 1.25-Dihydroxyvitamin D₃ [1.25 (OH)₂D₃] stimulated m to s calcium flux in the colon descendens but had no effect on Sr flux.The results demonstrate that Sr and Ca in the rat colon are transported by different mechanisms. In contrast to the Ca transport the Sr flux is only diffusive and insensitive to 1.25 (OH)₂D₃.Supported by the Deutsche Forschungsgemeinschaft SFB 38 Membranforschung Send offprint requests to U. Karbach at the above address     

A molecular survey of S. mutans and P. gingivalis oral microbial burden in human saliva using Relative Endpoint Polymerase Chain Reaction (RE-PCR) within the population of a Nevada dental school revealed disparities among minorities

ABSTRACT: BACKGROUND: The University of Nevada, Las Vegas School of Dental Medicine recently opened an orthodontic treatment clinic to address the needs of the racially and ethnically diverse population of Southern Nevada, primarily focusing on the treatment and care of low-income and minority patients. Although orthodontic treatment and therapy has been shown to induce changes in the oral cavity, much of this evidence was collected from traditional White, teenage orthodontic clinic populations. The primary goal of this study was to describe the microbial burden of the cariogenic and periodontal pathogens, Streptococcus mutans and Porphyromonas gingivalis within the UNLV-SDM patient population. METHODS: Representative saliva samples were collected from healthy adult patients for DNA isolation. Relative endpoint polymerase chain reaction (RE-PCR) was performed to ascertain the presence and relative microbial burden of these oral pathogens. RESULTS: Nearly one quarter (13/56) or 23.3% of these patients had elevated levels of S. mutans, while (10/56) and 17.8% of these samples were found to have elevated levels of P. gingivalis, - with (90%) of P. gingivalis-positive samples from minority patients (X2 = 17.921, d.f. = 1; p < 0.0001). CONCLUSIONS: These findings of elevated P. gingivalis levels, primarily among minority patients, may suggest underlying oral health practices contributing to adverse oral health conditions within this population. Oral health knowledge and practices among minority patients may be strongly influenced by other factors, including education and socioeconomic status, suggesting additional research may be needed to accurately determine the most appropriate standards for care and oral health education within this patient population.     

Monitoring cerebral oxygenation during balloon occlusion with multichannel NIRS

We report on oxygenation changes noninvasively recorded by multichannel continuous-wave near infrared spectroscopy (CW-NIRS) during endovascular neuroradiologic interventions requiring temporary balloon occlusion of arteries supplying the cerebral circulation. Digital subtraction angiography (DSA) provides reference data on the site, timing, and effectiveness of the flow stagnation as well as on the amount and direction of collateral circulation. This setting allows us to relate CW-NIRS findings to brain specific perfusion changes. We focused our analysis on the transition from normal perfusion to vessel occlusion, i.e., before hypoxia becomes clinically apparent. The localization of the maximal response correlated either with the core (occlusion of the middle cerebral artery) or with the watershed areas (occlusion of the internal carotid artery) of the respective vascular territories. In one patient with clinically and angiographically confirmed insufficient collateral flow during carotid artery occlusion, the total hemoglobin concentration became significantly asymmetric, with decreased values in the ipsilateral watershed area and contralaterally increased values. Multichannel CW-NIRS monitoring might serve as an objective and early predictive marker of critical perfusion changes during interventions—to prevent hypoxic damage of the brain. It also might provide valuable human reference data on oxygenation changes as they typically occur during acute stroke.     

Insights into Severe 5,10‐Methylenetetrahydrofolate Reductase Deficiency: Molecular Genetic and Enzymatic Characterization of 76 Patients

5,10‐Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common inherited disorder of folate metabolism and causes severe hyperhomocysteinaemia. To better understand the relationship between mutation and function, we performed molecular genetic analysis of 76 MTHFR deficient patients, followed by extensive enzymatic characterization of fibroblasts from 72 of these. A deleterious mutation was detected on each of the 152 patient alleles, with one allele harboring two mutations. Sixty five different mutations (42 novel) were detected, including a common splicing mutation (c.1542G>A) found in 21 alleles. Using an enzyme assay in the physiological direction, we found residual activity (1.7%–42% of control) in 42 cell lines, of which 28 showed reduced affinity for nicotinamide adenine dinucleotide phosphate (NADPH), one reduced affinity for methylenetetrahydrofolate, five flavin adenine dinucleotide‐responsiveness, and 24 abnormal kinetics of S‐adenosylmethionine inhibition. Missense mutations causing virtually absent activity were found exclusively in the N‐terminal catalytic domain, whereas missense mutations in the C‐terminal regulatory domain caused decreased NADPH binding and disturbed inhibition by S‐adenosylmethionine. Characterization of patients in this way provides a basis for improved diagnosis using expanded enzymatic criteria, increases understanding of the molecular basis of MTHFR dysfunction, and points to the possible role of cofactor or substrate in the treatment of patients with specific mutations.