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Biomedical subjects

A Hussein

Publications and source records attributed to A Hussein.

At least 37 records · Page 2Linked to original sources

Isolation and evaluation of Coxiella burnetii O-polysaccharide antigen as an immunodiagnostic reagent.

A lipid A - deprived lipopolysaccharide (LPS) from Coxiella burnetii (C.b.) Priscilla strain in virulent phase I was separated by steric-exclusion chromatography and high performance liquid chromatography (HPLC). The isolated O-specific polysaccharide (PS) fractions were analyzed by different physico-chemical methods and showed noticeable differences in their overall composition. The antigenic potential of the PS fractions was evaluated by ELISA with animal and human sera and in comparison with those of the native C.b. LPSs and phase I and II C.b. Nine Mile stain cells of which the latter are routinely used in diagnosis of Q fever. The results indicate that the high molecular mass PS antigen SG501 could be used in ELISA for a sensitive and specific detection of anti-C.b. antibodies in the examined sera.

Antibodies, Bacterial↗

[Transient ischemic ECG changes in a patient with acute cholecystitis without a history of ischemic heart disease].

That abdominal distention, nausea, and chest pain may be accompanied by ischemic ECG changes is well known and has been described in the literature. However, very few cases have been reported with acute cholecystitis and ECG changes not due to cardiac ischemia. We present a previously healthy 20-year-old woman admitted with acute cholecystitis. Prior to surgery routine ECG showed ST-depression and T-wave inversion. The day following cholecystectomy the ECG returned to normal. 1 month later, ergometry and echocardiography were both negative. Based on the literature and our personal experience, although ECG changes may occur in acute cholecystitis, the possibility of cardiac ischemia must be excluded. However, when no cardiac basis is found, ultrasound of the biliary system might reveal the cause of these ECG changes. Thus, in acute cholecystitis with ischemic ECG changes but no other laboratory or clinical evidence of cardiac ischemia, ECG changes alone are not a contraindication to cholecystectomy. Furthermore, delay in treatment could be harmful.

Adult↗

The gamma-glutamylcysteine synthetase of Onchocerca volvulus.

The tripeptide glutathione (GSH) plays an important role in the maintenance of the intracellular thiol redox state and in detoxification processes. The intracellular GSH level depends on glutathione reductase as well as on GSH synthesis. The first and rate limiting step in the synthetic pathway is catalysed by gamma-glutamylcysteine synthetase (gamma-GCS). The gamma-GCS was partially purified from the filarial parasite Onchocerca volvoulus and preliminary steady state kinetics were performed. The Ki-value for L-buthionine-S,R-sulphoximine (BSO), a specific inhibitor of gamma-GCS, was determined to be 0.13 microM, which is 54-fold lower than the Ki-value for the mammalian enzyme. Filarial gamma-GCS was also inhibited by cystamine with a Ki-value of 3.9 microM compared with 22.2 microM determined for the rat enzyme. Further, the cDNA and the gene of the O. volvulus gamma-GCS were cloned and sequenced. The gene of 5762 bp is composed of 14 exons and 13 introns. Southern blot analysis indicates that the gamma-GCS gene is present as a single-copy gene. In accordance with Northern blot analysis, the entire cDNA sequence encompasses 2377 bp. At its 5' end a nematode-specific spliced leader 130 bp upstream of the first in frame methionine was identified. The cDNA encodes a polypeptide of 652 amino acids with 50 and 69% sequence identity to the human and the Caenorhabditis elegans counterparts, respectively. The filarial gamma-GCS is proposed as a potential drug target.

Amino Acid Sequence↗

CYP2D6 phenotypes among Malays in Malaysia.

BACKGROUND: Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays. OBJECTIVE: To study debrisoquine metabolism phenotypes in healthy Malay volunteers. METHOD: We administered debrisoquine to 51 Malays and used HPLC to measure urinary debrisoquine and 4-hydroxy debrisoquine to calculate debrisoquine metabolic ratios (MR). RESULTS: Debrisoquine MR varied widely and with probit analysis we were able to identify population subsets. Although the frequency distribution for the MR showed a right shift, the shift was less than that reported for the Chinese population. We also found 2 poor metabolizers and one ultra rapid metaboliser in the population. CONCLUSION: The genetic polymorphism of debrisoquine in Malays differs from that in the Chinese. Both their PM prevalence and their MR distribution suggest that they are intermediate between Europeans and Chinese in relation to this polymorphism. Studies to compare CYP2D6 genotypes between them and related races would be useful to further define these differences.

