Prospective controlled randomized study of in vitro fertilization versus intracytoplasmic sperm injection in the treatment of tubal factor infertility with normal semen parameters

We report a case of aortitis syndrome, in which carotid ultrasonography was a useful approach for the diagnosis. A 21-year-old woman was admitted to our hospital for persistent fever. No specific physical findings or laboratory abnormalities were observed except high fever and marked increase of erythrocyte sedimentation rate and c reactive protein. Since clinical trial of antibiotics and antituberculosis agents resulted in no effectiveness, prednisolone was started, but the effect was limited. After that, she complained of the neck pain, and vascular murmur became apparently audible at the pain site. Ultrasonography of the carotid artery revealed the smooth lumen and homogeneous, non-hyperechoic intimal thickening. Then aortography confirmed the diagnosis of aortitis syndrome. Cyclophosphamide combined with steroid therapy diminished the disease activity. In this case, carotid ultrasonography gave us the important information to enforce the aortography. If ultrasonography of the carotid artery has been popularized for aortitis syndrome, and its findings have been standardized, non-invasive diagnosis of this disease will be taken a step forward.     

Dietary thiamin supply during gestation effects thiamin status of lactating rats and their suckling offspring

A paired-comparison study of manual and automated (PAPNET) screenings of cervico-vaginal smears (Pap tests) was conducted to determine whether primary PAPNET screening was a reliable alternative to manual screening. A series of 5,037 consecutive Pap tests was first screened by the manual method. Next they were scanned by the PAPNET system, the DAT tapes were reviewed, and using a nonspecific triage protocol, abnormal tests were identified for limited, manual rescreening. False-negative rates (FNR) for each method were calculated and analyzed for due cause. By manual and PAPNET screening, respectively, there were 436 (8.6%) and 250 (4.9%) abnormal results. Manual screening missed 18 abnormals (5 SIL) and PAPNET 202 (7 SIL). The primary, manual screenings relating to the PAPNET false-negative tests were reviewed and revised to normal in 30. Based on the changes in the other 172 tests, cellular features ostensibly missed by the PAPNET system were listed to form part of a specific triage protocol, and were used to scrutinize the companion 172 DAT tapes: 150 tapes were abnormal. The manual FNR for an abnormal (SIL) result was 4% and (8.8%), respectively. Equivalent FNR pre- and postreviews for the PAPNET system were 44.6% (10.6%) and 5.2% (1.3%), respectively. This study discovered that the evaluation of some cell features in monitor-based, video images was the most important factor limiting the application of the PAPNET system as a primary screener. When governed by a specific triage protocol incorporating these features, primary PAPNET screening has the potential to equal the laboratory threshold of manual screening and be a better detector of SIL.     

A quantitative evaluation of the glycogen content of the hepatocytes from different lobular ares of the normal human liver and in chronic hepatitides of different etiologies

Investigation of glycogen function in hepatocytes of different liver lobule zones is particularly important in understanding glycogen metabolism in humans and animals in norm and pathology. The present study was done to investigate glycogen contents in hepatocytes of different lobule zones of human liver in norm, and in patients with chronic hepatitis of viral or alcohol etiology. Quantitative analysis of glycogen content in hepatocytes of portal and central lobule zones was conducted on slices of human liver (the material of series live punctional biopsies) stained using a quantitative variant of PAS-reaction (Kudryavtseva et al., 1970, 1974). The measurements were done by image analyzer , which allows to make jointly cytophotometric analysis of substance in cells and definition of cell localization in tissue. The results showed clear differences of glycogen contents in different lobule zones in normal liver and in liver during chronic viral and alcohol hepatitis. Glycogen contents in hepatocytes of portal lobule zone were significantly higher than in the central lobule zone in patients with chronic viral hepatitis. Opposite data were obtained in patients with chronic alcohol hepatitis. Significantly higher glycogen contents were found in hepatocytes of the central liver lobule zone. Possible mechanisms of such a phenomenon are discussed . Thus, if glycogen contents in hepatocytes may be taken as an indicator of liver chronic damage degree (as has been shown elsewhere: Kudryavtseva, 1987; Kudryavtseva et al., 1988) the pattern of distribution of hepatocytes with different glycogen content in the liver lobule can be used as an indicator of etiology of chronic hepatitis. The obtained data seem to be important and actual, particularly for diagnostic of subclinical and symptomless forms of these diseases. Further investigation is required to find out reasons and mechanisms of this phenomenon.     

Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors

The development of a highly sensitive method for detection of telomerase activity, telomeric repeat amplification protocol (TRAP), has provided knowledge on telomerase activity in normal and cancer tissues. Subsequent several modifications have been achieved, including an introduction of the internal standard and hybridization protection technique that leads to simplicity and improvement of reproducibility and linearity of this method, and application of TRAP to in situ analysis to identify the cells responsible for telomerase activity. As for measurement of telomere length, fluorescence in situ hybridization technique appeared to give an information of telomere length on an individual chromosome in contrast to analysis of terminal restriction fragment, a conventional method which can express mean telomere length of all chromosomes. Further methodological improvement in this field is ongoing and showing a new sight on cell mortality and immortality.     

