Glycine modulation of the phencyclidine binding site in mammalian brain

Neurophysiological studies have shown that glycine potentiates the NMDA response in cultured neurons by a strychnine-insensitive mechanism. Autoradiographic data have demonstrated a correspondence between strychnine-insensitive [3H]glycine binding sites and NMDA-sensitive [3H]glutamate binding sites. Here we report that in synaptic plasma membranes from rat brain, the binding of a PCP analog, [3H]TCP, was enhanced more than 5-fold by 1 microM glycine. This glycine stimulation of binding of [3H]TCP was blocked by the competitive NMDA-receptor antagonist, D-AP7. These data provide support for the hypothesis that a unique amino acid recognition site is associated with the proposed NMDA/PCP receptor complex in brain.     

A perspective on the significance of maternally mediated developmental toxicity

The significance of maternally mediated developmental toxicity has been controversial from both a biological and a regulatory point of view. The open literature has at times been interpreted to mean that a number of the effects seen in fetuses from dams exposed to maternally toxic doses of chemicals were secondary consequences of maternal toxicity rather than direct effects on the conceptus. Recent experimental studies, however, indicate that although certain relatively species-specific manifestations of developmental toxicity may at times be maternally mediated, most are not. On occasion, even severe maternal toxicity can apparently occur without causing readily discernible effects on the embryo/fetus. The most important concern of a regulatory agency with regard to developmental toxicity is the possibility of the causation of significant, irreversible harm to the offspring. In practical terms, the margin of safety for exposure to a developmental toxicant is of much more importance than whether or not the agent's effects are maternally mediated. For protection of the unborn, it is obviously the end result that matters, regardless of the mechanism. Safeguarding the conceptus from specific developmental toxicants (i.e., agents with relatively high A/D ratios) requires the use of safety factors based on the developmental toxicity NOEL. Protecting the conceptus against agents with A/D ratios near unity could be based on the maternal toxicity NOEL, however, as the true NOEL for developmental toxicity may be near that for the mother, but the adult NOEL is likely to be more readily determinable.     

Balance algorithm for cluster randomized trials

Background  

Within cluster randomized trials no algorithms exist to generate a full enumeration of a block randomization, balancing for covariates across treatment arms. Furthermore, often for practical reasons multiple blocks are required to fully randomize a study, which may not have been well balanced within blocks.     

The extent of surface contamination of retailed chickens with Campylobacter jejuni serogroups.

Eighty-two chickens purchased at 11 retailers (supplied by 12 wholesalers) in the south of England were cultured for Campylobacter jejuni by a method involving total immersion. The organism was isolated from 22 (48%) of 46 fresh birds, 12 of 12 uneviscerated (New York dressed) birds, but only 1 of 24 frozen birds. Viable counts of up to 1.5 x 10(6)/chicken were obtained from fresh birds and 2.4 x 10(7)/chicken from uneviscerated birds. Surface swabbing of breasts, thighs, wings and vents of fresh chickens showed that contamination was generally distributed over the carcasses. Salmonellas were found in only 2 of 69 of the fresh chickens. The prevalence of several Lior and Penner C. jejuni serogroups was similar in chickens and sporadic human cases of enteritis. Penner serogroup 4 (mostly of Lior serogroup 1) was found in 26% of human isolates and 14% of chicken isolates. The rising incidence of campylobacter enteritis during the last 6 years could well be a reflection of the increasing proportion of fresh chickens consumed over that period (32% higher in 1986 than in 1981).     

