Observations from the CDC. Public health principles and women's environmental health: no more lost opportunities.
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Biomedical subjects
Publications and source records attributed to A Kelly.
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To assess the potential of gastrin receptor antagonists in the treatment of gastrointestinal cancer, the presence of an autocrine loop involving progastrin-derived peptides has been investigated in two colorectal and one gastric carcinoma cell lines. Progastrin, glycine-extended gastrin and amidated gastrin were detected in cell extracts or conditioned media by radio-immunoassay. Low-affinity binding sites for glycine-extended gastrin and amidated gastrin were present, but high-affinity binding sites were not detected with the appropriate iodinated ligands. In addition, neither glycine-extended gastrin nor amidated gastrin in the concentration range 10pmol/L-10nmol/L stimulated cell proliferation. We conclude that it is unlikely that the carcinoma cell lines LIM 1215, LIM 1839 and LIM 1899 use either amidated or glycine-extended gastrins as extracellular autocrine growth factors.
Experimental periodontitis was induced using ligatures in 6 beagle dogs over 57 days. Levels of elastase like activity in healthy sites, gingivitis sites, and in sites ligated for different time points were analyzed with respect to levels of histologically confirmed attachment loss. Attachment loss increased with increasing periods of ligation and reached a maximum of 0.15 mm at 57 days. Maximum loss of histological attachment was found to coincide with the period of maximum enzyme activity; during the first 7 days of ligature. Spearman correlation analysis of enzyme activity with attachment loss yielded a significant correlation (0.73, p=0.0396). The healthy and gingivitis sites were found to have minimal levels of enzyme activity throughout. Thus, this prospective study in beagle dogs found a relationship between histologically confirmed attachment loss and increased levels of elastase like activity indicating the probable usefulness of this parameter, either alone or in conjunction with other markers, for disclosing active periodontitis.
OBJECTIVE: To determine if there are any potential opportunities for patients to be discharged earlier and to determine what factors are responsible for delays in discharge. METHOD: A survey was completed by clinical staff of all patients on the wards of 12 adult psychiatry units in the Greater Vancouver Regional Hospital District (GVRD) for a 1-day period. The survey included a modified Brief Psychiatric Rating Scale (BPRS) and the Discharge Readiness Inventory (DRI). A 1-month follow-up measured discharge and nondischarge outcomes. RESULTS: Of the 327 patients surveyed, 42% were ready for discharge at the time of the assessment, and 37% of those who were ready were not discharged within 2 weeks. Delayed patients had significantly higher scores for disorientation, hallucinations, conceptual disorganization, and manifest psychopathology and significantly lower scores for Community Adjustment Potential (CAP) (P < 0.05). The most frequent reasons given for delays were ongoing medication adjustment, behaviour stabilization, and discharge planning. Patients who were delayed were more likely to need services, to need or be waitlisted for a residential placement, to be a client of the community-based mental health team that provides ongoing support to clients living in the community, to have a diagnosis of schizophrenia, and to have had no previous psychiatric hospital admission. CONCLUSION: The removal of all barriers to delays would reduce lengths of stay by 11% for this sample of patients. This would require a shift of about 42 out of 327 beds to an alternate level of care. These "earlier discharge patients" will need ongoing medication and behaviour monitoring through a variety of community services.
Two insoles designed to treat primary lesser metatarsalgia were compared in terms of their effect on plantar pressures and the subjective symptom relief. A prospective single blind randomized trial of 8 weeks' treatment in 46 feet in 33 patients was performed. Subjective outcome measures were visual analogue pain scores and estimated compliance. Objective outcome measures were dynamic plantar pressures using the Musgrave Footprint System. In group 1 (Viscoped), 6 of 18 patients rated themselves much improved or somewhat improved, and in group 2 (Langer) the proportion was 12 of 15 (P = 0.02). Reported mean compliance was 16% higher in the Langer group. Plantar forefoot pressure was lowered by the insoles in all cases. The reduction was significantly greater (P < 0.001) in group 2, both in absolute pressure and as a percentage of initial pressure. Group 2 (Langer) was significantly better in terms of reduction of peak metatarsal pressure. All the subjective outcome measures were better for the group 2 (Langer).
