Ketoconazole Impairs Early Pregnancy and the Decidual Cell Response via Alterations in Ovarian Function

Ketoconazole (KCZ) is an imidazole antifungal agent that alsoaffects P450 enzymes of the mammalian steroidogenic system.Several steps in the ovarian steroidogenesis pathway are knownto be inhibited by KCZ, but previous work has failed to addressthe ramifications of such inhibition with respect to early pregnancy.In initial studies, Holtzman rats (8–10/group) were administered10–100 mg/kg KCZ during days 1–8 of pregnancy. Onday 9, evaluations revealed a reduction at both 75 and 100 mgKCZ/kg in the number of implantation sites and serum progesteronelevels as well as an increase in ovarian weight The decidualcell response (DCR) was blocked by KCZ in parallel with decreasedserum progesterone and increased ovarian weight, indicatingdirect interference with uterine function. KCZ had no effectwhen given to long-term-ovariectomized rats that were hormonesupplemented to permit the DCR, indicating that the ovary wasat least one site of KCZ action on early pregnancy. Measurementof ovarian progesterone production in vitro from ovaries removedfrom rats treated in vivo with KCZ indicated a decline in progesteroneproduction, suggesting a direct effect of KCZ on ovarian steroidogenesis.These data demonstrate that KCZ can compromise early pregnancyand appears to do so by inhibiting progesterone synthesis inthe ovary.     

Right ventricular-pulmonary arterial interactions

The application of pulsatile models to hemodynamic data has made possible a more complete understanding of the relationship of pulmonary pressure and flow. To review the genesis of these concepts, the unique characteristics of the pulmonary artery and right ventricle are outlined as a basis for understanding why differences in their pulsatile properties from the systemic circuit must exist. The pulmonary impedance spectrum is introduced and the concept of optimal right ventricular-pulmonary artery coupling is explored based on a review of extensive experimental data. Finally, available studies of normal pulmonary impedance in man and abnormal impedance in human disease states are reviewed, with emphasis on disturbances in optimal ventricular-vascular coupling. The important implications of these concepts for understanding and treatment of cardiovascular disease are developed.     

Anomalies in dual energy X-ray absorptiometry measurements of total-body bone mineral during weight change using Lunar, Hologic and Norland instruments

A previous study showed that measurements of total-body bone mineral changes made with a Hologic QDR 1000W were unreliable when the subjects underwent weight change. The study has been extended to dual energy X-ray absorptiometry (DXA) apparatus from other manufacturers. Re-analysis of published results during weight loss using a Lunar DPX showed that they varied with the software used. Using the Extended mode, there was a 1% loss of bone mineral areal density (BMD), but no significant change in bone mineral content (BMC) or bone area (BA) following a weight loss of 16 kg, whereas the use of the Standard mode led to a larger fall of BMC and BMD. Similar findings arose from the consideration of two studies using Norland XR 26 HS absorptiometers. On the other hand, separation of two groups with similar weight changes from the population studied with a Hologic QDR 1000W confirmed that BMC changed directly with weight, but there was an inverse relationship for BMD, owing to an inappropriate change of BA. The use of Hologic Enhanced and Standard software modes led to significant differences in initial readings and measured changes. With each instrument there was a strong correlation between changes in BA and changes in BMC. When 6 kg of lard was wrapped around the limbs of volunteers or a semi-anthropomorphic phantom to simulate weight change, there were spurious increases of measured BMC and BA by about 5% with each instrument. There were no changes of BMD with Lunar, variable results with Norland, but decreases with Hologic. The results observed in vivo could be explained by the effects of fat changes, without there being any real change of bone mineral. Changes of BMD in the skeleton of the phantom were underestimated with all three brands. The anomaly observed with the Hologic QDR 1000W is less apparent with a Lunar DPX or a Norland XR 26, but there are sufficient uncertainties for all total-body measurements during weight change to be treated with suspicion.     

