Seroepidemiological studies of El Tor cholera in Bangladesh: association of serum antibody levels with protection

In rural Bangladesh, family contacts of patients with cholera were studied prospectively to examine whether protection against colonization and disease due to Vibrio cholerae O1 was associated with circulating antibodies to V. cholerae. Family contacts (1,071) of 370 patients with cholera were visited daily for 10 days, cultured for V. cholerae, and queried about diarrhea. Sera collected on days 1 and 21 were assayed for vibriocidal antibodies, IgG and IgA antibodies to cholera toxin, and IgG antibodies to lipopolysaccharide (LPS). Vibriocidal titers of greater than or equal to 20 present in 50% of contacts by 20 years of age were associated with protection against both colonization and disease. An elevated level of IgG antitoxin was not associated with protection against colonization or disease but was the most sensitive indicator of recent symptomatic cholera and of immune response to the oral immunogen B subunit. IgG antibody to LPS and IgA antitoxin were of little value in predicting colonization or disease.     

Low serum thyroxine and high serum triiodothyronine in nephrotic rats: etiology and implications for bioavailability of protein-bound hormone

Traditionally, it has been thought that the bioavailable fraction of circulating serum hormones, i.e. that which is available for cellular uptake and is physiologically active, is limited to the free (nonprotein bound) hormone. However, recent evidence, based on acute organ uptake of labeled hormone, suggests that the amount of hormone which is bioavailable in vivo may exceed that which is calculated to be free in vitro. To explore the bioavailability of circulating protein-bound thyroid hormones under steady state conditions in vivo, we altered serum thyroid hormone-binding proteins in rats by inducing nephrotic syndrome with puromycin aminonucleoside. Nephrotic rats (serum albumin, 1.1 g/dl) were found to have a marked reduction in serum T4 [2.1 +/- 0.2 (SEM) vs. 6.5 +/- 0.3 microgram/dl; P less than 0.01] and an elevation of serum T3 [141 +/- 8 vs. 51 +/- 2 ng/dl; P less than 0.01]. Estimated T4 production rate was normal in nephrotic rats, and the 3- to 4-fold increase in T4 MCR appeared to account for the marked reduction in serum T4. By contrast, increased serum T3 levels in nephrotic rats reflected both a reduction (55%) in T3 MCR and an increased rate of peripheral conversion of T4 to T3. A circulating inhibitor of T4 binding to serum proteins appeared to be present in nephrotic rats. The changes in the various serum components of thyroid hormone [T4-binding prealbumin (TBPA)-bound, albumin-bound, free] produced by nephrotic syndrome were compared with the corresponding changes in indices of thyroid hormone bioavailability (MCR, urinary excretion, hepatic content, TSH suppression, single pass extraction by liver). These comparisons suggested that nephrotic syndrome results in increased bioavailability of circulating T4 and decreased bioavailability of circulating T3. The bioavailable fraction of circulating T3 in vivo seemed to include both free T3 and that which is albumin bound in vitro. The bioavailable fraction of circulating T4 resembled free T4 more than non-TBPA-bound T4 (= albumin bound + free), although a nephrosis-induced increase in bioavailability of TBPA-bound T4 was also possible. We conclude that nephrotic rats have low serum T4, which is related to accelerated T4 clearance, and high serum T3, which is related both to decreased T3 clearance and increased peripheral conversion of T4 to T3. Under steady state conditions in vivo, bioavailable circulating T3 appears to include both free T3 and the T3 that is bound to albumin in vitro.     

Effect of misoprostol (PGE1) on glucose metabolism in type-2-diabetic and control subjects

In vitro and in vivo studies have demonstrated that prostaglandins of the E series enhance muscle glucose uptake. We examined the effect of acute misoprostol (PGE1) administration on whole body insulin-mediated glucose disposal, as well as the major intracellular pathways of glucose metabolism in type 2 diabetic (n = 10) and non-diabetic (n = 4) subjects. Each subject received two 240-min euglycaemic insulin (40 mU/m²/min) clamp studies with tritiated glucose and indirect calorimetry. During one of the insulin clamp studies, 200 µg of misoprostol was ingested at 90 and 150 min after the start of the insulin infusion. Insulin-mediated total body glucose disposal, glycolysis, glycogenesis and glucose oxidation were similar during the insulin clamp studies performed without and with misoprostol in both the diabetic and non-diabetic groups. These results demonstrate that the acute administration of misoprostol does not enhance insulin-mediated glucose disposal in either type-2-diabetic or non-diabetic subjects.     

