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Biomedical subjects

T Malik

Publications and source records attributed to T Malik.

At least 19 recordsLinked to original sources

Nodular fasciitis of the head and neck.

Nodular fasciitis is an unusual benign reactive process affecting superficial and deep fascia. Its rapid growth, rich cellularity, high mitotic activity and poorly circumscribed nature result in it being easily misdiagnosed as a sarcomatous lesion. Three cases of nodular fasciitis presenting as neck lumps are reported. They were successfully treated with local excision, with no signs of recurrence following two years of follow up. This paper describes the clinical presentation and microscopic features of this rare benign lesion and it emphasizes the need for accurate histopathology and clinical suspicion, if inappropriate aggressive management is to be avoided.

Adolescent↗

Endolymphatic sac tumours.

Endolymphatic sac tumours (ELST) are rare tumours of the petrous temporal bone. They may arise sporadically or be associated with von Hippel-Lindau disease. Their differential diagnosis is discussed. We present the clinical and histopathological features of two new patients with ELST and outline the management of their condition. In addition, we review a third case previously reported as a choroid plexus papilloma in which the histology has been re-assessed and the diagnosis changed to ELST. The controversy regarding the cellular origins of adenomatous tumours of the temporal bone is highlighted.

Adenocarcinoma↗

Hepatitis B vaccination practices in hospital newborn nurseries before and after changes in vaccination recommendations.

BACKGROUND: Routine use of hepatitis B vaccine for low-risk newborns was suspended on July 7, 1999, because of concern about the potential risk of thimerosal, a mercury-containing vaccine preservative. Reinstatement of the birth dose was recommended when a thimerosal-free vaccine became available. OBJECTIVE: To explore changes in hepatitis B vaccination practices for newborns related to the revised recommendations for low-risk infants (in this study, the terms newborn and infant are used interchangeably). DESIGN: A telephone survey of a random sample of 1000 US hospitals. PARTICIPANTS: Nurse managers, nursery directors, and staff nurses of the newborn nurseries. MAIN OUTCOME MEASURES: Nursery vaccination practices before and after July 7, 1999, and the availability and use of thimerosal-free vaccine. RESULTS: Interviews were conducted with 773 (87%) of 886 eligible hospitals. Before July 7, 1999, 78% of the hospitals reported vaccination practices that were consistent with recommendations at that time, although only 47% vaccinated all low-risk infants at birth. After July 7, 1999, almost all hospitals discontinued vaccination of low-risk infants, in accordance with the recommendation change; however, there was a 6-fold increase in the number of hospitals that were not vaccinating all high-risk infants. After the introduction of thimerosal-free vaccine, only 39% of the hospitals reported vaccinating all low-risk infants. CONCLUSIONS: Most hospital nurseries altered their newborn hepatitis B vaccination practices consistent with changes in national recommendations. However, unintended consequences included the failure of some hospitals to continue vaccinating all high-risk infants and the delay in reintroducing vaccination for low-risk newborns after the introduction of a thimerosal-free vaccine. Assessments of the appropriateness of this country's response to the threat of thimerosal in vaccines should consider these findings.

Data Collection↗

Combined 'trache-stent': a useful option in the treatment of a complex case of subglottic stenosis.

The authors describe the adaptation of a Montgomery T-tube laryngo-tracheal stent to incorporate an uncuffed fenestrated Shiley tracheostomy tube in the management of a complex case of subglottic stenosis. The combined 'trache-stent' provided a secure, unobstructed airway and optimal phonation. The presence of a removable inner tube facilitated cleaning and reduced patient anxiety regarding the perceived risks of stent obstruction with dried secretions. The combined 'trache-stent' was upsized at four weeks with minimal evidence of local granulation formation. The device was removed entirely six weeks later after direct laryngoscopy reconfirmed the above findings. Almost two years later the patient retains a good voice and airway using a simple fenestrated tracheostomy tube and speaking valve. The subglottic area is stable and the patient has returned to full-time employment.

Attitude to Health↗

Attitudes, practices, and preferences of pediatricians regarding initiation of hepatitis B immunization at birth.

