Achievement and safety of a low blood pressure goal in chronic renal disease. The Modification of Diet in Renal Disease Study Group

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.     

Response to intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy with only sensory symptoms

In an open prospective study we analysed the effect of treatment with intravenous immunoglobulin (IvIg) in three patients with clinically pure sensory neuropathy, two of whom met the clinical, electrophysiological, pathological and cerebrospinal fluid research criteria of the American Academy of Neurology for chronic inflammatory demyelinating polyneuropathy. In all patients, subclinical signs of demyelination were present in motor nerves. Treatment with IvIg resulted in improvement of neurological functions in all three patients and in improvement of the disability score in two of them.     

Study of calcium homeostasis in feline hyperthyroidism

Thirty cats with untreated hyperthyroidism were blood sampled and their calcium homeostatic mechanisms and renal function assessed. The results were compared with those obtained from 38 age-matched control cats. The hyperthyroid group of cats were found to have significantly lower blood ionised calcium and plasma creatinine concentrations and significantly higher plasma phosphate and parathyroid hormone concentrations. Hyperparathyroidism occurred in 77 per cent of hyperthyroid cats, with parathyroid hormone concentrations reaching up to 19 times the upper limit of the normal range. The aetiology, significance and reversibility of hyperparathyroidism in feline hyperthyroidism remains to be established but could have important implications for both bone strength and renal function.     

Maternal attachment status, psychosocial stressors and problem behaviour: follow-up after parent training courses for conduct disorder

37 Mothers of children with conduct disorder who had received Parent Management Training (PMT) were interviewed using the Adult Attachment Interview, 13-43 months after treatment. Child behaviour levels at follow-up were strongly associated with the scores at referral in the unresolved attachment group, but not in the resolved group. This was reflected in a statistical interaction between referral behaviour score and resolved/unresolved attachment status in a regression model. This model, which also included a strong independent contribution from a composite psychological stress index, explained 66% of the variance in follow-up behaviour scores. The implications of these results for predicting the outcome of PMT are discussed.     

A comparison of prophylactic ondansetron and metoclopramide administration in patients undergoing major neurosurgical procedures

In a prospective, randomised, double-blind trial, we assessed the relative efficacy of prophylactic ondansetron and metoclopramide administration in the reduction of postoperative nausea and vomiting in 60 patients undergoing routine major neurosurgical procedures. The patients were randomly allocated into one of two groups. Both groups received a standardised anaesthetic. When the dura mater was closed, patients in group A received an intravenous injection of metoclopramide 10 mg whilst group B received ondansetron 8 mg intravenously. Patients who received metoclopramide experienced less postoperative nausea and vomiting than those who received ondansetron in the 48 h following surgery (17 (56%) versus 9 (30%) p = 0.038). In the light of these findings, we believe that ondansetron is an inappropriate agent for the prevention of postoperative nausea and vomiting in the neurosurgical population.     

Sexual abuse, family environment, and psychological symptoms: On the validity of statistical control.

M. R. Nash et al (see record 1993-33781-001) reported on the effects of controlling for family environment when studying sexual abuse sequelae. Sexual abuse history was associated with elevated MMPI and Rorschach scores in a sample of 105 women, but many of the reported differences disappeared when a composite Family Functioning Scale score was used as a covariate. The present article considers the findings of Nash et al in terms of the theoretical and statistical constraints placed on analysis of covariance (ANCOVA) and other partializing procedures. Because family dysfunction is not always causally antecedent to sexual abuse, and given the quasi-experimental quality of most abuse research, the use of covariate techniques to test hypotheses about the causal role of family environment in the impacts of sexual abuse may be ill advised. Analyses of a 2,964-S data set illustrate these concerns. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypoxic activation of nuclear factor-kappa B is mediated by a Ras and Raf signaling pathway and does not involve MAP kinase (ERK1 or ERK2)

We have previously shown that hypoxia causes the activation of nuclear factor-kappa B (NF-kappa B), and the phosphorylation of its inhibitory subunit, I kappa B alpha, on tyrosine residues. With the use of dominant negative mutants of Ha-Ras and Raf-1, we investigated some of the early signaling events leading to the activation of NF-kappa B by hypoxia. Both dominant negative alleles of Ha-Ras and Raf-1 inhibited NF-kappa B induction by hypoxia, suggesting that the hypoxia-induced pathway of NF-kappa B induction is dependent on Ras and Raf-1 kinase activity. Furthermore, although conditions of low oxygen can also activate mitogen-activated protein kinases (ERK1 and ERK2), these kinases do not appear to be involved in regulating NF-kappa B by low oxygen conditions, as dominant negative mutants of mitogen-activated protein kinase do not inhibit NF-kappa B activation by hypoxia. Since Ras and Raf-1 have been previously shown to work downstream from membrane-associated tyrosine kinases such as Src, we determined if the Src membrane-associated kinase was also activated by low oxygen conditions. We detected an increase in Src proto-oncogene activity within 15-30 min of cellular exposure to hypoxia. We postulate that Src activation by hypoxia may be one of the earliest events that precedes Ras activation in the signaling cascade which ultimately leads to the phosphorylation and dissociation of the inhibitory subunit of NF-kappa B, I kappa B alpha.     

RanBP1 stabilizes the interaction of Ran with p97 nuclear protein import

Three factors have been identified that reconstitute nuclear protein import in a permeabilized cell assay: the NLS receptor, p97, and Ran/TC4. Ran/TC4, in turn, interacts with a number of proteins that are involved in the regulation of GTP hydrolysis or are components of the nuclear pore. Two Ran-binding proteins, RanBP1 and RanBP2, form discrete complexes with p97 as demonstrated by immunoadsorption from HeLa cell extracts fractionated by gel filtration chromatography. A > 400-kD complex contains p97, Ran, and RanBP2. Another complex of 150-300 kD was comprised of p97, Ran, and RanBP1. This second trimeric complex could be reconstituted from recombinant proteins. In solution binding assays, Ran-GTP bound p97 with high affinity, but the binding of Ran-GDP to p97 was undetectable. The addition of RanBP1 with Ran-GDP or Ran-GTP increased the affinity of both forms of Ran for p97 to the same level. Binding of Ran-GTP to p97 dissociated p97 from immobilized NLS receptor while the Ran-GDP/RanBP1/p97 complex did not dissociate from the receptor. In a digitonin-permeabilized cell docking assay, RanBP1 stabilizes the receptor complex against temperature-dependent release from the pore. When added to an import assay with recombinant NLS receptor, p97 and Ran-GDP, RanBP1 significantly stimulates transport. These results suggest that RanBP1 promotes both the docking and translocation steps in nuclear protein import by stabilizing the interaction of Ran-GDP with p97.