Several international standards and corresponding interpretation documents for quality management systems have been published. Although these standards are found useful to some extent, they are considered to be insufficient in several areas important for medical laboratories particularly in the pre- and post-examinational phases. The normative document for accreditation of laboratories (ISO/IEC Guide 25) is presently being revised and a document for medical laboratories (ISO/TC 212, CD 15189) is at draft stage. Both aim to include aspects of total quality management. The concept of total quality management is rather vague. Generally, its goal has been defined as "business excellence". This term, however, needs some explanation if applied to medical laboratories. Therefore, a project group of the European Confederation of Laboratory Medicine (ECLM) has developed a model for total quality management, which is based on a comprehensive management concept issued by the European Foundation for Quality Management. In the case of a medical laboratory, the term "business excellence" should be replaced by "good medical laboratory services". The proposed model could serve as a basis for future developments of total quality management standards in laboratory medicine. The goal of the "journey" should be clarified before it starts. To the best of our knowledge, this is the first attempt to develop a model of a good medical laboratory.
Three main fiber types (one slow [type I] and two fast [type IIA and IIB] can be distinguished using conventional actomyosin ATPase (AM-ATPase) histochemistry after acidic pretreatment in mature pig skeletal muscle. We report the isolation, characterization, and identification of four adult 3'-untranslated regions corresponding to types I, IIA, IIB, and IIX myosin heavy chains (MyHC) from a cDNA library. Identification of different type II clones was based on sequence homology, in situ hybridizations (ISH), AM-ATPase histochemistry, and immunocytochemistry. Enzyme histochemistry, immunocytochemistry, and ISH were performed on serial transverse sections of longissimus and red portion of semitendinosus muscle. Results showed that all three fast MyHC transcripts were expressed in the longissimus, whereas only type IIA and IIX transcripts were present in deep red semitendinosus muscle. Type I and IIA fibers contained mostly type I and IIA transcripts, respectively, whereas type IIB fibers contained a heterogeneous population of transcripts. In longissimus muscle, 18, 31, and 51% of conventional IIB fibers were pure IIX, hybrid IIX/IIB, and pure IIB fibers, respectively. Conversely, conventional IIB fibers were actually IIX in deep red semitendinosus muscle. Expression of the three fast adult MyHC isoforms in longissimus was spatially regulated around the typical islets of type I fibers encountered in pig skeletal muscle. Thus, IIA fibers were contiguous to type I fibers, pure IIX fibers were in the direct vicinity of type I and IIA fibers, and hybrid IIX/IIB fibers were located mostly within primary fascicles between the islets of type I fibers; however, pure IIB fibers were located mainly at the periphery of the rosettes near the edges of primary fascicles. In light of the present study, conventional IIB fibers, as defined with AM-ATPase staining, are a heterogeneous population that should be split into pure IIX, hybrid IIX/ IIB, and pure IIB fibers for a more accurate fiber typing.
In October 1995 the UK Committee of Safety of Medicine (CSM) issued a warning about the safety (thromboembolic disease) of the third generation oral contraceptive steroids (OCS) recommending a switch to older agents except where women were intolerant of first and second generation OCS. Advice by the Irish regulatory authority (Irish Medicines Board) did not recommend such a switch. This pill scare lead to some UK users stopping OCS mid-cycle and a rise subsequently in abortions and pregnancies was noted. To determine whether local or UK advice was followed we obtained data from the General Medical Service (GMS) Scheme on the use of contraceptive steroids prescribed before and after the CSM's warning. The results show a clear shift from usage of the third generation OCS to the second generation OCS and norgestimate-containing OCS. We have also noted a marked fall in the overall use of the combined OCS, a trend that was noted in the U.K. It is clear that prescribers and pill users were influenced more by advice from the UK than by Irish regulatory authority. There is now a centralised European mechanism to licence drugs in the European Union (EU). We need to develop an EU perspective to issues of drug safety, as constituent nations are no longer isolated islands.
We have demonstrated increased levels of the circulating soluble adhesion molecules (sCAMs), ICAM-1, VCAM-1, and E-selectin in patients with unstable angina compared with healthy controls. Our findings support the role of inflammation in clinically unstable coronary disease, and may indicate a potential role for measurement of peripheral sICAM levels as a marker for inflammatory activity in atherosclerotic plaque.
