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Biomedical subjects

R Ali

Publications and source records attributed to R Ali.

At least 37 records · Page 2Linked to original sources
PubMed2004

Interaction of amiloride and one of its derivatives with Vpu from HIV-1: a molecular dynamics simulation.

Vpu is an 81-residue membrane protein, with a single transmembrane segment that is encoded by HIV-1 and is involved in the enhancement of virion release via formation of an ion channel. Cyclohexamethylene amiloride (Hma) has been shown to inhibit ion channel activity. In the present 12-ns simulation study a putative binding site of Hma blockers in a pentameric model bundle built of parallel aligned helices of the first 32 residues of Vpu was found near Ser-23. Hma orientates along the channel axis with its alkyl ring pointing inside the pore, which leads to a blockage of the pore.

Amiloride↗
PubMed2004

Role of nitric oxide modified DNA in the etiopathogenesis of systemic lupus erythematosus.

The role of the nitric oxide (NO) radical in systemic lupus erythematosus (SLE) pathogenesis has been investigated in the present study. The binding characteristics of SLE autoantibodies with native calf thymus DNA, native and NO-modified plasmid DNA were assessed. Binding characteristics and specificity of antibodies were analysed by direct binding and inhibition ELISA, gel retardation assay and quantitative precipitin titration. The data shows preferential binding of SLE autoantibodies to NO-modified plasmid DNA (NO-DNA) in comparison with native plasmid DNA. Inhibition ELISA reiterates the direct binding results. Gel retardation assay further substantiated the enhanced recognition of NO-DNA by anti-DNA autoantibodies. The binding affinity of modified and native plasmid DNA with one of the SLE IgGs was calculated, using the Langmuir plot. The apparent association constant for NO-plasmid DNA was found to be highest, followed by native calf thymus DNA and native plasmid DNA. The results suggest that the NO radical modification of plasmid DNA causes perturbations, resulting in the generation of neo-epitopes, and making it a potential immunogen. The DNA modified with the NO radical may be one of the factors for the induction of circulating SLE anti-DNA autoantibodies.

Antibody Specificity↗
PubMed2003

Successful labor in the course of chronic lymphocytic leukemia (CLL) and management of CLL during pregnancy with leukapheresis.

We describe the successful management of a 30-year-old woman in the second trimester of her pregnancy with chronic lymphocytic leukemia (CLL) in stage IV by using only leukapheresis. We applied three sessions (courses) of leukapheresis throughout the pregnancy. The procedure did not have any significant adverse effect on the patient and the fetus. The patient gave birth vaginally to a healthy boy, weighing 3100 g, at 39 weeks of gestation. Seven months after delivery, Richter's syndrome developed in the patient. We conclude that leukapheresis may provide an alternative for palliative treatment to chemotherapy in pregnant patients with CLL. To our knowledge, this is the fourth reported case of CLL in pregnancy, and the first management of CLL during pregnancy with leukapheresis.

Adult↗
PubMed2003

Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes.

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by preeclampsia, one by ablatio placentae, and one by intrauterine death. Seven mothers received corticosteroid treatment, four high-dose immunoglobulin therapies, and one underwent splenectomy in the second trimester of gestation. At the time of delivery six mothers had normal platelet counts and seven had low platelet counts. Nine deliveries were by vaginal route and four were by cesarean section. Eleven infants were born with normal platelet counts and one was thrombocytopenic at the time of delivery. No infant showed any clinical signs of hemorrhage and there were no neonatal complications. Two fetuses died; one of them because of ablatio placentae and the other was intrauterine dead. In conclusion, ITP in pregnancy requires the management of two patients, the mother and her baby; hence, the close collaboration of a multidisciplinary group composed of a hematologist, obstetrician, anesthesiologist, and neonatologist is essential.

Adolescent↗
PubMed2003

Subcutaneous metallic mercury injection of the hand.

Poisoning by subcutaneous metallic mercury is rare and usually accidental. Although it does not carry the same risks as mercury-vapour intoxication, it may still cause destructive early and late local reactions. Two deaths resulting from subcutaneous mercury injection have been reported in the literature. We present a case of accidental subcutaneous injection of mercury in the hand and discuss its management with a review of the literature.

Abscess↗
PubMed2003

Successful treatment of acquired haemophilia with prednisolone therapy.

Acquired hemophilia is a rare, life threatening coagulopathy in adults caused by the development of autoantibodies against to factor VIII. No general consensus exists on the best therapeutic approach. We report here a case that presented with extensive cutaneous and mucosal bleedings due to factor VIII inhibitors and treated successfully with steroid therapy alone but complicated with a life threatening thromboembolic attack during her follow up. In conclusion, corticosteroids are "cost effective therapy" associated with high inhibitor elimination rates and although recurrence of inhibitor in a patient with factor VIII inhibitor is an expected clinical situation thrombosis risk should also be considered.

