Carrying out a bed census at a district hospital in Zambia.
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Bed Occupancy↗
Biomedical subjects
S Foster
Publications and source records attributed to S Foster.
G protein gene mutations in patients with multiple endocrinopathies.
Point mutations of G protein genes that result in the constitutive activation of G proteins have been described. Such mutations have been shown to occur in a number of endocrine diseases. We have examined tissues from patients having more than one organ affected by an endocrine disorder and patients having separate distinct endocrine diseases for G protein gene mutations. G protein genes encoding for Gs alpha and Gi2 alpha were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) using site-directed oligonucleotide hybridization and direct sequencing of tissue DNA amplified by polymerase chain reaction. Tissues from six patients were examined. The only mutation that was identified was at codon 201 of Gs alpha (gsp), which encoded a change from arginine to cysteine. Patient 1 had the mutation in a corticotroph adenoma, a chemodectoma, and a nodular hyperplastic adrenal gland. patient 2 had the mutation in an extraadrenal pheochromocytoma, but an adrenal gland with medullary hyperplasia was wild-type. Patient 3 had an aggressive corticotroph adenoma and developed Nelson's syndrome after bilateral adrenalectomy. The corticotroph adenoma was wild-type, but both hyperplastic adrenal glands had the mutation. Patient 4 had the mutation in a parathyroid adenoma and in two hyperplastic parathyroid glands. Patient 5 had the mutation in both a primary and a metastatic pheochromocytoma. Patient 6 had the mutation in a parathyroid adenoma and also in histologically normal thyroid and parathyroid tissue. Leukocyte DNA was examined from five patients and was found to be wild-type in all cases. We conclude that G protein gene mutations occur in a wider range of endocrine conditions than has been recognized hereto. In addition, the presence of gsp mutations in different endocrine disorders in the same patient is suggestive of a common underlying etiology.
Adult↗
The impact of HIV on the University Teaching Hospital, Lusaka, Zambia.
The article examines the impact of admission of AIDS (and related TB) patients to an African Teaching Hospital. Because of limited resources available in general but also because of the gravity of the AIDS patients' state, non-HIV patients are being discharged too early. The article explains patient management techniques for minimizing the general negative impact on the quality of patient care.
Adolescent↗
Parental stress and growth outcome in growth-deficient children.
OBJECTIVE: In order to examine the relationship between parental stress, child psychosocial factors, anemia, lead poisoning, and growth deficiency (GD), 48 children attending a GD referral program were recruited consecutively and matched with 50 comparison subjects from a primary care program. METHOD: Parents completed the Parenting Stress Index (PSI) with subscales and provided demographic data. Children received developmental screening, hemoglobin levels, Pb levels, and growth evaluation. They also received medical evaluation for GD. T tests were used to evaluate group differences. Spearman Rho correlation analyses were computed between group coefficients and PSI scales, Pb, and hemoglobin levels. RESULTS: No differences were found on the PSI with regard to overall parental stress. GD parents perceived themselves as less competent (P < .001), and their children as less adaptable (P < .006). They also reported more social isolation (P < .05). The GD group had more anemia and Pb poisoning (P < .002 and P < .001, respectively); however, these variables were not related to differences in child adaptability or growth outcome. A high sense of parental competence and high child adaptability were associated with improved growth outcomes (P < .001 and P < .02, respectively). CONCLUSIONS: We conclude that parents of GD children seen in an outpatient referral setting show no difference in overall perceived stress levels versus comparison subjects. Increased parental competence and child adaptability are strongly associated with improved growth outcome. Decreased child adaptability may contribute to GD pathology. These findings challenge the traditional view of GD etiology.
Adaptation, Psychological↗
Treatment of malaria outside the formal health services.
Self-medication for malaria is widely practised around the world, and although many home treatment episodes are successful, the risk of under or over-dosing is always present. Reasons for the widespread use of self-medication range from the distance and cost of seeking care from the formal health services to cultural beliefs which suggest that traditional care is more appropriate, and even that modern care may be fatal. But self-medication constitutes an important resource for malaria treatment, and much could be done to improve the self-medication practices of the population. Measures to be taken include dissemination of clear messages about malaria as a part of health education, formulation of realistic treatment policies which take account of resource constraints, lowering or removal of economic barriers, especially user charges, and further research into cultural beliefs about malaria and ways to promote compatibility of beliefs with appropriate treatment. If these suggestions could be taken into account in developing malaria treatment strategies, the chances of success would be greatly enhanced.
Attitude to Health↗
Health-care reform: the issues and the role of donors.
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Charities↗
Simultaneous expression of tissue factor and tissue factor pathway inhibitor by human monocytes. A potential mechanism for localized control of blood coagulation.