Controlled and uncontrolled studies of phosphodiesterase III inhibitors in contemporary cardiovascular medicine

The phosphodiesterase inhibitors are new inotrope vasodilators that have beneficial hemodynamic effects in patients with congestive heart failure (CHF). The most extensively studied agents are milrinone and enoximone. Both drugs have clearly been shown in numerous studies to improve hemodynamics in patients with CHF when given acutely by either the intravenous or oral route. In long-term studies, milrinone has been shown to have sustained beneficial hemodynamic effects during active treatment. Effects on exercise tolerance have been less clear-cut in several uncontrolled trials, but a recent large-scale randomized trial does show sustained improvement in exercise performance. When milrinone is withdrawn after long-term therapy, some studies show worsened cardiac performance; the exact cause remains ill-defined, but could be due to deterioration of baseline ventricular function or to "rebound." Both uncontrolled studies and a large recently reported randomized trial show that the hemodynamic response to readministration of milrinone after withdrawal is well-preserved, i.e., no tolerance is observed. Studies of enoximone show that its acute hemodynamic effects are similar to those of milrinone, but its long-term efficacy, using both hemodynamic and exercise end points, is less clear-cut, and no large-scale randomized trials of enoximone therapy have yet been reported. The studies of both these agents performed thus far indicate that the phosphodiesterase inhibitors have considerable promise for both acute and long-term treatment of patients with CHF.     

Joint custody: historical, legal, and clinical perspectives with emphasis on the situation in Canada

The search for ways to mitigate the effects of family breakdown on parents and children includes legislative and clinical efforts which to some extent influence each other. In the past year much public interest has been aroused in Canada, and particularly in Ontario, in the issue of legislative changes which would make joint custody the usual or "preferred" legal disposition of custody cases. This paper provides a discussion of the legislated preference, or "rebutable presumption" of joint custody from a historical, legal and clinical point of view. Definition and elaboration of what joint custody is from the legal and practical perspectives is provided with an emphasis on Canadian laws and practice. The legal rights of the non-custodial parent are explained, and relevant case law is highlighted. The relationship between joint custody, support orders and relitigation rates are elaborated. Following this is a critical overview of the empirical research on joint custody as it relates to the adjustment of children and parent satisfaction is included. It is concluded that while there is little question that shared parenting can be beneficial to children, the enthusiasm of legislators for joint custody has not been supported by empirical data. It is necessary to examine under what circumstances and for which kinds of parents and children joint custody might be beneficial since it is unlikely that one solution will fit the needs of all families and all stages of family life.     

The significance of alkalosis and hypochloremia in hypertrophic pyloric stenosis

Hypochloremic alkalosis is the "classical" electrolyte abnormality seen in hypertrophic pyloric stenosis (HPS), yet it occurs in only about half the patients. To define the clinical differences between infants who were alkalotic or hypochloremic and those who were not, we reviewed the records of 216 patients treated for HPS over a recent 5-year period at our institution. The 202 patients who had a full set of serum electrolytes drawn on admission were divided into nonalkalotic and alkalotic bicarbonate groups A (less than or equal to 25 mEq/L, n = 105) and B (greater than 25 mEq/L, n = 97) and also nonhypochloremic and hypochloremic chloride groups A (greater than or equal to 99 mEq/L, n = 117) and B (less than 99 mEq/L, n = 85). The alkalotic group B had a significantly higher proportion of black patients (17.5% v 8%), longer mean duration of illness (17.8 v 9.4 days), higher incidence of palpable pyloric mass (97% v 82%), greater degree of dehydration, lower mean serum sodium (136.3 v 137.7 mEq/L), lower mean serum potassium (4.50 v 5.15 mEq/L), and lower mean serum chloride (92.4 v 102.3 mEq/L) than did the nonalkalotic group A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isolation of nontoxigenic Vibrio cholerae O group 1 from a patient with severe gastrointestinal disease.

A nontoxigenic strain of Vibrio cholerae O group 1 was isolated in Florida from the stool of a patient with severe diarrhea. The strain had the same hemolytic and unique phage-sensitivity pattern as all toxigenic isolates from recent cases of cholera in Texas and Louisiana. Identical strains were transiently isolated from sewerage systems in two other Florida communities, suggesting that multiple human infections had occurred. This is the first indication that V. cholerae O1 strains which do not produce cholera toxin may be able to cause gastrointestinal disease in humans. The identification of these strains also raises questions about the relationship between toxigenic and nontoxigenic strains of V. cholerae O1 along the Gulf Coast of the United States.