Initiation of hormone replacement therapy after acute myocardial infarction is associated with more cardiac events during follow-up.

OBJECTIVES: This study explored the association between the initiation of hormone replacement therapy (HRT) and early cardiac events (<1 year) in women with a recent myocardial infarction (MI). BACKGROUND: Observational studies have linked postmenopausal hormone use with a reduced risk of death from heart disease. However, a recent randomized trial of HRT found no long-term benefit, primarily due to an increase in cardiac events in the first year. METHODS: The Coumadin Aspirin Reinfarction Study (CARS) database contains information on HRT use and menopausal status for women with a recent MI. We classified the 1,857 postmenopausal women in CARS as prior/current HRT users if they took HRT before enrollment, new users if they began HRT during the study period or never users. We assessed the incidence of cardiac events (death, MI, unstable angina [UA]) during follow-up. RESULTS: In our cohort, 28% (n = 524) used HRT at some point. Of these, 21% (n = 111) began HRT after their MI. New users had a higher incidence of death/MI/UA (41% vs. 28%, p = 0.001) during follow-up than never users, largely due to a higher incidence of UA (39% vs. 20%, p = 0.001). After adjustment, new users still had a significantly higher risk of death/MI/UA than never users during follow-up (relative risk [RR] = 1.44 [1.05-1.99]). Prior/current users had no excess risk of the composite end point after adjustment. Users of estrogen/progestin had a lower incidence of death/MI/UA during follow-up than users of estrogen only (RR = 0.56 [0.37-0.85]). CONCLUSIONS: Postmenopausal women who initiated HRT after a recent MI had an increased risk of cardiac events largely due to excess UA during follow-up.     

Gastrointestinal adaptation to diets of differing fat composition in human volunteers.

The effect of a low fat diet (9 MJ) v a high fat diet (19.26 MJ), each consumed separately for four and 14 days, on gastric emptying and mouth to caecum transit time of a high fat test meal and body weight and satiety were examined in groups of 10 and six normal male volunteers. The half time for gastric emptying (t1/2) and the mouth to caecum transit time of a high fat test meal was significantly faster after the high fat diet than the low fat diet when consumed for 14 days (t1/2=98 (80-116) v 147 (88-206) minutes (median (range)), p less than 0.05; mouth to caecum transit time 240 (130-350) v 360 (200-520) minutes, p less than 0.05), but not when consumed for only four days. The mean (SEM) body weight of all subjects significantly increased during the 14 day high fat diet (74.7 (1.3) v 72.7 (1.6) kg, p less than 0.05) but was not influenced during the consumption of the low fat diet. When subjects were given an appetising meal to consume on the day that they had consumed the transit test meal, they ate similar amounts irrespective of their recent dietary history, though the eating rate was significantly slower after the high fat diet (mean (SEM)) 46.7 (1.9) v 71.3 (14.8)/min, p less than 0.05). Maintaining normal subjects on a high or low fat diet for two weeks resulted in a desensitisation or sensitisation respectively of the mechanisms by which nutrients regulate gastrointestinal transit. These findings emphasise the importance of the recent dietary history in the interpretation of gastric emptying and small bowel transit time data.     

Oral health care needs and oral health‐related quality of life (OHIP‐14) in homeless people

Daly B, Newton T, Batchelor P, Jones K. Oral health care needs and oral health‐related quality of life (OHIP‐14) in homeless people. Community Dent Oral Epidemiol 2010. © 2009 John Wiley & Sons A/S Abstract – Objectives: The aim of this study was (i) to determine the oral health status and oral health care needs of this population, (ii) to assess oral health‐related quality of life using OHIP‐14 and (iii) to explore whether there is a relationship between oral health status and oral health‐related quality of life. Methods: A convenience sample was drawn from eight facilities catering for homeless people in south east London. Participants were invited to attend an outreach dental clinic and receive a clinical oral health and treatment needs assessment. The impact of oral disease was assessed using OHIP‐14. Results: There were 102 people from a range of vulnerable housing situations invited to participate in the study. The mean age was 39.5 (SD ± 12.3) and 92% (n = 92) were men. The mean DMFT of dentate participants (n = 94) was 15.5 (SD ± 7.6), mean DT was 4.2 (SD ± 5.2), mean MT was 6.8 (SD ± 6.0) and mean FT was 4.6 (SD ± 4.8). Normative needs were extensive with 76% having a restorative need, 80% having a need for oral hygiene measures and periodontal treatment and 38% having a prosthetic treatment need. Ninety one per cent of homeless people experienced at least one impact and the mean number of impacts (n = 90) was 5.9 (SD ± 4.8).The most commonly experienced oral health‐related quality of life impacts were in the dimension of pain, with aching in the mouth having a prevalence of 65% and discomfort while eating foods having a prevalence of 62%. Forty‐four per cent felt handicapped by their oral condition. The experience of oral impact had only a slight relationship with clinical status and there were no differences in clinical status or oral impact by vulnerability of housing situation. Conclusions: Oral health care needs were extensive and greater than that of the general population in the UK, although disease levels were similar. While homeless people experienced many more oral impacts (as measured with OHIP‐14) compared with adults of the same age in the general population in the UK, there was only a slight relationship with clinical status and oral health‐related quality of life.     

