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Biomedical subjects

A Sultan

Publications and source records attributed to A Sultan.

At least 19 recordsLinked to original sources
PubMed2006

PKC-B inhibition: a new therapeutic approach for diabetic complications?

PKC comprises a superfamily of isoenzymes that is activated in response to various stimuli. Hyperglycaemia induces the activation of different PKC isoforms. However, the PKC-B isoform appears to be preferentially activated by high glucose levels and has been shown to be associated with diabetic vascular complications. In vitro and in vivo animal studies have shown that ruboxistaurin mesylate, a novel selective inhibitor of PKC-B ameliorates the biochemical and functional consequences of PKC activation and may have the potential to reduce the burden of vascular complications associated with diabetes. Results of the first phase-II and phase-III trials evaluating the efficacy of this compound on diabetic microvascular complications have been published recently. They confirm that this compound may favorably influence the evolution of diabetic microvascular complications.

Diabetes Complications↗
PubMed2006

Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic patients with diabetes living in southern France.

AIMS: To assess the association between abnormal stress myocardial perfusion imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and with > or = 1 additional risk factor. Predictors of abnormal stress MPI were also evaluated. METHODS: Four hundred and forty-seven consecutive patients who underwent stress MPI were prospectively followed for 2.1 [0.5-4.1] years for the subsequent occurrence of hard CE (myocardial infarction and sudden or coronary death) and soft CE (unstable angina and ischaemic heart failure requiring hospitalization). Re-vascularization procedures performed as a result of the screening protocol were not included in the analysis. RESULTS: Follow-up was successful in 419 of 447 patients (94%), of whom 71 had abnormal MPI at baseline. Medical therapy was intensified in all subjects and especially in those with abnormal MPI. Twenty-three patients with abnormal MPI underwent a re-vascularization procedure. CEs occurred in 14 patients, including six of 71 patients (8.5%) with abnormal MPI and eight of 348 patients (2.3%) with normal MPI (P < 0.005). Only two patients developed a hard CE and 12 a soft CE. In multivariate analysis, abnormal MPI was the strongest predictor for CEs [odds ratio (OR) (95% CI) = 5.6 (1.7-18.5)]. Low-density lipoprotein cholesterol > or = 3.35 mmol/l [OR (95% CI) = 7.3; 1.5-34.7] and age > median [OR (95% CI) = 6.0 (1.2-28.6)] were additional independent predictors for CE. The independent predictors for abnormal MPI were male gender, plasma triglycerides > or = 1.70 mmol/l, creatinine clearance < 60 ml/min and HbA1c > 8%, with male gender the strongest [OR (95% CI) = 4.0 (1.8-8.8)]. CONCLUSIONS: Asymptomatic patients with diabetes in this study had a very low hard cardiac event rate over an intermediate period. This could be explained by the effects of intervention or by the low event rate in the background population. Randomized studies of cardiac heart disease screening are required in asymptomatic subjects with diabetes to determine the effectiveness of this intervention.

Aged↗
PubMed2006

Cullen's sign and massive ovarian enlargement secondary to primary hypothyroidism in a patient with a normal FSH receptor.

Ovarian hyperstimulation is a recognised complication of longstanding hypothyroidism. A 12 year old girl with atrophic thyroiditis who presented with abdominal pain and distension is reported. She was noted to have bruising in the vicinity of the umbilicus (Cullen's sign). She had pronounced ovarian enlargement on ultrasonography and it was hypothesised that this profound phenotype might reflect an abnormal FSH receptor. However sequencing of the FSH receptor was normal. The ovarian enlargement resolved with thyroxine replacement. Physicians and surgeons should consider longstanding hypothyroidism in patients presenting with Cullen's sign.

Adolescent↗
PubMed2004

The effect of vitamin D status on the severity of bone disease and on the other features of primary hyperparathyroidism (pHPT) in a vitamin D deficient region.