Cine magnetic resonance imaging for evaluation of anatomy and flow relations in infants and children with coarctation of the aorta

Sixteen cine magnetic resonance imaging (MRI) studies were performed in 14 patients aged 1 week to 17 years (mean age, 46 months), who had coarctation of the aorta confirmed at angiography or surgery. Conventional echocardiographic-gated MRI was first performed in axial and rotated sagittal views and was used to identify the slice locations for cine MRI. Cine MRI was performed by gradient-recalled acquisition in steady state with a 30 degree flip angle, 12-msec echo time, 22-msec pulse repetition time, and a 128 x 256 acquisition matrix. Coarctation anatomy was extremely well defined in all but one patient who had vascular clips at the coarctation repair site. The smallest descending aortic flow diameter on cine MRI showed excellent agreement with angiography (r = 0.90). Lucent jets of high-velocity flow through the site of coarctation were imaged in eight patients, and jet length correlated well with the angiographic severity of coarctation (r = -0.81). Two patients were restudied after surgery, and they exhibited excellent repair and normal flow patterns. Cine MRI provides high-resolution imaging of coarctation anatomy with a dynamic spatial and temporal visualization of flow and with excellent detail of vascular anatomy and flow both proximal and distal to the coarctation.     

Treatment of end-stage diabetic nephropathy: over a decade of experience at one institution

Results of treatment of end-stage renal disease in 139 patients with diabetes mellitus revealed survival of 76% at 1 year and 48% at 5 years. These results compare favorably with other reports from Europe and the United States, probably because of the greater number of patients receiving renal transplants, and possibly because of the use of continuous ambulatory peritoneal dialysis as a recent treatment modality. Patients not receiving transplants were much older (mean age, 47.8 years) than those receiving transplants. Of those not given transplants, survival was best on CAPD. Comparison of those surviving at least 3 years was made with those expiring in the first year. Long-term survivors were younger, had diabetes for a shorter period, but had higher mean blood pressures and serum creatinine values than short-term survivors. Short-term survivors also had over a 50% incidence of prior myocardial infarction or cardiorespiratory arrest, while no long-term survivors had such a history. Long-term survivors were also more likely to have received a transplant, and short-term survivors were more likely to have received intermittent peritoneal dialysis or hemodialysis. A transplant from a living related donor is the treatment of choice for diabetics under age 40 and perhaps for older patients as well. The choice among CAPD, hemodialysis and cadaver transplant requires consideration of many factors.     

Epidemiologic and clinical features of endemic Campylobacter jejuni infection in Bangladesh

Epidemiologic and clinical features of infection with Campylobacter jejuni in Bangladesh were examined in (1) diarrheal patients infected with C jejuni, (2) healthy control subjects, and (3) village children who were cultured monthly and at each diarrheal episode during a 10-month period. C jejuni was isolated from 437 (14%) of 3,038 outpatients with diarrhea. These patients had no distinct clinical presentation and were more likely to have a mixed infection than were patients infected with other pathogens (59% vs 42%, P less than 0.01). Age-specific infection rates were greatest in infants and did not differ significantly from those in control subjects. C jejuni was isolated less frequently from village children with diarrhea than from those cultured routinely (5% vs 9%, P less than 0.05). Forty percent of 47 patients with C jejuni vs 23% of 48 control subjects (P less than 0.01) had an elevated convalescent-phase antibody titer as determined by complement fixation test. In Bangladesh, enteric infection with C jejuni is common but often asymptomatic, although pathogenicity is suggested by serologic response in some patients.     

Simultaneous analysis of 29 synthetic cannabinoids and metabolites,amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs‐of‐abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs‐of‐abuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported‐liquid‐extraction (SLE) followed by liquid chromatography?tandem mass spectrometry (LC?MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante‐ and post‐mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB‐FUBINACA and/or acid (61%), 5F‐ADB and/or acid (40%), ADB‐FUBINACA (11%), 5F‐MDMB‐PICA acid (6%), and MDMB‐FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.     

Calcium sensitivity during staircase with sequential incompletely fused contractions

Activity dependent potentiation is thought to result from phosphorylation of the regulatory light chains of myosin, increasing Ca²⁺ sensitivity. Yet, Ca²⁺ sensitivity decreases early in a period of intermittent contractions. The purpose of this study was to investigate the early change in Ca²⁺ sensitivity during intermittent submaximal tetanic contractions. Flexor digitorum brevis muscle fibres were dissected from mice after cervical disarticulation. Fibres were superfused with Tyrode solution at 32 °C. Length was set to yield maximal tetanic force. Indo-1 was microinjected into fibres and allowed to dissipate for 30 min. Fluorescence was measured at 405 and 495 nm wavelength and the ratio was used to estimate [Ca²⁺]. A control force-Ca²⁺ relationship was determined with stimulation over a range of frequencies, yielding constants for slope, max force, and half-maximal [Ca²⁺] (pCa^2?+₅₀). Data were collected for sequential contractions at 40 Hz at 2 s intervals. Active force decreased over the first 1–4 contractions then increased. A force-pCa²⁺ curve was fit to each contraction, using the control values for the Hill slope and max force by adjusting pCa²⁺₅₀ until the curve passed through the target contraction. Data are presented for three contractions for each fibre: first, maximum shift to the right, and last contraction. There was a significant shift to the right for pCa²⁺₅₀ (decreased Ca²⁺ sensitivity), usually early in the series of intermittent contractions, then pCa^2?+₅₀ shifted to the left, but remained significantly different from the control value. Although potentiation is associated with increased Ca²⁺ sensitivity, this increase begins only after Ca²⁺ sensitivity has decreased and, in most cases, Ca²⁺ sensitivity does not increase above the control level.