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Biomedical subjects

A Husain

Publications and source records attributed to A Husain.

At least 19 recordsLinked to original sources
PubMed2006

Ovarian cancer in younger vs older women: a population-based analysis.

To compare the clinico-pathologic prognostic factors and survival of younger vs older women diagnosed with epithelial ovarian cancer. Demographic, clinico-pathologic, treatment, and surgery information were obtained from patients with ovarian cancer from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001 and analysed using Kaplan-Meier estimates. Of 28 165 patients, 400 were <30 years (very young), 11 601 were 30-60 (young), and 16 164 were >60 (older) years of age. Of the very young, young, and older patients, 261 (65.3%), 4664 (40.2%), and 3643 (22.5%) had stage I-II disease, respectively (P<0.001). Across all stages, very young women had a significant survival advantage over the young and older groups with 5-year disease-specific survival estimates at 78.8% vs 58.8 and 35.3%, respectively (P<0.001). This survival difference between the age groups persists even after adjusting for race, stage, grade, and surgical treatment. Reproductive age (16-40 years) women with stage I-II epithelial ovarian cancer who received uterine-sparing procedures had similar survivals compared to those who underwent standard surgery (93.3% vs 91.5%, P=0.26). Younger women with epithelial ovarian cancer have a survival advantage compared to older patients.

Adenocarcinoma, Clear Cell↗
PubMed2006

Estimates of dietary exposure of children to artificial food colours in Kuwait.

To assess the intake of artificial food colour additives by 5-14-year-old children in the State of Kuwait, a 24-h dietary recall was conducted twice on 3141 male and female Kuwaiti and non-Kuwaiti children from 58 schools. The determination of colour additives in 344 foods items consumed was performed using high-performance liquid chromatography with diode array detector. A comparison with the Food and Agriculture Organization and World Health Organization acceptable daily intakes (ADIs) was undertaken to evaluate the potential risk associated with the consumption of artificial colour additives by children in Kuwait. The results indicated that out of nine permitted colours, four exceeded their ADIs by factors of 2-8: tartrazine, sunset yellow, carmoisine and allura red. Further, follow-up studies to provide insight into potential adverse health effects associated with the high intakes of these artificial colour additives on the test population are warranted.

Adolescent↗
PubMed2006

Photochemistry of phenazopyridine hydrochloride.

Phenazopyridine hydrochloride (1) is an azo dye with local analgesic and anaesthetic effects on the urinary tract. Its photochemistry was studied in different reaction media including the drug adsorbed on silica gel. This resulted in photochemical cyclodehydrogenation, reductive photodegradation and rearrangement of the drug molecule. Four major products were isolated and identified on the basis of IR, NMR and mass spectral studies. The products are: pyrido[3,4-c]cinnoline-2,4-diamine (2), N3-phenylpyridine-2,3,4,6-tetraamine (3), pyridine-2,3,6-triamine (4), 2,6-diamino-1-(4-aminophenyl)pyridin-4(1H)-one (5).

Anesthetics, Local↗
PubMed2005

Photooxidation of acyclovir in aqueous solution.

Photodegradation of an aqueous solution of acyclovir in phosphate buffer (pH 7) under aerobic conditions was studied with light of wavelength > 270 nm. Three major products were isolated and identified on the basis of IR, NMR and mass spectral studies. The products are: (2-hydroxyethoxy)methyl spiroiminodihydantoin (2), (2-hydroxyethoxy)methyl(amino)-2-imino-1,2-dihydroimidazole-5-one (3), and 2,2-diamino-4-[(2-hydroxyethoxy)methyl]amino)-5-[2H]-oxazolone (4). Furthermore the effects of D2O as reaction medium, addition of sodium azide and absence of oxygen on the photodegradation of acyclovir were examined, the observations indicating the involvement of singlet oxygen. The formation of the products is explained by the photooxidation of acyclovir.

Acyclovir↗
PubMed2004

The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance.

BACKGROUND: Recent evidence indicates that patients with multiple myeloma receiving combination chemotherapy containing thalidomide are at a significantly high risk for venous thromboembolic disease (VTD). However, information on the occurrence of VTD in a related disorder, benign monoclonal gammopathy of undetermined significance (MGUS), is limited. PATIENTS AND METHODS: We prospectively investigated patients with MGUS for the occurrence of VTD. The diagnosis of MGUS was based on well known criteria for the disorder. The variables examined were sex, age, race, presence of underlying conditions, level and type of immunoglobulin [serum monoclonal (M)-protein] platelet counts and level of fibrinogen. RESULTS: Of a total of 310 patients with MGUS, 19 (6.1%) developed VTD after a median follow-up of 44 months (range 12-67 months). In a univariate analysis, age >/=65 years (P=0.01), M-protein >/=16 g/l (P=0.001) and progression to plasma cell or lymphoproliferative disorders (28 of 310 patients; P=0.001) were significant risk factors for VTD. In multivariate analysis, M-spike >/=16 g/l [risk ratio (RR)=6.3; 95% confidence interval (CI) 2.25-17.6; P=0.001] and future development of plasma cell or lymphoproliferative disorder (RR = 4.2; 95% CI 1.64-10.7; P=0.003) were variables strongly associated with the occurrence of VTD. A total of 46 patients (14.8%) died during the follow-up period of the study. CONCLUSION: This study demonstrates that patients with MGUS are at increased risk for VTD. Although a clear reason for the pre-thrombotic state in these patients is not currently evident, few risk factors were identified in the group of patients examined.

