Chronic prenatal ethanol exposure alters glucocorticoid signalling in the hippocampus of the postnatal Guinea pig.

The present study tested the hypothesis that chronic prenatal ethanol exposure causes long-lasting changes in glucocorticoid signalling in postnatal offspring. Pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding or water throughout gestation, and maternal saliva cortisol concentration was determined 2 h after treatment at different stages of gestation. Electrically-stimulated release of glutamate and GABA, in the presence or absence of dexamethasone, as well as glucocorticoid and mineralocorticoid receptor mRNA expression, was determined in the hippocampus and prefrontal cortex of adult offspring of treated pregnant guinea pigs. Maternal saliva cortisol concentration increased throughout pregnancy, which was associated with increased foetal plasma and amniotic fluid cortisol concentration. Ethanol administration to pregnant guinea pigs increased maternal saliva cortisol concentration during early and mid-gestation. In late gestation, ethanol administration did not increase saliva cortisol concentration above that induced by pregnancy. Chronic prenatal ethanol exposure had no effect on stimulated glutamate or GABA release, but selectively prevented dexamethasone-mediated suppression of stimulated glutamate release, and decreased expression of mineralocorticoid, but not glucocorticoid, receptor mRNA in the hippocampus of adult offspring. These data indicate that maternal ethanol administration leads to excessively increased maternal cortisol concentration that can impact negatively the developing foetal brain, leading to persistent postnatal deficits in glucocorticoid regulation of glutamate signalling in the adult hippocampus.

Peginterferon alfa-2a: a review of approved and investigational uses.

BACKGROUND: In October 2002, the US Food and Drug Administration approved peginterferon alfa-2a for the management of chronic hepatitis C virus (HCV) infection. The addition of polyethylene glycol (PEG) moiety to the interferon (IFN) molecule results in a product with altered pharmacokinetic properties. OBJECTIVE: The aim of this article is to review the pharmacology, medications interactions, adverse events (AEs), and approved or investigational uses of PEG-IFN alfa-2a for viral hepatitis and oncologic conditions. METHODS: Relevant articles were identified through searches of MEDLINE (1980-July 2003) and EMBASE (1980-July 2003). Search terms included, but were not limited to, peginterferon alfa-2a, pharmacokinetics, pharmacology, pharmacodynamics, and therapeutic use, as well as terms for specific disease states and AEs. Further publications were identified from citations of resulting papers. RESULTS: Pegylation of IFN alfa-2a results in major changes in the pharmacokinetics of the product. Absorption is prolonged and serum concentrations are sustained over the dosing regimen. PEG-IFN alfa-2a has been shown to be more effective with or without ribavirin (RBV), in the management of treatment-naive patients with chronic HCV infection, than unmodified IFN alfa-2a with or without RBV. Results in other disease states are still preliminary. AEs are similar, in incidence and severity, to those occurring with unmodified IFN. They include earlier hematologic symptoms and fewer influenza-like symptoms. Drug-drug interactions are the same as those occurring with the unmodified IFN product. CONCLUSIONS: The pharmacokinetic profile of IFN alfa-2a is improved by pegylation, which enables less frequent administration and results in improved efficacy with a similar side-effect profile. Combination of PEG-IFN alfa-2a with RBV is associated with a greater chance of achieving a sustained virologic response in treatment-naive patients with chronic HCV, compared with unmodified IFN alfa-2a/RBV combinations. Documentation of efficacy in other conditions awaits results of controlled clinical trials.

Investigation of calcium-binding sites on the surfaces of selected gram-positive oral organisms.

Dental plaque is rich in anionic groups with a high calcium-binding capacity which may affect mineral dynamics at the tooth surface. The two major calcium-binding sites on Gram-positive cell surfaces are carboxylate groups (in proteins and peptidoglycan cross-links) and phosphate groups (in lipoteichoic and teichoic acid). Equilibrium dialysis was used to measure calcium-binding capacities of whole cells and purified cell-wall material (CWM) from Streptococcus mutans R9, Strep. oralis EF186, Strep. gordonii NCTC 7865, Strep. downei NCTC 11391, Actinomyces naeslundii WVU627 and Lactobacillus casei AC413. This material was stripped of phosphate (PS-CWM) and treated to mask carboxylate groups (CM-CWM). Whole-cell calcium-binding capacities ranged from 240 (Strep. downei) to 50 (L. casei) mu mol/g (dry wt). Differences in CWM, PS-CWM and CM-CWM calcium-binding capacities demonstrated the greater importance of phosphate in comparison with carboxylate groups in cell calcium binding. These data indicate that, in streptococci, calcium binding is predominantly phosphate group-based, especially in the teichoic acid-containing Strep. oralis. In the other species tested, calcium binding is predominantly carboxylate group-based.

