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Real-time PCR and linkage studies to identify carriers presenting HPRT deleted gene.

Lesch-Nyhan syndrome (LNS) is an X-linked genetic disorder resulting in hyperuricemia, choreoathetosis, mental retardation, and self-injurious behavior. It is caused by loss of activity of the ubiquitous enzyme hypoxanthine-guanine-phosphoribosyltransferase (HPRT). The biochemical analysis of residual HPRT activity in patients' red blood cells is the first step in LNS diagnosis, and it precedes molecular study to discover the specific mutation. Unfortunately, biochemical diagnosis of healthy carriers is difficult because HPRT enzymatic activity in blood cells is similar in LNS carriers and in healthy people; genetic tests can help reveal mutations at the genomic or cDNA level, whereas gross deletions involving the first or last exons of HPRT gene are not detectable. Until now, a test based on 6-thioguanine-resistant phenotype of HPRT mutant cells from LNS patients is the only method accepted for the diagnosis of any kind of mutation in carriers. In this work, we introduce a new approach to identify carriers of large deletions in HPRT gene using real-time PCR. Results were validated in a blinded manner with a linkage study and with results obtained in Italian families previously analyzed with selective medium test. Real-time PCR analysis clearly confirmed the results obtained by selective medium; linkage data strengthened real time results, allowing us to follow the allele with the mutated HPRT through the family pedigree. We hope that the real-time PCR approach will provide a useful and reliable method to diagnose LNS carriers of large deletions in HPRT gene.

Female↗

Cervical cancer screening in women aged 65 and over.

Pap smear screening is an accepted method of detecting cervical dysplasia or malignancy, and use of this test has been shown to reduce the incidence of invasive squamous cervical cancer in young and middle aged women. Conflicting recommendations exist concerning the screening of women over the age of 65, and little information is available concerning the results of screening in this population. Elderly women are routinely omitted from screening, as it is generally believed that they usually refuse testing. This paper reports a study attempting to evaluate the feasibility of screening in women over the age of 64 attending a large urban outpatient geriatric clinic. It demonstrates that pap smear screening is acceptable to this population, particularly if performed by the usual primary care provider. It also confirms previous reports that women in this age group have had very little screening in the past, and that screening uncovers a large number of abnormalities. Of note is the high rate of false positive smears in this population.

Aged↗

[Required dose of imaging systems--nuclear medicine].

The required dose of imaging systems in nuclear medicine is based upon the statistical properties of radioactive decay. In contrast to the absorbed dose, the radioactivity can be directly and easily measured. The International Commission on Radiological Protection (ICRP) has developed the concept of effective dose. Based on this concept, radiation exposure by nuclear medicine and radiodiagnostic procedures can be compared to the natural radiation burden. In addition, the hypothetical risk associated with exposure to ionizing radiation can be estimated and compared to that in daily life. Radiation exposure in nuclear medicine procedures including PET remain within the limits of annual natural radiation exposure (1-6 mSv). The overall risk of any diagnostic procedure employing ionizing radiation in radiology appears to be negligible. The activity used for procedures in nuclear medicine is a compromise between radiation safety and image quality. A recent representative evaluation revealed that the average activity used for nuclear medicine procedures in Germany is lower than in other European states. While for most adult procedures a standard dose is given, the accepted method for children is the weight method. Any procedure employing ionizing radiation is usually performed only if alternative diagnostic imaging modalities such as ultrasound and MRI cannot answer a specific test question appropriately. In addition to the latter, there are several ways to minimize radiation exposure. The most important way of assuring quality in any procedure is a strong quality-control program. Furthermore, comprehensive knowledge encompassing the indications for a study, the technical aspects of its acquisition and processing, and the final interpretation of its results are of great importance. Finally, it is known that prolonged data acquisition will result in improved image quality; however, this is clearly limited by the acceptance of the patient.

Adolescent↗

[Accuracy of intraoperative urinary bladder temperature monitoring during intra-abdominal operations].

