Social isolation increases the density of [125I]omega-conotoxin GVIA binding sites in the rat frontal cortex and caudate nucleus.

Rats were reared from weaning either in isolation or in social groups for 12 weeks. Potential isolation-related changes in L- and N-type voltage-sensitive calcium channels (VSCCs) were assessed by the in vitro binding of [3H]isradipine (100 pM) and [125I]omega-conotoxin GVIA (4 pM) to membranes prepared from three discrete central nervous system regions: frontal cortex, caudate nucleus and hippocampus. The [3H]isradipine binding was generally not affected by isolation. However, [125I]omega-conotoxin GVIA binding was significantly higher in frontal cortex (52%) and caudate nucleus (75%) of isolated rats when compared with socially reared controls. The increased [125I]omega-conotoxin GVIA binding reflected an elevated density of binding sites without an alteration of receptor affinity. The possible contribution of an increased density of neuronal N-VSCCs (as labeled with [125I]omega-conotoxin GVIA) to the behavioral and neurochemical changes observed in 'isolation syndrome' is discussed.     

Drug mixture which improves survival of ischemic rabbit epigastric skin flaps

The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl₂ (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes. © 1994 Wiley-Liss, Inc.     

Case report 487

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official nor as reflecting the views of the United States Air Force     

Death anxiety, death competency and self-actualization in hospice volunteers.

A total of 248 hospice volunteers completed the Personal Orientation Inventory, the Templer/McMordie Death Anxiety Scale, the Bugen Coping with Death Scale, and a Death Self-Efficacy Scale constructed for this research. Death anxiety significantly negatively correlated with four Personal Orientation Inventory scales, Coping with Death Scale positively correlated with seven of the twelve Personal Orientation Inventory Scales, and the Self-Efficacy Scale significantly correlated with eleven of them. These findings suggest that death competency constructs may be more useful than the concept of death anxiety in conceptualizing people's emerging self-actualization in the process of confronting mortality.     

Reduced 293T cell susceptibility to acrolein due to aldose reductase-like-1 protein expression.

Acrolein is a highly reactive alpha,beta-unsaturated aldehyde produced endogenously during lipid peroxidation and naturally distributed pervasively in living environments, posing serious threats to human health if not properly metabolized. In this study, we report aldose reductase-like-1 (ARL-1) as a novel enzyme that catalyzes the reduction of acrolein and protects cells from their toxicity. Using purified ARL-1 protein, we determined its enzymatic activity in response to acrolein and defined its steady-state kinetics with K(m) and V(max) at 0.110 +/- 0.012 mM and 3122.0 +/- 64.7 nmol/mg protein/min, respectively. By introducing a functional Enhanced Green Fluorescent Protein (EGFP)/ARL-1 fusion protein into 293T cells, we demonstrated that plating efficiency in liquid culture and focus formation in soft agar increased by more than 60% (p < 0.05), compared to the vector control cells. More significantly, at a low dose of 5 microM acrolein, EGFP/ARL-1 expression enhanced both plating efficiency and focus formation by more than threefold, and the foci (in soft agar) of 293T cells expressing EGFP/ARL-1 were significantly larger than those of the vector control cells. At high concentrations of acrolein (25 and 50 microM), EGFP/ARL-1 protein prevented oncotic death of 293T cells induced by acrolein. In summary, our data demonstrated for the first time that the ARL-1 protein protects 293T cells from acrolein toxicity. Due to the high toxicity and wide distribution of acrolein, this finding is important to the understanding of its detoxification mechanisms.     

Requiring Consent vs. Waiving Consent for Medical Records Research: A Minnesota Law vs. the U.S. (HIPAA) Privacy Rule

The use of medical records in research can yield information that is difficult to obtain by other means. When such records are released to investigators in identifiable form, however, substantial privacy and confidentiality risks may be created. These risks become more common and more serious as medical records move to an electronic format. In 1996, the state of Minnesota enacted legislation with respect to consent requirements for the use of medical records in research. This legislation has been widely criticized because--it is claimed--it creates an unnecessary impediment to research. In this article, we show that these arguments rest upon misinterpretation and/or misrepresentation of the 1996 legislation. A consent requirement had actually been present in Minnesota since 1976 (though codified in a patient rights statute rather than a privacy statute). The 1996 law does not require specific consent, as often claimed, but rather only a general authorization. The campaign against the Minnesota legislation appears to have been motivated by concern with respect to the then impending federal privacy rule. The HIPAA rule, as enacted, is in fact less stringent with respect to consent than the Minnesota consent law. On the other hand, the Minnesota consent law has not been effectively applied or enforced. As we change the way we manage sensitive medical information, new efforts are needed to provide protection against the confidentiality risks in research. Patient consent is an important tool in this regard. New instrumentalities are needed to solicit and document consent.     