Tissue bonding: the bacteriological properties of a commercially-available cyanoacrylate adhesive.

The medical use of cyanoacrylate adhesives for tissue bonding is well established, and their use for tacking skin grafts into place is a regular procedure, for which purpose their case and speed of use seems highly advantageous. As medical grade cyanoacrylate tissue adhesives are fairly expensive, the bacteriological safety of using a commercially-available over-the-counter cyanoacrylate adhesive was investigated. The product was found to be sterile when purchased and remained so during use and between patients. There was also some evidence of bacteriostatic properties. These investigations suggest that the commercially-available product is bacteriologically acceptable, and at approximately 28% of the cost of the medical grade product would show considerable cost savings.

A clinical evaluation of an Erbium:YAG laser for dental cavity preparation.

OBJECTIVE: A randomised controlled trial to determine the acceptability to dentists and patients of cavity preparation with an Erbium:YAG laser as compared with conventional handpieces. METHODS: Fifteen dentists (9 GDPs, 1 community dentist and 5 hospital dentists) treated 77 patients (age range 3.5-68 years old) who had two matched cavities, in a split mouth, randomised trial. One cavity was prepared conventionally, the other with the laser, with dentist and patient preference determined by questionnaire. RESULTS: In the majority of cases, where dentists expressed a preference, it was for conventional cavity preparation, and this was significant (P < 0.001). In more than half of the laser appointments, dentists had to use conventional handpieces to complete the cavity. Principle difficulties reported with the laser were access (25 cases) and slow speed of cutting (11 cases). Patients aged > or = 10 years who expressed a preference, preferred laser treatment, and this was significant (P < 0.001). Patients aged < 10 years, assessed using a simplified pictorial questionnaire, did not show a significant preference for either technique. CONCLUSIONS: Dentists preferred conventional handpieces for cavity preparation while patients aged > or = 10 years old preferred laser treatment. Patients < 10 years old did not express a preference.

Results of surgical treatment of colic in miniature breed horses: 11 cases.

OBJECTIVE: To report on the outcome of surgical treatment of acute abdominal crises in miniature breed horses. DESIGN: Retrospective case series of miniature horses presented to the University Veterinary Centre, Camden with an acute abdominal crisis. METHODS: Hospital records of all miniature horses that underwent ventral midline laparotomy for acute abdominal crisis between 1997 and 2001 were reviewed. The signalment, history, clinical signs, results of ancillary diagnostic procedures, location and type of intestinal lesion, treatment and outcome were retrieved from each case record. Long-term survival was determined by telephone interview of owners. RESULTS: Eleven miniature horses including five females and six males underwent ventral midline laparotomies for acute abdominal crisis during the study period. Ages ranged between 1 month and 19 years. Surgical findings included faecalith obstruction (seven horses), enterolith (one horse), strangulating lipoma of the descending colon (one horse), jejunal infarction (one horse), and caecal infarction (one horse). Long-term survival rate (minimum 12 months post surgery) was 55%. Six of eight horses with simple intraluminal obstructions survived, while the three horses with gastrointestinal lesions associated with vascular compromise were euthanased either at surgery (caecal infarction), or postoperatively, due to complications (strangulating lipoma of the descending colon, jejunal infarction). Postoperative complications in this study included impaction of the descending colon (two horses), diarrhoea (two horses), peritonitis (one horse), hyperlipaemia (two horses), incisional infection (two horses) and abdominal adhesions (one horse). Hyperlipidaemia was present in five of seven horses in which serum triglycerides were measured at presentation. CONCLUSIONS: Simple intraluminal obstructions of the large intestine were frequently encountered during exploratory laparotomy in miniature horses presented for acute abdominal crises, and their surgical treatment was associated with a good prognosis. In contrast, this study suggested that abdominal pain associated with vascular compromise of gastrointestinal tissues in miniature horses was associated with a poorer prognosis, consistent with reports in other horse breeds. Possible contributing factors to faecalith formation, including poor quality roughage, dental disease, and inadequate water consumption, should be recognised and avoided in miniature horses. Serum triglyceride concentrations should be measured in miniature horses presented for acute abdominal pain. If elevated, nutritional supplementation should be provided.

