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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 217 records · Page 12Linked to original sources
PubMed1994

Menstrual symptoms in women infected by the human immunodeficiency virus.

OBJECTIVE: To determine whether there is a higher prevalence of menstrual symptoms in women seropositive for the human immunodeficiency virus (HIV) compared to a matched control group and to examine the relation between menstrual symptomatology and immunosuppression. METHODS: In a cross-sectional study, 55 HIV-seropositive women and a matched control group underwent detailed gynecologic assessment. The prevalence of regular cycles, oligomenorrhea, amenorrhea, menorrhagia, dysmenorrhea, and dyspareunia was assessed in the two groups. Any association with clinical disease or CD4 lymphocyte count was sought. RESULTS: There were no significant differences in the prevalence of oligomenorrhea, amenorrhea, menorrhagia, dysmenorrhea, or dyspareunia between the groups. Furthermore, no differences were demonstrated between symptomatic and asymptomatic women infected by HIV, nor was any correlation found between CD4 lymphocyte count and menstrual loss or dysmenorrhea. CONCLUSION: Infection with HIV and related immunosuppression do not seem to have a clinically significant effect on menstruation.

Adult↗
PubMed1994

Transposition of the imidazole ring substituents of angiotensin mimetics related to Losartan.

A series of analogues related to Losartan in which the imidazole ring substituents were transposed have been prepared. Biological evaluation, both in vitro and in vivo, demonstrated that the orientation of the imidazole ring has a subtle yet significant effect upon the potency of these analogues. This information has provided an insight into the possible mode of receptor binding of Losartan and related compounds.

Angiotensin Receptor Antagonists↗
PubMed1993

Synthesis and biological activities of angiotensin II, Sarilesin, and Sarmesin analogues containing Aze or Pip at position 7.

Analogues of [Sar1]angiotensin II, Sarilesin (type I antagonist), and Sarmesin (type II antagonist) with L-azetidine-2-carboxylic acid (Aze) and L-pipecolic acid (Pip) at position 7 have been prepared by the solid-phase method, purified by reverse-phase HPLC, and bioassayed in the rat uterus. Analogues of the superagonist [Sar1]ANGII with Aze or Pip at position 7 and sarcosine (Sar) or aminoisobutyric acid (Aib) at position 1 had high intrinsic activity in the rat isolated uterus assay (34-184%). Analogues of Sarilesin ([Sar1,Ile8]ANGII) with Aze or Pip at position 7 and Sar or Aib at position 1 retained high antagonist activity (pA2 = 7.1-8.3). Analogues of Sarmesin ([Sar1,Tyr-(OMe)4]ANGII) with Aze and Pip at position 7 had pA2 values of 7.4 and 6.5, respectively. [Aze7]-ANGII and [Pip7]ANGII had low activities (12% and 1%, respectively), and deletion of Sar at position 1 of Sarmesin analogues abolished binding (or affinity) as judged from pA2 values. Nuclear Overhauser effect (NOE) spectroscopy studies of [Sar1,Aze7]ANGII in DMSO-d6 have indicated a clustering of the three aromatic rings (Tyr, His, Phe) and proximity of Sar C alpha and Arg C delta protons to the Tyr/Phe ring protons. These data emphasize that replacement of Pro with the lower and higher homologs Aze and Pip does not greatly alter the structural requirements necessary for expression of agonist or antagonist activity, when sarcosine occupies position 1, but not when Asp occupies position 1, suggesting that there is an intimate relationship between the N-terminal and penultimate residues of the molecule in the biologically active conformation of the molecule.

Angiotensin II↗
PubMed1993

Structure and evolution of the promoter regions of the DQA genes.

HLA-DQ antigens are unique among the class II antigens in that their alpha chains are highly polymorphic. In the present study, we characterized the general structure of the promoter regions of the DQA genes derived from different DR haplotypes and defined their nucleotide sequence polymorphisms. The promoter of each DQA1 allele contains three sequence motifs which are not present in non-DQA related class II genes: one identical to a tumor necrosis factor (TNF alpha) response element, one similar to an NF kappa B binding element, and one similar to a W motif. All DQA alleles lack TATA and CCAAT boxes in the proximal promoter region but carry other sequence elements characteristic of MHC class II genes, including S, X, X2, and Y boxes, and a pyrimidine-rich tract upstream of the X box. Nucleotide sequence polymorphisms among the various DQA1 alleles were noted within the promoter region, with some of the differences mapping within, or close to, regulatory elements that are important for the expression of MHC class II genes. All DQA1 alleles carry an unrearranged, full length, Alu-Sx related repeat immediately upstream of the proximal promoter region. This repeat was not present in the DQA2 (DXA) genes analyzed, confirming that DQ locus duplication probably occurred before integration of the Alu repeat into the primordial DQA1 locus, some 31-43 million years (myr) ago. The DQA2 promoter region is highly conserved between DR4 and DR3 haplotypes, with the degree of conservation exceeding that expected from the neutral mutation rate.