OBJECTIVE: This study investigates whether the site of abdominal surgery or the urine flow rate affects the accuracy of urinary bladder temperature monitoring. METHODS: After approval by the local ethics committee we studied 7 patients during upper abdominal and 10 patients during lower abdominal surgery. Temperatures were recorded with a Hi-Lo Temp Esophageal-Stethoscope (Mallinckrodt Medical) and a Foley Catheter Temperature Sensor FC400-18 (Respiratory Support Products, Mallinckrodt Medical). Each probe and its recording unit were calibrated over a range of 30-40 degrees C against a reference quartz thermometer (Hewlett Packard Model 2801 A) in a water bath before the investigation. Urine flow rate was measured using a urometer. Temperatures and urine flow rate were recorded every 30 min. Agreement between the methods of measurement was assessed as described by Bland and Altman. RESULTS: 124 measuring points could be analyzed. Bladder temperature had a bias (B) of -0.06 degree C compared to oesophageal temperature. Limits of agreement (LOA; +/- 2 s) were +/- 0.68 degree C. In upper abdominal surgery (B: 0.02 degree C; LOA: +/- 0.42 degree C) a higher precision of oesophageal temperature estimation could be demonstrated compared to lower abdominal surgery (B: -0.14 degree C; LOA: +/- 0.82 degree C). Lower urine flow rates generally increased the limits of agreement. Regarding lower abdominal surgery the bias additionally increased to -0.22 degree C. CONCLUSION: Urinary bladder temperature recording is a clinically acceptable method to measure core temperature during abdominal surgery. The accuracy during lower abdominal surgery is decreased compared to upper abdominal surgery, especially in case of a urine flow rate below 250 ml/h.

Abdomen↗

A clinical index for selection of breast cancer patients for adrenalectomy.

Selection of patients with disseminated breast cancer for endocrine surgery has not been facilitated by sophisticated biochemical techniques. The present study was designed to produce a method of prognosis based exclusively on clinical data. Eighteen features were studied in 95 patients who underwent adrenalectomy and oophorectomy, and correlated with their degree of response to produce predictive variables. In a further group of 90 patients a prognostic score (the sum of the predictive variables) was calculated. There were 17 patients who scored less than 0 and in no case was a good response to endocrine surgery achieved. There were 40 who scored over 10, 29 of whom had a good response. The remaining 33 scored between 0 and 10 and there was no correlation between score and response. This predictive system offers significant advantages over accepted methods of clinical assessment (chi2 = 6-61, P less than 0-02). When patients with a score between 0 and 10 are excluded, its advantages are even more obvious (chi2 = 11-26, P less than 0-001). Patients who are likely to respond to endocrine surgery can be selected by clinical parameters alone, and total failure to respond can be forecast with complete accuracy. Between these two there is a third group whose response is unpredictable.

Adrenalectomy↗

Unattended home diagnosis and treatment of obstructive sleep apnea without polysomnography.

OBJECTIVE: To test the effectiveness of unattended home monitoring along with automatic titrating continuous positive airway pressure (auto-CPAP) as an acceptable method for diagnosing and prescribing proper CPAP pressure for treatment of patients presenting with classic symptoms of obstructive sleep apnea (OSA). DESIGN: Nonrandomized, prospective case study of 63 patients with a presumptive diagnosis of OSA. SETTING: University hospital and veterans affairs medical center ambulatory sleep disorders clinics. PARTICIPANTS: Fifty-eight men and 5 women were recruited for symptoms of excessive daytime sleepiness, heavy snoring, and witnessed apnea. INTERVENTION: Subjects with 10 or more respiratory events per hour were titrated by automatic, unattended home monitoring to an optimal CPAP pressure. MAIN OUTCOME MEASURES: Number of subjects able to be diagnosed by unattended home monitoring, titrated to optimal CPAP pressure, accepted an auto-CPAP machine for home use, and symptoms improved. RESULTS: Fifty-four (86%) of 63 patients completed sufficient diagnostic studies, and in 45 (83%) of these, a diagnosis of OSA was established. Nine subjects were unable to adjust to the nasal mask for an adequate diagnostic recording, and 9 had fewer than 10 respiratory events per hour. Ten subjects with OSA could not complete a titration study. Thirty-five of the subjects diagnosed with OSA accepted the auto-CPAP machine into their home, while 30 used it for therapy longer than 3 weeks. The estimated cost of performing in-home studies was less than one fourth of the estimated cost for in-laboratory polysomnographic examinations had they been performed. CONCLUSION: Unattended monitoring plus auto-CPAP allows cost-effective diagnosis and CPAP titration of most patients with OSA with straightforward symptoms.