Anterior cruciate ligament reconstruction using the Gore-tex ligament.

Twenty two Army patients with synthetic (Gore-tex) anterior cruciate ligament (ACL) reconstructions were reviewed (mean follow up 18 months). Reconstruction appeared to abolish the pivot shift sign in all cases, but some subjective instability persisted in all but 6 patients. Outcome was also assessed by medical (PULHHEEMS) grading: 6 patients were fully fit (graded L2), 7 returned to moderate activity but not full fitness (L3), and 9 remained severely incapacitated (L7 or L8) with 4 of this group being medically discharged. Specific operative complications included: prosthesis breakage (3 partial, 1 complete), infected prosthesis(1), and problems with the tibial screw(3). The range and frequency of complications was similar in other series. Physical fitness is an integral part of a soldier's job, placing particular demands on the knee and on surgical repair of knee injuries. Reports on the Gore-tex ACL prosthesis in other groups have been more encouraging, but there are difficulties in comparing this study with others. ACL insufficiency remains a serious problem, with implications for a soldier's fitness and career. The Gore-tex prosthesis improves stability but does not always allow a soldier to return to full fitness.

Attempted improvement in mammography by inducing a phase transition in silicone gel.

An attempt was made to achieve a temporary alteration of the molecular structure (a "phase transition") of silicone gel, the end result of which would be to improve mammography. It was hoped that a phase transition of this type would result in either a reduction in gel volume or increased radiopenetration. Unfortunately, an electrically induced phase transition of silicone gel was not seen. In fact, a temporarily altered molecular orientation (phase transition) was not even possible under the extremes of voltage confirming the fact that silicone is extremely inert.

Cellulose crystallites.

This article discusses advances in understanding the structural and physicochemical characteristics of suspensions of cellulose crystallites prepared by acid hydrolysis of natural cellulose fibres. Consideration of recent developments in visualization of crystallite ultrastructure may provide clues to suspension behavior. In addition, novel applications in a diverse range of fields are presented, from iridescent pigments to biomolecular NMR studies.

Familial Hypercholesterolaemia Regression Study: a randomised trial of low-density-lipoprotein apheresis.

Low-density-lipoprotein (LDL) apheresis has the theoretical advantage over anion-exchange resins and hydroxymethylglutaryl coenzyme A inhibitors of decreasing lipoprotein(a) as well as LDL. To confirm this advantage, patients with heterozygous familial hypercholesterolaemia and coronary artery disease were randomised to receive LDL apheresis fortnightly (with disposable dextran sulphate/cellulose columns) plus simvastatin 40 mg daily, or colestipol 20 g plus simvastatin 40 mg daily. Quantitative coronary angiography was repeated after a mean of 2.1 years in 20 patients undergoing apheresis and in 19 on combination drug therapy. Changes in serum lipoproteins were similar in both groups apart from greater lowering by apheresis of LDL cholesterol (3.2 vs 3.4 mmol/L in drug group, p = 0.03) and lipoprotein(a) (geometric means 14 vs 21 mg/dL, p = 0.03). There were no significant differences in primary angiographic endpoints per patient but lesion-based and segment-based secondary endpoints were biased in favour of the drug group (change in minimum lumen diameter of lesions 0.07 vs -0.004 mm, p = 0.046; change in mean lumen diameter of segments 0.02 vs -0.06 mm, p = 0.01). None of the angiographic changes correlated with lipoprotein(a) concentrations. Per patient changes in % diameter stenosis and minimum lumen diameter in the two groups were as or more favourable than those observed in five published trials that assessed lipid-lowering drug therapy by quantitative coronary angiography. Although LDL apheresis combined with simvastatin was more effective than colestipol plus simvastatin in reducing LDL cholesterol and lipoprotein(a), it was less beneficial in influencing coronary atherosclerosis and should be reserved for patients unresponsive to drugs. Decreasing lipoprotein(a) seems to be unnecessary if LDL cholesterol is reduced to 3.4 mmol/L or less.