Biomedical subjects
Publications and source records attributed to M Ibrahim.
This paper reports a panel discussion--Opportunities for and Limitations to Greater Collaboration Across the Disciplines--held at the conference. It highlights the need for greater collaboration between demographers and epidemiologists and notes the institutional and disciplinary challenges to and opportunities for promoting greater cooperation.
Partial anomalous pulmonary venous connection to the coronary sinus is rare. This anomaly is even more rare in the absence of interatrial communication. Usually, the anomalous right pulmonary veins drain to the right atrium or venae cavae, while the anomalous left veins connect to the coronary sinus or left innominate vein. The present report is the first in the English literature to document a situs solitus case in which all three right pulmonary veins drained directly into the coronary sinus without an atrial septal defect. Closure of the coronary sinus orifice and unroofing of the coronary sinus into the left atrium is a safe and effective way of treating this anomaly.
Studies in the uremic rat indicate that insulin resistance and glucose intolerance leading to dyslipidemia are associated with a hyperparathyroid-induced increase in cytosolic calcium ([Ca++i]). These alterations are reversed with verapamil, but recur after discontinuation of the drug, suggesting that increased [Ca++i] is responsible for the metabolic derangement. To our knowledge, no similar studies have been conducted in humans. We retrospectively examined, over 12-year period, the effects of factors that lower [Ca++i] on total serum cholesterol and triglycerides in 176 peritoneal dialysis (PD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on the morbidity and mortality outcome related to atherosclerotic vascular disease. Diabetic patients were excluded from the study, because their dyslipidemia and vascular disease are mediated via a different mechanism. The patients were classified into four groups. Group I [high parathyroid hormone (PTH) in the absence of calcium channel blockers (CCBs), n = 56] represented the highest [Ca++i]. Group II (high PTH in the presence of CCBs, n = 43) and group III (lower PTH in the absence of CCBs, n = 37) represented intermediate [Ca++i]. Group IV (lower PTH in the presence of CCBs, n = 40) represented the lowest [Ca++i]. High PTH was defined as > or = 3.0 times normal; lower PTH, as < 3.0 times normal. Lower [Ca++i] was achieved through the use of CCBs, or through lower PTH, or both. Lower PTH was achieved by parathyroidectomy or calcitriol administration. The four groups showed no differences in age, sex, race, weight, dialysis duration, or primary disease. Group I showed a mean serum cholesterol of 358 +/- 27 mg/dL and serum triglycerides of 469 +/- 41 mg/dL. Group II showed mean serum cholesterol of 198 +/- 21 mg/dL and serum triglycerides of 147 +/- 17 mg/dL. Group III showed a mean serum cholesterol of 205 +/- 20 mg/dL and serum triglycerides of 174 +/- 16 mg/dL. Group IV showed mean serum cholesterol of 184 +/- 10 mg/dL (p = 0.008) and serum triglycerides of 103 +/- 8 mg/dL (p = 0.005). The cardiovascular morbidity and mortality incidences were: group I, 64%; group II, 27%; group III, 31%; and group IV, 20% (p = 0.002). We conclude that, in non diabetic PD patients, dyslipidemia is related to a hyperparathyroid-induced increase in cytosolic calcium [Ca++i]. Lowering [Ca++i] by decreasing the parathormone level (via parathyroidectomy or calcitriol administration), or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long-term morbidity and mortality related to atherosclerotic vascular disease.
In this study we outline a method for constructing an inexpensive chamber used in the transfection of organotypic brain slices. This chamber differs from most commercially available chambers in that DNA-coated gold microcarriers are directly carried by a flow of helium at low pressure (26 psi). Most other chambers employ macrocarriers onto which DNA-coated gold is first loaded, and then released by a shock of helium onto the reverse side of the macrocarriers. This home constructed device has been successfully employed in the transfection of organotypic brain slices cultured using the air-medium interface method. Mammalian expression vectors containing cytomegalovirus (CMV) and simian virus (SV40) enhancers/promoters were used to express enhanced green fluorescence protein (EGFP). DNA was coated onto 0.6-microm gold microcarriers. Transfected cells were visualised under a fluorescence microscope and included identifiable neurones and oligodendrocytes. Also included in this study are step-by-step methods for the preparation of gold microcarriers and organotypic brain slices.