Diagnosis, Differential↗

Prevalence of penicillinase-producing Neisseria gonorrheae in Korea.

An almost two-fold increase in the monthly reported case rate for sexually transmitted disease (STD) in U.S. military members assigned in the Republic of Korea in April 1981 prompted an epidemiologic assessment of that population. Inasmuch as previously nonexistent treatment failures for Neisseria gonorrheae were also being reported, a demographic slice of 253 symptomatic military members was surveyed in June and July, 1981, for gonorrhea prevalence and the proportion of this that could be attributed to penicillinase-producing Neisseria gonorrheae (PPNG). Using standard and accepted methods, the gonorrhea prevalence rate in symptomatic military members was found to be 100% while the proportion that could be attributed to PPNG was 43%. In order to compare this to the contact population of local prostitutes, 116 asymptomatic women who presented to local STD clinics for routine, often legally-mandated examinations, were surveyed. The expected lower gonorrhea prevalence rate was 13.9% but the proportion attributed to PPNG was 27.6%. This data was similar to the sudden increase in PPNG experienced by U.S. military forces at Subic Bay in the Philippines in 1979 and reflected the slow but steady migration of this resistance throughout Asia. The long-accepted norm for gonorrhea treatment using penicillin was changed to spectinomycin in the U.S. military population and was being considered for implementation by the Korean official health community. Further organism resistance can be expected, and close monitoring is taking place.

Adolescent↗

The painful scapulothoracic articulation: surgical management.

To clarify the indications and effectiveness of surgical decompression for scapulothoracic bursitis, 16 patients were evaluated, who during a 5-year period, had surgical treatment of refractory pain and snapping in the scapulothoracic region. Twelve women and four men with a mean age of 41 years had one of five methods of surgical decompression of the scapulothoracic articulation. Six patients had an open resection of the scapulothoracic bursa with excision of the superomedial portion of the scapula, two had this procedure using an arthroscopic method, and six had a combined approach with arthroscopic scapulothoracic bursectomy and open resection of the superomedial scapula through a small incision. One patient had an arthroscopic and one an open scapulothoracic bursectomy only. At final followup of an average of 36 months (range, 24-69 months), 81% of patients reported satisfaction with the procedure and indicated they would have it again based on the relief they obtained from pain. The Simple Shoulder Test was 9.8 (range, 2-12). Although there was no statistical difference in the success using any given technique, we thought that the combined open and arthroscopic approach was the most effective, and surgical treatment is an acceptable method for treatment of refractory painful scapulothoracic bursitis.

Adult↗

Home uroflowmetry: improved accuracy in outflow assessment.