Adrenal Cortex Hormones↗
PubMed2003

Oxygen free radicals and systemic autoimmunity.

Reactive oxygen species generated during various metabolic and biochemical reactions have multifarious effects that include oxidative damage to DNA leading to various human degenerative and autoimmune diseases. The highly reactive hydroxy radical (*OH) can interact with chromatin and result in a wide range of sugar and base-derived products, DNA-protein cross-links and strand breaks. Studies from our laboratory have demonstrated that after modification the DNA becomes highly immunogenic and the induced antibodies exhibit variable antigen-binding characteristics. Systemic lupus erythematosus, a prototype autoimmune disease, is characterized by the presence of autoantibodies to multiple nuclear antigens. The detection of 8-hydroxyguanosine in the immune complex derived DNA of systemic lupus erythematosus patients reinforces the evidence that reactive oxygen species may be involved in its pathogenesis. Increased apoptosis and decreased clearance of apoptotic cells as observed in systemic lupus erythematosus (SLE) might well be a contributory factor in systemic autoimmunity. Clinically, titres of autoantibodies are closely related to the degree of renal inflammation. Anti-DNA antibodies may combine with circulating antigen and contribute to the deposition of immune complexes in renal glomeruli.

Antibodies, Antinuclear↗
PubMed2003

[Prevalence of HIV in Mayotte].

Mayotte is a little French island, located in the Indian ocean, between Madagascar and Mozambic. Officially, the population goes up to 150,000 inhabitants, but in fact, it probably comes up to about 200,000 people, because of a very numerous illegal immigration, especially coming from Anjouan, the nearest Comorian island. Up to now there are no data about HIV in Mayotte. There is only one adult medical unit (except intensive care). All patients detected as seropositive for HIV are sent for treatment in this unit. The only case of systematically proposed HIV serology is pregnancy, and this since 1994. 70% to 80% of women accept it. There are annually 6000 deliveries in Mayotte. When a seropositivity is detected, screening is systematically proposed to other members of the family. Epidemiology does not seem to worsen, even if detection is increasing: 8675 tests done in 1998, 9142 in 1999, 12,085 in 2000. All cases of seropositivity attended to at present time in our unit have been registered and studied, apart from patients who died before this study, and those who did not consult for more than two years. There were 8 HIV positive people who died since 1990 in Mayotte, most of them in 1991, 1992. There was no death in the last years, nor sanitary evacuation, except one. 50 people are registered: 20 males, 30 females. Average age is 34. 39 Comorian people, 10 metropolitans, and one from another origin. Contamination was heterosexual in 43 cases, intravenous drug user in 1 case, homosexual in 2 cases, professional in 1 case, unknown in 3 cases. There are 4 double contamination Ag Hbs/HIV, and 2 HCV/HIV. 39 subjects are at A stage, 5 B, 6 C. The beginning of the epidemic in Mayotte took place probably around 1990, among militaries and prostitutes. Now, transmission keeps going on, in most cases, heterosexual, as it occurs in the nearby Africa. Polygamy, official or officious, has a leading role. Females who were detected during pregnancy have obtained zidovudine, or have been able to pursue previous therapy. Medical care and therapy are free in Mayotte, but sometimes there are delays in supplying medicines or in returning results. Epidemic has not increased up to now; even though screening has. There are very few pediatric cases: only 4 cases were notified in Mayotte until now: one who died very soon, one who has gone to live in Reunion island, and two who are still in Mayotte: one is 12 years old, and another one 5 years old.

Adult↗
PubMed2002

Methadone at tapered doses for the management of opioid withdrawal.