A clear relationship between vitamin D status and the clinical indices of primary hyperparathyroidism (pHPT) severity has not been convincingly established. We proposed that such a relationship might exist, in so far as vitamin D deficiency could contribute to the severity of metabolic bone disease and promote the growth of the parathyroid tumor. Accordingly, we undertook a retrospective study and analyzed the clinical, biochemical, radiological and histopathological findings in a group of 49 patients who underwent parathyroidectomy at our center. Patients who had skeletal X-rays were grouped, according to their X-ray findings, in group A (19 patients; 45%) if they had severe bone changes, or group B (23 patients; 55%) if they had mild or no bone changes. Patients were also stratified according to their 25-hydroxyvitamin D (25-OHD) levels in tertiles. The 2 groups were compared using Fisher's exact test or analysis of variance as appropriate. Group A patients were younger (p=0.001), had more musculoskeletal symptoms (p=0.0003), and complained more frequently of fatigue (p=0.02). They had higher alkaline phosphatase (AP; p=0.0002), PTH index (p=0.0007), and serum Ca level (p=0.006). There were more patients from the lower and middle vitamin D tertiles and fewer patients from the upper vitamin D tertile in group A (p=0.02). Post-operative severe hypo-calcemia was more prevalent in group A patients (p<0.0001). Resected parathyroid tumors were larger in size in group A patients (p=0.01), and weighed more (p=0.01). There was a positive correlation between the weight of the parathyroid tumor and the PTH index (p=0.002), and AP level (p=0.0007). We concluded that vitamin D deficiency is a contributing factor to both the severity of bone disease and the high activity of parathyroid tumors seen in many patients with pHPT in vitamin D deficient regions.

Adenoma↗
PubMed2002

Impact of cervical lymph node dissection on serum TG and the course of disease in TG-positive, radioactive iodine whole body scan-negative recurrent/persistent papillary thyroid cancer.

In the management of papillary thyroid cancer (PTC), surgery is indicated for locoregional recurrent/persistent disease. In this study, we examined the effect of such surgery on serum TG and the course of the disease in 21 patients with PTC (mean age 38.5 yr), who after the initial surgery and radioactive iodine (RAI) ablation developed high TG (>10 ng/ml) and negative 123I whole body scan (DxWBS). All patients had neck persistent/recurrent PTC that was confirmed by ultrasound-guided fine needle aspiration. Prior to neck re-exploration, radiological studies (chest X-rays, CT scan of the chest, and fluoro-18-deoxyglucose positron emission tomography [FDG-PET]) showed no evidence of distant metastases. TG autoantibodies were negative in 19 patients. Second surgery consisted of unilateral (13 patients) or bilateral (8 patients) modified neck dissection. The mean+/-SE TG prior to neck re-exploration was 184.8+/-79.0 ng/ml and declined after surgery to 127.5+/-59.0 ng/ml (p=0.25). The corresponding TSH values were 150.6+/-23.0 and 143.4+/-20.0 mU/l, respectively (p=0.34). After a mean follow-up of 20.7+/-3 months, TG increased to 168+/-68.0 ng/ml. This increase, however, was NS (p=0.67). The corresponding TSH values were 143.4+/-20.0 and 132.0+/-22.0 mU/l (p=0.27). Following second surgery, only 4 patients achieved remission, the other 17 patients received one or more of the following therapies; RAI (10 patients), third surgery (5 patients), and/or external radiation (7 patients). Thirteen patients continued to have persistent disease and 4 patients showed progressive course of their disease (distant metastases or grossly palpable neck disease). In conclusion, second surgery for recurrent/persistent PTC leads to remission in only a minority of cases but the course of the disease tends to be stable in most cases.

Adult↗
PubMed2002

Diagnosis of diabetes mellitus and intermediate glucose abnormalities in obese patients based on ADA (1997) and WHO (1985) criteria.

