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Biomedical subjects

S Ibrahim

Publications and source records attributed to S Ibrahim.

At least 55 records · Page 3Linked to original sources

Therapeutic strategies against epilepsy in Mediterranean countries: a report from an international collaborative survey.

A collaborative survey was performed to compare prescribing strategies for the treatment of epilepsy in Mediterranean countries, based on analysis of 500 questionnaires compiled by physicians in 14 different countries. For partial seizures, carbamazepine was the drug of choice in most countries, whereas the second choice of drug differed widely. For primarily generalized tonic-clonic seizures, valproic acid was usually preferred, but other drugs used widely in some countries included phenobarbital, phenytoin and carbamazepine. Lamotrigine was the most popular second-line drug for primarily generalized tonic-clonic seizures in the European countries. In patients where the initial drug failed, switching to an alternative monotherapy was usually the preferred strategy, but advocates of early use of combination therapy exceeded 30% in the respondents of seven countries. Most respondents, in all countries except Turkey, did not prescribe drugs to prevent recurrence of febrile seizures; however, intermittent prophylaxis with a benzodiazepine was advocated by a considerable number of physicians, and continuous prophylaxis was prescribed by a significant minority of respondents in France, Syria and Tunisia. New drugs were rarely used as first-line treatment due to high cost and inadequate experience. Overall, this survey indicates that there is a wide variability in therapeutic practices between and within countries. This information may be useful for the implementation of national educational activities and for the design of pragmatic trials aimed at comparing different therapeutic strategies.

Adult↗

A PCR amplification method reveals instability of the dodecamer repeat in progressive myoclonus epilepsy (EPM1) and no correlation between the size of the repeat and age at onset.

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare, autosomal recessive disorder characterized by onset at age 6-16 years, generalized seizures, incapacitating myoclonus, and variable progression to cerebellar ataxia. The gene that causes EPM1, cystatin B, encodes a cysteine proteinase inhibitor. Only a minority of EPM1 patients carry a point mutation within the transcription unit. The majority of EPM1 alleles contain large expansions of a dodecamer repeat, CCC CGC CCC GCG, located upstream of the 5' transcription start site of the cystatin B gene; normal alleles contain two or three copies of this repeat. All EPM1 alleles with an expansion were resistant to standard PCR amplification. To precisely determine the size of the repeat in affected individuals, we developed a detection protocol involving PCR amplification and subsequent hybridization with an oligonucleotide containing the repeat. The largest detected expansion was approximately 75 copies; the smallest was approximately 30 copies. We identified affected siblings with repeat expansions, of different sizes, on the same haplotype, which confirms the repeat's instability during transmissions. Expansions were observed directly; contractions were deduced by comparison of allele sizes within a family. In a sample of 28 patients, we found no correlation between age at onset of EPM1 and the size of the expanded dodecamer. This suggests that once the dodecamer repeat expands beyond a critical threshold, cystatin B expression is reduced in certain cells, with pathological consequences.

Adolescent↗

Ultrasound-detected hepatic periportal thickening in patients with prolonged pyrexia.

Hepatic periportal thickening (HPT) detected by ultrasonography has been established as a reliable tool for measuring hepatic morbidity due to schistosomiasis. During ultrasonographic examination of patients with prolonged pyrexia, we frequently noticed minimal grades of HPT in patients without a history of schistosomiasis. This led to ultrasonographic studies of conditions other than schistosomiasis in which HPT may occur. Subjects included 460 patients with Schistosoma haematobium infection, 107 urban patients with prolonged pyrexia without previous exposure to schistosomiasis, and 288 healthy controls unexposed to schistosomiasis. Grade I HPT was more prevalent (P < 0.001) in patients with pyrexia (56.1%) than in those with S. haematobium (32.2%) and was more frequent (P < 0.001) in patients with S. haematobium than in controls (11.1%). Typhoid fever was the most common febrile illness causing HPT. Grade II lesions were rare in patients with pyrexia (2.8%) or schistosomiasis (0.9%). Grade III lesions were present in only one patient with S. haematobium. Mild grades of HPT can occur in infectious diseases other than schistosomiasis. Cellular infiltration in the portal tract from chronic infectious diseases can frequently give the ultrasonographic appearance of grade I HPT.

