Quality-adjusted life-years.
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Health Resources↗
Biomedical subjects
A Smith
Publications and source records attributed to A Smith.
Qualms about QALYs.
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Actuarial Analysis↗
Social factors and disease: the medical perspective.
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Health↗
Prevalence of antibodies to human immunodeficiency virus, gonorrhoea rates, and changed sexual behaviour in homosexual men in London.
The prevalence of antibody against human immunodeficiency virus (anti-HIV), which rose among British homosexual/bisexual men attending a London sexually-transmitted-disease clinic from 3.7% (4/107) in March, 1982, to 21% (26/124) in July, 1984, was 18.1% (17/94) in April/May 1985, 24.5% (61/249) in January, 1986, and 25.3% (25/99) in November/December, 1986. This slower rise in anti-HIV prevalence coincided with a fall in the annual gonorrhoea rate from 15.3% in 1982 to 5.1% in the first half of 1986 in the same male homosexual clinic population. Over the same period a reduction in the number of sexual partners and a change to safer sexual practices has been documented among homosexual and bisexual men taking part in a prospective study of the natural history of HIV infection. These data support the value of continuing preventive efforts to control viral spread in the absence of an effective vaccine or therapy.
Acquired Immunodeficiency Syndrome↗
Expression of leukocyte adherence-related glycoproteins during differentiation of HL-60 promyelocytic leukemia cells.
We used the HL-60 human promyelocytic leukemia cell line to analyze the surface expression of a family of adherence-related leukocyte surface antigens during myeloid differentiation. These antigens are composed of discrete alpha subunits, designated alpha L, alpha M, and alpha X, that are each noncovalently associated with a common beta subunit. Monoclonal antibodies directed against the individual subunits served as markers in both indirect immunofluorescence studies and immunoprecipitations from HL-60 cells differentiated preferentially towards mature granulocytes (DMSO, retinoic acid) or monocyte/macrophages (PMA, vitamin D3). In undifferentiated HL-60 cells, the alpha L and alpha X subunits were constitutively expressed, whereas the alpha M subunit was not. Differentiation of HL-60 cells along the granulocytic pathway with DMSO resulted in a marked increase in alpha M and minimal increases in alpha L and alpha X. The phenotypic expression of these antigens on DMSO-treated HL-60 cells closely resembled that on normal circulating PMN. Differentiation along the monocyte/macrophage pathway when using PMA or vitamin D3 resulted in major increases in alpha L and alpha X expression, as well as alpha M. These changes resulted in a surface phenotype characteristic of that present on human monocyte-derived macrophages. Triggering of undifferentiated HL-60 cells with PMA caused no increase in subunit expression, whereas stimulation of DMSO-differentiated HL-60 cells with PMA produced more than a 1.5-fold enhancement of both the alpha M and alpha X subunits, and stimulation of human PMN with PMA increased the surface expression of alpha M more than fourfold and alpha X subunit twofold. Stimulation with PMA produced no change in expression of the alpha L subunit in any of the three cell populations. These results indicate that the alpha subunits of this glycoprotein family can be selectively regulated during in vitro differentiation of a human promyelocytic leukemia cell line. Second, DMSO-differentiated HL-60 cells and human PMN possessed an intracellular pool of alpha M and alpha X, but not alpha L, that could be translocated to the surface. Thus, despite structural and functional relationships among the alpha subunits in this glycoprotein family, they undergo disparate surface expression and intracellular regulation during differentiation.
Antigens, Surface↗
Prenatal cytogenetic diagnosis. Amniotic cell culture versus chorionic villus sampling.
Chorionic villus sampling is under evaluation throughout the world. Amniocentesis with amniotic cell culture is reliable for the diagnosis of certain types of genetic disease in the second trimester, and has been the subject of extensive clinical and laboratory audit. Chorionic villus sampling has the advantage of the early diagnosis (for example, at 10 weeks) of chromosomal abnormalities, a shorter delay with results after the diagnostic procedure, and is, for some couples, a more socially and morally acceptable method of antenatal diagnosis. In current experience, the disadvantages of chorionic villus sampling include an increased fetal loss and an increased diagnostic error rate. Another factor is the early diagnosis of fetuses with chromosomal abnormalities--a proportion of whom would have miscarried spontaneously before being detected at an amniocentesis at 16 weeks. This has implications for an increased rate of therapeutic terminations of pregnancy. Chorionic villus sampling and amniotic cell culture are discussed and comparisons are drawn that concern the clinical advantages and diagnostic issues which are inherent in each method of prenatal diagnosis.