OBJECTIVES: To explore practices and attitudes of pediatricians toward administration of the first dose of hepatitis B vaccine to infants, and to identify factors influencing the decision of pediatricians to initiate immunization at birth versus at 1 to 2 months of age. METHODS: A random sample of 600 pediatricians obtained from the American Academy of Pediatrics membership database was surveyed by mail. RESULTS: Three hundred eighty (68%) of the 563 pediatricians who were located responded to the survey. Of these 380 pediatricians, 279 provided routine immunizations to children. Of the 270 pediatricians who vaccinated children with hepatitis B vaccine and indicated their practice regarding the birth dose, 50% offered the first dose of hepatitis B vaccine at birth to all infants; the rest either offered the vaccine at birth only to infants of hepatitis B surface antigen-positive mothers and mothers whose serostatus is unknown, or did not offer the birth dose to any infants at all. Practicing in the inner city, working for a medical school or government hospital, and living in a state with universal immunization supply policies were associated with the respondent giving the birth dose. The strongest perceived barriers to giving the birth dose in the hospital were the difficulty tracking these vaccines (39%), the increased cost (27%), and the lack of reimbursement from insurance companies (26%). If a combination vaccine that includes hepatitis B; diphtheria, tetanus, pertussis (diphtheria and tetanus toxoids and acellular pertussis vaccine); and polio (inactivated poliovirus vaccine) antigens become available in the near future, then 38% of physicians who currently give the birth dose to all infants would prefer to wait until 2 months of age to initiate hepatitis B immunization. CONCLUSIONS: Efforts to achieve high implementation of hepatitis B birth dose administration may falter once a hepatitis B-containing pentavalent combination vaccine becomes available. Programmatic efforts should ensure prevention of perinatal hepatitis B virus transmission through universal prenatal hepatitis B surface antigen screening and immunoprophylaxis of high-risk newborn infants.

Health Knowledge, Attitudes, Practice↗

Hypoglycaemic action of the flavonoid fraction of Cuminum nigrum seeds.

The seeds of Cuminum nigrum were screened phytochemically and were found to contain 8% flavonoids and 0.01% alkaloids. When studied for their effect on blood glucose levels, oral administration of the flavonoid contents of the plant caused a hypoglycaemic effect at a dose range of 0.5 to 1.5 g/kg, both in normal and alloxan-diabetic rabbits. The hypoglycaemic effect started 2 h after drug administration, reaching a maximum within 4-8 h and the blood glucose levels returned close to normal within 24 h of drug administration. The glibenclamide (5 mg/kg), produced a hypoglycaemic effect in the normal rabbits, whereas it had no effect on the blood glucose levels of alloxan-diabetic rabbits. The alkaloids isolated from C. nigrum seeds, however, failed to exert any significant hypoglycaemic effect in either the normal or diabetic rabbits. A 7 day acute toxicity study in rabbits did not produce any apparent adverse effect at doses as high as 5 g/kg orally. These data indicate that the total flavonoid contents of C. nigrum seeds exhibited considerable hypoglycaemic activity in rabbits and may therefore be responsible for the previously reported antidiabetic activity of the seeds. Furthermore, it is conceivable that the C. nigrum flavonoids possess insulin triggering and/or insulin-like properties.

Administration, Oral↗

Unsafe injections and the transmission of hepatitis B and C in a periurban community in Pakistan.

Following reports of frequent deaths associated with jaundice and chronic liver disease among adults in a periurban community of Karachi, Pakistan, an investigation was conducted to evaluate the relationship between injections and viral hepatitis infections, to identify the reasons why patients received frequent injections, and to observe the injection practices employed in clinics. Two hundred and three adult patients were interviewed as they left each of the 18 area clinics. Practitioners were interviewed and three consecutive injections were observed at each clinic. Eighty-one per cent of patients received an injection on the day of the interview. Of the 135 patients who provided a serum sample, 59 (44%) had antibodies against hepatitis C virus and 26 (19%) had antibodies against hepatitis B virus. Patients who received more injections were more likely to be infected with hepatitis C. If oral and injected medications were equally effective, 44% of patients preferred injected medication. None of the practitioners knew that hepatitis C could be transmitted by injections. Non-sterile syringes and needles that had been used earlier in the day on other patients were used for 94% of the observed injections. Interventions to limit injections to those which are safe and clinically indicated are needed to prevent injection-associated infections in Pakistan and other low-income countries.

Adult↗

Trans-dominant mutations in the 3'-terminal region of the rpoB gene define highly conserved, essential residues in the beta subunit of RNA polymerase: the GEME motif.