Adult↗
PubMed2004

Impact of diverticular disease on hospital costs and activity.

BACKGROUND: Diverticulosis is very common in the UK and patients with clinically significant diverticular disease present regularly to departments of surgery as acute emergencies or chronic problems. There are no national data on the hospital prevalence, clinical implications or financial impact of diverticular disease hence the extent of the clinical problem is as yet not quantified. AIM: To detect the prevalence, clinical implications and financial impact of diverticular disease over a one year period in a large district hospital. METHODS: Retrospective review of all patients treated for diverticular disease during one financial year. Clinical and cost analysis of inpatient and outpatient investigations, treatment and hospitalization. RESULTS: A total of 148 patients were treated of whom 83 were admitted for more than 1 day, 55 of those were emergency admissions. Five of 83 admitted patients died (in-patient mortality 6%, peri-operative mortality 26.3%). There was a total number of 982 hospitalization days of which 94 Intensive Care Unit days and 68 High Dependency Unit days. Nineteen operations were performed (16 sigmoid colectomies, 1 oversewing of perforated sigmoid, 2 reversal of colostomy). The investigations generated were 48 colonoscopies, 77 flexible sigmoidoscopies, 77 Barium enemas, 2 CT scans and 34 ultrasound scans. A total number of 410 clinic appointments were generated. One year after discharge 134/148 (90.5%) patients were alive. The total cost of this activity was pound 465263 or 5.3% of the total annual budget for General Surgery. Seventy percent of the cost was bed-days expenses with ICU hospitalization accounting for 25% of the total cost. CONCLUSION: Diverticular disease is a major cause of morbidity in a large district hospital and a significant burden on resources. More research should be done on prevention of complications and management in the community. The current methods of management do not appear to be cost-effective and attempts should be made to produce protocols for evidence-based, cost-efficient management of the disease. A UK national audit should be undertaken.

Adult↗
PubMed2002

Syntheses and reactions of some new 2-arylidene-4-(biphenyl-4-yl)-but-3-en-4-olides with a study of their biological activity.

2-Arylidene-4-(biphenyl-4-yl)but-3-en-4-olides also known as 3-arylidene-5-(biphenyl-4-yl)-2(3H)-furanones were prepared from 3-(4-phenyl-benzoyl) propionic acid and aromatic aldehydes. Some of the selected butenolides were reacted with ammonia and benzylamine to give corresponding pyrrolones and N-benzylpyrrolones respectively, which were characterized on the basis of 1H NMR and MS data and elemental analysis results. These compounds were tested for anti-inflammatory and anti-microbial actions. A few compounds were found to have promising anti-inflammatory activity while a fair in number of compounds showed a good anti-fungal activity and a promising antibacterial activity against S. aureus and E. coli.

Animals↗
PubMed2001

Changes in zinc ligation promote remodeling of the active site in the zinc hydrolase superfamily.

The zinc hydrolase superfamily is a group of divergently related proteins that are predominantly enzymes with a zinc-based catalytic mechanism. The common structural scaffold of the superfamily consists of an eight-stranded beta-sheet flanked by six alpha-helices. Previous analyses, while acknowledging the likely divergent origins of leucine aminopeptidase, carboxypeptidase A and the co-catalytic enzymes of the metallopeptidase H clan based on their structural scaffolds, have failed to find any homology between the active sites in leucine aminopeptidase and the metallopeptidase H clan enzymes. Here we show that these two groups of co-catalytic enzymes have overlapping dizinc centers where one of the two zinc atoms is conserved in each group. Carboxypeptidase A and leucine aminopeptidase, on the other hand, no longer share any homologous zinc-binding sites. At least three catalytic zinc-binding sites have existed in the structural scaffold over the period of history defined by available structures. Comparison of enzyme-inhibitor complexes show that major remodeling of the substrate-binding site has occurred in association with each change in zinc ligation in the binding site. These changes involve re-registration and re-orientation of the substrate. Some residues important to the catalytic mechanism are not conserved amongst members. We discuss how molecules acting in trans may have facilitated the mutation of catalytically important residues in the active site in this group.

Amino Acid Sequence↗
PubMed2001

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data.

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Arg(1098) is critical for the chloride dependence of human angiotensin I-converting enzyme C-domain catalytic activity.

