Projections between the hypothalamus and the dorsal vagal complex in the cat: An HRP and autoradiographic study

The hypothalamus is known to be intimately involved in the control of autonomic function. This study provides detailed information about pathways between the hypothalamus and the dorsal vagal complex in cat. Injection of horseradish peroxidase into the dorsomedial medulla produced retrograde neuronal labeling in the paraventricular nucleus of the hypothalamus. Injection of 3H-leucine into the paraventricular nucleus produced dense anterograde labeling in the dorsal motor nucleus of the vagus, and lighter labeling in the nucleus of the tractus solitarius, particularly in its medial subnucleus. The subnucleus gelatinous was virtually free of label, except in its medial and lateral portions. Anterograde labeling was distributed bilaterally, with an ipsilateral predominance. Injection of horseradish peroxidase into the area of the paraventricular nucleus produced retrograde neuronal labeling bilaterally in the nucleus of the tractus solitarius and the reticular formation ventrolateral to the dorsal vagal complex. anterograde terminal labeling overlapped the distribution of retrogradely labeled neurons. These findings are compared to those in rat, and discussed in relation to their functional implications.     

Quality of life and its correlates in octogenarians. Use of the SEIQoL-DW in Wave 5 of the Aberdeen Birth Cohort 1921 Study (ABC1921)

Background The direct-weighted Schedule for the Evaluation of Individual Quality of Life, Direct Weighting (SEIQoL-DW) is an individualised measure of QoL that has been little used in very elderly people. Methods We administered SEIQoL-DW during Wave 5 of the Aberdeen Birth Cohort 1921 Study (ABC1921) and sought statistical correlations with other variables in the data set. ABC1921 participants had been IQ-tested in 1932 at age 11. Since 1997, data about cognition, mental/physical function, personality, health, and socioeconomic status have been gathered in five waves of investigations. Results Ninety-six out of 98 individuals, mean age 82.2, completed the SEIQoL-DW. Health, family, relationships, finances and social pastimes were the commonest cues nominated, but age/gender differences existed. The mean SEIQoL-DW score (74.0) was significantly lower than in an approximately 60% sample from Wave 3, the fall being greater in men. Variables statistically associated with Wave 5 SEIQoL-DW usually reflected current rather than past status [including Short-Form 36 Health Survey (SF-36) components and depression], although there were weaker correlations with years of education, housing in childhood, conscientiousness, and IQ in 1998. Conclusions SEIQoL-DW proved feasible and acceptable in community-dwelling octogenarians. Recent (i.e. statelike) rather than early or long-standing (i.e. traitlike) influences appeared to have the greater effect on QoL.     

Suppression of the tumorigenic phenotype of a rat liver epithelial tumor cell line by the p11.2–p12 region of human chromosome 11

Comparative chromosomal mapping studies and investigations of tumor-associated chromosomal abnormalities suggest that the development of hepatic tumors in humans and rats may share a common molecular mechanism that involves inactivation of the same tumor suppressor genes or common genetic loci. We investigated the potential of human chromosomes 2 and 11 to suppress the tumorigenic phenotype of rat liver epithelial tumor cell lines. These tumor cell lines (GN6TF and GP7TB) display elevated saturation densities in culture, efficiently form colonies in soft agar, and produce subcutaneous tumors in 100% of syngeneic rat hosts with short latency periods. Introduction of human chromosome 11 by microcell fusion markedly altered the tumorigenicity and the transformed phenotype of GN6TF cells. In contrast, the tumorigenic potential and phenotype of GP7TB cells was unaffected by the introduction of human chromosome 11, indicating that not all rat liver tumor cell lines can be suppressed by loci carried on this chromosome. Introduction of human chromosome 2 had little or no effect on the tumorigenicity or cellular phenotype of either tumor cell line, suggesting the involvement of chromosome 11–specific loci in the suppression of the GN6TF tumor cell line. The GN6TF-11^neo microcell hybrid cell lines displayed significantly reduced saturation densities in monolayer cultures, and their ability to grow in soft agar was completely inhibited. Although GN6TF-11^neo cells ultimately formed tumors in 80–100% of syngeneic rat hosts, the latency period for tumor formation was much longer. Molecular characterization of GN6TF-11^neo microcell hybrid cell lines indicated that some of the clonal lines had spontaneously lost significant portions of the introduced human chromosome, partially delineating the chromosomal location of the putative tumor suppressor locus to the region between the centromere and 11p12. Molecular examination of microcell hybrid–derived tumor cell lines further defined the minimal portion of human chromosome 11 capable of tumor suppression in this model system to the region 11p11.2-p12. © 1995 Wiley-Liss, Inc.     

