Pelvic ultrasound findings in different forms of sexual precocity

Recently produced reference curves for various ultrasound dimensions were used to retrospectively assess 67 pelvic ultrasound scans carried out at the initial presentation in girls with sexual precocity. At presentation the group with precocious puberty had significantly increased uterine lengths and ovarian volumes compared with the normal population, and a significantly increased fundal–cervical ratio. Ovarian volume was also significantly increased in thelarche and thelarche variant. The fundal–cervical ratio was significantly increased in thelarche variant. There was considerable overlap between individuals with sexual precocity and normal subjects. The ultrasound findings that best discriminated early or precocious puberty from other forms of sexual precocity were the presence of a midline endometrial echo, and a uterine length above the 97th centile for age. An entirely normal pelvic ultrasound at presentation did not rule out the possibility of precocious puberty.     

Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children

Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children.     

Cost savings and health losses from reducing inappropriate admissions to a department of internal medicine

OBJECTIVES: Inappropriate hospital admissions are commonly believed to represent a potential for significant cost reductions. However, this presumes that these patients can be identified before the hospital stay. The present study aimed to investigate to what extent this is possible. METHODS: Consecutive admissions to a department of internal medicine were assessed by two expert panels. One panel predicted the appropriateness of the stays from the information available at admission, while final judgments of appropriateness were made after discharge by the other. RESULTS: The panels correctly classified 88% of the appropriate and 27% of the inappropriate admissions. If the elective admissions predicted to be inappropriate had been excluded, 9% of the costs would have been saved, and 5% of the gain in quality-adjusted life-years lost. The corresponding results for emergency admissions were 14% and 18%. CONCLUSIONS: The savings obtained by excluding admissions predicted to be inappropriate were small relative to the health losses. Programs for reducing inappropriate health care should not be implemented without investigating their effects on both health outcomes and costs.     

Short-term carcinogenicity testing of 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) and 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) in E{micro}-pim-1 transgenic mice

The usefulness of transgenic Eµ-pim-1 mice over-expressingthe pim-1 oncogene in lymphoid tissues, as sensitive test organismswas studied in a short-term carcinogenicity study. The micewere fed standard diet Altromin 1314 supplemented either with0.03% 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP)for 7 months or with 0.03% 2-amino-3-methylimidazo[4, 5-f] quinoline(IQ) for 6 months. PhIP and IQ are heterocyclic amines formedduring cooking of meat and fish and are mutagenic to bacteriaand cultured mammalian cells. PhIP is a potent mouse lymphomagen,while IQ is a liver carcinogen and also causes lung tumors andtumors of the forestomach in mice. We found that transgenicEµ-pim-1 mice are highly susceptible to PhIP induced lymphomagenesisbut do not respond to the IQ treatment. PhIP feeding of Eµ-pim-1mice not only increased the total number of T-cell lymphomasbut also decreased the latency time compared to either transgenicor wild-type controls. The effect was most pronounced in thetreated female Eµ-pim-1 mice, which showed a higher incidenceof PhIP induced T-cell lymphomas than transgenic males and astrongly reduced latency period after PhIP treatment comparedto non-transgenic mice. Our results suggest that the transgenicEµ-pim-1 mouse may be a useful model for short-term carcinogenicityscreening of potential genotoxic carcinogens having the lymphoidsystem as target tissue. The carcinogen IQ which does not havethe lymphoid system as a target was not recognized in this model.     

Cost and health consequences of reducing the population intake of salt

STUDY OBJECTIVE: The aim was to estimate health and economic consequences of interventions aimed at reducing the daily intake of salt (sodium chloride) by 6 g per person in the Norwegian population. Health promotion (information campaigns), development of new industry food recipes, declaration of salt content in food and taxes on salty food/subsidies of products with less salt, were possible interventions. DESIGN: The study was a simulation model based on present age and sex specific mortality in Norway and estimated impact of blood pressure reductions on the risks of myocardial infarction and stroke as observed in Norwegian follow up studies. A reduction of 2 mm Hg systolic blood pressure (range 1-4) was assumed through the actual interventions. The cost of the interventions in themselves, welfare losses from taxation of salty food/subsidising of food products with little salt, cost of avoided myocardial infarction and stroke treatment, cost of avoided antihypertensive treatment, hospital costs in additional life years and productivity gains from reduced morbidity and mortality were included. RESULTS: The estimated increase in life expectancy was 1.8 months in men and 1.4 in women. The net discounted (5%) cost of the interventions was minus $118 millions (that is, cost saving) in the base case. Sensitivity analyses indicate that the interventions would be cost saving unless the systolic blood pressure reduction were less than 2 mm Hg, productivity gains were disregarded or the welfare losses from price interventions were high. CONCLUSION: Population interventions to reduce the intake of salt are likely to improve the population's health and save costs to society.     