An improved method of right ventricular gated equilibrium blood pool radionuclide ventriculography

Gated blood pool radionuclide ventriculography provides a means for obtaining repeated studies of both cardiac ventricles with a single dose of radionuclide. Quantitative assessment of right ventricular (RV) function using this technique has been complicated by several technical problems. We describe a new method of RV blood pool analysis which attempts to solve these problems using well-established concepts for left ventricular (LV) blood pool analysis: (1) variable regions of interest; (2) computer edge detection with operator intervention; and (3) computer selected background. Results showed a strong linear correlation between gated first pass RV ejection fraction (RVEF) and the gated blood pool RVEF (n = 22; r = 0.93; blood pool RVEF = 0.03 + 0.89 X first pass RVEF; Sy.x = 0.04). There was also a strong linear correlation between LV and RV stroke counts in patients without valvular regurgitation, intracardiac shunts, or ventricular aneurysms (n = 19; r =0.86; RV counts = 72 + 0.94 X LV counts; Sy.x = 116). In terms of both of these validation standards this method proved superior to three published methods of RV blood pool analysis that used hand-drawn regions, and is suitable for analysis of rest, exercise, and intervention studies of RV function.     

High prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis

Summary. Recent findings have indicated the importance of factor V (FV) in causing resistance to activated protein C (APC) in a high proportion of patients with venous thrombosis. This prompted us to investigate whether resistance could be due to defective inactivation of FVa by APC. Consequently, we amplified a 3.2 kb fragment of the FV gene sequence encoding the heavy chain APC cleavage site. DNA analysis showed a guanine to adenine transition at nucleotide 1691 in all affected members of two families with inherited APC resistance associated with thrombosis and confirmed suspected homozygosity in two individuals. The mutation, in heterozygous form, was also found in ˜3.5% of our normal population (n = 144) and correlated with low APC resistance. The high prevalence of this mutation suggests that it may be a major contributory factor in early thrombosis.     

Aplastic anaemia following exposure to 3,4-methylenedioxymethamphetamine ('Ecstasy')

Summary. We report two cases of aplastic anaemia following exposure to 'Ecstasy' (MDMA, 3,4-methylenedioxymethamphetamine). In both cases the aplastic anaemia resolved spontaneously 7–9 weeks after presentation. Long-term bone marrow culture study of one patient demonstrated complete normalization of haemopoiesis at time of haematological recovery, suggesting either that damage to the haemopoietic stem cell had been only transient, or that a more mature, committed progenitor cell was the target. Because MDMA may have been a factor in the aetiology of the bone marrow suppression in these two cases, we recommend close haematological monitoring of young adults presenting with toxicity from MDMA, and a detailed history of exposure to recreational drugs in all new patients presenting with aplastic anaemia.     

Evidence for heterogeneity between pre- and postjunctional alpha-2 adrenoceptors using 9-substituted 3-benzazepines

