Effects of danazol on mineral homeostasis in normal postmenopausal women: preliminary communication.

The effects of danazol on calcium homeostasis in normal postmenopausal women was examined in a 14-day study utilizing a dosage of 800 mg per day. Danazol caused significant falls in plasma ionized calcium and in the fasting urinary calcium/creatinine ratio, indicating inhibition of bone resorption. Retention of phosphate was also observed as expected with this anabolic agent. The plasma total alkaline phosphatase was also depressed by the drug, which had no effect on hepatocellular function as measured by plasma AST. Certain effects induced by treatment with danazol were still apparent two weeks after cessation of treatment. The drug was well tolerated and androgenic side effects were not seen. It is suggested that the minimal dose regimen of danazol which exerts a calcium-sharing effect should be identified, and that this regimen should be considered for use in a prospective study of the effects of danazol on bone mineral content in the postmenopause.     

In vitro cytotoxicity and phototoxicity of N-piperazinyl quinolone derivatives with a 2-thienyl group.

We examined the cytotoxic potential of nine N-[2-substituted-2-(2-thienyl)ethyl] piperazinyl quinolone derivatives on human oral epithelial mouth carcinoma (KB) and human squamous carcinoma (A431) cell lines. Phototoxic properties of these compounds were also evaluated by mouse 3T3 fibroblast under ultraviolet-A (UVA) irradiation. The percent of cell viability was evaluated by MTT assay. Compound 6 having a 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] group attached to N4 position of piperazine ring of enoxacin showed the highest cytotoxicity potential on both A431 and KB cell lines (IC50 of 3.11+/-0.52 and 4.91+/-1.94 microg/ml, respectively). While some of the other tested compounds exhibited clear phototoxic potential in 3T3 cell line, compound 6 showed only a minor potential of phototoxicity. These findings suggest the high potential of 4-[2-(phenylmethoxyimino)-2-(2-thienyl)ethyl] derivative of enoxacin as a cytotoxic compound with low potency of phototoxic reactions. The mentioned chemical was identified to be of special interest for further characterization.     

Hyperglycemic crises in diabetes mellitus: diabetic ketoacidosis and hyperglycemic hyperosmolar state.

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) potentially are fatal but largely preventable acute metabolic conditions of uncontrolled diabetes, the incidence of which continues to increase. Mortality from DKA has declined remarkably over the years because of better understanding of its pathophysiology and treatment. The mortality rate of HHS remains alarmingly high, however, owing to older age and mode of presentation of patients and associated comorbid conditions. DKA and HHS also are economically burdensome; therefore, any resources invested in their prevention would be rewarding.     

The effects in the rat of two fragments of parathyroid hormone-related protein on uterine contractions in situ.

Synthetic parathyroid hormone fragment PTH(1-34) has been reported recently to inhibit uterine contractions stimulated by a variety of agonists. We have studied the effect in this system of the parathyroid hormone-related protein fragment PTHrP(1-34) which shows 60% homology with PTH over the first thirteen amino acid residues. The effects of two different PTHrP fragments on acetylcholine-stimulated uterine contractions in vitro were studied. Whereas synthetic hPTHrP(75-86 amide) (10(-9)-10(-7) M) was without effect, synthetic hPTHrP(1-34) (10(-9)-10(-7) M) was capable of inhibiting, in a dose-related fashion, uterine muscle contractions precontracted with 10(-6) M-acetylcholine. In a second series of experiments the bovine PTH(3-34) fragment itself was shown to have no stimulatory effect on acetylcholine-stimulated contractions. Also this fragment in an equimolar concentration (10(-7) M) failed to antagonize the effects of PTHrP(1-34) on acetylcholine-stimulated uterine contractions. However, a 100-fold excess molar concentration of bPTH(3-34) (10(-6) M) completely abolished the inhibitory action of hPTHrP(1-34) (10(-8) M) on acetylcholine-stimulated uterine contractions. These results clearly show that the inhibitory action of PTH(1-34) and PTHrP(1-34) on uterine contractions depends on the integrity of the amino-terminal region of the molecule.     

Diabetes prevalence in England, 2001--estimates from an epidemiological model.

