Renal sensitivity to endothelium-derived-relaxing-factor-mediated vasodilatation in the spontaneously hypertensive rat.

1. The sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation has been investigated in the spontaneously hypertensive rat and the Wistar-Kyoto normotensive rat using an isolated perfused rat kidney model. 2. No difference in the slope, ED50 or maximum of the concentration-response curves for the endothelial-dependent vasodilators A23187, a calcium ionophore, and acetylcholine could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. 3. No difference in the slope or the ED50 of the concentration-response curve for the endothelial-independent vasodilators, atrial natriuretic factor and sodium nitroprusside, could be demonstrated between kidneys obtained from the spontaneously hypertensive and the Wistar-Kyoto normotensive rats. However, in the spontaneously hypertensive rats, the maximum vasodilator response to atrial natriuretic factor, but not to sodium nitroprusside, was increased. 4. The perfused kidney from the spontaneously hypertensive rat also showed an increase in the maximum but not in the slope or ED50 of the concentration-response curve for vasoconstriction induced by the alpha 1-adrenoceptor agonist methoxamine. 5. The involvement of endothelium-derived relaxing factor in mediating the renal vasodilator response to A23187 and acetylcholine was confirmed in experiments performed in perfused kidneys obtained from normotensive Wistar rats. 6. It is concluded that the sensitivity of the kidney to endothelium-derived-relaxing-factor-mediated vasodilatation is not modified in the spontaneously hypertensive rat. This does not, however, exclude a role for the synthesis of endothelium-derived relaxing factor in the maintenance of blood pressure in the spontaneously hypertensive rat.     

Increased rates of hepatic cholesterogenesis and fatty acid synthesis in septic rats in vivo: evidence for the possible involvement of insulin

1. Sepsis induced by caecal ligation and puncture increased the rates of hepatic cholesterogenesis and fatty acid synthesis in vivo compared with sham-operated rats. These changes were accompanied by higher concentrations of lactate and pyruvate in blood and liver and an increase in plasma insulin. 2. The total activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.88) in liver was increased by sepsis, but there was no significant change in the expressed activity. Short-term insulin deficiency (induced by mannoheptulose or streptozotocin) decreased the rates of cholesterogenesis and fatty acid synthesis in livers of septic rats but did not alter the expressed/total activity of HMG-CoA reductase. 3. It is concluded that the increased rate of hepatic cholesterogenesis in septic rats is in part a result of the higher plasma insulin, the hormone acting to maintain the total activity of HMG-CoA reductase and to stimulate a step before the formation of HMG-CoA. 4. These changes may contribute to the hypertriacylglycerolaemia associated with sepsis.     

Congenital myopathy with focal loss of cross-striations revisited

In 1977 Wijngaarden et al. reported a Dutch family with a congenital myopathy characterized by external ophthalmoplegia and a remarkable histological feature, focal loss of cross-striations. A small number of other families with similar clinical and pathological features led to the consideration of this congenital myopathy as a distinct entity. Here we present more than 30 years of follow-up from the Dutch family and report recently identified compound heterozygous mutations in the skeletal muscle ryanodine receptor (RYR1) gene, c.10627-2A>G and p.Arg3539His (c.10616G>A). Focal loss of cross-striations on muscle biopsy is another histopathological feature that should raise the possibility of RYR1 involvement.     

Prevalence of and referred pain from myofascial trigger points in the forearm muscles in patients with lateral epicondylalgia