Relation of percutaneous coronary intervention of complex lesions to clinical outcomes (from the NHLBI Dynamic Registry)

Advances in percutaneous coronary intervention (PCI) have reduced complications but expanded indications. We used the National Heart, Lung, and Blood Insitute Dynamic Registry to determine clinical outcomes up to 1 year after PCI in 2,839 patients with at least 1 treated complex lesion (defined as a lesion showing evidence of thrombus, calcification, bifurcation or ostial location, or chronic occlusion) and 1,790 patients with only simple lesions treated. Complex lesion interventions were associated (p <0.05) with more sustained major dissections, distal embolization, side branch occlusion, and persistent flow reduction. Patients with treated complex lesions had a lower procedural success rate (93.8% vs 97.3%, p <0.001) and increased in-hospital rates (p <0.001) of death (2.0% vs 0.6%), death/myocardial infarction [MI] (5.2% vs 2.4%), or death/MI/coronary artery bypass graft [CABG] surgery (6.5% vs 2.9%). After adjustment for potential confounders, patients treated for multiple complex lesions were more likely to experience the in-hospital combined end points of death/MI (odds ratio 3.22, 95% confidence interval 2.10 to 4.92), or death/MI/CABG (odds ratio 2.55, 95% confidence interval 1.71 to 3.80). At 1 year, patients with treated complex lesions were more likely (p <0.001) to die (6.2% vs 3.7%), suffer death/MI (11.7% vs 7.5%), or death/MI/CABG/repeat PCI (27.2% vs 23.4%). Patients treated for multiple complex lesions were approximately 50% more likely to die or to have major adverse events than with patients only treated for simple lesions. An increased in-hospital adverse clinical event rate was independently noted for thrombotic, bifurcation, and calcified lesions, and bifurcation lesions had worse long-term event rates.     

An unusual case of left internal mammary artery ostial disease: clarifying role of intravascular ultrasound.

Stenosis at the origin of the left internal mammary artery graft is rare. We present a case with a suspected stenosis involving the origin of the left internal mammary artery that conventional angiography failed to demonstrate convincingly. Intravascular ultrasound illustrated a severe stenosis and the patient underwent successful stenting of the left internal mammary artery origin. The intravascular ultrasound finding of a dissection flap, just distal to the left internal mammary artery origin, suggests that local trauma to the vessel from prior catheterization procedures may have been responsible for the progressive narrowing at the left internal mammary artery ostium.     

Dietetic intervention for inpatients on fluid‐only diets helps to achieve nutritional requirements

Aim

The present study aimed to assess whether dietetic intervention helps patients on fluid‐only diets to meet their energy and protein requirements. This topic has not been previously investigated.

Methods

A quasi‐experimental study of 57 patients receiving fluid‐only diets was conducted at The Townsville Hospital. The fluid consumption of participants was observed over 24 hours and was used to calculate total energy and protein intakes. The percentage of protein and energy requirements met was compared between patients receiving dietetic intervention and patients who were not.

Results

Patients receiving dietetic interventions met a higher percentage of their energy requirements (75.88) than the control group (18.10) based on median intakes (P < 0.001). Patients receiving dietetic intervention also met a higher percentage of their protein requirements (75.99) than the control group (13.80) based on median intakes (P < 0.001). Stratification for age, body mass index (BMI) and fluid diet type showed no change in effect.

Conclusions

This study shows that dietetic intervention enabled patients on fluid‐only diets to meet up to 80% more of their energy requirements and up to 95% more of their protein requirements. These results were consistent across age, BMI and fluid diet type. The significance of these differences has resulted in a change of clinical practice at the study hospital. All patients on fluid‐only diets for three days or longer are now blanket referred for dietetic intervention.     

Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features

The clinical, electrocardiographic, and coronary hemodynamic responses to sequential 90-second occlusions of the left anterior descending coronary artery in 12 patients undergoing elective percutaneous transluminal coronary angioplasty were examined. Transmyocardial lactate metabolism was examined in an additional group of seven patients with clinical and hemodynamic features similar to the first group. We noted that in comparison with the initial balloon occlusion the second occlusion was characterized by less subjective anginal discomfort, less ST segment shift (0.44 +/- 0.13 versus 0.21 +/- 0.07 mV, p = 0.01), and lower mean pulmonary artery pressure (25 +/- 1.0 versus 20 +/- 1.7 mm Hg, p = 0.005). In addition, for the same heart rate-blood pressure product, cardiac vein flow during the second inflation was significantly lower than that recorded during the first inflation (96 +/- 1.4 versus 83 +/- 2.4 ml/min, p = 0.005). Finally, there was significantly less myocardial lactate production during the second inflation (lactate extraction ratio: first inflation, -0.11 +/- 0.03; second inflation, -0.03 +/- 0.02; p = 0.04). We conclude that the lessened clinical, electrocardiographic, hemodynamic, and metabolic evidence of myocardial ischemia during the second of two periods of coronary artery occlusion during percutaneous transluminal coronary angioplasty supports the concept of adaptation to myocardial ischemia (ischemic preconditioning).