AIMS: To estimate the total prevalence of diabetes mellitus (diagnosed and undiagnosed) at national, regional and local level in England to support health-care planning and delivery. METHODS: An epidemiological model was constructed by applying age-sex-ethnic-specific reference prevalence rates from epidemiological studies to resident populations (2001 census) of England at national, regional, and local authority/Primary Care Trust levels. RESULTS: Estimated prevalence of total diabetes for all persons in England was 4.41% in 2001, equating to 2 168 000 persons. Type 2 diabetes was estimated to affect 2 002 000 persons (92.3%) and Type 1 diabetes 166 000 persons (7.7%). Diabetes prevalence was estimated to be higher in women (5.17%) than men (3.61%). People from ethnic minority groups had higher crude prevalence than White Europeans (4.29, 5.69, 6.63 and 2.13% among White Europeans, Black African/Caribbeans, South Asians and 'other' groups, respectively). Prevalence increased sharply with age (0.33, 3.37 and 13.92%, respectively, in those aged 0-29, 30-59 and 60+ years). The model allows use of user-defined population denominator estimates to derive numbers and prevalence of people with diabetes for a given local population group, such as at ward or general practice level. CONCLUSIONS: Self-reported diabetes prevalence estimates from community surveys underestimate the true burden of diabetes. The model can be used to derive the expected total prevalence of diabetes in health areas that lack reliable data to facilitate the implementation of the National Service Framework for diabetes. It will also allow estimates of future diabetes prevalence to be derived, and can potentially be used for prevalence estimates in all of the UK.     

Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery.

OBJECTIVE: The purpose of this study was to examine the effect of peri-operative red blood cell (RBC) transfusion on 30-day and 1-year mortality following coronary artery bypass grafting (CABG). METHODS: We retrospectively analysed 3024 consecutive patients who underwent isolated CABG between January 1999 and December 2001. Patient records were linked to the National Strategic Tracing Service, which records all mortality in the UK. Thirty-day and 1-year mortality were derived from Kaplan-Meier curves. Confounding variables were controlled for by constructing a propensity score for the probability of receiving a transfusion from core patient characteristics including the lowest recorded laboratory haemoglobin (LL Hb) from a clinical chemistry database (C statistic 0.81). The propensity score and the comparison variable (transfusion versus no transfusion) were included in a Cox proportional hazards analysis, allowing calculation of adjusted hazard ratios (HR) and Kaplan-Meier survival curves. RESULTS: Nine hundred and forty (31.1%) patients received RBC transfusion during or within 72h of surgery. Predictors of the need for transfusion were LL Hb and lower body mass index, use of cardiopulmonary bypass, female sex, number of grafts, renal dysfunction, increased age, extent of disease, and prior CABG; these factors were all included in the propensity score. After 1-year of follow-up, 122 (4.03%) deaths occurred. The crude HR for 1-year mortality in patients transfused was 3.0 (P<0.001). After adjusting for the propensity score, re-operation for bleeding, peri-operative blood loss and post-operative complications, the adjusted 30-day mortality was 1.9% in transfused patients compared to 1.1% in patients not transfused (P<0.05). The adjusted HR for 1-year mortality in patients transfused was 1.88 (P<0.01). CONCLUSIONS: Peri-operative RBC transfusion after CABG is associated with an increased risk of mortality during a 1-year follow-up period, with a large proportion of deaths occurring within 30-days.     

Hollow viscus injury in children: Starship Hospital experience

Starship Children's Hospital in Auckland, New Zealand, serves a population of 1.2 million people and is a tertiary institution for pediatric trauma. This study is designed to review all cases of abdominal injury (blunt and penetrating) that resulted in injury of a hollow abdominal viscus including the stomach, duodenum, small intestine, large intestine and urinary bladder. The mechanism of injury; diagnosis and outcome were studied. This was done by retrospective chart review of patients admitted from January 1995 to December 2001. Thirty two injuries were found in 29 children. The age ranged from 7 months to 15 years with boys represented more commonly. Small bowel was the most frequently injured hollow viscus. Computerized Tomography (CT scan) is an extremely useful tool for the diagnosis of HVI.     

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.