To study home uroflowmetry and to compare this method to free or "traditional" uroflowmetry in the evaluation of the patient with symptomatic benign prostatic hyperplasia (BPH), and the relationship between the values of home uroflowmetry parameters and bladder outlet obstruction (BOO). Twenty-five patients (mean age, 67 years) with symptomatic BPH were examined with home uroflowmetry, free uroflowmetry, and pressure-flow measurement. The patients were assessed using the International Prostate Symptom score; digital rectal examination; routine blood chemistry, including serum prostate-specific antigen level; urinanalysis; transrectal ultrasonography; and post-void residual urine. The 24 hr were divided into "active time" (AT) and "sleep time" (ST). AT home uroflowmetry parameters were compared to ST ones. The home uroflowmetry parameters were compared to respective ones of the free uroflowmetry as well and those obtained by pressure-flow measurement. The patients were asked about their opinion of home uroflowmetry. Home uroflowmetry was found to be a simpler and more acceptable method than free uroflowmetry. The mean Qmax of AT was significantly greater than the mean Qmax of ST, but the mean voided volume and mean voiding time of ST were significantly larger than those of AT. There was a close relationship between the mean Qmax at home and the Qmax in hospital, but the voided volume and voiding time measured in hospital were significantly larger than those at home. Home uroflowmetry provided an estimation of BOO for 46% of the patients as low if the home mean Qmax was >14 ml/sec, and as high if the home mean Qmax was <10 ml/sec. Home uroflowmetry was well accepted by the patients and gave more information than free uroflowmetry. In 46% of the cases, an estimation of BOO was obtained with home uroflowmetry.

Aged↗

Immunohistochemical detection of neuroblastoma in frozen sections of bone marrow trephine biopsy specimens.

Frozen sections from bone marrow trephine biopsy specimens from children with disseminated neuroblastoma were stained using the monoclonal antibody UJ13A. An immunoalkaline phosphatase technique was the preferred staining method. Acceptable histological detail was obtained from this material and deposits of tumour cells detected. Some apparently fibrous tissue was also stained by this antibody. The results show that this immunohistological approach is feasible and provide encouragement for its addition to the range of investigations currently available for assessing the marrows of children with this disease.

Antibodies, Monoclonal↗

A pilot study on the acceptability of levonorgestrel-releasing intrauterine device by young, single, nulliparous Chinese females following surgical abortion.

This study investigated the acceptability of the levonorgestrel-releasing intrauterine device (LNG-IUS) as contraception among young, single women after termination of pregnancy. Twenty subjects, with a median age of 21 years, had LNG-IUS inserted immediately after suction termination of first-trimester pregnancy. The subjects were followed-up at 6 weeks, 3 months, 6 months and 12 months. Fifteen subjects (75%) had other pregnancies terminated in the past. There were no serious complications or pregnancies. The acceptability of the LNG-IUS was generally above 86% during each follow-up visit. A total of seven (35%) subjects were lost to follow-up at different periods of the study. Overall, four subjects (22%) had the LNG-IUS removed. Nine subjects were seen at the end of the 1-year study period and all continued with the LNG-IUS for contraception. Side effects were commonly observed and irregular vaginal bleeding was the most common. We conclude that the LNG-IUS may be an acceptable method among selective young, single, nulliparous clients after termination of pregnancy and could be offered as an option of contraception to them. However, the small sample size and the high lost-to-follow-up rate are the major limitations of this study.

Abortion, Induced↗

A rapid and sensitive method for the detection of Yersinia enterocolitica strains from clinical samples.

AIMS: To compare three culture methods to detect Yersinia enterocolitica from oral or rectal swabs from experimentally infected pigs. METHODS AND RESULTS: The three methods used were: direct plating on Cefsulodin-Irgasan-Novobiocin (CIN) agar, cold enrichment in phosphate buffered saline (PBS) followed by plating on CIN agar and selective enrichment with Luria-Bertani-Bile Salts Irgasan (LB-BSI) followed by plating on CIN agar. Selective enrichment with LB-BSI produced the highest recovery rate (63%), when compared with cold enrichment (52%) and plating on CIN agar alone (43%). Selective enrichment with LB-BSI was significantly (P < 0.02) more sensitive than direct plating on CIN agar and more sensitive than cold enrichment (P < 0.1). CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Selective enrichment with LB-BSI was more sensitive than the widely accepted method of cold enrichment and it reduced the time required for detection of Y. enterocolitica by three weeks. Selective enrichment with LB-BSI was also compatible with a multiplex PCR technique.