BACKGROUND: Despite use in many countries of tapered methadone for detoxification from opiate, the evidence of efficacy to prevent relapse and promote lifestyle change has not been systematically evaluated. OBJECTIVES: To determine whether tapered methadone is effective to manage withdrawal from opioids. SEARCH STRATEGY: We searched: Cochrane Controlled Trial Register (Issue 1, 2000), MEDLINE (OVID 1966-2000), EMBASE (1980-2000); reference list of relevant articles; personal communication; conference abstracts; trials from pharmaceutical industry; Internet. SELECTION CRITERIA: All randomised controlled trials on the use of tapered methadone versus all other detoxification treatments, placebo and different modalities of methadone detoxification programs for the treatment of opiate withdrawal. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction. The overall process were confirmed by consultation between reviewers. MAIN RESULTS: 20 studies were included, with 1357 people randomised. 10 studies compared methadone with adrenergic agonists, 7 compared different modalities of methadone detoxification, 2 compared methadone with other opioid agonists, 1 study compared methadone with chlordiazepoxide one with placebo. 10 studies that compared methadone with adrenergic agonists showed clinical differences of the treatments; 6 studies that compared different methadone schedules, showed different withdrawal responses; 2 studies that compared methadone and other opioid agonists showed that methadyl acetate performed similarly to methadone, while propoxyphene produced more severe withdrawal symptoms and more drop-outs than methadone; chlordiazepoxide and methadone (1 study) resulted similar in terms of overall effectiveness; more severe withdrawal and more drop outs in the placebo group than in methadone one (1 study). The results indicate that tapered methadone and other medications used are effective although symptoms experienced differed according to the medication used and the program adopted. The medications are similar in terms of overall effectiveness. Improvements were achieved when other services supporting services were offered contemporaneously with detoxification. REVIEWER'S CONCLUSIONS: Data from literature are hardly comparable; programs vary widely with regard to duration, design and treatment objectives, along with reporting impairing the application of meta-analysis. The studies included confirm that slow tapering with temporary substitution of long acting opioid can reduce withdrawal severity. Nevertheless the majority of patients relapsed to heroin use, abstinence cannot be considered a goal as heroin dependence is a chronic, relapsing disorder and the purpose of detoxification should be to remove or reduce dependence on heroin in a controlled and human fashion and not a treatment for heroin dependence.

Humans↗
PubMed2002

Reconstruction of the natal cleft with a perforator-based flap.

Recurrent chronic conditions of the natal cleft, such as pilonidal sinuses, are difficult problems to treat. The deep natal cleft and the rolling effect of one buttock surface over the other contribute to the high recurrence rate. Wide excision of the affected area is the treatment of choice; to cover the defect many techniques have been described that flatten the natal cleft and shift the suture line away from the midline to try to reduce recurrence. These techniques include Z-plasties, rhomboid flaps, V-Y flaps, gluteus maximus myocutaneous flaps and others. Five patients with recurrent natal-cleft problems were operated on over a 1 year period. After wide excision of the natal cleft, the defect was reconstructed with a parasacral perforator-based flap. Preoperatively, a perforator situated superolaterally to the defect is identified with a Doppler probe; the flap is then designed horizontally around the perforator and, after elevation, is rotated 908 over the defect. The mean hospital stay was 5 days. Follow-up ranged from 3 months to 15 months, with no signs of recurrence. We believe this to be a simple and reliable technique, with the advantages of placing the scars away from the midline and flattening the natal cleft - factors that help to prevent recurrence.

Adult↗
PubMed2001

Antigen binding characteristics of antibodies induced against nitric oxide modified plasmid DNA.

Nitric oxide (NO) generated by the reduction of sodium nitrite with sodium dithionite caused damage to plasmid Bluescript DNA leading to strand breaks and base modifications. The NO-plasmid DNA was highly immunogenic in rabbits. The antibody activity was inhibited to the extent of 86% with the immunogen as inhibitor, indicating the induction of immunogen specific antibodies. However, delineating the antigenic specificity of anti-NO-plasmid DNA antibodies by competition ELISA, multiple cross-reactivity was observed. The antibodies recognised B-, A- and allied conformations. The visual detection of immune complex formation with native and NO-plasmid DNA reiterated preferential binding with modified plasmid DNA. DNA modified by nitric oxide presents unique epitopes which may be one of the factors in antigen-driven autoimmune response in systemic lupus erythematosus.

Antibodies↗
PubMed2001

Hyperalgesic responses in methadone maintenance patients.

Opioid substitution treatment for dependence may alter sensitivity to pain. Previous studies on pain sensitivity in methadone maintenance patients have yielded contradictory results. This study compared nociceptive responses between 16 patients on stable, once daily, doses of methadone and 16 matched control subjects. Two types of nociceptive stimuli were used: (1) electrical stimulation; and (2) a cold pressor test. Two parameters were measured: detection for onset of pain, and pain tolerance. Methadone patients were tested over an inter-dosing period: at the time of trough plasma methadone concentration (0 h), and 3 h after their daily dose. Control subjects were tested twice 3 h apart. Blood samples were collected to determine plasma methadone concentration. In methadone patients, trough to peak increases in mean R-(-)- and S-(+)-methadone concentrations (118 and 138 ng/ml to 185 and 259 ng/ml, respectively) resulted in significant increases in pain detection and tolerance values for both nociceptive stimuli. Using electrical stimulation, methadone patients' pain tolerance values were lower than controls at 0 h, but higher than controls at 3 h; no significant differences in pain detection values were found. For the cold pressor test, methadone patients detected pain significantly earlier than controls at 0 h, and were also substantially less pain tolerant than controls at both 0 and 3 h. There were no significant differences in pain detection values between the two groups at 3 h. Pain tolerance to pain detection ratios for methadone patients were significantly lower than controls for the cold pressor test at 0 and 3 h, and for electrical stimulation at 0 h only. In summary, the relative pain sensitivity of methadone maintenance patients is determined by the nature of the nociceptive stimulus (e.g. cold pressor test versus electrical stimulation), the plasma methadone concentration (trough versus peak plasma concentration), and whether thresholds are determined for detection of pain or pain tolerance. Although responding to changes in plasma methadone concentration, maintenance patients are markedly hyperalgesic to pain induced by the cold pressor test.