Cells of monocytic lineage can initiate extravascular fibrin deposition via expression of blood coagulation mediators. This report is about experiments on three mechanisms with the potential to modulate monocyte-initiated coagulation. Monocyte procoagulant activity was examined as a function of lipid cofactor, protein cofactor, and specific inhibitor expression during short-term culture in vitro. Lipid cofactor activity was measured as the initial rate of factor X activation by intrinsic-pathway components, the assembly of which depends on this cofactor. Lipid cofactor activity levels changed by < 30% during 48-h culture. Protein cofactor, i.e., tissue factor (TF) antigen was measured by enzyme immunoassay. It increased from 461 pg/ml to a maximum value of 3,550 pg/ml at 24 h and remained at 70% of this value. Specific TF activity, measured as factor VII-dependent factor X activation rate, decreased from 54 to 18 nM FXa/min between 24 and 48 h. TF activity did not correlate well with either lipid cofactor or TF protein levels. In contrast, the decrease in TF activity coincided in time with maximal expression of tissue factor pathway inhibitor (TFPI) mRNA, which was determined using reverse transcriptase polymerase chain reaction (RT-PCR), and with maximal TFPI protein levels measured by immunoassay. The number of mRNA copies coding for TFPI and TF in freshly isolated blood monocytes were 46 and 20 copies/cells, respectively. These values increased to 220 and 63 copies/cell during short-term cell culture in the presence of endotoxin. Results demonstrate concomitant expression by monocytes of genes coding for both the essential protein cofactor and the specific inhibitor of the extrinsic coagulation pathway. Together with functional and antigenic analyses, they also imply that the initiation of blood clotting by extravascular monocyte/macrophages can be modulated locally by TFPI independently of plasma sources of the inhibitor.
Blood Coagulation↗
Economic prospects for a new antimalarial drug.
The market for antimalarial drugs consists of the 2.8 billion (2.8 x 10(9) people living in malaria endemic areas and about 20-30 million people, mainly Europeans and North Americans, who travel or live in malarious areas, and the wealthy elite of malarious developing countries. Some of the largest markets include China, India, and Indonesia with a total of 1.9 billion people exposed; Latin America, with 119 million; and sub-Saharan Africa with 400 million. An estimated 200 million clinical cases occur each year, with around 2 million deaths annually, primarily in African children. Antimalarial drugs are distributed through several different networks and are purchased by governments and private individuals. At present the world market is dominated by chloroquine by virtue of its safety, wide availability and low price. Approximately 20% of the total production of chloroquine was distributed through national control programmes and 80% through other channels; chloroquine is probably the second or third most widely consumed drug in the world. The global market for antimalarial drugs is likely to be of the order of US$100-120 million, with chloroquine making up about US$64-80 m, sulfadoxine/pyrimethamine about US$20 m, and other drugs making up US$10-20 m. Chloroquine is rapidly losing its effectiveness against the malaria parasite, and a safe, effective, cheap replacement is urgently needed. Another product which was found to be safe and effective against malaria, with a price per treatment held at or near the present price of chloroquine, could quickly replace chloroquine as the first-line treatment against malaria.(ABSTRACT TRUNCATED AT 250 WORDS)
Antimalarials↗
Presacral Neurectomy for Treatment of Midline Pelvic Pain: Laparoscopic Approach with Laparoscopic Treatment of a Single Major Complication
The treatment of midline dysmenorrhea and pelvic pain with laparoscopic presacral neurectomy (LPSN) has been reported previously. In this prospective study, 27 women experienced severe midline dysmenorrhea/pain, and 12 of these women also had significant lateral pain. Other procedures including lysis of adhesions, excision/vaporization of endometriosis, and appendectomy were completed prior to LPSN. Twenty-two women reported no midline pain in follow-up 5 to 35 months postoperatively, 4 noted significant reduction of midline pain, and 1 had persistence of severe pain. Of the 12 women with lateral and midline pain, 3 had persistence of pain. Laparoscopic repair of a left common iliac vein laceration was accomplished with hemoclips. This report supports the view that LPSN is a safe and effective procedure for treating midline dysmenorrhea/pelvic pain when performed by experienced laparoscopic surgeons. Selected complications may be managed laparoscopically.
Journal Article↗
Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours.