Information for clinical governance: analysis of routine hospital activity data in Wales

BACKGROUND: Variations in hospital admission rates have been extensively reported for many years, but this evidence has not had a wide impact on clinical practice. Understanding local reasons for high variation to improve quality of healthcare should be a focus of clinical governance. Our aim was to convert routine hospital activity data into information on a category of high-variation, discretionary, hospital admissions and provide a tool for analysis for clinical governors in Local Health Groups (LHG). METHODS: We undertook a cross-sectional analysis of hospital activity data for the 22 LHGs in Wales and 101 general practices in Gwent Health Authority. Hospital spells for 1998-1999 and 1999-2000 were classified into Healthcare Resource Groups (HRGs). Using the systematic component of variation we identified a category of high-variation admissions for which the only plausible explanation was medical discretion. Using scatter plots we compared the proportion of these discretionary admissions with the age-, sex- and deprivation-adjusted standardized admission ratio. (SAR) for each LHG and practice. RESULTS: We found a two-fold variation in SARs between LHGs and a three-fold variation between practices. Mean discretionary activity was 55 per cent (range 50-59 per cent) of total activity for LHGs and 56 per cent (51-62 per cent) for practices. Greatest variation was found for elective admissions. The relation between discretionary admissions and the SAR was identified for each LHG and practice as the starting point for further investigation. CONCLUSION: This method provides useful information to LHG clinical governors to contribute to the process of reducing medical practice variation, increasing equity, improving the quality of care and making more cost-effective use of resources.     

Current developments in LC-MS for pharmaceutical analysis

The current developments in liquid chromatography-mass spectrometry (LC-MS) and its applications to the analysis of pharmaceuticals are reviewed. Various mass spectrometric techniques, including electrospray and nanospray ionization, atmospheric pressure chemical ionization and photoionization and their interface with liquid chromatographic techniques are described. These include high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography and the advantages and disadvantages of each technique are discussed. The applications of LC-MS to the studies of in vitro and in vivo drug metabolism, identification and characterization of impurities in pharmaceuticals, analysis of chiral impurities in drug substances and high-throughput LC-MS-MS systems for applications in the "accelerated drug discovery" process are described.     

Breast cancer during pregnancy

Opinion statement The concurrent diagnosis of breast cancer and pregnancy is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. Modified radical mastectomy, the preferred surgical option in women with breast cancer during pregnancy, can be accomplished with minimal fetal risk. Although breast-conserving surgery (lumpectomy or quadrantectomy) can be performed, the radiation therapy required to complete local therapy for the breast must be delayed until after delivery because of the risks associated with fetal exposure to radiation. Although much of the literature on the pharmacologic treatment of breast cancer during pregnancy is anecdotal, recently published data from our institution support the premise that breast cancer can be treated safely during the second and third trimesters of pregnancy with combination chemotherapy consisting of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). Therapeutic abortion does not appear to improve survival for the mother, but it may be an option if maternal health is jeopardized or fetal anomalies are seen or suspected.     

The absence of CD20 messenger RNA in recurrent cutaneous B-cell lymphoma following rituximab therapy

BACKGROUND: Rituximab has been used to treat relapsed low-grade or advanced non-Hodgkin's lymphoma since 1997, targeting the CD20 antigen expressed by B cells. Single-agent rituximab therapy is safe and well tolerated. Recurrences showing a loss of CD20 expression following rituximab therapy have been reported. METHODS: Four patients with CD20-positive cutaneous B-cell lymphoma received rituximab therapy with subsequent recurrences. The biopsies were assessed for cytoplasmic CD20 expression; CD20 messenger RNA was also assessed where tissue was available. RESULTS: Cutaneous relapses occurring within 1.5-3 months following the last dose of rituximab were CD20 negative. In three cases, subsequent relapses showed renewed expression of CD20. Those biopsies demonstrating a loss of surface and cytoplasmic CD20 by immunohistochemistry also showed no evidence of messenger RNA for CD20 using an in situ polymerase chain reaction-based methodology. CONCLUSIONS: Rituximab may be associated with the emergence of CD20-negative B-cell clones, potentially rendering a tumor insensitive to this drug. Conversely, following cessation of the drug, a re-expression of CD20 within the neoplastic cells may occur allowing therapeutic intervention with this monoclonal antibody. The loss of CD20 expression appears to be a direct effect of the drug on CD20 messenger RNA synthesis.