The nonopioid actions of spinal dynorphin may promote aspects of abnormal pain after nerve injury. Mechanistic similarities have been suggested between opioid tolerance and neuropathic pain. Here, the hypothesis that spinal dynorphin might mediate effects of sustained spinal opioids was explored. Possible abnormal pain and spinal antinociceptive tolerance were evaluated after intrathecal administration of [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO), an opioid mu agonist. Rats infused with DAMGO, but not saline, demonstrated tactile allodynia and thermal hyperalgesia of the hindpaws (during the DAMGO infusion) and a decrease in antinociceptive potency and efficacy of spinal opioids (tolerance), signs also characteristic of nerve injury. Spinal DAMGO elicited an increase in lumbar dynorphin content and a decrease in the mu receptor immunoreactivity in the spinal dorsal horn, signs also seen in the postnerve-injury state. Intrathecal administration of dynorphin A(1-17) antiserum blocked tactile allodynia and reversed thermal hyperalgesia to above baseline levels (i.e., antinociception). Spinal dynorphin antiserum, but not control serum, also reestablished the antinociceptive potency and efficacy of spinal morphine. Neither dynorphin antiserum nor control serum administration altered baseline non-noxious or noxious thresholds or affected the intrathecal morphine antinociceptive response in saline-infused rats. These data suggest that spinal dynorphin promotes abnormal pain and acts to reduce the antinociceptive efficacy of spinal opioids (i.e., tolerance). The data also identify a possible mechanism for previously unexplained clinical observations and offer a novel approach for the development of strategies that could improve the long-term use of opioids for pain.
Recently identified chondroitin sulphate proteoglycans in perineuronal nets include neurocan and phosphacan. However, the function and assembly of these components has yet to be resolved. In this study we show morphological alteration in Wisteria floribunda labelled nets around cortical interneurones both in tenascin-R knockout and tenascin-R/parvalbumin double knockout mice. This alteration reflects the loss of phosphacan and neurocan from cortical nets in mice deficient in tenascin-R. No effect on the membrane related cytoskeleton, as revealed by ankyrin(R), was observed in any of the mice. These results on mice lacking tenascin-R substantiate previously reported in vitro interactions between tenascin-R and phosphacan and neurocan.
The presence of neurones in the rat anterior medullary velum (AMV) has been investigated by using antibodies to the calcium-binding proteins, parvalbumin (PV), calretinin (CR), and calbindin-D28k (CB). Disparate populations of mainly GABAergic neurones were located in the rostral and caudal regions of the AMV. The rostral region of the AMV was characterised by GABAergic CR-labelled or PV-labelled neurones. CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network. PV-labelled neurones had round somata (diameters between 6 and 10 microm) and were bi-tufted, with beaded dendrites. Both CR-labelled and PV-labelled dendrites formed punctate pericellular associations with unlabelled somatic profiles. In the caudal region of the AMV, PV-labelled neurones were GABAergic, multipolar cells, having round somata (diameters between 9 and 12 microm), with either beaded or nonbeaded dendrites forming a network of interconnecting dendrites. PV-labelled pericellular associations were made around both PV-labelled and unlabelled somatic profiles. CR labelled unipolar brush cells (UBCs) were not GABAergic. UBCs were characterised by a round to oval somata (10-15 microm in diameter) from which a single primary dendrite emerged to form a distal expansion having small terminal dendrites. From the distal expansion, there also appeared to be CR-labelled processes emanating and extending for up to 250 microm. CB occasionally labelled "Purkinje-like cells" (PLCs). The rat AMV is a more complex structure than first envisaged with the presence of predominantly inhibitory neurones expressing different calcium-binding proteins. Functional and anatomic aspects of this circuitry are further discussed.
Explore the source record for details and available documents.
Neuropathic pain is often associated with the appearance of pain in regions not related to the injured nerve. One mechanism that may underlie neuropathic pain is abnormal, spontaneous afferent drive which may contribute to NMDA-mediated central sensitization by the actions of glutamate and by the non-opioid actions of spinal dynorphin. In the present study, injuries to lumbar or sacral spinal nerves elicited elevation in spinal dynorphin content which correlated temporally and spatially with signs of neuropathic pain. The increase in spinal dynorphin content was coincident with the onset of tactile allodynia and thermal hyperalgesia. Injury to the lumbar (L(5)/L(6)) spinal nerves produced elevated spinal dynorphin content in the ipsilateral dorsal spinal quadrant at the L(5) and L(6) spinal segments and in the segments immediately adjacent. Lumbar nerve injury elicited ipsilateral tactile allodynia and thermal hyperalgesia of the hindpaw. In contrast, S(2) spinal nerve ligation elicited elevated dynorphin content in sacral spinal segments and bilaterally in the caudal lumbar spinal cord. The behavioral consequences of S(2) spinal nerve ligation were also bilateral, with tactile allodynia and thermal hyperalgesia seen in both hindpaws. Application of lidocaine to the site of S(2) ligation blocked thermal hyperalgesia and tactile allodynia of the hindpaws suggesting that afferent drive was critical to maintenance of the pain state. Spinal injection of antiserum to dynorphin A((1-17)) and of MK-801 both blocked thermal hyperalgesia, but not tactile allodynia, of the hindpaw after S(2) ligation. These data suggest that the elevated spinal dynorphin content consequent to peripheral nerve injury may drive sensitization of the spinal cord, in part through dynorphin acting directly or indirectly on the NMDA receptor complex. Furthermore, extrasegmental increases in spinal dynorphin content may partly underlie the development of extraterritorial neuropathic pain.
Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.
Explore the source record for details and available documents.
Health questionnaires and parasitologic examinations of urine and stool were performed upon a stratified random sample of 7,710 individuals from 1,109 households in 21 rural communities in Fayoum Governorate, Egypt in 1992 to investigate the prevalence of, risk factors for, and changing pattern of, infection with Schistosoma sp. in the governorate. A subset, every fifth household, or 1,038 subjects, had physical and ultrasound examinations to investigate prevalence of, and risk factors for, morbidity. The prevalence of S. haematobium ranged from 0% to 27.1% and averaged 13.7%. The geometric mean egg count (GMEC) was 10.0 eggs/10 ml of urine. Age-stratified prevalence and intensity of infection were 18-25% and 10-15 eggs/10 ml of urine in those 5-25 years of age. Schistosoma mansoni were detected in inhabitants of 13 communities, but 78.5% of the infections were focally present in a group of 4 satellite hamlets around a single village. The overall prevalence of S. mansoni in the governorate was 4.3% and the GMEC was 44.0 ova/g of stool. Risk factors for infection with either species were male gender, an age <20 years, living in smaller communities, and exposures to canal water by males. Histories of burning micturation, blood in the urine, or prior schistosomiasis and reagent strip-detected hematuria and proteinuria were risks for S. haematobium, but not for S. mansoni. Both urinary tract and higher grades of hepatic morbidity were rare. Obstructive uropathy was present in 6.3% of the subjects and was more common in males and older people. Ultrasonography-detected bladder lesions were present in 5.2% and correlated with S. haematobium only in younger subjects and in those with hematuria and proteinuria. The prevalences of hepatomegaly, splenomegaly, and periportal fibrosis (PPF) were associated with each other and increased with age and in males. Ultrasonography-detected hepatomegaly and splenomegaly were weakly associated with S. mansoni infections only in children. The prevalence of PPF was greater in the 4 communities with >25% S. mansoni infection rates in comparison with the 17 other villages and ezbas. Transmission of S. mansoni is focally well established in Fayoum, which also has the highest prevalence of S. haematobium in the governorates surveyed by the Epidemiology 1, 2, 3 Project. However, both urinary tract and hepatic morbidity are relatively rare in the governorate. This probably results from the long-standing schistosomiasis control program in Fayoum, which suppressed intensity more than prevalence of infection, leading to less community morbidity.
The ability of some N,N-dialkylaminosubstituted chromones and isoxazoles to inhibit the protein kinase C (PKC) dependent signal transduction pathway was tested. As a cellular model, human neutrophils stimulated with either phorbol myristate acetate (PMA) or formylmethionine-leucine-phenylalanine (f-MLF) were used. The efficiency of the compounds was established by their capacity to reduce the O2- production by activated human neutrophils. Compounds carrying a 3-bis(2-methoxyethyl)amino group, a substituent found active in previously tested tricyclic compounds, do not show significant anti-PKC activity in this study. On the other hand, substitution with a 1-piperidinyl group leads all tested compounds to a high biological activity against stimulated neutrophils.
The co-administration of morphine at spinal (i.th.) and supraspinal (i.c.v.) sites to the same rat produces antinociceptive synergy, a phenomenon which may underlie the clinical analgesic utility of this drug. In animals with peripheral nerve injury, however, the antinociceptive potency and efficacy of i.th. morphine is significantly decreased. Here, the possible loss of spinal/supraspinal morphine antinociceptive synergy and relationship to elevation of spinal dynorphin content was studied. Ligation of lumbar spinal nerves resulted in elevated dynorphin in the ipsilateral lumbar and sacral spinal cord. In sham-operated rats supraspinal/spinal co-administration of morphine produced synergistic antinociception which was unaffected by i.th. MK-801 or dynorphin A((1-17)) antiserum. In nerve-injured rats, i.th. morphine was inactive against tactile allodynia and showed diminished in potency against acute nociception without supraspinal/spinal antinociceptive synergy. Antiserum to dynorphin A((1-17)) or the non-competitive NMDA antagonist MK-801 increased the antinociceptive potency of i.th. morphine, restored supraspinal/spinal morphine antinociceptive synergy and elicited a dose-related i.th. morphine antiallodynic action. These agents did not demonstrate antinociceptive or antiallodynic activity alone and did not alter morphine actions in sham-operated animals. The loss of spinal/supraspinal antinociceptive synergy and lack of antiallodynic activity of spinal morphine appear to be due to the elevation across multiple spinal segments of dynorphin following nerve injury. Pathological actions of elevated dynorphin may directly or indirectly modulate the NMDA receptor, result in a loss of supraspinal/spinal morphine synergy and may thus account for the decreased clinical analgesic efficacy of morphine in peripheral neuropathies.