Abortion, Induced↗
S-antigen. Experimental autoimmune uveitis following immunization with a small synthetic peptide.
Experimental autoimmune uveitis was observed following the immunization of Lewis rats with a small synthetic peptide, peptide M (18 amino acids in length), which corresponds to the amino acid sequence of a well-characterized region of S-antigen (404 amino acids in length). Rats were immunized with varying doses of peptide M ranging from 1 to 100 micrograms in complete Freund's adjuvant. As little as 5 micrograms of the synthetic peptide was sufficient for the induction of disease. Clinically, the disease that developed was characterized by iris and pericorneal hyperemia followed by exudates in the anterior chamber. Histopathologically, a severe inflammatory response was observed in animals immunized with high doses of the peptide (greater than 50 micrograms). In these eyes the photoreceptor cell layer of the retina was completely destroyed. A massive subretinal exudate containing mononuclear cells and polymorphonuclear leukocytes was also present. The inflammatory changes were generally less severe following immunization with low doses of the peptide (less than 50 micrograms), and in some eyes only occasional focal lesions were observed. In addition, animals with ocular inflammatory disease had associated pinealitis characterized by a lymphocytic infiltration of the subcapsular and central area of the pineal gland. Both clinically and histopathologically, the experimental autoimmune uveitis produced by the synthetic peptide was indistinguishable from the disease caused by native S-antigen. We comment on the significance of these findings and the relationship of S-antigen in the pathogenesis of experimental autoimmune uveitis.
Amino Acid Sequence↗
Salvage autotransfusion in aortic surgery: initial studies using a disposable reservoir.
Transmission of disease by allogeneic transfusion can be avoided using several techniques by which a patient receives his own blood. Sixty patients undergoing aortic surgery consented to salvage interoperative autotransfusion. A mean of 895 ml shed blood was reinfused under full heparinization, representing 12-74 per cent of total blood loss. Bank blood requirements fell from 4.9 units to 3.4. No important haematological or clinical complications were noted (including coagulation studies) but haemolysis was detected 4 h postoperatively by plasma haemoglobin levels of 0.05 +/- 0.03 g/dl. This preliminary study confirms the applicability of salvage autotransfusion during elective vascular surgery by demonstrating an appreciable saving in bank blood transfusion (70 per cent).
Aorta↗
Human immunodeficiency virus (HIV) infection in the regular sexual partners of homosexual men with AIDS and persistent generalised lymphadenopathy.
Thirty-five homosexual men who had been the regular sexual partners (for at least 6 months) of anti-HIV-positive patients with AIDS (N = 18) or PGL (N = 17) were studied. Twenty-one (60%) were seropositive, but 14 (40%) were consistently anti-HIV-negative. The duration of relationship with the index case was not statistically different in seropositive compared to seronegative partners; median 26 months (range 7-60) vs 30 months (range 7-60). However, seropositive partners had a significantly higher monthly number of other sexual partners and sexually transmitted diseases and a higher frequency of insertive and receptive anal intercourse in the preceding five years. The risk of acquiring HIV infection was significantly increased by frequent receptive anal intercourse when the frequency of insertive was controlled for but not the converse. Seronegative partners had undetectable antibodies by live and fixed cell immunofluorescence and by radioimmunoprecipitation and were repeatedly negative by competitive enzyme immunoassay. Furthermore, the sera of seronegative partners lacked HIV neutralising activity. Peripheral blood mononuclear cells (PBMCs) from seronegative partners, stained with monoclonal antibodies to seven different CD4 epitopes, revealed no differences when compared to those from heterosexual controls and no qualitative differences from cells from seropositive individuals. In addition, PBMCs from seronegative partners could be productively infected by HIV in vitro. If resistance to infection in seronegative partners exists, then it is likely that mechanisms other than a specific humoral immunity or CD4 polymorphisms are involved.
AIDS-Related Complex↗
31P NMR studies on recovery from hypoxia of human tumor cells.