Relationship between lateral subluxation and widening of medial joint space in Legg-Calvé-Perthes disease

Fifty-five patients (61 affected hips and 49 unaffected hips) with Perthes disease were reviewed to evaluate the relationship between widening of medial joint space and lateral subluxation of the femoral head in radiographs. The components of the medial joint space were evaluated by using T1, T2, proton, and Gd-enhanced T1WI magnetic resonance images (MRI). The widened medial joint space in radiographs was filled with overgrown cartilage at the initial stage (27 hips) in MRI, with both overgrown cartilage and widened true medial joint space at the fragmentation stage (23 hips) and widened true medial joint space at the healing stage (11 hips). Between affected hips and unaffected hips, the mean difference of medial joint space in radiographs between hips at the initial stage and at the fragmentation stage was 2 and 4.5 mm, respectively; the mean difference in percentage of lack of coverage of the femoral head between hips at the initial stage and at the fragmentation stage was 3 and 15%, respectively. During the healing stage, widening of the medial joint space decreased or normalized because of ossification of overgrown cartilage despite the existence of lateral subluxation because of coxa magna. We concluded that widening of the medial joint space may be used as an index of lateral subluxation at only the fragmentation stage in Perthes disease.     

Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM

Recent studies have shown that mutations in the hepatocyte nuclear factor (HNF)-1alpha gene are the cause of maturity-onset diabetes of the young type 3 (MODY3). We have screened 193 unrelated Japanese subjects with NIDDM for mutations in this gene: 83 with early-onset NIDDM (diagnosis at <30 years of age) and 110 with late-onset NIDDM (diagnosis > or = 30 years of age). All of the members of the latter group also had at least one sibling with NIDDM. The 10 exons, flanking introns, and promoter region were amplified using polymerase chain reaction and were sequenced directly. Mutations were found in 7 of the 83 (8%) unrelated subjects with early-onset NIDDM. The mutations were each different and included four missense mutations (L12H, R131Q, K205Q, and R263C) and three frameshift mutations (P379fsdelCT, T392fsdelA, and L584S585fsinsTC). One of the 110 subjects with late-onset NIDDM was heterozygous for the missense mutation G191D. This subject, who was diagnosed with NIDDM at 64 years of age, also had a brother with NIDDM (age at diagnosis, 54 years) who carried the same mutation, suggesting that this mutation contributed to the development of NIDDM in these two siblings. None of these mutations were present in 50 unrelated subjects with normal glucose tolerance (100 normal chromosomes). Mutations in the HNF-1alpha gene occur in Japanese subjects with NIDDM and appear to be an important cause of early-onset NIDDM in this population. In addition, they are present in about 1% of subjects with late-onset NIDDM.     

Optimization of hydrolysis of protein substrates by yeast proteases from Saccharomyces carlsbergenis

Maximizing efficiency of staff and resources is one method of reducing costs without affecting quality. Using a methodology similar to that used to maximize efficiency of airline-gate use, we developed a model with which to evaluate nursing support staff and clinical examining-room resources in a general otolaryngology clinic. For 144 patients over 7 consecutive clinic days, with four otolaryngologists and various combinations of support staff and examining rooms, we measured space and staff resource use, including total clinic time, number of patients seen, patient waiting time, physician and nurse productivity, and examining-room use. A simulation model was used as the medium of analysis to define parameters of the patient encounter. We identified optimal efficiency when there were three examining rooms and one and one-half nursing staff per physician or five examining rooms and three nursing staff for two simultaneously practicing physicians. Compared with a model of two rooms and one nursing staff member, our ideal model increased the percentage of the physicians' time spent in direct contact with patients from 84% to 92%. Visit length decreased from 81 minutes to 57 minutes, the average time from check-in to examination decreased from 47 to 16 minutes, and it became possible for three additional patients to be seen each day. Additional rooms and support staff, in comparison with the optimally efficient distribution, did not significantly affect these parameters. Maximizing efficiency with the use of this methodology can decrease waiting times for patients, resulting in greater patient satisfaction, improved physician productivity, total number of patients seen, and increased total contact time between physicians and patients.     

Structural elucidation by electrospray mass spectrometry: an approach to the in vitro metabolism of the macrolide immunosuppressant SDZ RAD

SDZ RAD [40-O-(2-hydroxyethyl)rapamycin] is a macrolide immunosuppressant that is currently under clinical investigation after organ transplantation. The elucidation of its metabolic pathway is essential to improve the understanding of its therapeutic potentials and safety. In this article we describe investigations on the structural identification of some major metabolites of the drug produced by human liver microsomes in vitro. The principles described may be generally applicable for the structural elucidation of complex compound mixtures in biological matrices. Under the conditions of electron impact ionization, SDZ RAD undergoes extensive fragmentation and no information sufficient for structural elucidation is obtained. Therefore, mass spectrometry based on soft electrospray ionization (ESI) in conjunction with collision-induced fragmentation was the method of choice. High-performance liquid chromatography coupled to an ESI mass spectrometer resulted in separation and identification of 16-O-demethyl-SDZ RAD, the ring-opened form of SDZ RAD, and its dehydrate. Additionally, we characterized several demethylated and hydroxylated metabolites.