Adult↗
PubMed2001

Opioid antagonists under sedation or anaesthesia for opioid withdrawal.

BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. OBJECTIVES: To assess the effectiveness of interventions involving the administration of opioid antagonists to induce opioid withdrawal with concomitant heavy sedation or anaesthesia. SEARCH STRATEGY: Multiple electronic databases (including MEDLINE, EMBASE, PsycLIT, Australian Medical Index, Cochrane Clinical Trials Register, and CINAHL) were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared the administration of opioid antagonists under sedation or anaesthesia with another form of treatment. DATA COLLECTION AND ANALYSIS: One reviewer assessed studied for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all three reviewers. MAIN RESULTS: As yet, no studies have been published comparing treatment regimes involving the administration of opioid antagonists under sedation or anaesthesia with other approaches to detoxification. Treatment regimes for the studies considered for this review varied in the opioid antagonist used, the dose and mode of administration, the anaesthetic agent, duration of anaesthesia and adjunct medications employed. More detailed monitoring of withdrawal is required before any conclusions can be drawn as to what comprises a typical pattern of withdrawal and what factors might influence the pattern. There is only very limited information on referral to ongoing treatment, and relapse to opioid use. Together with the lack of adequate comparisons, this makes it impossible to draw any conclusions about the long-term effectiveness, or the cost-effectiveness, of withdrawal induced by opioid antagonists under sedation or anaesthesia. REVIEWER'S CONCLUSIONS: Considerably more research evidence will be needed before any conclusions can be drawn regarding the effectiveness of managing withdrawal by administration of opioid antagonists under sedation or anaesthesia. The risk of vomiting during sedation and respiratory depression point to the approach being limited to facilities equipped for intubation and assisted ventilation, and with the capacity to respond to adverse events that might occur. The approach must be regarded as experimental with both risks and benefits remaining uncertain.

Anesthetics↗
PubMed2001

Alpha2 adrenergic agonists for the management of opioid withdrawal.

BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. OBJECTIVES: To assess the effectiveness of interventions involving the use of alpha2 adrenergic agonists (clonidine, lofexidine, guanfacine, guanabenz acetate) to manage the acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched and relevant pharmaceutical companies contacted. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared alpha2 adrenergic agonists with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all four reviewers. MAIN RESULTS: Twenty-four studies, involving 1956 participants, were included. Nineteen were randomised controlled trials; in two allocation was by participant choice, one used alternate allocation and in two the method of allocation was unclear. Ten studies compared a treatment regime based on an alpha2 adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis. From the comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone, withdrawal intensity is similar to, or marginally greater with alpha2 adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects (low blood pressure, dizziness, dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. REVIEWER'S CONCLUSIONS: Treatment regimes based on the alpha2 adrenergic agonists clonidine and lofexidine, and those based on reducing doses of methadone over a period of around 10 days, have similar efficacy in the management of withdrawal from heroin or methadone. Participants stay in treatment longer with methadone regimes and experience less adverse effects. The lower incidence of hypotension makes lofexidine more suited to use in outpatient settings than lofexidine. There are insufficient data available to support a conclusion on the efficacy of guanfacine.

Acute Disease↗
PubMed2001

Identification of Candida tropicalis HSR1, a gene of the heat-shock factor-related family, which confers salt tolerance in Saccharomyces cerevisiae.

A genomic library of Candida tropicalis in a yeast multicopy plasmid has been screened for clones conferring salt tolerance upon transformation into S. cerevisiae. The best halotolerance clone contained an open reading frame encoding a predicted protein of 728 amino acids with homology to transcription factors of the heat-shock family. This novel gene was named HSR1 and is present in single copy in the C. tropicalis genome. Upon transformation into S. cerevisiae it increases the expression of ENA1, a major determinant of salt tolerance encoding a cation-extrusion pump. The sequence of CtHSR1 has been deposited in the EMBL data library under Accession No. AJ296093.

Adenosine Triphosphatases↗