We describe the use of 31P NMR spectroscopy in the study of metabolic changes related to hypoxia in cultured human tumor cells in vitro. The 31P NMR spectrum can easily distinguish between metabolically active cells, metabolically inactive "dormant" cells, and necrotic cells. A crucial observation was that of the ability of the "dormant" cells to resume active metabolism on incubation with oxygen after long periods of hypoxia.
Adenocarcinoma↗
Spatial organization of human perioral reflexes.
Reflex responses recorded from the upper and lower divisions of the human orbicularis oris muscle were studied as a function of the site of stimulation. Stimuli were applied to 11 sites, ranging from the glabrous skin of the upper and lower lip vermilion borders to the hairy skin of the cheek. Highly localized, innocuous mechanical stimuli were created by displacing a servo-controlled probe over the surface of the perioral skin. Reflex response amplitude was strongly dependent on the site of stimulation. Stimulation of some sites, for example the ipsilateral corner of the mouth, the chin, and cheek, produced no responses, whereas stimulation of other sites, particularly the ipsilateral vermilion borders, produced large reflex responses. Changes in response amplitude as a function of stimulation site were the same for the upper lip and lower lip muscle recordings, with the largest responses at both recording sites produced by stimulation of the ipsilateral upper lip vermilion border. These results suggest that the upper and lower divisions of orbicularis oris share common synaptic drive, at least from inputs generated via reflex pathways, and that the upper vermilion border may be more densely innervated with mechanoreceptors than the lower. The latter hypothesis was supported by an additional experiment examining two-point discrimination thresholds for the glabrous skin of the upper and lower lips. Two-point thresholds were significantly smaller for the upper compared with the lower lip vermilion border.
Adult↗
Another treatment for primary biliary cirrhosis.
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Humans↗
Cytogenetic findings in cell lines derived from four ovarian carcinomas.
Six cell lines, established from four primary ovarian carcinomas were examined cytogenetically. The lines varied greatly in their chromosome complement. All cells from the lines were aneuploid, although one cell line contained two populations having a pseudodiploid and a pseudotetraploid modal chromosome number. Every chromosome group was involved with loss and gain of chromosomes, but some individual chromosomes were more prone to aneuploidy than others. Chromosome #6 was the most stable throughout. Structural changes gave rise to many marker chromosomes. Although most markers were random and the majority unidentifiable, some abnormalities of clonal origin were found. Deletions especially of chromosome #1, were the most common change. Further sequential studies may elicit the origin, stability, and timing of the chromosome abnormalities.
Adenocarcinoma↗
Hypothesis: common bacterial toxins are a possible cause of the sudden infant death syndrome.
It is hypothesised that common toxins produced by bacteria growing in the respiratory tract following a viral infection are a cause of SIDS. This hypothesis is consistent with evidence that viral infections pre-dispose to SIDS, minimal morphological change at autopsy, maximum incidence during sleep and the age incidence of this disease. We present evidence of nasopharyngeal bacterial overgrowth in victims of SIDS and have developed a mathematical model based on the hypothesis which closely predicts the age distribution. The model predicts other age distribution patterns for less common toxins and these may apply to other diseases of childhood. The hypothesis can be tested and if sustained would offer hope of prevention.
Age Factors↗
Tumour markers in diagnosis and management.