A simple technique for removal of the distal fragment of the broken intramedullary interlocking nail is described. It was successfully used in three patients with a broken nail due to nonunion. The technique requires only cerclage wire, which is available in any operating room, avoiding the difficulties obtaining the custom made hook and of excessive exposure to radiation.
This study showed that impoverished Nigerian children at risk for cancrum oris (noma) had significantly reduced plasma concentrations of zinc (< 10.8 micromol/L), retinol (< 1.05 micromol/L), ascorbate (< 11 micromol/L), and the essential amino acids, with prominently increased plasma and saliva levels of free cortisol, compared with their healthy counterparts. The nutrient deficiencies, in concert with previously reported widespread viral infections (measles, herpesviruses) in the children, would impair oral mucosal immunity. We postulate, subject to additional studies, that evolution of the oral mucosal ulcers including acute necrotizing gingivitis to noma is triggered by a consortium of microorganisms of which Fusobacterium necrophorum is a key component. Fusobacterium necrophorum elaborates several dermonecrotic toxic metabolites and is acquired by the impoverished children via fecal contamination resulting from shared residential facilities with animals and very poor environmental sanitation.
The idea that all modern humans share a recent (within the last 150, 000 years) African origin has been proposed and supported on the basis of three observations. Most genetic loci examined to date have (1) shown greater diversity in African populations than in others, (2) placed the first branch between African and all non-African populations in phylogenetic trees, and (3) indicated recent dates for either the molecular coalescence (with the exception of some autosomal and X-chromosomal loci) or for the time of separation between African and non-African populations. We analyze variation at 10 Y chromosome microsatellite loci that were typed in 506 males representing 49 populations and every inhabited continent and find significantly greater Y chromosome diversity in Africa than elsewhere, find the first branch in phylogenetic trees of the continental populations to fall between African and all non-African populations, and date this branching with the (deltamu)2 distance measure to 5800-17,400 or 12,800-36,800 years BP depending on the mutation rate used. The magnitude of the excess Y chromosome diversity in African populations appears to result from a greater antiquity of African populations rather than a greater long-term effective population size. These observations are most consistent with a recent African origin for all modern humans.
BACKGROUND AND AIM OF THE WORK: To review a general hospital's experience with sarcoidosis and the clinical pattern of the disease among the Saudis. METHODS: Retrospective file review was carried out of all patients with proven diagnosis of sarcoidosis in a general hospital in Western Saudi Arabia over a period of 11 years (1985-1996). RESULTS: Twenty-one patients, of whom 17 were native Saudis, had been diagnosed to have sarcoidosis during the study period. There were 5 males and 16 females. The mean age was 45 years with a range of 20-69 years. The commonest presentations were cough (43%), dyspnoea (43%), joint pain (38%), hepatomegaly (29%), splenomegaly (24%) and lymphadenopathy (24%). The biochemical analysis showed raised alkaline phosphatase in 66%, calcium level was elevated in 5% and urinary calcium was elevated in 3 out of 7 patients tested. Angiotensin Converting Enzyme was elevated in 11 of 15 patients. Tuberculin test was negative in all those tested (17 patients). The patients were classified using the Siltzbach staging into 0-3. Stage 0 (14%), Stage 1 (33%), Stage 2 (43%) and Stage 3 (10%). The gallium scan was positive in 90% of those who were tested (7 patients). The diagnosis in all except one patient was proven histologically. The outcome was favourable in most patients (76%), though 52% received active treatment. CONCLUSIONS: Sarcoidosis does occur in native Saudis. On comparison with Western patterns of the disease, there is a female predominance and relative lack of cardiac, eye, parotid and central nervous system involvement. The rarity of cardiac and central nervous system involvement was comparable with other Middle Eastern studies. Sarcoidosis, though rare in our community, should still be considered in the differential diagnosis of patients with the typical presentation after excluding tuberculosis which is epidemic.