Alleles↗
PubMed1993

Localization of temporal lobe seizures with quantitative EEG.

In this study, we describe a quantitative EEG method for localization of seizure onset in 29 patients with temporal lobe epilepsy. We used right-left differences in relative power and a logistic regression to predict the side of seizure onset. The optimum bipolar channels were T4-T6/T3-T5 and the optimum frequency band was 4-10.5 Hz. Using a threshold probability of 0.75 for classification, the best quantitative EEG method classified 23 patients (79%) correctly, 2 patients (7%) incorrectly, and 4 patients (14%) as undetermined localization. In comparison, 3 electroencephalographers visually interpreted these same EEGs and classified 20-25 patients (69-86%) correctly, 1 patient (3%) incorrectly and 3-8 patients (10-28%) as undetermined localization. In the 8 patients classified as undetermined localization by at least one interpreter, the quantitative EEG method classified 5 patients correctly, 1 patient incorrectly and 2 patients as undetermined localization. These results suggest that quantitative EEG might improve the reliability of ictal EEG localization and potentially reduce the need for invasive intracranial EEG monitoring.

Adolescent↗
PubMed1993

Infection due to Chlamydia trachomatis in pregnancy and the newborn.

Bacteria in the genus Chlamydia comprise three species, C. trachomatis, C. psittaci and C. pneumoniae. C. trachomatis infection is common, varying in prevalence in women from 0% to 37%. In the United States, the prevalence rate is estimated currently to be about 5%. Pregnancy may predispose to an increased chance of infection with C. trachomatis, through physiological immunosuppression and/or cervical ectopy. Maternal antibodies to C. trachomatis provide limited, if any, protection for the newborn. C. trachomatis causes pelvic inflammatory disease--which can result in tubal infertility or ectopic pregnancy and postabortal or late postpartum endometritis. It may also cause chorioamnionitis and premature delivery of the fetus. The incidence of vertical transmission of chlamydiae from mother to baby varies; if the mother is untreated, 20-50% of the newborns will develop conjunctivitis and 10-20% will develop pneumonia. C. psittaci infection in pregnancy is rare, but can cause spontaneous abortion. Whether C. pneumoniae infection in pregnancy has any influence on the outcome has not been ascertained. C. trachomatis can be detected by one or more of several methods; enzyme immunoassays are the least sensitive, but the most widely used. Screening for C. trachomatis in pregnancy may be of benefit in areas of high prevalence, and is generally regarded as being cost-effective if the prevalence rate is more than 5%. Pregnant women are best treated with erythromycin, 250 mg four times daily for 7 days. This will prevent infection of the newborn in more than 90% of cases. The infected neonate should be treated with erythromycin, given systemically and also with topical tetracycline if conjunctivitis is present.

Chlamydia Infections↗
PubMed1993

Is HIV infection associated with an increase in the prevalence of cervical neoplasia?