Adolescent↗

[Unverricht-Lündborg disease: clinical and electrophysiologic study of 19 Maghreb families].

We describe clinical, electrophysiological and genetic features in 44 patients with Unverricht-Lündborg disease from 19 families living in North African countries (Tunisia, Algeria and Morocco). The mean age of patients was 25.3 years; mean age was at onset 11.3 years. The disease began more frequently with seizures (91 per cent) or myoclonus (80 p. 100) than ataxia (16 p. 100). Subsequently myoclonus and generalized seizures were present in all patients, cerebellar signs were absent in four cases. EEG findings included normal background activity (90 p. 100), spontaneous fast generalized spikes (93 p. 100) and photosensitivity (70 p. 100). Antiepileptic polytherapy (clonazepam and/or phenobarbital and/or valporic acid) was used in 84 per cent of cases. Antiepileptic drugs were more effective in controlling epileptic seizures (less than one seizure/month in 60 p. 100) than myocloni which persisted daily in 64 p. 100 of cases. Mean duration of the disease was 13.5 years. One patient died of status epilepticus. Consanguinity was noted in 17 families (first degree in 15 families). Linkage to chromosome 21q 22.3 was confirmed in 11 families. We noted an inter and intrafamilial variability of clinical signs and disease course.

Adolescent↗

A Shannon entropy analysis of immunoglobulin and T cell receptor.

In 1970, before any antigen-bound immunoglobulin structure had been solved, Elvin Kabat proposed that regions of high amino acid diversity would be the antigen binding sites of immunoglobulin (Kabat, 1970). Conversely, sites of low variability were proposed to be structural, framework regions. This variability was defined by Wu and Kabat as the number of different amino acids found at a site divided by the relative frequency of the most common amino acid at that site (Wu and Kabat, 1970). Several groups have subsequently devised improvements of Kabat-Wu variability analysis (Litwin and Jores, 1992). While these methods are somewhat better than Kabat-Wu, they still suffer from Kabat-Wu's basic limitation: they account for only the most common one or two amino acids in estimating diversity. This leads to underestimates of low diversities and exaggerations of high diversities. Shannon information analysis eliminates serious bias and is more stable than Kabat-Wu and second generation measures of diversity (Jores et al. 1990; Wu and Kabat, 1970). Statistical reliability can be measured using Shannon analysis, and Shannon measurements can be provided with error estimates. Here we use Shannon's method to analyze the amino acid diversity at each site of T cell receptor Valpha and Vbeta to identify complementarity determining regions and framework sites. Our results reveal that the T cell receptor is significantly more diverse than immunoglobulin-suggesting T cell receptor has more than the previously-discovered four complementarity determining regions. These new complementarity determining regions may represent a larger antigen combining site, additional combining sites, or an evolutionary strategy to avoid inappropriate interaction with other molecules.

Animals↗

Evaluation of an ultrasonographic score for urinary bladder morbidity in Schistosoma haematobium infection.

An ultrasonographic urinary bladder morbidity score was developed and tested in 510 patients with schistosomiasis haematobia, and then evaluated for screening 1,134 randomly selected children from villages endemic for Schistosoma haematobium. The ultrasonographic urinary bladder morbidity score had four grades ranging from normal to marked thickening of the urinary bladder wall or any polyps or masses. Among both patients and randomly screened subjects, the ultrasonographic score was greater (P = 0.01 and P < 0.01) in males than in females. Children examined in the clinic had higher (P = 0.03) ultrasonographic scores than adults. Infected subjects in communities were more likely (P < 0.001) to have urinary bladder morbidity than uninfected subjects, and clinic patients with egg counts > or = 20 eggs/10 ml of urine had higher (P = 0.03) ultrasonographic urinary bladder morbidity scores than those with lighter infections. The geometric mean egg count was higher (P = 0.04) in clinic patients with grade II and III lesions than in those with grade 0 and I lesions. There was progressive improvement of the grade of urinary bladder morbidity scores in patients treated with praziquantel at each follow-up examination (P < 0.001) and there was a positive relationship (P < 0.01) between urinary bladder morbidity scores and ultrasonographic-detected renal back pressure changes. The ultrasonographic urinary bladder morbidity score objectively measured the severity of urinary bladder morbidity and correlated with intensity of S. haematobium infection in our subjects. It can be used in evaluating both morbidity in patients and in community surveys and in following the outcome of chemotherapy.