Agar↗

Do certain atypical antipsychotics increase the risk of diabetes? A critical review of 17 pharmacoepidemiologic studies.

BACKGROUND: Some atypical antipsychotics have been linked to hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. We reviewed evidence comparing excess risk and relative risk of type-2 diabetes associated with atypical antipsychotics. METHODS: Studies were identified on MEDLINE (January 1966-June 2003) using "antipsychotics and diabetes," "atypical antipsychotics and diabetes," and "schizophrenia and diabetes" as search terms. Studies presented at psychiatric scientific meetings between January 2000-June 2003 were identified via meeting attendance, conference proceedings, and published abstracts. The authors examined all retrospective epidemiologic studies including secondary data analyses addressing relative risk of developing diabetes in patients receiving atypical antipsychotics. Case reports, prospective trials, review articles, and MedWatch data were excluded. Extracted data were reviewed by all investigators according to predetermined criteria related to study design, treatment and comparison groups, definition of outcome measure, inclusion of covariates, and statistical analysis. RESULTS: Four studies meeting criteria for acceptable methods demonstrated that olanzapine, but not risperidone, is associated with a significantly increased risk of new-onset diabetes versus untreated major psychiatric disorder. Studies of relative risk did not demonstrate greater risk of diabetes with risperidone versus conventional antipsychotics. Of nine studies comparing relative risk of diabetes with olanzapine and risperidone, six demonstrated significantly greater risk with olanzapine. Risk was higher in women in two studies. Definitive conclusions could not be reached for clozapine and quetiapine due to limited data. CONCLUSIONS: The preponderance of current epidemiologic evidence indicates that olanzapine therapy poses a higher risk of diabetes than untreated major psychiatric illness, and that olanzapine confers greater risk of diabetes than risperidone.

Antipsychotic Agents↗

Decontamination: a microbiologist's perspective.

The primary objective of decontamination is to protect healthcare workers who handle medical devices from infectious diseases that may be present on those devices. Ideally, the decontamination process should provide both cleaning and biocidal activity. A wide range of equipment, from automatic washer/sterilizers to semi-automated washer/sanitizers are commercially available to satisfy this need. The primary difference between these pieces of equipment, from a microbiology perspective, is in the level of safety they provide. A summary comparison of the decontamination methods is shown in Table 1. Without a doubt, steam sterilization as a method of decontamination provides a greater safety level than may be required. However, the question is, "Do disinfection and sanitization provide an adequate safety level?" Although items do not necessarily need to be sterile to be safe to handle, sterilization processes provide the greatest margin of safety because of the significant microbial lethality and the ability to effectively monitor the process via biological indicators. Sterilization effectively eliminates the concern regarding the nearly unanswerable question of bioburden. Unfortunately, not all items are capable of being processed through a washer/sterilizer. Therefore, consideration must be given to the process compatibility of each device. Disinfection processes provide the next level of safety. Unfortunately, there is no recognized or accepted method for quantitatively describing or monitoring a thermal disinfection process. As is the case with sterilization consideration must be given to the process compatibility of each device. Sanitization provides the lowest level of safety for the decontamination process.(ABSTRACT TRUNCATED AT 250 WORDS)

Central Supply, Hospital↗

Gated blood pool scintigraphy as a tool for non-invasive measurements of left ventricular function.