The 20-year period since the discovery of AFP by Abelev has seen the introduction of a wide range of new tumour markers and it is now clear that PLC is biologically heterogeneous. Hepatoblastomas, fibrolamellar carcinomas, hepatocellular carcinomas and cholangiocarcinomas may secrete a variety of distinctive markers which are predominantly glycoproteins, and may resemble those found in placenta or fetal liver. Diagnostically, AFP remains the best marker for HCC, both in sensitivity and specificity; it is known to consist of isoforms. In patients with elevated serum AFP and filling defects on liver scan, Con A reactive AFP may differentiate PLC from hepatic metastases, whilst fucosylated AFP may distinguish PLC from benign disorders when AFP is non-diagnostically elevated. With this recognition of tumour heterogeneity the value of a multiple-marker approach has become apparent. The measurement of vitamin B12 binding protein and neurotensin should lead to the detection of most patients with the fibrolamellar variant of HCC and many of these should be resectable. In patients with normal serum AFP levels, HCC-associated GGTP is of major value whilst in low-incidence areas for HCC, patients should also be screened for H-ALP; using a multiple marker approach in high-risk groups, 90% of clinically diagnosed hepatocellular carcinomas are serologically positive. The Chinese and Alaskan studies, in which small, potentially resectable tumours were detected, suggest that it is now possible to achieve 5-year survival figures of up to 60% in HCC patients detected by screening. The value of such a strategy in low-incidence countries is currently under study. In patient monitoring, as in diagnosis, AFP remains the outstanding marker. In AFP-negative patients, other markers including vitamin B12-binding protein, neurotensin, HCC-specific isoenzymes, des-gamma-carboxy-prothrombin and alpha-fucosidase, are of undoubted diagnostic value, but their value as indicants of disease progression remains to be established. In monitoring the response of hepatic metastases, CEA remains the least unsatisfactory marker but should always be used in conjunction with serial ultrasound scans. Tumour markers now play an important role in the diagnosis and monitoring of PLC but a role is also emerging in tumour imaging and drug targeting. The next 20 years should see the introduction of tumour markers of high sensitivity and specificity which make a fundamental contribution not only to detection and monitoring, but also to the effective treatment of liver cancer.
Adenoma, Bile Duct↗
A controlled trial of colchicine in primary biliary cirrhosis. Trial design and preliminary report.
Colchicine (1 mg/day), or an identical placebo, was given to 64 patients with primary biliary cirrhosis in a double-blind controlled trial. Due to a novel, pair-matched trial design, the two groups were exceptionally well matched at entry. In comparison with placebo, colchicine produced a beneficial effect on serum albumin and bilirubin levels at 3 months in patients who had abnormal liver function (bilirubin greater than 20 mumol/l) at entry: (albumin, P = 0.047; bilirubin, P = 0.022). In patients with normal liver function at entry (bilirubin less than 20 mumol/l), beneficial effects were noted on total globulin levels at 3 months (P = 0.013) and on immunoglobulin G levels at 3 and 6 months (P = 0.044 and 0.001, respectively). At 18 months, survival estimate in the colchicine and placebo groups were 84% and 69%, respectively. The difference did not reach significance. Colchicine produced an early improvement in liver function and immunoglobulin levels. Few serious side effects were encountered, and colchicine clearly merits long-term study in the treatment of primary biliary cirrhosis.
Bilirubin↗
Disharmony between atrioventricular connections and segmental combinations: unusual variants of "crisscross" hearts.
Two congenitally malformed hearts are described, one studied in life and the other at autopsy, in which the topology of the ventricular mass was not as expected for the atrioventricular (AV) connection present. In Case 1, studied at autopsy, there was the usual atrial arrangement with a concordant AV connection. The morphologically right ventricle, however, was left-sided and the ventricular mass was of left-hand topology (l loop) rather than the expected right-hand pattern (d loop). In Case 2, studied during life, there was the usual atrial arrangement and a discordant AV connection. Rather than the anticipated left-hand topology (l loop), the ventricular mass was arranged in right-hand fashion (d loop) and the morphologically right ventricle was right-sided. The cases emphasize that for a full description of a congenitally malformed heart, it is often necessary to account for the topology of each segment as well as the connections (or alignment) among the segments.
Crisscross Heart↗
Reflex responses in human jaw, lip, and tongue muscles elicited by mechanical stimulation.
Reflex responses in human jaw, lip, and tongue muscles were elicited with brief, innocuous mechanical stimuli. Stimuli were applied to the masseter (and overlying tissue), the lower lip vermilion, and the tongue dorsum. Reflex responses occurred in masseter, orbicularis oris inferior, and genioglossus muscles upon direct stimulation of the sites associated with each of these muscles. In contrast, reflex responses to stimulation of "distant" sites occurred almost exclusively in masseter; that is, stimulation of the lip and tongue produced responses in masseter, but, stimulation of jaw muscle spindle afferents and overlying cutaneous receptors had no observable effect on activity in genioglossus or orbicularis oris inferior muscles. It could be hypothesized that the motoneuron pools controlling jaw muscles are more sensitive to synaptic inputs generated by reflex pathways originating in other structures. The sensitivity of the masseter muscle to inputs from the lip and tongue may serve to link these structures functionally.
Adult↗