Adolescent↗

Evaluation of doctors trained at Diarrhoea Training Unit of National Institute of Child Health, Karachi.

Diarrhoeal diseases are a major contributory factor for high infant mortality and morbidity in Pakistan. To overcome this, Government of Pakistan launched a National Programme for Control of Diarrhoeal Disease. A Diarrhoea Training Unit (DTU) was established at the National Institute of Child Health, Karachi, where apart from proper case management, 17 training workshops were held between July, 1989 to July, 1991. Eighty-five doctors from various facilities in Sindh were trained in proper management of diarrhoea and establishment of Oral Rehydration Therapy (ORT) units in their regions. Evaluation of DTU training, assessment of the knowledge of trained doctors, case management and function of ORT Units were done between September, 1992 and October, 1993. Two teams each consisting of a doctor and a lady health visitor, visited 30 such facilities. An observation check list was used for assessing the ORT unit and diarrhoea case management and a test questionnaire for the knowledge of facility physician and paramedic. Of the 29 facilities, 17 had DTU trained doctors. ORT corner had been established in 26, weighing scales were used in 21, record keeping in eight and soap and water was available for hand washing in seven centres. The presence of untrained doctors provided an opportunity to compare the two groups. Dehydration assessment was fairly good, weight was recorded in fewer cases than desirable, case management was similar in the two groups, except for infrequent use of antibiotics by the trained group. Prevention was poorly advised. Physicians' knowledge in both groups was similar but deficient in advising the use of ORS, feeding in diarrhoea and nutritional assessment. The trained ones had significantly better knowledge about drugs and this was reflected in their case management. Paramedic case management were similar to those in doctors. The study thus showed positive and beneficial effects of training.

Anti-Bacterial Agents↗

Sagodana based verses rice based oral rehydration solution in the management of acute diarrhoea in Pakistani children.

This study was carried out to compare the efficacy of a cereal based ORS (prepared with 50 G of sagodana (cereal), 3.5 G/L sodium chloride, 1.5 G/L potassium chloride, 2.9 G/L trisodium citrate) with rice based oral rehydration solution (using same amounts of rice and electrolytes) for treatment of diarrhoea. One hundred and twelve children aged 3 months to 2 years with watery diarrhoea of less than 5 days duration with mild to moderate dehydration and no sepsis, were included in the study. The amount of ORS intake, stool volume and frequency were similar in both groups. Clinical success was seen in 79% of rice ORS group and 81% in sagodana group. Both can be used as a cereal based ORS in the management of acute diarrhoea in communities where it is culturally accepted and used as a weaning diet.

Acute Disease↗

CTLA4Ig inhibits alloantibody responses to repeated blood transfusions.

Allosensitization is a fundamental problem that limits the effectiveness of blood transfusions. Patients who receive multiple transfusions of blood or blood components frequently develop alloantibodies against donor alloantigens. Allosensitized patients are refractory to further transfusion and difficult to transplant successfully. CTLA4Ig fusion protein, which blocks the CD28-B7 costimulatory pathway in T-lymphocyte activation, was tested for its capacity to inhibit allosensitization to blood transfusions. Groups of LEW (RT1') rats were transfused with ACI blood (RT1a) together with L6 (a human immunoglobulin G1 [IgG1] antibody as isotype control) or CTLA4Ig in different doses (0.004, 0.02, 0.1, and 0.5 mg). Rats were retransfused with ACI blood after 28 and 84 days without any additional CTLA4Ig therapy. Weekly sera samples were tested for alloantibody against donor leukocytes using flow cytometry. CTLA4Ig caused a dose-dependent decrease in the IgM alloantibody response against donor major histocompatibility complex (MHC) class I antigens. In addition, 0.02-, 0.1-, and 0.50-mg doses of CTLA4Ig totally inhibited the IgG responses to the first transfusion, and this immunosuppressive effect persisted for the second and third transfusions. To study the capacity of CTLA4Ig to prevent a secondary immune response, three groups of LEW rats were transfused with ACI blood with no accompanying treatment. Animals were retransfused 28 days later with ACI blood together with L6 control antibody or 0.5 or 2.5 mg CTLA4Ig. CTLA4Ig, but not L6, prevented an increase in IgG alloantibody response despite repeated transfusions. The effects of CTLA4Ig treatment on helper T-lymphocyte proliferation was tested by limiting dilution analysis (LDA). Peripheral blood cells taken 30 days after blood transfusion and CTLA4Ig treatment contained significantly decreased donor-specific T-lymphocyte precursors compared with L6-treated rats. These data support the idea that blocking the B7/CD28 signal of T-lymphocyte activation by CTLA4Ig treatment at the time of transfusion may be an important therapeutic tool to inhibit alloantibody responses to blood transfusions.