INTESTINAL AGANGLIONOSIS IN THE SMITH-LEMLI-OPITZ SYNDROME

ABSTRACT. Two unrelated cases with clinical and autopsy findings of the Smith-Lemli-Opitz syndrome are described. Narrowing of the terminal ileum and congenital intestinal aganglionosis was found in both. This is a rare association and the importance of microscopic examination of the intestine in cases of the Smith-Lemli-Opitz syndrome is emphasized.     

Expressing effects of osteoporosis interventions in terms of postponing of fractures

OBJECTIVE: To estimate the effect from an osteoporosis intervention in terms of postponement of hip fractures. DESIGN: A Markov model using Nordic data on mortality and hip fracture incidence. PATIENTS: Women aged 50 years and older with increased risk of hip fracture. INTERVENTION: A hypothetical intervention that reduces the risk of hip fracture by 50%. MAIN OUTCOME MEASURES: Postponement of hip fractures--that is increase in expected fracture-free survival from osteoporosis interventions. RESULTS: A 1-year treatment would on average postpone hip fracture by 12 days if therapy were started at the age of 50 years and 23, 55, 90 or 74 days if the treatment were started at the ages of 60, 70, 80 or 90 years, respectively. For 10 years of treatment, the benefit was 146, 260, 369, 373 and 167 days, respectively. The younger the patient, the lower the risk of fracture and, consequently, the greater the benefit for those few who actually could benefit. CONCLUSIONS: The benefit in terms of average postponement of hip fractures from osteoporosis intervention was, other things being equal, greatest in women aged 70-90 years. Fracture postponement may represent an alternative to risk reductions in expressing the effect of osteoporosis interventions.     

Novel class of potent 4-arylalkyl substituted 3-isoxazolol GABA(A) antagonists: synthesis,pharmacology, and molecular modeling

A number of analogues of the low-efficacy partial GABA(A) agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL, 5), in which the 4-position of the 3-isoxazolol ring was substituted by different groups, were synthesized and tested as GABA(A) receptor ligands. Substituents of different size and structural flexibility such as alkyl, phenylalkyl, diphenylalkyl, and naphthylalkyl were explored. Pharmacological characterization of the synthesized compounds was carried out using receptor binding assays and by electrophysiological experiments using whole-cell patch-clamp techniques. Whereas none of these compounds significantly affected GABA(B) receptor sites or GABA uptake, they did show affinity for the GABA(A) receptor site. While alkyl or benzyl substitution, compounds 7a-h, provided receptor affinities comparable with that of 5 (K(i) = 9.1 microM), diphenylalkyl and naphthylalkyl substitution, as in compounds 7m-t, resulted in a dramatic increase in affinity relative to 5. The 3,3-diphenylpropyl and the 2-naphthylmethyl analogues, compounds 7s and 7m, respectively, showed the highest affinities of the series (K(i) = 0.074 microM and K(i) = 0.049 microM). In whole-cell patch-clamp recordings from cultured cerebral cortical neurons, all of the tested compounds were able to inhibit the effect of the specific GABA(A) agonist isoguvacine (1), compounds 7m and 7s showing antagonist potency (IC(50) = 0.37 microM and IC(50) = 0.02 microM) comparable with or markedly higher than that of the standard GABA(A) antagonist 4 (IC(50) = 0.24 microM). Highly potent convulsant activity was demonstrated in mice with compounds 7m (ED(50) = 0.024 micromol/kg) and 7s (ED(50) = 0.21 micromol/kg) after intracerebroventricular administration, whereas no effects were found after subcutaneous administration. According to a previously proposed pharmacophore model for GABA(A) receptor agonists, a receptor cavity in the vicinity of the 4-position of the 3-isoxazolol ring in 4-PIOL exists. A molecular modeling study, based on compounds 7o,m,l,q,s, was performed to explore the dimensions and other properties of the receptor cavity. This study demonstrates the importance of the arylalkyl substituents in 7m and 7s and the considerable dimensions of this proposed receptor cavity.     

Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro

Treatment failures are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa when triple therapy including metronidazole is used. In patients with treatment failure and metronidazole-resistant H. pylori, a higher eradication rate for H. pylori was found after secondary treatment with bismuth/ranitidine in combination with antibiotics including metronidazole, compared with the same antibiotics combined with a standard dose of omeprazole. This agrees with our previous finding that bismuth was able to reduce the susceptibility of H. pylori to metronidazole. In this study, we have found that nizatidine, an H(2)-receptor antagonist, is also able to reduce the susceptibility of H. pylori to metronidazole in vitro, despite having no direct inhibitory effect on the growth of H. pylori. This agrees with earlier findings that compounds having the ability to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit the activity of fumarate reductase of H. pylori. This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could be an inhibition of a proton pump in H. pylori. Reversal of antimicrobial resistance with the help of different non-antibiotics seems to be possible by using quite different compounds, and is therefore to be explained by different molecular mechanisms.