BACKGROUND: The multimeric DNA-dependent RNA polymerases are widespread throughout nature. The RNA polymerase of Escherichia coli, which is the most well characterized, consists of a holoenzyme with subunit stoichiometry of alpha2betabeta'sigma. The beta subunit is conserved and has been implicated in all stages of transcription. The extreme C-terminus of the beta subunit, which includes two well-conserved sequence segments, contributes to the active centre and has been proposed to act in transcriptional termination. We describe a genetic system for further characterizing the role of the extreme C-terminus of the beta subunit of E. coli RNA polymerase. This involves random, PCR (Polymerase Chain Reaction)-mediated mutagenesis of the 3' region of rpoB encoding the C-terminal 116 amino acids of beta, followed by the isolation and characterization of trans-dominant-negative mutations. RESULTS: Substitutions of conserved residues in this region were obtained that exhibited different degrees of growth inhibition in a host expressing the chromosomal-encoded wild-type form of the beta subunit. A number of different substitutions were isolated within the highly conserved sequence motif GEME (residues 1271-->1274 of the E. coli beta subunit). In addition, substitutions were obtained in the extreme C-terminal (surface-exposed) region of beta and at two residues previously proposed to be in the active site (H1237, K1242). The properties of the purified mutant holoenzymes, assessed by transcription assays in vitro, suggested a promoter blockading action. CONCLUSIONS: We have identified an important, highly conserved motif in the beta subunit, GEME (residues 1271-->1274). The nature and effect of the amino acid substitutions at the Gly residue in GEME emphasize the importance of a small, uncharged residue at this position. The in vitro properties of the most extreme trans dominant-negative mutants altered in the GEME motif (and the mutant characteristics in vivo) were similar to those of certain previously identified active-site mutants, suggesting that the altered RNA polymerases were capable of promoter binding and RNA chain initiation but were deficient in the subsequent transcriptional stage.

Amino Acid Sequence↗

Intragenic suppression of trans-dominant lethal substitutions in the conserved GEME motif of the beta subunit of RNA polymerase: evidence for functional cooperativity within the C-terminus.

BACKGROUND: The ubiquitous multimeric RNA polymerases contain two large, conserved subunits, of which the beta subunit has been implicated in all three stages of transcription. We have previously described a genetic system involving random, PCR-mediated mutagenesis of the region of rpoB encoding the C-terminal 116 amino acids of the beta subunit of Escherichia coli RNA polymerase and the characterization of dominant-negative mutations. This study identified the invariant motif GEME (residues 1271-->1274; Cromie et al. 1999). Starting with three of these GEME-motif lethal mutations (G1271E, G1271V, M1273V), we have selected for intragenic suppressors, located within the same 3'-region, that prevent expression of the trans-dominant phenotype. RESULTS: We isolated a total of 24 missense mutants and a further 14 frameshift alleles (the latter generating a nested set of C-terminal deletions of the beta subunit) and studied the effect of the missense suppressors in vivo and in vitro. The majority of the second-site substitutions pinpoint highly conserved residues and were allele-specific. In contrast, one particular missense substitution (S1332P) acted on all three primary site mutations whilst not appreciably affecting assembly proficiency, suggesting motif-specific suppression. Two missense substitutions were found to perturb assembly of the beta subunit (M1232T and L1233P) and define a small conserved region (1228-->1233) adjacent to one of the active-site residues identified by affinity-labelling, H1237. The majority of primary mutations were located in three main clusters within the 116 amino acid region. CONCLUSIONS: The importance and functional co-operativity of the three main clusters pinpointed is supported by the present isolation of suppressors of three different GEME primary mutations in the same three regions (whereas the suppressors of G1271V and M1273V are located in all three clusters, those for G1271E are all C-terminal of this residue). Moreover, the location of the suppressors suggests that the GEME and HLVDDK regions are present as alpha-helices in holoenzyme, and that functional co-operativity is through one particular face of each helix.

Amino Acid Motifs↗

The dynamics of glomerular filtration after Caesarean section.

The objective of this study was to determine whether the glomerular hyperfiltration of pregnancy is maintained even after Caesarean section and, if so, to define the responsible hemodynamics. The dynamics of glomerular filtration were evaluated in 12 healthy women who had just completed an uncomplicated pregnancy and were delivered by Caesarean section. Age-matched but non-gravid female volunteers (n = 22) served as control subjects. GFR in postpartum women was elevated above control values by 41%; 149+/-10 versus 106+/-3 ml/min per 1.73 m2, respectively (P < 0.001). In contrast, corresponding renal plasma flow was the same in the two groups, such that the postpartum filtration fraction was significantly elevated by 20%. Computation of glomerular intracapillary oncotic pressure (piGC) from knowledge of plasma oncotic pressure and the filtration fraction revealed this quantity to be significantly reduced in postpartum women, 20.6+/-1.7 versus 26.1+/-2.0 mmHg in control subjects (P < 0.001). A theoretical analysis of glomerular ultrafiltration suggests that depression of piGC, the force opposing the formation of filtrate, is predominantly or uniquely responsible for the observed postpartum hyperfiltration.