AIM: To assess the accuracy of the 1997 ADA criteria for diagnosing diabetes mellitus and related glucose disturbances in comparison with the reference WHO 1985 criteria in obese subjects. PATIENTS AND METHODS: In 286 men and 881 women, 15-84 years of age, with obesity (body mass index (BMI) > or = 30 kg/m2), an oral glucose tolerance test (OGTT) was carried out according to WHO standard. Patients were classified into three categories of glucose tolerance using WHO 1985 (Normal Glucose Tolerance (NGT), Impaired Glucose Tolerance (IGT) and Diabetes Mellitus (DM)) and ADA (Normal Fasting Glucose (NFG), Impaired Fasting Glucose (IFG) and DM) criteria. Prevalence of each category was compared and agreement between the two classifications was assessed. The relation between fasting plasma glucose value and diabetes, as diagnosed by WHO 1985 criteria, was studied using various regression models, cumulative frequency curves, Finch method and ROC curve. RESULTS: Compared with WHO 1985, ADA criteria strongly underestimated the prevalence rate of diabetes (3.7% vs. 10.6%) and intermediate glucose abnormalities (6.0% vs. 22.4%). Agreement between the two classifications was poor (kappa = 0.23). Moreover, many patients defined as glucose-intolerant by the WHO 1985 criteria were shifted to a more favourable metabolic status by ADA criteria. Thus, ADA criteria failed to detect 69% of WHO diabetic patients and 89% with IGT were considered as normal. According to the method, cut-off value of fasting blood glucose for detecting WHO 1985-diagnosed diabetes varied widely, from 5.3 to 6.3 mmol/l and none was satisfactory because of poor sensitivity and positive predictive value. CONCLUSION: The ADA criteria do not appear to be a good substitute for those of the WHO 1985 at identifying diabetes and intermediate glucose abnormalities in an obese population. Since it appears impossible to determine a reliable cut-off value for fasting blood glucose to identify diabetic obese subjects with sufficient sensitivity, our results justify the retention of the OGTT in clinical practice or for epidemiological studies.

Adolescent↗
PubMed2001

Palmitic acid opens a novel cyclosporin A-insensitive pore in the inner mitochondrial membrane.

An assortment of agents can induce mitochondria to undergo a permeability transition, which results in the inner mitochondrial membrane becoming nonselectively permeable to small (<1500 Da) solutes. This mitochondrial permeability transition (MPT) is characterized by a strict dependence on matrix Ca2+ and sensitivity to cyclosporin A (CsA). However, it is becoming increasingly clear that other experimental conditions can elicit increases in mitochondrial permeability that are distinct from this classic MPT. For example, butylated hydroxytoluene (BHT; Sokolove, P. M., and Haley, L. M. (1996) J. Bioenerg. Biomembr. 28, 199-206) and signal peptides (Sokolove, P. M., and Kinnally, K. W. (1996) Arch. Biochem. Biophys. 336, 69-76) promote increases in mitochondrial permeability that are CsA-insensitive. It has been suggested (Gudz, T., Eriksson, O., Kushnareva, Y., Saris, N.-E., and Novgorodov, S. A. (1997) Arch. Biochem. Biophys. 342, 143-156) that BHT might be opening a CsA-insensitive pore by increasing phospholipase A2 activity and thereby producing an accumulation of free fatty acids and lysophospholipids. We have therefore examined the effect of the saturated free fatty acid, palmitic acid (PA), on the permeability of isolated rat liver mitochondria. The following results were obtained: (1) In the absence of additional triggers, PA (20-60 microM) induced concentration-dependent, CsA-insensitive mitochondrial swelling. (2) Swelling required mitochondrial energization. (3) PA-induced swelling was fast and occurred without a lag. (4) Both Ca2+ and Sr2+ supported PA-induced swelling; the site of cation action was the matrix. (5) EGTA and BSA were potent inhibitors of PA-induced swelling. (6) PA opened a pore rather than disrupting mitochondrial membrane structure. (7) The pore opened by PA closed spontaneously. These results suggest that palmitic acid promotes a nonclassic permeability increase that is clearly distinguishable from the occurrence of the MPT.

Animals↗
PubMed2001

Free fatty acid effects on mitochondrial permeability: an overview.