OBJECTIVE: Referred pain and pain characteristics evoked from the extensor carpi radialis brevis, extensor carpi radialis longus, extensor digitorum communis, and brachioradialis muscles was investigated in 20 patients with lateral epicondylalgia (LE) and 20-matched controls. METHODS: Both groups were examined for the presence of myofascial trigger points (TrPs) in a blinded fashion. The quality and location of the evoked referred pain, and the pressure pain threshold (PPT) at the lateral epicondyle on the right upper extremity (symptomatic side in patients, and dominant-side on controls) were recorded. Several lateral elbow pain parameters were also evaluated. RESULTS: Within the patient group, the elicited referred pain by manual exploration of 13 out of 20 (65%) extensor carpi radialis brevis muscles, 12/20 (70%) extensor carpi radialis longus muscles, 10/20 (50%) brachioradialis muscles, and 5/20 (25%) extensor digitorum communis muscles, shares similar pain patterns as their habitual lateral elbow and forearm pain. The mean number of muscles with TrPs for each patient was 2.9 [95% confidence interval (CI) 1,4] of which 2 (95% CI 1,3) were active, and 0.9 (95% CI 0,2) were latent TrPs. Control participants only had latent TrPs (mean: 0.4; 95% CI 0,2). TrP occurrence between the 2 groups was significantly different for active TrPs (P<0.001), but not for latent TrPs (P>0.05). The referred pain pattern was larger in patients than in controls, with pain referral to the lateral epicondyle (proximally) and to the dorso-lateral aspect of the forearm in the patients, and confined to the dorso-lateral aspect of the forearm in the controls. Patients with LE showed a significant (P<0.001) lower PPT (mean: 2.1 kg/cm; 95% CI 0.8, 4 kg/cm) as compared with controls (mean: 4.5 kg/cm; 95% CI 3, 7 kg/cm). Within the patient group, PPT at the lateral epicondyle was negatively correlated with both the total number of TrPs (rs=-0.63; P=0.003) and the number of active TrPs (rs=-0.5; P=0.02): the greater the number of active TrPs, the lower the PPT at the lateral epicondyle. DISCUSSION: Our results suggest that in patients with LE, the evoked referred pain and its sensory characteristics shared similar patterns as their habitual elbow and forearm pain, consistent with active TrPs. Lower PPT and larger referred pain patterns suggest that peripheral and central sensitization exists in LE.     

Association study of the vesicular monoamine transporter gene SLC18A2 with tardive dyskinesia

Tardive dyskinesia (TD) is an involuntary movement disorder that can occur in up to 25% of patients receiving long-term first-generation antipsychotic treatment. Its etiology is unclear, but family studies suggest that genetic factors play an important role in contributing to risk for TD. The vesicular monoamine transporter 2 (VMAT2) is an interesting candidate for genetic studies of TD because it regulates the release of neurotransmitters implicated in TD, including dopamine, serotonin, and GABA. VMAT2 is also a target of tetrabenazine, a drug used in the treatment of hyperkinetic movement disorders, including TD. We examined nine single-nucleotide polymorphisms (SNPs) in the SLC18A2 gene that encodes VMAT2 for association with TD in our sample of chronic schizophrenia patients (n = 217). We found a number of SNPs to be nominally associated with TD occurrence and the Abnormal Involuntary Movement Scale (AIMS), including the rs2015586 marker which was previously found associated with TD in the CATIE sample ( Tsai et al., 2010), as well as the rs363224 marker, with the low-expression AA genotype appearing to be protective against TD (p = 0.005). We further found the rs363224 marker to interact with the putative functional D2 receptor rs6277 (C957T) polymorphism (p = 0.001), supporting the dopamine hypothesis of TD. Pending further replication, VMAT2 may be considered a therapeutic target for the treatment and/or prevention of TD.     

Diagnostic accuracy of the double-contrast enema for colonic polyps in patients with or without diverticular disease

The accuracy of the double-contrast enema for the diagnosis of polypoid lesions in the presence or absence of diverticula was evaluated by retrospectively reviewing the medical records of 202 patients subjected to examination and endoscopy. Analysis of the data on 215 polypoid lesions showed that (a) the diagnostic accuracy of the examination is not affected significantly by the presence of diverticula; (b) the sensitivity of the examination is highly dependent on the size of the polyps (smaller or larger than 0.5 cm) but not on the form (sessile or pedunculated); and (c) the positive predictive value is higher in patients without diverticula. The doublecontrast enema was confirmed to be a valid method for the diagnosis of polypoid lesions.     

Microbiologic risk of invasive hemodynamic monitoring in patients undergoing open-heart operations

The microbiologic risk of invasive hemodynamic monitoring was studied prospectively in 574 patients undergoing open-heart surgery under cover of cephalothin prophylaxis. Of a total of 2277 catheters inserted in these patients, 1.5% yielded positive cultures. The rate of positive cultures was not significantly different between percutaneous and surgically placed catheters (1.7% vs. 0.8%, respectively). Specifically, the incidence of positive catheter tips for intravenous, central venous, arterial, and pulmonary artery catheters was 1.1%, 3.9%, 1.5%, and 2.1%, respectively; while the corresponding rates for surgically inserted right atrial and left atrial catheters were 0.8% and 0, respectively. Pulmonary artery catheters had a significantly (p less than .01) higher incidence of positive catheter tips after 72 h in situ. However, there was no relationship between the in situ time and the incidence of positive tips for arterial and intravenous catheters. Although the rate of positive catheter tip cultures was low, it affected 4.9% of the patients. Nevertheless, no patient developed catheter-related septicemia or endocarditis, and the data generally supported the microbiologic safety of invasive hemodynamic monitoring in patients undergoing open-heart surgery.