Abatacept↗

Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts.

Complement (C) inhibition alone using a recombinant soluble form of complement receptor type 1 (sCR1) prevents hyperacute rejection but not subsequent irreversible accelerated acute rejection of discordant pig-to-cynomolgus monkey cardiac xenografts, which occurs within 1 week. To inhibit accelerated acute rejection, which is associated with a rise in serum xenoreactive antibody (Ab) and a cellular infiltrate, triple therapy with standard immunosuppressive agents (cyclosporine, cyclophosphamide, and steroids [CCS]) was combined with continuous C inhibition using sCR1. Each of two monkeys that received sCR1 + CCS showed minimal evidence of rejection when killed on days 21 and 32 in comparison to a monkey that received sCR1 + subtherapeutic CCS (rejected at 11 days) and a control that received CCS alone (rejected at 38 min). Prolonged xenograft survival was associated with low Ab levels and a minimal cellular infiltrate, suggesting that combined inhibition of C, xenoreactive Ab responses, and cellular immunity may be a useful approach in overcoming the immune barriers to discordant xenotransplantation.

Animals↗

Cytokine control of parasite-specific anergy in human urinary schistosomiasis. IL-10 modulates lymphocyte reactivity.

Humans chronically infected with schistosomiasis usually have impaired parasite Ag-specific lymphocyte proliferation and IFN-gamma production that may facilitate persistence of the parasite while producing little clinical disease. The mechanisms that contribute to the immunologic hyporesponsiveness in these patients remain undefined. IL-10 has been shown to exert an inhibitory effect on cell-mediated immunity. To determine whether endogenous IL-10 has a role in regulating parasite-specific anergy in schistosomiasis, neutralizing anti-IL-10 added to PBMC from Schistosoma haematobium patients' enhanced adult worm (SWAP)- or egg Ag (SEA)-driven lymphocyte proliferation and/or IFN-gamma production by 2- to >100-fold in 32 of 38 subjects. In contrast, anti-IL-10 failed to significantly augment the mycobacterial Ag, purified protein derivative (PPD)-driven lymphocyte proliferation, or IFN-gamma production in 9 or 10 of 14 individuals, respectively. SWAP or SEA triggered IL-10 release from PBMC of both patients and healthy individuals; however, CD4+ cells were a significant source of IL-10 only in infected subjects. PPD relative to SWAP induced fivefold less IL-10 release by CD4+ cells (p < 0.01). A possible mechanism whereby IL-10 suppressed Ag-specific T cell responses was demonstrated by the ability of SWAP and not PPD to suppress B7 expression on PBMC. Anti-IL-10 completely inhibited the parasite Ag-induced down-regulation of B7 expression. These studies indicate that IL-10 contributes to parasite Ag-induced T cell hyporesponsiveness observed in patients with chronic schistosomiasis hematobia.

Adolescent↗

Factors Influencing Pyrethroid Resistance in a Permethrin-Selected Strain of the Soybean Looper, Pseudoplusia includens (Walker)