A variety of experimental conditions elicit increases in mitochondrial permeability that can be differentiated from the classic cyclosporin A (CsA)-sensitive mitochondrial permeability transition (MPT). For example, butylated hydroxytoluene, signal peptides, and the hormone thyroxine have been shown to promote increases in mitochondrial permeability that are CsA-insensitive. Our laboratory has recently demonstrated that palmitic acid, a saturated 16-carbon free fatty acid (FFA), can also open a CsA-insensitive pore. This nonclassic permeability transition (NCPT) is further distinguished by a nonselective dependence on divalent cations and by spontaneous closure. To determine if induction of the NCPT is specific to palmitic acid and to resolve conflicting reports as to the mechanisms by which FFAs alter mitochondrial permeability, we examined in detail mitochondrial swelling induced by FFAs that differ in chain length and degree of saturation. The following results were obtained: (1) In the presence of modest Ca2+ concentrations (75 nmol/mg protein), medium-chain FFAs (C12-C18) were more effective in eliciting mitochondrial swelling than were shorter or longer FFAs; medium-chain alkanols and amines had no effect. (2) Under these conditions, saturated FFAs induced CsA-insensitive swelling with all the characteristics of the NCPT, while unsaturated FFAs triggered the MPT. (3) When matrix Ca2+ concentration was further elevated, unsaturated FFAs triggered the NCPT. (4) Mitochondrial swelling induced by saturated FFAs was inhibited by unsaturated FFAs but not by other saturated FFAs or medium-chain alkanols. These results suggest that ambient conditions can greatly influence the nature of the increase in mitochondrial permeability induced by FFAs. They are also consistent with our earlier proposal that Ca2+ (or Sr2+) binding to FFAs in the inner leaflet of the inner mitochondrial membrane underlies the NCPT.

Animals↗
PubMed2000

Hydrostatic reduction of intussusception: barium, air, or saline?

While there is agreement that hydrostatic reduction (HR) is the ideal first-line treatment for childhood intussusception, there is controversy about which technique is best, namely, barium, air, or saline. We present our experience in the Pediatric Surgical Center, University of Alexandria, in HR of intussusception under ultrasound (US) guidance. The study was divided into two phases: between 1983 and 1990 and between 1991 and 1998. HR was started gradually in phase I, and became routine in phase II. Diagnosis and reduction were done by the pediatric surgical staff. The success rate was 71.7% in phase I and 85.5% in phase II. Most unreduced cases were the ileo-ileocolic type: 58.6% in phase I and 69.3% in phase II. HR under US guidance is equal or superior to other techniques of reduction, while having the obvious advantage of avoiding radiation exposure.

Air↗
PubMed1999

Vaccination against Schistosoma mansoni infection using 74 kDa Schistosoma protein antigen.

An IgG2a anti-Schistosoma mansoni mouse monoclonal antibody was shown to passively protect Swiss mice. The 74 kDa target antigen was isolated from antigenic extracts of S. mansoni adult worms. Swiss and C57 BL/6J mice were immunized with 30, 50, 100 and 200 microg antigen/mouse doses with and without Freund's adjuvant. Sera of immunized mice showed high reactivity against 74 kDa antigen. The highest protection level (76.6% in Swiss mice and 50.1% in C57 BL/6J mice) was obtained using the 50 microg antigen dose with and without Freund's adjuvant. A marked reduction in granuloma number and intensity of collagen and reticular granuloma fibers was observed. The 74 kDa antigen has the ability to protect mice of different strains and to modulate the host immune system.

Adjuvants, Immunologic↗
PubMed1999

Evaluation of cell mediated immunity in advanced pancreatic carcinoma before and after treatment with interleukin-2 (IL-2).

