Relationship between zona pellucida-induced acrosome reaction,sperm morphology,sperm-zona pellucida binding,and in vitro fertilization

OBJECTIVE: To evaluate the possible relationships between sperm morphology, acrosome responsiveness to solubilized human zona pellucida, and sperm-zona binding potential among [1] consecutive andrology referrals and [2] randomly selected in vitro fertilization (IVF) cases. DESIGN: Prospective analytical study. SETTING: Academic training hospital.Randomly selected couples consulting for infertility. INTERVENTION(S): Acrosome reaction response to solubilized human zona pellucida was recorded. MAIN OUTCOME MEASURE(S): We determined the difference in the percentage of sperm that acrosome reacted after exposure to solubilized zona pellucida and spontaneous acrosome reaction. The results were expressed as percentage zona induced acrosome reaction (ZIAR). RESULT(S): Data were analyzed using correlation coefficients (r) and receiver operator characteristics (ROC curve analyses). The ROC curve analyses indicated ZIAR to be a sensitive indicator for fertilization failure during IVF therapy, with sensitivity and specificity of 81% and 75%, respectively. For andrology referrals, a positive and statistically significant correlation existed between ZIAR data and sperm morphology (r = 0.65) and sperm-zona binding (r = 0.57). CONCLUSION(S): ZIAR results provide further information regarding dysfunctional sperm and can be used as an additional diagnostic test. Our results predicted fertilization failure during IVF treatment.     

Development of a LC method for pharmaceutical quality control of the antimetastatic ruthenium complex NAMI-A

Imidazolium trans-tetrachloro(dimethylsulfoxide)imidazoleruthenium(III) (NAMI-A) is a novel ruthenium complex with selective activity against metastases currently in Phase I clinical trials in the Netherlands. Pharmaceutical quality control of NAMI-A drug substance and lyophilized product warranted the development of an assay for determination and quantification of NAMI-A and degradation products. A high performance liquid chromatography (HPLC) method was developed, consisting of a C18 column with 0.50 mM sodium dodecylsulfate in 3% methanol at pH 2.5 (acidified using trifluoromethanesulfonic acid) as the mobile phase and UV-detection at 358 nm. The HPLC method was proven to be linear, accurate and precise. Stress testing showed that degradation products were separated from the parent compound. By combining results of nuclear magnetic resonance (NMR) and HPLC experiments, one degradation product was identified as the mono-hydroxy species of NAMI-A. HPLC analysis with off-line detection of the eluate with flameless atomic absorption spectrometry (F-AAS) showed that under most conditions, all ruthenium-containing compounds show a peak in the HPLC chromatogram and that all ruthenium applied to the column is recovered quantitatively. For completely degraded solutions of NAMI-A some ruthenium is retained on the column. Suitability of the HPLC method for the pharmaceutical quality control of NAMI-A lyophilized product was demonstrated.     

Continuing education: the 1998 Survey of the Royal Australasian College of Dental Surgeons

BACKGROUND: Continuing education (CE) is an essential professional activity. In the last decade, CE has been actively pursued by the medical profession in Australia and abroad. However, the uptake of CE in dentistry has been much slower and there is minimal Australian data on dental CE. METHODS: To determine the level of CE activity, in 1998, postal questionnaires were sent to all fellows of the Royal Australasian College of Dental Surgeons. The responses were analysed. RESULTS: There was a high response rate (90 per cent) but a moderate usable rate (54 per cent). The results show a biphasic distribution between high and low CE activity. The average amount of activity of those involved in CE was 116 hours per year, above the usually accepted minimum of 100 hours/year. Some groups, particularly members of the specialist divisions of oral and maxillofacial surgeons (215 hours) and periodontists (205 hours), have high levels of CE. However, approximately 25 per cent of college fellows reported little or no CE activity. The survey revealed that inactive fellows are more likely to be older and in general practice. Inactive fellows were also tardy in replying to the questionnaire. CONCLUSION: The high activity CE group needs to be recognised and encouraged to continue. Specific plans to help the low CE activity group should be developed. Although these findings relate directly to the Royal Australasian College of Dental Surgeons, they are presented as they have implications for the dental profession at large.     

Magnetic resonance features of focal nodular hyperplasia of the liver

The magnetic resonance imaging (MRI) features of 11 biopsy-proven lesions of focal nodular hyperplasia (FNH) of the liver were reviewed retrospectively. Only three lesions showed atypical features. It is believed MRI can reliably differentiate FNH from other liver tumours when strict criteria are fulfilled.     

Ethanol consumption produces a small increase in circulating miR-122 in healthy individuals

Introduction: MicroRNA 122 (miR-122) is a new circulating biomarker for liver injury, which increases earlier than conventional markers in patients with acetaminophen hepatotoxicity. However, as co-ingestion of ethanol is common with drug overdose, a confounding effect of acute ethanol consumption on serum miR-122 must be examined. Methods: Blood was collected from healthy volunteers before and after recreational consumption of ethanol. Routine biochemistry and haematology measurements were performed, and serum miR-122 was measured by qPCR. The primary outcome was the difference in serum miR-122 with ethanol consumption. Results: We recruited 18 participants (72% male). Their mean serum ethanol concentration was 113?mg/dl (95% confidence interval [CI] 91–135?mg/dl) after consuming ethanol. Serum miR-122 increased from a mean of 71.3 million (95% CI 29.3–113.2 million) to 139.1 million (95% CI 62.6–215.7 million) copies/ml (2.2-fold increase). There was no significant difference in serum alanine aminotransferase activity before and after ethanol consumption. Conclusion: miR-122 increased with moderate ethanol consumption, but the fold change was modest. As increases with acetaminophen toxicity are 100- to 10 000-fold, moderate ethanol intoxication is unlikely to confound the use of this biomarker of hepatotoxicity.     

Visit-to-visit lipid variability: Clinical significance,effects of lipid-lowering treatment,and (pharmaco) genetics

In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial. While we identified suggestive associations (P < 1 × 10^?6) at 3 different loci (KIAA0391, amiloride-sensitive cation channel 1 neuronal [ACCN1], and Dickkopf WNT signaling pathway inhibitor 3 [DKK3]), previously published data from the genome-wide association study literature did not suggest plausible mechanistic pathways. Given the large degree of both clinical and methodological heterogeneity in the literature, additional research is needed to harmonize visit-to-visit variability parameters across studies and to definitively assess the possible role of (pharmaco)genetic factors.     

Physical therapy in Parkinson's disease: Evolution and future challenges

Even with optimal medical management using drugs or neurosurgery, patients with Parkinson's disease (PD) are faced with progressively increasing mobility problems. For this reason, many patients require additional physical therapy. Here, we review the professional evolution and scientific validation of physical therapy in PD, and highlight several future challenges. To gain insight in ongoing, recently completed or published trials and systematic reviews, we performed a structured literature review and contacted experts in the field of physical therapy in PD. Following publication of the first controlled clinical trial in 1981, the quantity and quality of clinical trials evaluating the efficacy of physical therapy in PD has evolved rapidly. In 2004 the first guideline on physical therapy in PD was published, providing recommendations for evidence‐based interventions. Current research is aiming to gather additional evidence to support specific intervention strategies such as the prevention of falls, and to evaluate the implementation of evidence into clinical practice. Although research focused on physical therapy for PD is a relatively young field, high‐quality supportive evidence is emerging for specific therapeutic strategies. We provide some recommendations for future research, and discuss innovative strategies to improve the organization of allied health care in PD, making evidence‐based care available to all PD patients. © 2008 Movement Disorder Society