Unlike the random distribution of fiber types seen in skeletal muscles of most mammals, pig muscle exhibits a rosette pattern consisting of islets of slow fibers surrounded by concentric circles of type IIA and IIB fibers. Within each islet of slow fibers, one of the central fibers is a primary myofiber, whereas all others are secondary fibers. The present study demonstrates that a subpopulation of the slow secondary fibers transiently expresses alpha-myosin heavy chain (MHC). Two cDNA libraries were made from longissimus dorsi skeletal muscle of 14-day-old piglet and adult pig atrium; the latter muscle is mainly composed of alpha-MHC. Screening of the libraries with a human anti-alpha-MHC mAb (F8812F8) demonstrated the presence of positive MHC clones in both libraries; the nucleotide sequence of the 3'-untranslated region (3'-UTR) was identical in both libraries. As this MHC 3'-UTR had 75% homology with the human alpha-MHC, it was identified as pig alpha-MHC. Using specific cRNA probes and mAbs against pig alpha-cardiac and beta/slow/type I MHC, we studied the expression of these MHCs in developing pig semitendinosus muscle by combining in situ hybridization and immunocytochemistry on serial sections at 90 days of gestation, and at 1, 6, 35 days and 6 months of age. The results showed that a subpopulation of secondary fibers that directly abut primary fibers, transiently produced alpha-MHC, both at the levels of the protein and its transcript. Subsequently, these fibres expressed beta-MHC. At 1 day, immunocytochemistry showed that 16% of the secondary fibers expressed alpha-MHC, among which 20% did not yet express beta-MHC. At 6 days, alpha- and beta-MHCs were mostly present in the same fibers, i.e., 23% of the secondary fibers. Thereafter, the proportion of secondary fibers reacting with alpha-MHC mAb decreased to 10% at 5 weeks and 0% at 6 months, whereas beta-MHC was still accumulating in about 38% of the secondary fibers. During the period studied, the distribution of alpha- and beta-MHC transcripts closely matched that of the corresponding proteins. Expression of alpha-MHC was not detected in primary type I muscle fibers and slow type I secondary fibers at the periphery of the rosettes of slow fibers. This study is the first unequivocal demonstration of a transitory expression of alpha-MHC in a subpopulation of secondary fibers in a limb skeletal muscle during mammalian development.
The bronx waltzer (bv) mutation is an autosomal recessive mutation that is manifested as head tossing and circling in the mouse. The mutation affects the inner hair cells (IHCs) and pillar cells in the organ of Corti of the cochlea and the maculae and cristae of the vestibular part of the inner ear. IHCs begin to degenerate by a controlled mechanism of cell death as early as gestational day 17 (G17) in the basal coil of the cochlea, and few surviving IHCs are seen in the adult. As a first step towards the identification of bv, we analyzed a total of 20 loci in 118 mice from an intraspecific backcross giving the gene order: centromere-D5Mit1-D5Mit73-D5Mit55-[D5Mit12, Nds4 (Afp)]-D5Mit87-[D5Mit205, 20, 88, 208, 93-D5Mit338]-D5Mit25-D5Mit209-bv-D5Mit188-D5M it367-D5Mit95-D5Mit43-D5Mit102. A total of 701 mice were then analyzed for the markers D5Mit93 and D5Mit95, defining a region of 12.08 cM flanking bv. Mice that were recombinant between D5Mit93 and D5Mit95 were analyzed for D5Mit338, D5Mit25, D5Mit209, bv, D5Mit188, and D5Mit367. bv maps 0.14 cM distal of the marker D5Mit209 and 1.14 cM proximal of the marker D5Mit188 in 701 backcross progeny.
Small cell carcinoma of the oesophagus is an uncommon malignancy. Only 272 cases have been reported to date. Inconsistency in therapeutic approaches reflects the paucity of individual experience and the unsatisfactory response to current management strategies. We report 11 cases drawn from a series of 1012 cases of oesophageal malignancy and perform a statistical analysis on treatment and survival data of 189 cases drawn from the world literature. Small cell carcinoma of the oesophagus was seen to have an incidence of 1%. Seven of 11 patients were female. A variety of therapeutic modalities were employed, and the median survival was 6.6 months. Statistical analysis of these and worldwide data showed a significant survival advantage for patients who received multimodality therapy.