A series of alpha adrenoceptor antagonists, including both reference compounds and the novel benzazepine antagonists, SK&F 86466 (6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine) and two of its 9-substituted derivatives, SK&F 101253 and SK&F 104078, were tested in vitro for affinity at central and peripheral alpha adrenoceptor subtypes. Peripheral alpha-1 adrenoceptor antagonist potency of these agents, as assessed by the receptor dissociation constant (KB) against norepinephrine-induced contraction in the rabbit aorta, correlated with the Ki value for inhibition of [3H]prazosin binding to central alpha-1 adrenoceptors in rat brain homogenates. Central alpha-2 adrenoceptor affinity, measured as the Ki for inhibition of [3H]rauwolscine binding to rat brain homogenates, correlated well with antagonist activity at peripheral postjunctional alpha-2 adrenoceptors as reflected by the KB against B-HT 920-induced contraction in canine saphenous vein. The 9-substituted benzazepines, SK&F 101253 and SK&F 104078, produce preferential blockade of postjunctional vs. prejunctional alpha-2 adrenoceptors in peripheral models. The high affinity of SK&F 104078 for postjunctional alpha-2 adrenoceptors in the canine saphenous vein was confirmed by its ability to inhibit [3H]rauwolscine binding to postjunctional alpha-2 adrenoceptors in this tissue. The observation that the Ki values for these antagonists against [3H] rauwolscine binding correlate with their KB values at the postjunctional alpha-2 adrenoceptors, rather than those at the prejunctional neuroinhibitory alpha-2 adrenoceptor, suggests a pharmacologic similarity between the postjunctional vascular alpha-2 adrenoceptors and the central [3H]rauwolscine binding site.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanism of action and in vitro and in vivo activities of S-6123, a new oxazolidinone compound.

The in vitro activity of S-6123, a synthetic antimicrobial compound of the new oxazolidinone series, was compared with those of other orally administered agents against 328 clinical isolates. The compound was moderately active (MICs, 16 to 64 micrograms/ml) against 90% of staphylococci, nonenterococcal streptococci, and Haemophilus influenzae, including strains resistant to beta-lactam antibiotics. S-6123 was minimally active against enterococci and facultative gram-negative bacilli. Nevertheless, the compound had significant activity in a lethal rat Escherichia coli peritonitis model at serum concentrations of one-tenth the MIC against the infecting organism. The drug demonstrated only bacteriostatic activity against susceptible organisms. Studies to define the mechanism of antibacterial action revealed that S-6123 inhibited ribosomal protein synthesis without inhibiting DNA or RNA synthesis. This compound represents a new series of antibacterial agents not related to any other antibacterial compound of natural or synthetic origin.     

Training vs practice: A tale of opposition in acute cholecystitis

Acute cholecystitis is one of the most common surgical diagnoses encountered by general surgeons. Despite its high incidence there remains a range of treatment of approaches. Current practices in biliary surgery vary as to timing, intraoperative utilization of biliary imaging, and management of bile duct stones despite growing evidence in the literature defining best practice. Management of patients with acute cholecystitis with early laparoscopic cholecystectomy (LC) results in better patient outcomes when compared with delayed surgical management techniques including antibiotic therapy or percutaneous cholecystostomy. Regardless of this data, many surgeons still prefer to utilize antibiotic therapy and complete an interval LC to manage acute cholecystitis. The use of intraoperative biliary imaging by cholangiogram or laparoscopic ultrasound has been demonstrated to facilitate the safe completion of cholecystectomy, minimizing the risk for inadvertent injury to surrounding structures, and lowering conversion rates, however it is rarely utilized. Choledocholithiasis used to be a diagnosis managed exclusively by surgeons but current practice favors referral to gastroenterologists for performance of preoperative endoscopic removal. Yet, there is evidence that intraoperative laparoscopic stone extraction is safe, feasible and may have added advantages. This review aims to highlight the differences between existing management of acute cholecystitis and evidence supported in the literature regarding best practice with the goal to change surgical practice to adopt these current recommendations.     

Effects of captopril and a combination of hydralazine and isosorbide dinitrate on myocardial sympathetic tone in patients with severe congestive heart failure.

Changes in circulating catecholamines and transmyocardial catecholamine balance associated with improved left ventricular function were studied in patients with chronic heart failure after treatment with captopril (10 patients) and hydralazine in combination with isosorbide dinitrate (eight patients). Cardiac performance improved in response to both captopril and hydralazine-nitrate treatment. The systemic haemodynamic effects were also qualitatively similar, but the hydralazine-nitrate combination caused a greater increase in cardiac index and heart rate. Captopril did not change arterial adrenaline concentrations (0.63 to 0.60 nmol/l), arterial noradrenaline (4.2 to 3.9 nmol/l), or net transmyocardial noradrenaline release (390 to 317 pmol/min), while hydralazine-nitrate increased arterial adrenaline (0.91 to 1.47 nmol/l) and transmyocardial noradrenaline release (225 to 554 pmol/min). Although both captopril and hydralazine-nitrate treatment improve left ventricular performance in patients with chronic heart failure, hydralazine-nitrate enhances cardiac sympathetic tone and captopril does not. The clinical relevance of these findings, however, is not known.