Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [¹⁸F]FDG and [¹¹C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).     

Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study

Thiazide diuretics may preserve bone mass and prevent elderly women's osteopenic fractures, but studies have not distinguished between thiazide preparations or examined former users. We performed a case-control study looking at thiazide use and subsequent hip fracture in postmenopausal female members of the Framingham Study cohort. Cases who had experienced a first hip fracture (n = 176) were compared with age-matched controls (n = 672). Results showed a modest protective effect of any recent thiazide use (not significant). However, recent pure thiazide users experienced significant protection against fracture (adjusted odds ratio, 0.31; 95% confidence interval, 0.11 to 0.88), whereas recent users of combination drugs containing thiazides experienced no protection (adjusted odds ratio, 1.16; 95% confidence interval, 0.44 to 3.05). Combination drugs generally contained only 25 mg of hydrochlorothiazide, suggesting that the small amount of thiazide was insufficient to preserve bone mass. Former thiazide users were not protected against fracture. In sum, recent pure thiazide use in women protects against hip fracture.     

THE RELEVANCE OF EVOLUTIONARY PSYCHOLOGY FOR PSYCHOTHERAPY

ABSTRACT The claims made for the contribution of Evolutionary Psychology to psychotherapy are questioned. The relevance of human evolutionary history is not disputed, but it is argued that insufficient account is taken of the unique features of human beings, that the polemical attacks made on the social and human sciences are irrational, that the hypothetical reconstructions of human evolution are frequently arbitrary and biased, and that the extent to which evolved innate'mentalities'are said to determine social roles ignores the evidence for the plasticity of human brains and for social influences in individual development. In its consistent bias in favour of innate rather than learned and culturally formed processes and in its language and assumptions EP underestimates the inherited and acquired capacities of human societies and individuals to change. It fails to take adequate account of the key evolutionary development whereby humans became symbol-making and symbol-using social animals whose individual psychological development involves processes, the understanding of which requires a new theoretical perspective. These features, combined with the absence of a clear model of practice, seriously limit the contribution of EP to psychotherapy.     

Relationship of MAO-A promoter (u-VNTR) and COMT (V158M) gene polymorphisms to CSF monoamine metabolites levels in a psychiatric sample of caucasians: A preliminary report.

Monoamine oxidase A gene promoter (MAOA-uVNTR) and catechol-O-methyltransferase V158M (COMT-V158M) gene functional polymorphisms are reported to be associated with impulsive-aggression, but a biological intermediate effect remains to be determined. This study assessed the association of these polymorphisms with cerebrospinal fluid (CSF) monoamine metabolites as endophenotypes. Ninety-eight Caucasian psychiatric subjects were assessed for Axis I and II diagnosis. Subjects were genotyped for the functional polymorphisms, MAOA-uVNTR and COMT-V158M. CSF was obtained by lumbar puncture. Relationships of the two polymorphism to monoamine metabolites: HVA, 5-HIAA, and MHPG were examined. The higher-expressing MAOA-uVNTR genotype was associated with higher CSF-HVA levels in males only (n = 46) (195.80 pmol/ml, SD = 61.64 vs. 161.13, SD = 50.23, respectively; P = 0.042). No association was found with diagnosis. COMT-V158M had no association with CSF monoamine metabolites. The association of MAOA-uVNTR with dopaminergic activity in males is a preliminary finding that needs to be replicated in a larger sample of Caucasian males and relationships sought with clinical phenotypes. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.     

A simple nutrition screening tool for hemodialysis nurses.

OBJECTIVE: To assess the reliability of a nurse-performed nutrition screening tool (NST) for hemodialysis (HD) patients to identify nutritionally at-risk patients. DESIGN: Tool reliability assessment. SETTING AND PARTICIPANTS: The setting was nine non-hospital private (n = 3) and public (n = 6) HD units in Australia (two rural and seven metropolitan). Participants were 112 HD patients. RESULTS: A total of 112 HD patients (male = 65, female = 47) from 9 non-hospital HD units in Australia (seven metropolitan and two rural) were screened with the NST and the outcome of dietitian referral compared with Standard Dietitians Assessment. The mean age of patients was 57.6 years. Overall, the NST showed a sensitivity of 0.84 (range, 0.71 to 0.94; P < .05) and a specificity of 0.9 (range, 0.82 to 0.98; P < .05). The NST was more sensitive (sensitivity, 0.93 [range, 0.87 to 0.99; P < .05]) and was more specific for men (specificity, 0.92 [range, 0.85 to 0.99; P < .05]). Specificity was very strong in metropolitan patients (specificity, 0.94 [range, 0.87 to 1.01; P < .05]). CONCLUSIONS: The tool was more sensitive and specific than the NST previously reported by the same investigators. The tool is particularly specific in that it screens those patients not requiring dietitian intervention. The use of this tool may benefit HD units that do not have on-site or regular dietetic support to prioritize patients needing dietitian intervention.     