A group of 52 women following hysterectomy with conservation of one or both ovaries was compared with an age-matched control group attending with menstrual irregularity/menorrhagia, in terms of proportions of women with postmenopausal endocrine profiles, and climacteric symptoms. The mean age for the groups was 42 years, and the mean interval between hysterectomy and the time of the study was 3.5 years. Endocrine levels were postmenopausal in six study and two control patients, and this difference was not significant. Vasomotor symptoms were a complaint of 28 (54%) of the study group and 18 (35%) of the control group, while 30 (58%) and 18 (35%) respectively had at least two other non-specific symptoms. In the absence of prospective studies elucidating the effect of hysterectomy on ovarian function, endocrine profiles should be performed in hysterectomised women complaining of symptoms.
Human T-lymphocytic virus type 1 (HTLV-1) carriage is associated with a 2% to 5% lifetime risk of developing a severe, if not fatal, disease. In our Inner London antenatal population, we found that the carrier rate was 0.3%. The antenatal transmission rate is known to be very low, but if the infant is breastfed the transmission rate is up to 25%. It is therefore possible to interrupt the transmission cycle by advising against breastfeeding. The ethical and fiscal issues surrounding antenatal testing are addressed.
A survey of dental schools in the European Union was carried out for two main reasons. Firstly to promote the exchange of information in respect of curriculum objectives in the different countries and secondly to ascertain the differences in the interpretation of the 1978 EU sectoral directives for dental education and training. Out of 127 schools, only 30 responded, yet the information provided is of considerable importance. It demonstrates wide divergence in the interpretation of the 1978 Directives and methods of assessment of clinical competence. There is a considerable difference throughout Europe in hours devoted to the various subjects included in the Dental Directives. There is little evidence of convergence in methods of assessment or quality assurance. The survey demonstrates the difference in resources, levels of staff, availability of clinical training places, output in research and patient treatments throughout the European Union. The results question the effectiveness of the 1978 Dental Directives in promoting convergence of standards. As there is free movement of dentists throughout the European Union, it is concluded that a different approach may be necessary to ensure that all European Union dental graduates achieve comparable standards in their education and training.
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The influence of the TAP complex on T-cell allorecognition of MHC class II molecules was examined using human B-cell lines that have mutations in the TAP 1 or 2 genes. The TAP mutations led to the loss of allorecognition for two of 28 anti- HLA-DR T-cell clones. Restoration of TAP expression by transfection of a TAP 2 cDNA clone led to recovery of the alloresponse for both clones. These results could be explained in two ways. First, TAP dependence could reflect specificity for a peptide derived from an MHC class I molecule that is less efficiently generated by the endocytic pathway in the TAP-deficient stimulator cells owing to reduction in surface class I expression. The proliferative responses of these clones to the TAP-deficient stimulator cells was not restored by rescue of cell-surface expression of class I molecules by low temperature culture or by the addition of class I-binding peptides. These data therefore favor the alternative explanation that class II loading by some peptides is TAP dependent. Circumstances that lead to the amplification of this minority pathway of endogenous presentation by class II MHC molecules may have the potential to interrupt self-tolerance.
BACKGROUND: Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma. We conducted a prospective, randomized trial comparing surgery alone with combined chemotherapy, radiotherapy, and surgery. METHODS: Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 (fluorouracil, 15 mg per kilogram of body weight daily for five days, and cisplatin, 75 mg per square meter of body-surface area on day 7) and a course of radiotherapy (40 Gy, administered in 15 fractions over a three-week period, beginning concurrently with the first course of chemotherapy), followed by surgery. The patients assigned to surgery had no preoperative therapy. RESULTS: Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery, 10 and 1, respectively, were withdrawn for protocol violations. At the time of surgery, 23 of 55 patients (42 percent) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases, as compared with 45 of the 55 patients (82 percent) who underwent surgery alone (P<0.001). Thirteen of the 52 patients (25 percent) who underwent surgery after multimodal therapy had complete responses as determined pathologically. The median survival of patients assigned to multimodal therapy was 16 months, as compared with 11 months for those assigned to surgery alone (P=0.01). At one, two, and three years, 52, 37, and 32 percent, respectively, of patients assigned to multimodal therapy were alive, as compared with 44, 26, and 6 percent of those assigned to surgery, with the survival advantage favoring multimodal therapy reaching significance at three years (P=0.01). CONCLUSIONS: Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus.