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Biomedical subjects

A Haider

Publications and source records attributed to A Haider.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of pregnancy in renal allograft recipients: SIUT experience.

The course of pregnancy and its outcome was studied in renal allograft recipients. Between November 1985 and November 2005, a total of 1481 renal transplants were carried out at the Sindh Institute of Urology and Transplantation (SIUT); among them were 348 females, with 73 potential females for pregnancy. All patients received cyclosporine and prednisolone, with 82% also receiving azathioprine and 4 patients mycophenolate mofetil as a third immunosuppressant drug. We evaluated incidence of hypertension, diabetes, pre-eclampsia, urinary tract infection (UTI), rejection during pregnancy and during 3 months' postdelivery as well as outcomes of pregnancy. Among 73 potential candidates, 31 had 47 pregnancies, after an average of 31 months (8-86 months). Of 31 subjects, 21 subjects were hypertensive on one or two drugs prior to conception. A rise in blood pressure during pregnancy was noticed in 7 patients. Albuminuria from trace to 3+ appeared in 13 patients and glycosuria in one other. Blood sugar levels remained within normal range in all subjects. UTIs occurred during pregnancy in 7 patients. Among 47 pregnancies, 9 had abortions (7 spontaneous, 2 therapeutic) and 6 had preterm deliveries. The others were full-term deliveries: 12 via a lower segment caesarean section and 20 were normal vaginal deliveries. Average birth weight was 4.8 lbs. At an average follow-up of 38 months the serum creatinine values ranged from 0.94 to 2.3 mg %. One patient developed acute irreversible graft dysfunction soon after delivery. Our study demonstrated that pregnancy did not reduce renal graft survival, but newborns are at greater risk of premature birth and low birth weight.

Albuminuria↗
PubMed2003

Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort.

BACKGROUND: Multiple genetic studies have shown linkage of atopy-related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL-4, IL-5 and IL-13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness. OBJECTIVE: The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort. METHODS: Atopy-related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight-hundred and seventy-two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses. RESULTS: CD14-159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed. CONCLUSION: The CD14-159 SNP might not play a major role in the development of atopy in German children.

Follow-Up Studies↗
PubMed2001

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study.

Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)-beta and tumor necrosis factor-alpha in BM stroma. TGF-beta production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.

Binding Sites↗
PubMed2000

Cyclooxygenase-2 is required for tumor necrosis factor-alpha- and angiotensin II-mediated proliferation of vascular smooth muscle cells.

Tumor necrosis factor-alpha (TNF-alpha) and angiotensin II (Ang II) induced a transient increase in vascular smooth muscle cell (VSMC) cyclooxygenase-2 (COX-2) mRNA accumulation, without affecting COX-1 mRNA levels. The kinetics of COX-2 mRNA accumulation were similar in VSMCs challenged with either TNF-alpha or Ang II; mRNA accumulation peaked at 2 hours and decreased to control levels by approximately 6 hours. Accumulation of COX-2 mRNA was associated with a time-dependent increase of COX-2 protein expression that displayed similar kinetics in response to either TNF-alpha or Ang II. Both the increase in COX-2 mRNA accumulation and protein expression in response to either TNF-alpha or Ang II were inhibited by the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD098059. In addition, the AT(1)-selective receptor antagonist losartan attenuated the Ang II-mediated increase in COX-2 mRNA accumulation; the AT(2)-selective antagonist PD123319 had no effect. Prostacyclin I(2) synthesis was tightly coupled to expression of COX-2, whereas prostaglandin E(2) and thromboxane A(2) (TXA(2)) synthesis may be associated with differential usage of COX-1 and COX-2. The COX-2-selective inhibitors NS-398 and nimesulide and the TXA(2) receptor antagonist BMS 180,291 inhibited TNF-alpha- and Ang II-mediated increases in DNA content and cell number by approximately 95%. These findings suggest that a prostanoid derived from COX-2, possibly TXA(2), may contribute to VSMC hyperplasia in vessel injury or pathophysiological conditions associated with elevated levels of either TNF-alpha or Ang II.

Angiotensin II↗
PubMed2000

Effects of preprotachykinin-I peptides on hematopoietic homeostasis. A role for bone marrow endopeptidases.

Hematopoiesis is maintained by "fine-tuned" regulation among cytokines, neuropeptides, neurotransmitters, and neurotrophic factors. Neurotransmitters, derived from PPT-I exert immune and hematopoietic regulation. PPT-I is also expressed locally in bone marrow (BM) stromal cells. PPT-I peptides induce the production of cytokines in BM cells, resulting in regulation of both committed progenitors (CFU-GM) and primitive hematopoietic progenitors (CAFC). Both types of progenitors are regulated differently by the two major PPT-I peptides, SP and NK-A. Endopeptidases, present in BM cells, can digest SP to produce SP(1-4) and SP(4-11). In this study, we investigated the hematopoietic effects of these fragments on CFU-GM and CAFC. Similar to the two major intact PPT-I peptides (SP and NK-A), we observed different hematopoietic effects by SP(1-4) and SP(4-11). Whereas SP(1-4) exerted inhibitory effects on CFU-GM and CAFC, SP(4-11) mediated stimulatory effects. Similar to NK-A, the inhibitory effects of SP(1-4) can be partly explained by the induction of suppressive cytokines (TGF-beta, TNF-alpha, and INF-gamma). Use of antagonists and screening of a dodecapeptide expression library determined that the effects of SP(1-4) were mediated by NK-1. These results show that PPT-I peptides and their endopeptidase-derived fragments may add to the fine-tuned regulation on hematopoiesis. Furthermore, PPT-I may be exerting autoregulation to protect hematopoietic stem cells. These studies have relevance to stem cell protection and BM transplant.

Adult↗
PubMed2000

An evidence-based review of ACE inhibitors in incipient diabetic nephropathy.

Diabetic nephropathy develops in approximately 35% of diabetics and is the leading cause of end-stage renal disease in North America. End-stage renal disease is associated with increased morbidity and mortality, and a large economic burden. Treatments that can prevent or postpone diabetic nephropathy are important therapeutic advances. Interventional studies in type I diabetes and type II diabetes have demonstrated a beneficial effect of improved glycemic control and good blood pressure control in delaying the progression of diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors have been found to be effective in delaying the progression of diabetic nephropathy in hypertensive as well as normotensive diabetics with early and advanced nephropathy. Microalbuminuria or incipient diabetic nephropathy is the earliest clinical expression of diabetic nephropathy and identifies patients at risk of further progression. Advanced or overt nephropathy is associated with a greater risk for coronary artery disease and mortality. It is possible that interventions aimed earlier in the cascade at preventing the development of overt nephropathy may result in greater clinical benefit. There is compelling evidence of the benefit of ACE inhibitors in preventing the progression of incipient diabetic nephropathy to overt diabetic nephropathy in normotensive diabetics.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Phacoemulsification and combined management of intraocular silicone oil.

We report two techniques in which cataract extraction is carried out by phacoemulsification through a corneal incision. If silicone oil is to be removed, a posterior continuous curvilinear capsulorhexis is performed, allowing aspiration of oil through the capsulorhexis followed by lens implantation into the remaining capsular bag. If silicone oil is to be left in situ, the remaining capsule is removed, converting the cataract extraction to an intracapsular-type procedure that retains the advantages of small incision surgery. These techniques offer good improvement in vision and retinal view with more rapid rehabilitation than conventional large incision surgery. The 20% retinal redetachment is comparable to that of other studies and we have not encountered any other significant complications with these techniques.

Adult↗
PubMed1998

Prednisolone-induced alteration in hepatic and muscular protein and glycogen level: its correlation with blood glucose level in mice.

Prednisolone, a potent glucocorticoid, is well known for its immunosuppressive effects on animals. A single dose of 100 microg, 200 microg and 300 microg prednisolone/kg body weight was administered in Swiss albino male mice. Seven days after treatment, the animals were sacrificed to investigate the effect of prednisolone on hepatic and muscular protein contents and glycogen levels along with the level of blood glucose. A catabolic effect on the protein level was evidenced but at the same time the mice became hypoglycemic.

Animals↗
PubMed1997

Multiple endocrinopathies in an infant with fatal neurodegenerative disease.

We report on a male infant with congenital hypoparathyroidism who developed primary hypothyroidism at 3 months and insulin-dependent diabetes mellitus at 25 months. He had evidence of widespread and progressive neurologic dysfunction characterized by severe developmental delay, blindness, deafness, seizures, atrophy of the cerebellar and frontal lobes, and elevated spinal fluid protein. Also noted were renal hypoplasia, hyporeninemic hypoaldosteronism, chronic anemia, persistent elevation of liver transaminase levels, abnormal intraventricular cardiac conduction, reduction in numbers of helper T-cells, and distinctive facial anomalies. The child died of multiorgan failure at 29 months. A mitochondrial basis for the syndrome was considered but a molecular mechanism has, as yet, not been identified.

Abnormalities, Multiple↗
PubMed1997

Testing the hypothalamic-pituitary-adrenal axis in survivors of childhood brain and skull-based tumors.

The objective of this study was to determine whether a low dose of ACTH (0.2 microg/kg) improves the sensitivity of ACTH testing in detecting hypothalamic-pituitary-adrenal (HPA) axis abnormalities in survivors of childhood brain and skull-based tumors. Twenty-two children who had undergone treatment for brain or skull-based tumors were enrolled in a prospective study to extensively evaluate the HPA axis. Five tests of the adrenal axis were evaluated in each patient, including determination of basal serum cortisol, a standard ACTH test (250-microg i.v. bolus), a low dose ACTH test (0.2 microg/kg i.v. bolus), an insulin tolerance test, and a single dose metyrapone test. Cortisol responses to both ACTH tests were nearly identical. Two patients (9%) failed the low dose ACTH test, whereas three (14%) failed the standard ACTH test; five of the children (23%) failed the insulin tolerance test, and five (23%) had abnormal responses to metyrapone. One child who initially passed the metyrapone test failed the test 19 months later after becoming symptomatic. All children with abnormal metyrapone test results had low levels of basal cortisol secretion. In this study, the low dose ACTH test did not improve the sensitivity of ACTH testing for evaluation of the HPA axis. We conclude that a single morning basal cortisol level is a good screen for testing the HPA axis in children. We recommend confirming HPA axis dysfunction with the single dose metyrapone test, although this test also has limitations.

Adrenocorticotropic Hormone↗
PubMed1997

Follow up study of thyroidectomy.

One hundred thyroidectomized patients were followed up. The male:female ratio was 1:4. Majority (62%) of the patients were in the 4th and 5th decades. Multinodular goiter was the commonest lesion found in 74, diffuse colloid goiter in 12 and carcinoma in 14 cases. After operation, sixty-five patients were relieved of all preoperative symptoms of thyroid disease. Thirteen patients had some persistent symptoms. Rest 22 had developed different types of complication in addition to some preoperative symptoms. Three patients developed hoarseness of voice due to recurrent laryngeal nerve injury. Hypoparathyroidism occurred in 1, hypothyroidism in 4 and recurrent neck swelling in 14 patients. One patient died. It seems that a thorough knowledge of the surgical anatomy and meticulousness during the procedure would reduce the rates of such complications in future.

Adenocarcinoma, Follicular↗
PubMed1996

Cerebellar astrocytoma: report of 13 cases aged over 20 years and review of the literature.

Cerebellar astrocytoma in adulthood is a distinct neoplasm with a variable prognosis. We reviewed retrospectively 13 cases in patients aged 21 years or over, seen between 1976 and 1992. These accounted for 19% of all cases of cerebellar astrocytoma seen during that period. The tumour was located in the midline in six patients and laterally in seven; seven patients were females and six were males. The low grade tumours had an overall favourable course, similar to that seen in cerebellar astrocytoma in childhood, with follow-up ranging from 4 to 10 years. The poorly differentiated form, seen in four of the cases, showed progression or recurrence within 4-24 months, regardless of the extent of removal or post-operative radiation therapy.

Adult↗
PubMed1996

Seizure control: how to use the new antiepileptic drugs in older patients.

Three new antiepileptic drugs--vigabatrin, gabapentin, and lamotrigine--provide alternatives in the management of older patients with refractory partial seizures. Each appears to have a unique mechanism of action. Clinical trials indicate that routine lab monitoring is not necessary for the safe and effective use of these drugs. They also do not induce liver enzymes or alter the metabolism of other antiepileptic drugs, thus minimizing the risk of interactions. Potential side effects of these agents include dizziness, somnolence, and other signs of CNS depression.

Acetates↗
PubMed1995

Clinical effect of converting antidepressant therapy from fluoxetine to sertraline.

The effect of replacing fluoxetine with sertraline at two dosage-conversion ratios was studied. Outpatients at a Veterans Affairs mental health clinic who were being treated with fluoxetine were randomly assigned to receive either 50 or 75 mg of sertraline hydrochloride for every 20 mg of fluoxetine (as the hydrochloride salt) or to continue to receive their current dosage of fluoxetine. The subjects were given the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) at baseline and were re-examined at one-month intervals for three months with the HDRS and BDI and the Clinical Global Impression of Change. Each patient was re-evaluated by the same blinded investigator. A total of 45 patients (42 men and 3 women) completed the study. The final overall response did not differ significantly among the three groups. There were also no significant differences among the groups in the proportions of patients with HDRS and BDI scores classified as improving, worsening, or not changing. Improvement was more common in patients receiving the higher dosage of sertraline. Few adverse effects were reported. Outpatients receiving fluoxetine were switched to sertraline therapy without a loss of control of depression and without substantial adverse effects.

1-Naphthylamine↗