BACKGROUND AND OBJECTIVE: Activating mutations of Gs alpha (gsp) and Gi2 alpha (gip) have been described in various endocrine neoplastic conditions. The objective of this study was to assess the prevalence of gsp and gip mutations in clinically non-functioning pituitary tumours (NFTs) and to compare the clinical phenotypic characteristics of tumours bearing G protein gene mutations with wild-type tumours. DESIGN: Twenty-two NFTs and 20 normal anterior pituitary glands screened for G protein gene mutations. PATIENTS: Twenty-two patients; 14 female (median age 59 years, range 19-76) and 8 males (median age 66.5 years, range 50-77). MEASUREMENTS: Site-directed hybridization or direct sequencing of polymerase chain reaction amplified Gs alpha and Gi2 alpha DNA. RESULTS: G protein gene mutations were identified in 3/22 (13%) of NFTs. Two tumours demonstrated gsp mutations, one at codon 201 arginine to cysteine, and the second at codon 227 glutamine to arginine. Three tumours demonstrated gip mutations at codon 205 glutamine to arginine. Two tumours with gsp mutations also harboured gip mutations. All tumours with G protein gene mutations demonstrated local bone infiltration into the surrounding structures. CONCLUSIONS: G protein gene mutations have been demonstrated in a proportion of non-functioning pituitary tumours. The presence of dual gsp and gip mutations in two tumours suggests the possibility of multiple hits in a stepwise pathogenesis of pituitary neoplasia.
Adenoma↗
Effect of the 5-lipoxygenase inhibitor ZD2138 on aspirin-induced asthma.
BACKGROUND: The cysteinyl leukotrienes may play a central part in the mechanisms of aspirin-sensitive asthma. Previous work has shown that individuals with aspirin-sensitive asthma have high basal urinary LTE4 levels which increase further upon aspirin ingestion, and that sulphidopeptide leukotriene receptor antagonists attenuate aspirin-induced airflow obstruction. If the cysteinyl leukotrienes cause aspirin-induced asthmatic reactions, inhibition of the 5-lipoxygenase pathway should prevent aspirin-induced bronchospasm. This hypothesis has been tested with ZD2138, a specific non-redox 5-lipoxygenase inhibitor. METHODS: Seven subjects (four men) with aspirin-sensitive asthma with baseline FEV1 values > 67% were studied. ZD2138 (350 mg) or placebo was given on two separate occasions two weeks apart in a randomised double blind fashion. A single dose of aspirin was administered four hours after dosing and FEV1 was measured for six hours. Inhibition of the 5-lipoxygenase pathway by ZD2138 was assessed by measurements of urinary LTE4 levels and ex vivo calcium ionophore stimulated LTB4 generation in whole blood, before administration of drug or placebo and at regular time intervals after dosing and aspirin administration. RESULTS: ZD2138 protected against the aspirin-induced reduction in FEV1 with a 20.3 (4.9)% fall in FEV1 following placebo compared with 4.9 (2.9)% following ZD2138. This was associated with 72% inhibition of ex vivo LTB4 generation in whole blood at 12 hours and a 74% inhibition of the rise in urinary LTE4 excretion at six hours after aspirin ingestion. CONCLUSIONS: In aspirin-sensitive asthma the 5-lipoxygenase inhibitor ZD2138 inhibits the fall in FEV1 induced by aspirin and this is associated with substantial inhibition of 5-lipoxygenase.
Adult↗
HIV and AIDS in Africa. 1. Assisting those in the early stages of HIV infection.
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Acquired Immunodeficiency Syndrome↗
Therapeutic conservatism.
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Costs and Cost Analysis↗
DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non-malignant phenotype.
There are many reports of cell lines being established from human oral squamous-cell carcinomas but apparently none of cell lines from dysplastic or "pre-malignant" oral mucosa. We describe here the isolation and characterization of a cell line, DOK (dysplastic oral keratinocyte), from a piece of dorsal tongue showing epithelial dysplasia. The tissue was obtained from a 57-year-old man who was a heavy smoker prior to the appearance of a white patch on his tongue. Eleven years later a squamous-cell carcinoma developed at the site and was excised. Subsequently the remaining dysplasia was removed, and it was from a piece of this that the primary cell cultures which eventually gave rise to DOK were initiated. The DOK line has been single-cell cloned and is apparently immortal. It grows in the absence of 3T3 feeder cells, is anchorage-dependent for growth and is non-tumorigenic in nude mice. The keratin profile of the cells shows a striking similarity to that of the original tongue dysplasia. The karyotype of DOK is aneuploid and complex. By PCR and oligonucleotide hybridization on dot blots, codons 12, 13 and 61 of Ha-ras, Ki-ras and N-ras in DNA extracted from DOK cells were shown to be normal. Immunohistochemistry showed no abnormal, i.e., elevated expression of the onco-suppressor protein p53. Because of its origin and partially transformed phenotype, DOK presents an opportunity to study whether specific carcinogens associated with tobacco and areca nut can cause malignant transformation of oral keratinocytes in vitro.
Animals↗
Zambia: drought in Monze.