Long-term outcome and complications of children born with meningomyelocele

The long-term functional outcome of 101 children born with meningomyelocele between 1971 and 1981 was assessed, by a combination of retrospective chart review and follow-up assessments. The children had been managed at birth using a process ofnonstandardized selection. Eighty-three of the 101 patients survived after a minimum follow-up of 8.6 years, for a mortality rate of 18%. Forty-four of 83 children (53%) were community ambulators, and this correlated well with the presence of intact quadriceps function. Forty-eight children (58%) attended normal school and were grade-appropriate. Sixty-two of 83 patients (75%) were socially continent of urine, and 71/83 (86%) were socially continent of stool. Hydrocephalus was present in 93 of the 101 children in the study, and 85 children were shunted. Half of the shunted children required a shunt revision in the first year of life, and thereafter the rate of revision decreased, so that after 2 years the risk of revision was approximately 10% per year.     

Magnesium carbonate is an effective phosphate binder for chronic hemodialysis patients: a pilot study.

OBJECTIVE: This study was designed to evaluate the efficacy of magnesium carbonate as a phosphate binder in hemodialysis patients. DESIGN: This study was a prospective, randomized, open-label trial comparing magnesium carbonate/calcium carbonate versus calcium acetate as a sole phosphate binder. SETTING: This study involved outpatient hemodialysis. PARTICIPANTS: We recruited 30 stable hemodialysis patients without a history of frequent diarrhea. INTERVENTION: After receiving informed consent, we randomized patients 2:1 to magnesium carbonate versus calcium acetate. The dose of each binder was titrated to achieve the Kidney Disease Outcomes Quality Initiative (K/DOQI) phosphate target of <5.5 mg/dL. MAIN OUTCOME MEASURE: The efficacy-phase serum phosphorus concentration and the percentage of patients meeting K-DOQI targets for phosphorus, along with the daily elemental calcium intake, were the primary outcome measures. RESULTS: Magnesium carbonate provided equal control of serum phosphorus (70.6% of the magnebind group and 62.5% of the calcium acetate group had their average serum phosphorus within the K-DOQI target during the efficacy phase), while significantly reducing daily elemental calcium ingestion from phosphate binders (908 +/- 24 vs. 1743 +/- 37 mg/day, P < .0001). CONCLUSION: Magnesium carbonate was generally well-tolerated in this selected patient population, and was effective in controlling serum phosphorus while reducing elemental calcium ingestion.     

Biochemical Abnormality Associated with Smith-Lemli-Opitz Syndrome in an Infant with Features of Rutledge Multiple Congenital Anomaly Syndrome Confirms that the Latter Is a Variant of the Former

We describe a female infant with morphologic features of Rutledge multiple-congenital-anomaly syndrome (RMCAS) and biochemical features of Smith-Lemli-Opitz syndrome (SLOS). She had microcephaly with hypoplastic cerebral frontal lobes and cerebellum, agenesis of the splenium of corpus callosum, abnormal facies including hypertelorism with bilateral inner epicanthal folds, a broad nasal bridge with slightly anteverted nares and patent choanae, low set ears and complex conchal formation, high-arched palate and thick maxillary alveolar ridges, and micrognathia. Her chest was broad, genitalia were ambiguous, and uterus was bicornuate. Skeletal abnormalities included a hypoplastic appendicular skeleton, post-axial hexadactyly of the right hand and the left foot, syndactyly of bilateral 2nd-3rd toes and left 5th-6th toes, right talipes varus and left talipes valgus, and fused L5-S1 vertebrae. Congenital heart disease consisted of hypoplastic left heart, coronary sinus agenesis, ostium secundum and ostium primum defects, and a thickened septum primum. The lungs were hypolobated and the kidneys manifested oligopapillary hypoplasia. Total colonic Hirschsprung disease was noted microscopically. Analysis of liver tissue taken at postmortem examination revealed the ratio of 7-dehydrocholesterol and cholesterol to be 143 (expected, 0.28 +/- 0.28). Although initially described as a distinct syndrome, RMCAS was merged with the severe form of SLOS, because of significantly overlapping features [Online Mendelian Inheritance in Man (OMIM) #268670]. The biochemical data showing an excess of 7-dehydrocholesterol and low cholesterol in the liver tissue of our case supports this viewpoint.