Cytochrome P450 monooxgenase activity toward p-nitroanisole was measured in larvae of three strains of soybean looper, Pseudoplusia includens (Walker), including a laboratory susceptible (S) strain, a resistant (R) strain selected for several generations with permethrin, and a nonselected (NS) strain from the same field collections as the R strain. Activity was significantly higher in R strain larvae than in the S and NS strains (1.8- and 1.4-fold, respectively), and there was no significant difference between activity in the S and NS strains. Resistance to the alpha-cyano pyrethroids deltamethrin and cypermethrin was similar to or higher than that observed with permethrin (RR = 70.0, 62.4, 145.3 and 12.1, 32.3, and 27.0 for permethrin, deltamethrin, and cypermethrin in R and NS strains, respectively). The R strain was less resistant (RR = 4.3) to tefluthrin, a pyrethroid with a fluorinated-phenyl alcohol moiety, and a nonester (ether) pyrethroid, BRC 429 (RR = 17.7). Piperonyl butoxide (PB) significantly increased the toxicity of each insecticide tested in the R and NS strains. In addition, penetration of 14C-cypermethrin was decreased significantly at 24 hr after treatment when R strain larvae were pretreated with PB, with 21.1% of the applied dose unpenetrated in PB-treated larvae and 7.6% unpenetrated in larvae not treated with PB.

Journal Article↗

Chronic venous insufficiency: mechanisms and management.

CVI is a common disease with significant morbidity that results from venous hypertension of the extremities. Increased perfusion pressure probably traps excessive numbers of white blood cells in the capillaries. Activated leukocytes subsequently damage capillary endothelium, increase capillary permeability, and cause ischemia of the overlying skin as a result of leakage of fibrinogen and formation of a fibrin cuff. Diagnosis of CVI is not difficult because its clinical manifestations are usually evident. Vascular compression therapy remains the foundation of medical management for CVI. Refractory cases may require a combined medical and operative approach.

Adult↗

Oil of bitter orange: new topical antifungal agent.

BACKGROUND: Superficial dermatophyte infection is one of the most common dermatologic diseases. Some of these infections are extremely resistant to therapy. METHODS AND PATIENTS: Sixty patients participated in this study; they were classified into three groups (20 patients in each). All groups had comparable numbers of patients with tinea corporis, cruris, and pedis. Group 1 was treated with a 25% emulsion of oil of bitter orange (OBO) three times daily; group 2 was treated with 20% OBO in alcohol three times daily and group 3 was treated with pure OBO, once daily. Clinical and mycologic examinations were performed before therapy and every week until a complete cure had occurred. RESULTS: In group 1, 80% of patients were cured in 1 to 2 weeks and 20% in 2 to 3 weeks. In group 2, 50% were cured in 1 to 2 weeks, 30% in 2 to 3 weeks and 20% in 3 to 4 weeks. In group 3, 25% of patients did not continue the trial. Of the remaining patients, 33.3% were cured in one week, 60% in 1 to 2 weeks, and 6.7% in 2 to 3 weeks. Oil of bitter orange produced no side effects except mild irritation seen with the use of the pure form. CONCLUSIONS: An in vitro study showed that OBO (natural product) exerts fungistatic and fungicidal activity against a variety of pathogenic dermatophyte species. It is a promising, cheap, and available topical antifungal therapeutic agent.

Administration, Topical↗

High-performance liquid chromatographic determination of pyridinium crosslinks in serum, urine and dialysate of patients in chronic renal failure.

This study describes an isocratic reversed phase high-performance liquid chromatographic method for the analysis of pyridinium crosslinks in serum, urine and dialysates obtained from patients with chronic renal failure on haemodialysis. The mean (SD) urine pyridinoline (PYD) and deoxypyridinoline (DPD) to creatinine (Cr) ratio in 19 healthy volunteers was 28.9 (6.3) and 9.1 (3.6) mumol/mol, respectively. In the 22 patients the PYD/Cr and DPD/Cr ratio was 244.6 (436.5) and 66.5 (116.8) mumol/mol, respectively. The mean serum PYD concentration in 29 patients of 268.5 (334.4) nmol/L was significantly higher than that of 5.9 (1.5) nmol/L found in normal volunteers: the mean DPD concentration was 82.9 (93.7) nmol/L in the patients but was undetectable in the serum from the normal volunteers. The concentration of crosslinks in pre-dialysis serum samples was higher than those found post-dialysis reflecting a significant removal of the crosslinks during dialysis. The assay of pyridinium crosslinks in serum, urine and dialyses fluid could potentially provide evidence of bone collagen turnover in patients in renal failure. Their measurement in serum and dialysate could be particularly useful in anuric patients.

Adult↗