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Acquired Immunodeficiency Syndrome↗
The effectiveness of pretreatment with soluble or membrane-bound donor class I major histocompatibility complex antigens in the induction of unresponsiveness to a subsequent rat renal allograft.
We have examined the ability of two physical forms of RT1.A class I molecules to induce immunologic unresponsiveness to renal allografts in the rat. Both preparations of class I MHC antigen were derived from rat liver. Class I MHC antigen was presented either as purified membrane-bound molecules incorporated into protein micelles or as a water-soluble preparation containing soluble RT1.A class I molecules. The amount of RT1.A class I contained in each preparation was compared with the amount of class I antigen expressed by whole viable liver cells by quantitative absorption analysis using F16.4.4.11 mAb. The results demonstrated that DA recipients pretreated with a single dose of 1.75 x 10(10) cellular equivalents or multiple doses of 5 x 10(9) cellular equivalents of purified LEW membrane-bound class I molecules, delivered in aggregated micelle form, accepted their LEW renal allografts indefinitely (MST greater than 100 days). In contrast, no prolongation of graft survival was observed using the liver cell cytosol preparation containing soluble RT1.A class I molecules (MST 10 days) at the concentrations tested (10(8) -3 x 10(8) cell equivalents). However, when preoperative treatment with single (greater than or equal to 5 x 10(7) cellular equivalents of soluble class I MHC antigen) or multiple doses (greater than or equal to 10(7) cellular equivalents per dose) of the liver cell cytosol preparation was combined with a subtherapeutic dose of CsA given postoperatively (day +2, 10 mg/kg), suppression of renal allograft rejection was achieved with long-term survival (MST greater than 100 days). The immunologic unresponsiveness observed in both cases was donor specific.
Animals↗
Intracoronary PGE2 and veratrine inhibits renin release in conscious dogs via chemosensitive ventricular afferents.
1. Prostaglandins (PG) and veratrum alkaloids stimulate ventricular sensory receptors with non-myelinated vagal afferents and mediate inhibitory circulatory responses. 2. The present study in conscious instrumented dogs was carried out to determine the effects of intracoronary artery infusions of veratrine (Ver-IC) and PGE2 (PGE2-IC) on plasma renin activity (PRA). 3. A 15-20 mmHg decrease in arterial pressure was produced during Ver-IC (0.2-0.8 micrograms/kg per min) and PGE2-IC (10-50 ng/kg per min), but there was no change in PRA or heart rate. 4. In contrast, significant increases in PRA (+3.51 +/- 0.37 ng angiotensin I/mL per h; P less than 0.01) and heart rate (+38.5 +/- 6.2 beats/min; P less than 0.001) were elicited in response to a 15-20 mmHg decrease in arterial pressure produced by intravenous infusions of nitroprusside. 5. Pharmacological blockade of afferent fibres in the pericoronary region of the left main coronary artery during Ver-IC resulted in significant hypotension-induced increases in PRA (P less than 0.001) and heart rate (P less than 0.001), thus removing the inhibitory influence of chemosensitive ventricular afferents. 6. Therefore, intracoronary veratrum alkaloids and prostaglandins inhibit hypotension-induced increases in PRA and heart rate in the conscious dog. This is mediated by chemosensitive receptors located in the left ventricular myocardium along with afferent nerves in the pericoronary region and cervical vagi.
Animals↗
Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures.
The effects of endothelin-1 (ET) on several tissues are mediated by prostaglandins. In this study, we investigated the actions of ET on bone and determined whether they are mediated through prostaglandin-dependent pathways. Bone resorption, collagen, and non-collagen protein synthesis and inositol phosphate (IP) production were studied in neonatal mouse calvaria and fetal rat limb bone cultures. The effects of ET in the calvaria model were examined in the presence or absence of the cyclooxygenase inhibitor indomethacin (INDO). Bone resorption was stimulated by ET in the neonatal mouse calvaria, and this effect was inhibited by INDO. 45Ca release in the fetal rat limb bones was not affected by ET. ET stimulated collagen and noncollagen protein synthesis significantly in the calvaria model in the presence but not in the absence of INDO, suggesting that the anabolic effects of ET were masked by endogenous prostaglandin production. ET increased phosphatidylinositol turnover in both bone organ cultures. Although the addition of INDO reduced IP production slightly in the mouse calvaria, it was still significantly stimulated by ET. Our results demonstrate that ET has marked effects on bone tissue in vitro. Effects on resorption appear to be prostaglandin dependent, whereas the anabolic effects were not prostaglandin mediated. The stimulatory effects of ET on protein synthesis could be mediated through the IP signaling pathway. Since ET stimulates both bone resorption and anabolism, this peptide may have a role in the coupling of bone remodeling.
Animals↗