OBJECTIVE: To test the hypotheses: (1) that HIV infection predisposes to cervical intraepithelial neoplasia (CIN); (2) that this CIN is a result of HIV related immunosuppression; and (3) that this CIN is a result of immunosuppression causing increased expression of the potentially oncogenic viruses, human papilloma virus (HPV), Epstein Barr virus (EBV) and herpes simplex virus (HSV). DESIGN: A matched cross sectional study. SETTING: The Department of Gynaecological Oncology, The Samaritan Hospital, London; the Department of Genitourinary Medicine, St Mary's Hospital, London; and the Family Planning Clinic, Claremont Terrace, Glasgow. SUBJECTS: Fifty HIV seropositive women enrolled from the Genitourinary Medicine Department and the Drug Dependency Unit at St Mary's Hospital, London, and the Unit of Infectious Diseases at Ruchill Hospital, Glasgow. Forty-three HIV seronegative controls enrolled from the Department of Genitourinary Medicine at St Mary's Hospital, matched against 43 of the seropositive women for age, age at first intercourse, lifetime number of sexual partners, and smoking habit. MAIN OUTCOME MEASURES: Associations between CIN, as detected by cytology and histology, and HIV infection. Association was also sought between CIN and immunosuppression, as measured clinically by T4 cell number, beta-2-microglobulin and p24 antigen. Associations of these with: (1) HPV, as detected by Southern blot testing and the polymerase chain reaction; (2) EBV, as detected by Southern blot testing; and (3) HSV, as detected by tissue culture of endocervical swabs, was also studied. RESULTS: There was no significant difference in the prevalence of CIN or oncogenic viruses between HIV seropositive and seronegative women in the absence of immunosuppression. If the HIV infected women showed signs of immunosuppression, the prevalence of CIN was increased. No association was shown between detection of HPV, EBV and HSV and immunosuppression or CIN. CONCLUSION: HIV infection may only be associated with an increased risk of CIN when immunosuppression is present.

Adult↗
PubMed1993

Is endometrial infection with Candida albicans a cause of recurrent vaginal thrush?

OBJECTIVE: It was hypothesised that the endometrium might act as a reservoir for candida, thus infecting the vagina as the endometrium is shed during menstruation. DESIGN: A prospective study of women with recurrent vulvo-vaginal candidiasis. The endometrium was sampled and cultured for candida species. SETTING: Central London STD clinic. SUBJECTS: 26 women were enrolled, of whom 20 completed the study. RESULTS: One patient had a positive endometrial culture for candida species, the isolate being Candida krusei. CONCLUSIONS: The endometrium is not a common resevoir for candida species and therefore, infection at this site is an unlikely cause of recurrent vaginal candidiasis.

Candida albicans↗
PubMed1993

Women with HIV presenting at three London clinics between 1985-1992.

OBJECTIVE: To determine the changing patterns of HIV infection in women in three units in London. SUBJECTS: Three hundred and fifty seven HIV seropositive women who have attended outpatient clinics between 1984 and 1992. METHODS: A retrospective review of data obtained from a computerised database and supplemented by direct inspection of the notes. RESULTS: The number of newly identified women with HIV has risen steadily over the period of study with a significant shift towards a heterosexual mode of transmission. This is a reflection of increasing numbers of women from Sub-Saharan Africa rather than a rise in the incidence of HIV in women born in the UK. CONCLUSIONS: The increase in women infected by HIV remains predominantly restricted to women in "high risk" groups. Although encouraging, our data should be interpreted with caution since it suffers from the inherent bias of selective testing. Safer sex education and epidemiological surveillance should continue despite the apparent low risk to women born in the UK.

Africa South of the Sahara↗
PubMed1993

Seizure localization in temporal lobe epilepsy: a comparison of scalp-sphenoidal EEG and volumetric MRI.

We determined the accuracy of volumetric MRI (based on identification of unilateral hippocampal atrophy) and scalp-sphenoidal EEG (based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters) for seizure focus localization in 20 patients with temporal lobe epilepsy. All patients became seizure-free or had rare seizures following temporal lobectomy. Among the 20 patients, nine (45%) met both MRI and EEG localization criteria, six (30%) met MRI localization criteria alone, three (15%) met EEG localization criteria alone, and two patients (10%) did not meet either localization criteria. In the 18 patients meeting MRI or EEG localization criteria, the predicted localization agreed with the side of temporal lobectomy. These results suggest that a noninvasive approach combining MRI and EEG will correctly localize the side of seizure onset in most patients with temporal lobe epilepsy.

Adolescent↗
PubMed1993

Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy.

We examined the relationship of Wada memory performance and MRI hippocampal volume measurements to laterality of ultimate seizure localization in 20 patients with complex partial seizures who later underwent temporal lobectomy. Discriminant function analysis employing both Wada memory test asymmetries and hippocampal volume asymmetries correctly classified 100% of the patients into left and right temporal lobe groups. Wada memory asymmetries alone correctly classified 90% of the sample (80% of the sample when the discriminant function included all patients except the one being classified), and hippocampal volume asymmetries alone correctly classified 90% of the patients. A significant correlation was present between Wada memory asymmetries and hippocampal volume asymmetries (r = 0.78), indicating that structural evidence of reduced hippocampal volume has a functional correlate reflected by Wada memory performance. These data suggest that the combination of functional and structural measures is of value in the preoperative evaluation for epilepsy surgery.