Adult↗

A survey of vitamin A and D contents of fortified fluid milk in Ontario.

High performance liquid chromatographic methods for measuring the concentration of vitamins A and D in fluid milk were validated and used to assess the level of these nutrients in Ontario retail milk samples. Thirteen and fifteen fortified milk samples were tested for vitamins A and D, respectively. Repeatability relative standard deviation values for vitamins A and D in milk were generally less than 10%. Recoveries varied from 87 to 107%. Vitamin D results indicated that only 20% of skim, 40% of 2% fat milk, and 20% of whole milk contained the recommended levels, whereas 46% of skim, and 77% of 2% fat milk had the required levels of vitamin A. The results indicate that vitamin level varies widely in Ontario retail milk.

Animals↗

The impact of brushing teeth on carbon-14 urea breath test results.

OBJECTIVE: The 14C urea breath test noninvasively detects the presence of the urease-producing bacteria Helicobacter pylori in the stomach. Several sources of errors have been identified to cause false or indeterminate results on the test. The objective of this study was to identify whether brushing teeth affects the test results. METHODS: We performed the 14C urea breath test on 168 patients, with breath samples counted at 10 and 20 min after oral administration of 2 microCi (74 kBq) 14C urea. Ninety-four patients brushed their teeth before the test while 74 did not. RESULTS: Thirty-six of the 74 patients (49%) who did not brush their teeth had positive results at 10 min, which became negative at 20 min. None of the 94 patients who brushed their teeth before testing showed this pattern with agreement of results at 10 and 20 min. CONCLUSION: We recommend brushing teeth before the 14C urea breath test since it significantly decreased the ambiguous results of the test in our laboratory.

Administration, Oral↗

Diabetic autonomic neuropathy.

OBJECTIVE: The diabetic autonomic neuropathy is a poorly studied subject in our medical literature. This study is aimed at investigating the presence of diabetic autonomic neuropathy in a group of Sudanese diabetic patients and its relationship to factors like glycemic control, duration of diabetes and presence of peripheral neuropathy. METHODS: During one year we examined 120 diabetic patients and an age-matched control group of 42 by applying a battery of 5 cardiovascular autonomic tests, beside a full history and clinical examination. The patients were also tested for glycemic control and presence of peripheral neuropathy. RESULTS: Diabetic autonomic neuropathy was diagnosed in 48 patients (40%) of a mean age of 48.411 + 12.50 years, type 1/2 diabetes was 10/38, mean duration of diabetes 16.2 + 7.3 years, 41 with poor glycemic control (81%) and peripheral neuropathy was present in 32 patients (66%). We found a significant association between diabetic autonomic neuropathy and prolonged duration of diabetes (P<0.001), poor glycemic control (0.01>P>0.001) and presence of peripheral neuropathy (0.02>P>0.01). CONCLUSION: Diabetic autonomic neuropathy (both asymptomatic and symptomatic) is a common problem among our diabetic patients. It is significantly associated with prolonged duration, poor control of diabetes and presence of peripheral neuropathy. We need to augment the awareness of diabetes care providers to the occurrence, and peculiar features and tests of this syndrome.

Adult↗

[Fulminant meningococcemia presenting as a gastroenteritis-like syndrome].

Neisseria meningitidis infection (meningococcemia) is very common throughout the world. It usually presents as meningitis or sometimes pharyngitis. A gastroenteritis-like syndrome, with diarrhea, vomiting and abdominal pain, may occur in children but is very rare in adults. Search of the medical literature revealed only 3 such cases, all in young adults. We report an 80-year-old woman who presented with fever, diarrhea and abdominal pain. Meningococcus infection was later suspected, and proved by culture. Although treatment was intensive and included ceftriaxone (Rocephin) and garamycin, she did not respond and died 40 hours after admission. We draw attention to the possibility that what is usually a common symptom can be the first presentation of a serious, often fatal condition.

Abdominal Pain↗

Comparison of soy-based formulas with lactose and with sucrose in the treatment of acute diarrhea in infants.