Gated Blood Pool Scintigraphy (GBPS), i.e. the noninvasive evaluation of ventricular performance following the administration of radionuclides as intravascular tracers has had a major impact on many aspects of cardiology and has proven its clinical value and reliability in the past years. Today it is an accepted method in clinical practice, permitting the assessment of both global and regional cardiac function. The most important parameters derived from GBPS volume curves for the determination of left ventricular global function are ejection fraction (EF) at rest and under exercise and peak filling rate of the left ventricle at rest. In addition, GBPS permits the assessment of regional left ventricular function by determining regional EF and phase shifts. Echocardiography is no true alternative to GBPS due to frequent problems in quantitative evaluation and unpredictable errors in patients with non-uniform heart geometry or dyskinetic left ventricles. Thus, GBPS is not only useful in a wide variety of clinical settings, but has become an accepted tool in the methodological approach for non-invasive evaluation of new drugs and sequential drug therapy monitoring. This application of GBPS can be particularly recommended for the investigation of two different problems: a) exclusion of adverse drug effects on left ventricular performance in the process of drug safety evaluation, and b) demonstration of hemodynamic effects of new drugs particularly after long-term medication. GBPS provides valuable information as to the type, onset and duration of hemodynamic changes, permitting the determination of regional changes in myocardial function as well as its global evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

Wavelet packet fractal analysis of neuronal morphology.

An image analysis method called two-dimensional wavelet packet analysis (2D WPA) is introduced to quantify branching complexity of neurons. Both binary silhouettes and contour profiles of neurons were analyzed to determine accuracy and precision of the fractal dimension in cell classification tasks. Two-dimensional WPA plotted the slope of decay for a sorted list of discrete wavelet packet coefficients belonging to the adapted wavelet best basis to obtain the fractal dimension for test images and binary representations of neurons. Two-dimensional WPA was compared with box counting and mass-radius algorithms. The results for 2D WPA showed that it could differentiate between neural branching complexity in cells of different type in agreement with accepted methods. The importance of the 2D WPA method is that it performs multiresolution decomposition in the horizontal, vertical, and diagonal orientations.

Algorithms↗

Use of UNAIDS tools to evaluate HIV voluntary counselling and testing services for mineworkers in South Africa.

HIV voluntary counselling and testing (VCT) is now an integral part of many HIV care and control programmes. However, very little work has been done to assess the quality of VCT services. An evaluation of VCT services for mineworkers in Welkom, South Africa was conducted to assess client and counsellor satisfaction, the quality of the services and to identify barriers to uptake of VCT. A cross-sectional survey was carried out using tools developed by UNAIDS, consisting of semi-structured interviews and observation of counselling sessions. Twenty-two nurse counsellors and six community volunteers were interviewed. Twenty-four counselling sessions were observed and 24 client exit interviews were conducted. Although nine of the 22 nurse counsellors had only in-service rather than formal training for HIV counselling whereas all community volunteers had been formally trained, nurse counsellors demonstrated better interpersonal skills than did community volunteers. Both clients and counsellors identified fear of a positive result as a major barrier to HIV testing. Clients also raised concerns about confidentiality. UNAIDS evaluation tools were a feasible and an acceptable method of assessing VCT in this operational setting. The study identified areas where training needs to be strengthened and suggested ways of improving the services, and changes to the service have now been implemented in line with these recommendations.

Counseling↗

A comparative study of envelope mastectomy and immediate reconstruction (EMIR) with standard latissimus dorsi immediate breast reconstruction.

BACKGROUND: Latissimus dorsi breast reconstruction has problems with scars at the donor site and on the reconstructed breast. We report the feasibility and aesthetic results of Envelope Mastectomy and Immediate Reconstruction (EMIR), which utilises a single lateral mammary fold incision. PATIENTS AND METHODS: Between 2001 and 2002, 20 EMIRs were performed in 19 patients, one as a staged bilateral procedure. Twenty consecutive patients, matched for body habitus, who had undergone standard latissimus dorsi breast reconstruction by the same surgeon from 1996 to 2000 were used as controls. Patient satisfaction was assessed using a validated Body Image Scale. Standard post-operative photographs were scored by three independent observers. RESULTS: Length of stay and complication rates were equivalent between both groups. Cosmetic self-assessment scores on the Body Image Scale and scores by the independent observers were satisfactory for both groups but no statistically significant difference was observed between groups. CONCLUSIONS: EMIR is a technically feasible and cosmetically acceptable method of immediate breast reconstruction.

Breast Neoplasms↗