Adult↗
PubMed1993

Possible novel action of ouabain: allosteric modulation of vascular serotonergic (5-HT2) and angiotensinergic (AT1) receptors.

Experiments were carried out to determine the effects of ouabain and dihydroouabain, both at 10 microM, on the vasoconstrictor responses of isolated rabbit blood vessel rings to both serotonin and angiotensin II. Ouabain plus dihydroouabain increased the sensitivity of central ear artery to serotonin and markedly reduced the antagonist potency of 0.1 microM prazosin against serotonin in this blood vessel; dihydroouabain alone had no effect. Ouabain, markedly reversed the reduction of maximal contractile response by both 2-brom-d-lysergic acid diethylamide against serotonin in aorta and 2-n-propyl-4-trifluoromethyl-1-[(2'-1H-tetrazol-5yl)biphenyl -4- yl)methyl]imidazole-5-carboxylic acid (EXP 3892) against angiotensin II in femoral artery; dihydroouabain had no effect. Whereas both 10 microM ouabain and dihydroouabain produced nearly maximal inhibition of Na+K+ATPase, dihydroouabain failed to modulate the vasoconstrictor responses to either serotonin or angiotensin II. Thus, it is concluded that the vasoconstrictor modulatory effects of ouabain are mediated by mechanisms unrelated to Na+K+ATPase inhibition. The present results are consistent with the hypothesis that both 5-hydroxytryptamine2 and angiotensinergic receptors can exist in high and low activity states. It is proposed that 5-hydroxytryptamine2 receptors exist in a low activity state in the ear artery, or are converted to the low activity state by 2-brom-d-lysergic acid diethylamide in the aorta. Hypothetically, 2-n-propyl-4-trifluoromethyl-1- [(2'-(1H-tetrazol-5yl)biphenyl-4-yl)methyl]imidazole-5-carbo xylic acid also converted the angiotensinergic receptor to the low activity state in femoral artery. In all three cases, ouabain enhanced vasoconstriction to serotonin and angiotensin II, respectively, possibly by allosterically modulating the respective receptors in these vessels to their high activity states.

Allosteric Regulation↗
PubMed1993

Imidazole based non-peptide angiotensin II receptor antagonists. Investigation of the effect of the orientation of the imidazole ring on biological activity.

Non-peptide angiotensin II receptor antagonists related to losartan (DuP 753, CAS 114798-26-4) were prepared and evaluated for antagonist activity in the rat isolated uterus assay. The synthetic strategy concentrated on changes in the orientation of the imidazole ring relative to the substituents, which were maintained in a similar pattern to that found in losartan. The results indicate that biological activity of such antagonists shows little dependence on the orientation of the imidazole ring, but that the spacing of the substituents of primary importance.

Acrylates↗
PubMed1993

Creating an integrated health care delivery system: a regional nonprofit provider case study.

The development of integrated health care systems holds many pitfalls as well as potentials. This case study describes the development of the strategy that has moved the structure, mission, and vision of a health care system. It examines the questions of what members, payers, and providers' needs are when defined around the paradigm of responsibility for the health as well as the health care of a population. It starts by examining the background of the development of the strategies used by the health system during the past decade, and the environmental climate that has led to a redefinition of the mission and vision of the organization. This movement has moved the focus on acute health services to the development of a regional integrated health care system based on collaboration and on a responsibility to improve the health of those we serve through treatment, prevention, and education. Finally, the chapter reviews the options facing all of us: do we compete, collaborate, or both?

Comprehensive Health Care↗
PubMed1993

Current status of epilepsy surgery.

In the United States, there are approximately 75,000 patients with medically intractable epilepsy of focal origin who are candidates for ablative surgery. Currently, about 1500 epilepsy operations are performed per year in the United States. Candidates for ablative surgery (i.e., removal of epileptogenic tissue) are those with a reasonable chance of reduction in seizure frequency and improvement of overall lifestyle. The epileptogenic tissue must be localized preoperatively by either non-invasive or invasive recordings, or by imaging studies (e.g., MRI). Nearly 60% of all patients who undergo resection of a temporal or extra-temporal seizure focus become seizure free, and about 70% have no seizures or only rare ones. The most commonly performed operation is anterior temporal lobectomy. This update article will also review the results of other epilepsy operations which are currently performed--hemispherectomy, corpus callosotomy, and multiple subpial transection.

Adult↗