Adult↗

Primary non-Hodgkin's lymphoma of the larynx in an AIDS patient.

A case of primary non-Hodgkin's lymphoma of the larynx in an AIDS patient is presented with a review of the literature. Non-Hodgkin's lymphomas in AIDS patients are common but the primary laryngeal presentation is very rare. The symptoms usually include dysphonia and progressive airway obstruction requiring tracheostomy. As with laryngeal non-Hodgkin's laryngeal lymphomas in non-HIV positive patients the majority are of B cell lineage and respond well to radiotherapy. Our patient had a high grade lymphoma of B cell lineage which showed a good response to radiotherapy. The role of chemotherapy and surgery is not yet established. We suggest that the diagnosis of AIDS should not influence the management of these patients unless the individual is in the terminal disease stage.

Adult↗

Nature of glomerular dysfunction in pre-eclampsia.

BACKGROUND: Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia. METHODS: Physiologic techniques were used to estimate glomerular filtration rate (GFR), renal plasma flow and afferent oncotic pressure immediately after delivery in consecutive patients with pre-eclampsia (PET; N = 13). Healthy mothers completing an uncomplicated pregnancy served as functional controls (N = 12). A morphometric analysis of glomeruli obtained by biopsy and mathematical modeling were used to estimate the glomerular ultrafiltration coefficient (Kf). Glomeruli from healthy female kidney transplant donors served as structural controls (N = 8). RESULTS: The GFR in PET was depressed below the control level, 91 +/- 23 versus 149 +/- 34 ml/min/1.73 m2, respectively (P < 0.0001). In contrast, renal plasma flow and oncotic pressure were similar in the two groups (P = NS). A reduction in the density and size of endothelial fenestrae and subendothelial accumulation of fibrinoid deposits lowered glomerular hydraulic permeability in PET compared to controls, 1.81 versus 2.58 x 10(-9) m/sec/PA. Mesangial cell interposition also curtailed effective filtration surface area. Together, these changes lowered the computed single nephron Kf in PET below control, 4.26 versus 6.78 nl/min x mm Hg, respectively. CONCLUSION: The proportionate (approximately 40%) depression of Kf for single nephrons and GFR suggests that hypofiltration in PET does not have a hemodynamic basis, but is a consequence of structural changes that lead to impairment of intrinsic glomerular ultrafiltration capacity.

Adult↗

Cholera in a developing megacity; Karachi, Pakistan.

Despite rapid urbanization and increasing affluence in Karachi, cases of cholera are frequent. We analysed computerized isolation data from the AKUH Clinical Microbiology Laboratory, Karachi, from 1990-6 to examine microbiological, temporal and demographic trends in Vibrio cholerae infections. During this period 888 strains of V. cholerae (566 V. cholerae serogroup O1, and 204 V. cholerae serogroup O139) were isolated from specimens from 886 patients; 214/464 were adult inpatients, and 250/464 paediatric inpatients, the remaining 422 outpatients. Isolations peaked between June and August. Overlapping epidemics occurred in 1993 and 1994 of serogroup O1 (May to August), and serogroup O139 (August to October). All ages and social and economic strata were affected. Forty-four percent of all isolates were from children under the age of 5 years. The mean age of all patients with serogroup O1 infections was 19.6 years (+/-0.9) compared with 367 (+/-1.7) for serogroup O139 infections (P < 0.0001, t test). More than a quarter (27%) of all serogroup O1 isolates were from babies under 2 years of age. One patient had a serogroup O1 infection followed by a serogroup O139 infection 1 year later. Another patient was infected with serogroup O1 strains 5 years apart. Emergence of resistant strains was observed, but by 1996 serogroup O139 had disappeared. An aquatic organism, cholera nevertheless continues to take its toll in this city of 11 million situated in a desert.

Adolescent↗

The purB gene of Escherichia coli K-12 is located in an operon.

The structural gene (purB) for succinyl-AMP (S-AMP) lyase and three additional ORFs are on the same DNA strand of the chromosome of Escherichia coli. Cassette mutagenesis and primer extension mapping demonstrated that purB is co-transcribed with an upstream gene (ORF23, or ycfC) encoding a 22.9 kDa membrane-associated protein of non-essential, but unknown, function unrelated to purine biosynthesis. The purB operon lies between phoP and an ORF expressing an essential function which may correspond to asuE (trmU). S-AMP lyase was purified to near homogeneity. The purified enzyme is a homotetramer of 50 kDa subunits, has a K(m) for S-AMP of 3.7 microM and a pH optimum of 7.4-7.6.

Adenylosuccinate Lyase↗