Scale-up of adhesive transdermal drug delivery systems.
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Biomedical subjects
Publications and source records attributed to A Hussain.
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Preoperatively administered midazolam may contribute to postoperative sedation and delayed recovery from brief outpatient general anesthesia, particularly in patients who receive significant postoperative opioid analgesics. We evaluated the effects of midazolam premedication (0.04 mg/kg) on postoperative sedation and recovery times after laparoscopic tubal sterilization (Falope rings) in 30 healthy women in a randomized, double-blind, placebo-controlled study. Patients received midazolam or saline-placebo intravenously 10 min before anesthesia. General anesthesia was induced with fentanyl, propofol, and mivacurium and was maintained with N2O and isoflurane. Sedation was quantified before and after premedication and 15, 30, and 60 min after emergence from anesthesia, using the digit-symbol substitution (DSST) and Trieger dot (TDT) tests. Management of postoperative pain and nausea and discharge criteria were standardized. Groups were similar with respect to age, weight, and duration of surgery and anesthesia. Midazolam was associated with impairment of performance on the TDT and DSST after premedication administration and 15 (TDT and DSST) and 30 (DSST) min after postanesthesia care unit (PACU) arrival. There were no differences in PACU time and time to discharge-readiness. In conclusion, midazolam premedication augments postoperative sedation in this population but does not prolong recovery times.
In seropositive individuals Epstein-Barr virus (EBV) establishes a virus reservoir in peripheral blood lymphocytes (PBLs). Transmission from one individual to another occurs via saliva due to a lytic (virion productive) phase of infection in the oropharynx. EBNA-1 is responsible for maintaining viral episomes in the host cell and could, therefore, also affect the persistence of the virus in different cell lineages. Based on sequence analysis of EBNA-1 we now demonstrate that (i) in addition to the prototype EBNA-1 (identical to the B95.8 virus EBNA-1), EBV in normal individuals encompasses multiple EBNA-1 subtypes, both in PBLs and in oral secretions; (ii) although EBV with prototype EBNA-1 is the predominant virus in normal individuals, it is very rarely associated with either nasopharyngeal carcinoma (NPC) or Burkitt's lymphoma (BL); (iii) EBV with an EBNA-1 subtype (V-val) frequently associated with NPC is also selectively detected in oral secretions and not in PBLs; (iv) EBV with the EBNA-1 subtype V-pro is restricted to PBLs, while a mutated version of this subtype is present in BL, but not in NPC. These findings suggest that the variations in EBNA-1 may be relevant to the ability of EBV to persist in different cell types, and hence relevant to its oncogenic potential.
SETTING: Karachi and Hyderabad, Pakistan. OBJECTIVE: To describe the level and quality of tuberculosis (TB) case management by non-TB control program (TCP) physicians in urban Sindh, Pakistan. DESIGN: We interviewed 152 adults with pulmonary TB confirmed by Karachi's TB control program regarding the initial management of their TB symptoms before entering the TCP. We also surveyed 65 general practitioners (GPs) attending continuing education seminars with a multiple choice test to assess their management of suspected pulmonary TB. We compared both results to guidelines from the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). RESULTS: Eighty percent (122/152) of patients first sought GPs. Only 14% of GPs performed any sputum test. At most, 17 (40%) of the 42 patients recalling their GP's treatment, received the recommended 4-drug regimen. However, 68% (45/65) of surveyed GPs chose correct treatment from a multiple choice format. But their initial laboratory investigations, follow-up, and treatment cessation criteria (9%, 9-31%, and 11% correct, respectively) demonstrated under-utilization of sputum tests and over-reliance on unhelpful tests. CONCLUSIONS: GPs first saw most of these TCP patients, but their weak management likely hinders TB control. A partnership between TB control programs and GPs could improve case management and hasten TB control.
Cross-sectional surveys were conducted to assess prevalence of night-blindness and dietary habits prior to intervention (in 1986), after 3 years of intervention (in 1989) and 3 years after the termination of active intervention (in 1992), in the northern part of Bangladesh. The prevalence of night-blindness per thousand children decreased from 1986 to 1989 (during intervention) and rose from 1989 to 1992, but remained significantly lower in 1992 than the 1986 prevalence. Household income declined from 1989 to 1992, and lower consumption of beta-carotene rich food, protein items and vitamin A capsules was registered in 1992 despite almost the same level of awareness relating to the prevention of night-blindness in the community during the period 1989-1992. The results indicate that the long-term impact of a health education programme to prevent night-blindness is uncertain. Improvement in socioeconomic conditions, in addition to relevant knowledge, is probably a precondition for maintaining a sustainable impact of health education.