OBJECTIVE: To evaluate the effect of feeding infants a soy-based formula with lactose compared with a soy-based formula with sucrose during an acute diarrheal episode. PARTICIPANTS AND METHODS: Two hundred boys, aged 3 to 18 months, who were admitted to the hospital with acute diarrhea and signs of dehydration were randomly assigned to receive a soy-based formula with lactose or sucrose after initial rehydration. Intake and output (stool, urine, and vomit) were measured and recorded every 3 hours until diarrhea resolved. RESULTS: The stool output during the first 24 hours of maintenance therapy, the total stool output during maintenance therapy, and the stool output during the entire illness (measured in grams per kilograms) were significantly lower among patients who received the soy-based formula with sucrose (P<.05, P<.001, and P<.001, respectively) than among patients who received the soy-based formula with lactose. The duration of diarrhea was significantly shorter among patients who received the soy-based formula with sucrose (P<.001). The relative risk of being withdrawn from the study increased to 1.95 (95% confidence interval, 0.65-9.2) and the relative risk of recurrence of dehydration after feeding was initiated increased significantly to 3.49 (95% confidence interval, 1.1-9.6; P<.01) in the group receiving the soy-based formula with lactose. CONCLUSION: During diarrheal episodes, feeding infants a soy-based formula with sucrose has a better outcome (lower stool output, shorter duration of diarrhea, and lower failure rates) than feeding infants a soy-based formula with lactose.

Acute Disease↗

Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.

PURPOSE: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy. PATIENTS AND METHODS: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses. RESULTS: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci (</= 2 v > 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases (</= 2 v > 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143). CONCLUSION: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.

Adult↗

Impact of consolidation radiotherapy in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow rescue.

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Adult↗

Chlamydia psittaci lipopolysaccharide. A reinvestigation of its chemical composition and structure.

A lipopolysaccharide (LPS) of Chlamydia psittaci PK 5082 strain associated with enzootic abortion in ewes was isolated from embryonated hen eggs-grown elementary bodies (EBs) by a phenol/water procedure. Compositional analyses revealed the presence of 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo), glucosamine (GlcN), phosphorus, and fatty acids in a molar ratio of 2.6:2.0:2.4:4.4. GlcN was the only amino sugar detected. Methylation analysis of the LPS confirmed the presence of a Kdo trisaccharide proximal to lipid A having the structure Kdo-(2-->8)-Kdo-(2-->4)-Kdo, which appears to be a highly conserved region in native chlamydial LPSs. The complex fatty acid composition revealed the presence of ten different straight or branched (iso and anteiso) nonhydroxy fatty acids and thirteen 3-hydroxy fatty acids. The major nonhydroxy fatty acid was icosanoic acid and the most prominent 3-hydroxy fatty acid was 3-hydroxyicosanoic acid followed by 3-hydroxy-18-methylicosanoic acid. The 3-hydroxy fatty acids represented more than two thirds of the total fatty acid content and most of them were bound in amide linkages. In contrast, most nonhydroxy fatty acids were ester-linked. It appears that LPSs from various chlamydial species differ in fatty acid composition and distribution.

Animals↗

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.

PURPOSE: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. METHODS: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. RESULTS: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. CONCLUSION: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.

Antiemetics↗

Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver.

Clinical trials involving breast cancer in the Duke University Bone Marrow Transplant Program were evaluated to assess the association between type of hematopoietic support and treatment-related morbidity/mortality. Case histories of patients treated with high-dose chemotherapy and hematopoietic rescue on three separate protocols between 1986 and 1994 were reviewed. This included 307 patients with stage IV disease and 85 patients with high-risk (10 or more positive axillary lymph nodes) stage II or III disease. One hundred and twenty-eight of these patients were rescued with autologous bone marrow (BM) alone and 264 additionally received autologous peripheral blood progenitor cells (PBPC). The 100 day transplant-related mortality rate in those patients who received BM alone was 20.3%, with an overall mortality rate due to the high-dose chemotherapy procedure of 24.2%. The PBPC-treated group experienced a 100 day transplant-related mortality of only 6.1% and an overall trans-plant- related mortality of 10.2%. Sixteen of 31 deaths were attributed to veno-occlusive disease (VOD) in the group that received BM alone compared to only one VOD-related death in the PBPC group. These data demonstrate a marked improvement in transplant-related mortality which is related to the use of PBPC. This effect has been almost entirely due to a reduction in mortality from hepatic veno-occlusive disease.

Adult↗