BACKGROUND/AIMS: The administration of high doses of Interleukin-2 (IL-2) either alone or in combination with other cytokines demonstrated that immunologic manipulation is capable of mediating the regression of established cancer in humans. Thus, there is an urgent need to develop and evaluate the effect of treatment with IL-2 on immunological parameters and outcome of patients with inoperable pancreatic carcinoma. METHODOLOGY: Twenty-one patients with advanced pancreatic cancer were the subjects of this study and all patients were diagnosed as unresectable pancreatic carcinoma on a clinical, surgical, radiological and laboratory basis. The patients were classified as group I: 10 patients treated by IL-2, and group II: 11 non-treated patients. We used a novel method of intra-arterial therapy. Patients in group I were subjected to surgical exploration for assessing the inoperability and catheterization of the splenic artery, gastroduodenal artery and hepatic artery in patients with liver metastasis. The course of therapy that started 15 days after catheterization included the following for 10 days, lipiodol 2.5ml, 0.5ml urographin 58%, and IL-2 1ml. After 15 days of immunostimulation bolus injection of chemotherapy was given including, lipiodol 10ml, urographin 2ml, mitomycin C 0.2mg/kg, carboplatin 1.5mg/kg, farmorubicin 1mg/kg, 5-fluorouracil 10mg/kg, and leukovorin 1.5mg/kg. Forty-five days following locoregional chemotherapy, the same procedure was followed in the same sequence with 10 daily courses of locoregional immunotherapy. RESULTS: The results showed that there is a 70% relief of pain in group I compared to 0% in group II. Also, there is an improvement in body weight in 50% of group I in comparison to group II. Tumor size was decreased in 70% of the cases in group I. The mean survival was 11.9+/-4.9 months in group I compared to 5.6+/-1.5 in group II (p<0.0008). A highly significant increase of CD3 (p<0.0001), CD4 (p<0.001), CD8 (p<0.0001), CD16 (p<0.001), CD14 (p<0.0001), NK cytotoxicity (p<0.0001), T cell cytotoxicity (p<0.001), ICAM-1 (p<0.001), TNFalpha (p=0.001) IL-2 (p<0.001), and IL-2R (p=0.001) was seen in group I patients compared to group II patients. CONCLUSIONS: Immunotherapy is a new modality for treatment of pancreatic carcinoma. Local administration of therapy seems to be an attractive way for delivering the optimum concentration of IL-2 target tissues avoiding the toxic side effects associated with high dose systemic treatment.

Adult↗
PubMed1995

Endosonography of the anal sphincters in solitary rectal ulcer syndrome.

Twenty-one patients with histologically proven solitary rectal ulcer syndrome (SRUS) were examined by anal endosonography (AES) in order to determine the frequency of any ultrasound abnormality. Comparison was made with a group of 17 age and sex matched asymptomatic subjects. Four patients with SRUS had anal sphincter defects on AES. All were of the internal anal sphincter (IAS), which appeared fragmented in two patients with complete rectal prolapse. Measurements of internal and external anal sphincter (EAS) diameter and cross-sectional area were taken, excluding the 4 patients with defects. The submucosa was inhomogeneous (P = 0.0016) and thickness increased in patients with SRUS (median 4.0 mm vs 2.0 mm; P < 0.0001). IAS diameter was increased (median 3.8 mm vs 2.0 mm; P < 0.0001), as was cross-sectional area (median 241 sq mm vs 112 sq mm; P < 0.0001). EAS diameter was also increased (median 8.5 mm vs 7.0 mm; P = 0.0173), as was cross-sectional area (median 905 sq mm vs 594 sq mm; P = 0.0052). The ratio of EAS to IAS thickness was reduced in patients with SRUS (median 2.6 vs 4.0; P = 0.0029). The mechanism of these changes is unclear but apparent muscle hypertrophy on ultrasound may diagnose those patients with SRUS in whom defecatory difficulty is a predominant symptom.

Adult↗
PubMed1995

Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium falciparum.

A gene encoding a novel cdc2-related protein kinase has been identified in Plasmodium falciparum, using degenerate oligonucleotides designed to hybridise to regions that are conserved in members of the cdc2 gene family. This gene, called Pfcrk-1, is located on chromosome 4. It is most closely related to the p58GTA gene family, members of which are negative regulators of cell growth in vertebrates. Pfcrk-1 is developmentally regulated, as indicated by stage-specific accumulation of mRNA in gametocytes.

Amino Acid Sequence↗
PubMed1993

Interactions of cadmium and nickel with K channels of vascular smooth muscle.