Use of the risk-rescue rating scale with adolescent suicide attempters: A cautionary note

The assessment of the medical lethality and intent of suicide attempts has been considered an important area of research for those interested in suicide. The current study examined the usefulness of the Risk-Rescue Rating Scale with 109 adolescent suicide attempters and found a restricted range of variability, which, in turn, resulted in poor interrater reliability on a number of items. Results suggest that the Risk-Rescue Rating Scale is of limited usefulness with adolescents, and alternative approaches to assessing lethality and suicidal intent with this age group are discussed.     

Prostate thermal therapy with high intensity transurethral ultrasound: the impact of pelvic bone heating on treatment delivery.

PURPOSE: This study was designed to assess pelvic bone temperature during typical treatment regimens of transurethral ultrasound thermal ablation of the prostate to establish guidelines for limiting bone heating. METHODS: Treatment with transurethral planar, curvilinear, and sectored tubular applicators was simulated using an acoustic and biothermal pelvic model that accommodates applicator sweeping, boundary temperature control, and changes in perfusion and attenuation with thermal dose to more accurately model ultrasound energy penetration. The effects of various parameters including power and frequency (5-10 MHz) on bone heating were assessed for a range of prostate cross-sections (3-5 cm) and bone distances (1-3 cm). RESULTS: All devices can produce significant bone heating (temperatures >50 degrees C, thermal dose >240 EM(43 degrees C)) without optimization of applied frequency or power for bone <3 cm from the prostate boundary. In small glands ( approximately 3 cm) increasing operating frequency of curvilinear and planar devices can increase bone temperatures, whereas the tubular applicator can be used at 10 MHz to avoid likely bone damage. In larger prostates (4-5 cm wide) increasing frequency reduces bone heating but can substantially increase treatment time. Lowering power can reduce bone temperature but may increase thermal dose by increasing treatment duration. All applicators can be used to treat glands 4-5 cm with limited bone heating by selecting appropriate power and frequency. CONCLUSIONS: Pubic bone heating during ultrasound thermal therapy of the prostate can be substantial in certain situations. Successful realization of this therapy will require patient-specific treatment planning to optimally determine power and frequency in order to minimize bone heating.     

Multi-detector CT angiography for lower gastrointestinal bleeding: Can it select patients for endovascular intervention?

This is a retrospective review of the results at our institution of using multi-detector CT angiography (CTA) to localise lower gastrointestinal (GI) bleeding. We hypothesised that in our patient population: (i) CTA was unlikely to demonstrate bleeding in patients who were haemodynamically stable; (ii) in haemodynamically unstable patients in whom CTA was undertaken, the results could be used to select patients who would benefit from catheter angiography; and (iii) in haemodynamically unstable patients in whom CTA was undertaken, a subgroup of patients could be identified who would benefit from primary surgical treatment, avoiding invasive angiography completely. A retrospective review was conducted of the clinical records of all patients undergoing CTA for lower GI haemorrhage at our institution between 1 January 2005 and 30 June 2007. Out of the 20 patients examined, 10 had positive CTAs demonstrating the bleeding site. Nine were haemodynamically unstable at the time of the study. Four patients with positive CT angiograms were able to be treated directly with surgery and avoided invasive angiography. Ten patients had negative CTAs. Four of these were haemodynamically unstable, six haemodynamically stable. Only one required intervention to secure haemostasis, the rest stopped spontaneously. No haemodynamically stable patient who had a negative CTA required intervention. CTA is a useful non-invasive technique for localising the site of lower GI bleeding. In our patient population, in the absence of haemodynamic instability, the diagnostic yield of CTA was low and bleeding was likely to stop spontaneously. In haemodynamically unstable patients, a positive CTA allowed patients to be triaged to surgery or angiography, whereas there was a strong association between a negative CTA and spontaneous cessation of bleeding.     

Predictive value of local and core laboratory echocardiographic assessment of cardiac function in patients with chronic stable angina: The ACTION study.

AIMS: To evaluate the relationship between echocardiographic cardiac function and outcome in patients with stable symptomatic angina. METHODS: Baseline echo left ventricular ejection fraction and volume data measured in a central laboratory was available for 7016 patients (92% of the total) participating in the ACTION trial (A Coronary disease Trial Investigating Outcome with Nifedipine GITS). Ejection fraction was also measured by investigators. Evaluation of the different echocardiographic variables was based on adjusted hazard ratios comparing the unfavourable limit of the 90% range of the variable concerned to the favourable limit. RESULTS: The centrally measured ejection fraction was the most powerful predictor of all-cause death (adjusted hazard ratio=2.5), myocardial infarction, any stroke or transient ischaemic attack and overt heart failure (adjusted hazard ratio=4.5). The addition of either end systolic volume or end diastolic volume to ejection fraction did not materially affect the power of prediction. Compared to the central ejection fraction measurement, the investigator-measured ejection fraction was a less powerful predictor for all outcomes considered. CONCLUSION: Routine echocardiography carefully analysed by standardised methods provides useful prognostic information in patients with stable angina, including for total mortality.