Angiotensin (Ang) I-converting enzyme (ACE) is a Zn(2+) metalloprotease with two homologous catalytic domains. Both the N- and C-terminal domains are peptidyl dipeptidases. Hydrolysis by ACE of its decapeptide substrate Ang I is increased by Cl(-), but the molecular mechanism of this regulation is unclear. A search for single substitutions to Gln among all conserved basic residues (Lys/Arg) in human ACE C-domain identified R1098Q as the sole mutant that lacked Cl(-) dependence. Cl(-) dependence is also lost when the equivalent Arg in the N-domain, Arg(500), is substituted with Gln. The Arg(1098) to Lys substitution reduced Cl(-) binding affinity by approximately 100-fold. In the absence of Cl(-), substrate binding affinity (1/K(m)) of and catalytic efficiency (k(cat)/K(m)) for Ang I hydrolysis are increased 6.9- and 32-fold, respectively, by the Arg(1098) to Gln substitution, and are similar (<2-fold difference) to the respective wild-type C-domain catalytic constants in the presence of optimal [Cl(-)]. The Arg(1098) to Gln substitution also eliminates Cl(-) dependence for hydrolysis of tetrapeptide substrates, but activity toward these substrates is similar to that of the wild-type C-domain in the absence of Cl(-). These findings indicate that: 1) Arg(1098) is a critical residue of the C-domain Cl(-)-binding site and 2) a basic side chain is necessary for Cl(-) dependence. For tetrapeptide substrates, the inability of R1098Q to recreate the high affinity state generated by the Cl(-)-C-domain interaction suggests that substrate interactions with the enzyme-bound Cl(-) are much more important for the hydrolysis of short substrates than for Ang I. Since Cl(-) concentrations are saturating under physiological conditions and Arg(1098) is not critical for Ang I hydrolysis, we speculate that the evolutionary pressure for the maintenance of the Cl(-)-binding site is its ability to allow cleavage of short cognate peptide substrates at high catalytic efficiencies.

Allosteric Site↗
PubMed2001

Oral tuberculosis.

Although rare, doctors and dentists should be aware of the possible occurrence of oral lesions of tuberculosis and consider them in the differential diagnosis of suspicious oral ulcers.

Adult↗
PubMed2001

Targeted inactivation of Gh/tissue transglutaminase II.

The novel G-protein, G(h)/tissue transglutaminase (TGase II), has both guanosine triphosphatase and Ca(2+)-activated transglutaminase activity and has been implicated in a number of processes including signal transduction, apoptosis, bone ossification, wound healing, and cell adhesion and spreading. To determine the role of G(h) in vivo, the Cre/loxP site-specific recombinase system was used to develop a mouse line in which its expression was ubiquitously inactivated. Despite the absence of G(h) expression and a lack of intracellular TGase activity that was not compensated by other TGases, the Tgm2(-/-) mice were viable, phenotypically normal, and were born with the expected Mendelian frequency. Absence of G(h) coupling to alpha(1)-adrenergic receptor signaling in Tgm2(-/-) mice was demonstrated by the lack of agonist-stimulated [alpha-(32)P]GTP photolabeling of a 74-kDa protein in liver membranes. Annexin-V positivity observed with dexamethasone-induced apoptosis was not different in Tgm2(-/-) thymocytes compared with Tgm2(+/+) thymocytes. However, with this treatment there was a highly significant decrease in the viability (propidium iodide negativity) of Tgm2(-/-) thymocytes. Primary fibroblasts isolated from Tgm2(-/-) mice also showed decreased adherence with culture. These results indicate that G(h) may be importantly involved in stabilizing apoptotic cells before clearance, and in responses such as wound healing that require fibroblast adhesion mediated by extracellular matrix cross-linking.

Animals↗
PubMed2001

The role of laparoscopy in second-look evaluations for ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy and safety of laparoscopic second-look operations in patients with ovarian cancer. METHODS: We retrospectively reviewed the medical records of all patients who have undergone laparoscopic second-look procedures for ovarian cancer at our institution. RESULTS: From July 1993 to December 1998, 150 patients underwent laparoscopic second-look operations. The mean age of patients was 53 years (range, 25-78 years). The majority of patients (87%) had Stage III or IV disease at initial surgery; the remainder were Stage II or unstaged. Eighty-two patients (54%) had had optimal cytoreduction at the time of their initial surgery. All patients had completed primary chemotherapy and were clinically disease-free based on imaging studies and CA-125 levels at the time of second look. Sixty-nine patients (46%) were found to have pathologically negative second looks; thus, the rate of positive second-look evaluations was 54%. The rate of conversion to laparotomy was 18/150 (12%). In 3 cases this was secondary to bowel injury; one patient sustained a bladder injury; the remainder of conversions to laparotomy were for secondary cytoreduction. There was only 1 case where the patient was found to have extensive adhesions and laparoscopy was abandoned. The overall rate of major complications was 2.7%. CONCLUSIONS: In our experience, laparoscopy is a safe and accurate method of second-look assessment in patients with ovarian cancer. The incidence of complications is low, particularly in this group of patients, all of whom have undergone prior abdominal surgery. The rate of negative evaluations and the rate of recurrences in patients with negative second looks are equivalent to those described in studies of second-look assessment by laparotomy.

Adult↗