Previous studies have shown that environmentally significant concentrations (< 1 microM) of large divalent cations increased vascular tone in resistance arteries. Because K channels are important regulators of vasoactivity, we studied the interactions of Cd and Ni on K channels of smooth muscle from bovine mesenteric artery using the planar bilayer method. We describe one type of small, Ca-insensitive K channel (Ks), and two types of large, Ca-activated K channels ([BK(Ca)], Kc1 and Kc2, that were identical with respect to single-channel conductance and K/Cl selectivity, but differed in Ca/voltage sensitivity. Neither metal affected the open probability (po) of Ks but both Cd and Ni, in concentrations greater than or equal to 100 nM, similarly decreased po of Kc1 and Kc2 from the intracellular side of the channel in the presence of 1 microM Ca. The effects of both Cd and Ni were reversed by 0.1 mM Ca. It is concluded that Cd and Ni, in concentrations less than 1 microM, can interact with the Ca/voltage sensor and inhibit BK(Ca) channels of vascular smooth muscle. These effects may partially explain the vascular tension induced by large divalent cations.

Analysis of Variance↗
PubMed1993

Ten years of experience with patients with chronic active liver disease variceal bleeding: ablative versus selective decompressive therapy.

BACKGROUND: Variceal hemorrhage is an added major threat to survival in patients with chronic active liver disease (CALD). The hemodynamic consequences of surgical therapy and the continued activity of the underlying liver disease both contribute to the hepatic dysfunction and determine patient survival. METHODS: Two hundred and seventy two consecutive cases of (Child A or B) variceal bleeding with chronic hepatitis were surgically treated during a 10-year period. Histologic chronic active hepatitis (CAH) was documented in 160 (59%) patients, whereas chronic persistent hepatitis (CPH) was evident in 112 (41%). The applied surgical procedure was distal splenorenal shunt (DSRS) in 99 (36%) patients, splenectomy and gastroesophageal devascularization (SGD) in 108 (40%), and splenectomy with left gastric ligation (SLGL) in 65 (24%) patients. The preoperative data base obtained on these patients was matched comparing the three surgical modalities within each pathologic group (p > 0.05). RESULTS: The operative mortality was low among the patients with CAH (DSRS, 5.1%; SGD, 4.2%) with no deaths occurring in the CPH group. Among the individuals with CAH, recurrent variceal hemorrhage occurred significantly (p < 0.05) more often after SLGL (26%) and SGD (17%) than after DSRS (5%). Sclerotherapy rescued 93% (SGD) and 70% (SLGL) of the patients with rebleeding. DSRS significantly (p < 0.05) increased the risk of encephalopathy (28%) compared with SGD (4.2%) and SLGL (8%). The morbidity rates were quite low among the patients with CPH with no significant (p > 0.05) differences noted when the three surgical modalities were compared. Both groups experienced a significant (p < 0.05) increase in aspartate aminotransferase levels after the three procedures with a significant (p < 0.05) increase in bilirubin level occurring only after DSRS. The 5-year survival rate for the patients with variceal bleeding with CAH was 76% (DSRS), 73% (SGD), and 88% (SLGL). The leading causes of death were liver failure after DSRS (70%), variceal hemorrhage after SLGL (60%), and equally divided between septicemia (43%) and liver failure (43%) after SGD. The patients with CPH had a better 5-year survival of 89% (DSRS) and 100% (nonshunt operation). CONCLUSIONS: These data showed that (1) CALD is common among cases of variceal bleeding; (2) elective surgical treatment of variceal hemorrhage in patients with Child A or B CALD has a low operative mortality; (3) SLGL backed up by sclerotherapy is a better surgical alternative to either selective shunt or SGD in patients with active hepatitis, and (4) both DSRS and nonshunt operation are equally good surgical options for patients with CPH.

Adult↗
PubMed1983

The vestibular aqueduct in congenital deafness: evaluation by the axial projection.

Thirty-two patients with congenital neurosensory hearing loss demonstrated dilatation of the peripheral limb of the vestibular aqueduct as visualized on pluridirectional tomograms. Multiple additional anomalies involving most frequently the cochlea (15 patients) but also the ossicles (three patients) or vestibule (one patient) were associated. The axial-pyramidal (Poschl) projection was of great value in evaluation of the vestibular aqueduct and cochlea. The technique, clinical correlation, and surgical implications are discussed.

Adolescent↗