The occurrence of night blindness and serum vitamin A concentrations among children in rural Bangladesh were studied in relation to protein energy malnutrition, dietary habits and intake of vitamin A capsules. In 1992, 124 night-blind children were registered in a cross-sectional survey in the northern part of Bangladesh, and age-, sex- and neighbourhood-matched controls were selected. Of these, the first reported night-blind child from a household (n = 105) and their controls were included in the analyses. Our results showed that night blindness was associated with protein energy malnutrition when using the mid-upper arm circumference (MUAC) as a measure of nutritional status. The odds ratio for a confirmed diagnosis of night blindness among children with a MUAC < 80% of the reference versus normal children was 5.4 (CI 1.9-15.5). Low MUAC was associated with low intake of beta-carotene-rich and vitamin A-containing foods as well as with low serum vitamin A in the total series of cases and controls. This may indicate that night blindness is only one aspect of the general protein energy malnutrition problems in this population. We therefore suggest that measures to prevent vitamin A-related morbidity and mortality should include improvement of the general diet with increased consumption of dietary vitamin A.
The purpose of this study was to examine socio-economic conditions, demographic factors, use of vitamin A capsules and dietary practices in relation to the risk of low serum vitamin A. One hundred and twenty four night blind cases were identified by parents in a cross-sectional survey in Bangladesh in 1992. Age-, sex- and neighbourhood-matched controls were selected. Venous blood was collected from 87 cases and 97 controls for the determination of serum vitamin A. Information about socio-economic conditions, demographic factors, use of vitamin A capsules and dietary practices was obtained by interview. The level of serum vitamin A was strongly related to age and consumption of beta-carotene rich foods. The preschool years (2-6 years) are important risk periods for vitamin A deficiency among children. We conclude that long-term prevention of vitamin A deficiency should rely on efforts to improve local diet.
Percutaneous endoscopic gastrostomy (PEG) is now the technique of choice for patients requiring long-term enteral feeding. It is a good method for feeding patients with neurological dysphagia and can safely be kept in situ for long periods. PEG feeding requires a multidisciplinary approach, involving doctors, nurses, pharmacists, speech therapists, dieticians and carers. The insertion of a PEG, which requires two operators and two endoscopy nurses, is described in full. Feeding can commence after a few hours. Various types of feed and feed-ing patterns are described and their relative merits discussed. Although psychological problems may occur following PEG insertion, the procedure is usually well accepted by patients.
Studies of human TSH (hTSH) structure and function have been limited by difficulties in producing large quantities of recombinant hormone. We describe a system for the stable expression of high levels of recombinant human TSH (rec hTSH) using a mutant form of dihydrofolate reductase (dhfr) as an amplifiable dominant selectable marker. A vector expressing both the hTSH alpha-subunit and the mutant dhfr was cotransfected with a hTSH beta-subunit expression vector into dhfr-deficient cells. Amplification of the transfected sequences by methotrexate selection, followed by cell culture in a hollow fiber perfusion system, yielded rec hTSH production as high as 100,000 microU/ mL. Immunoradiometric assays using five different antibodies revealed no differences in the immunological activities of rec hTSH and pituitary hTSH. Bioactivity was measured in a novel TSH bioassay coupling the generation of cAMP by a transfected hTSH receptor to the cAMP-dependent regulation of a luciferase reporter gene. The ED50 for bovine TSH in this bioassay was 1.4 ng/mL (3.5 x 10(-11) mol/L). The ratio of the ED50 values for rec hTSH and pituitary hTSH was 1.0:1.1 (P = NS), indicating that the two TSHs were of equivalent potency. In conclusion, we have developed techniques for the high level production of rec hTSH that is immunologically and biologically equivalent to pituitary hTSH. The ability to produce large quantities of rec hTSH using standard laboratory techniques should facilitate future studies, such as the development of clinically useful TSH analogs.
The purpose of the study was to estimate the association of environmental factors (water and sanitation), health behavior (breast feeding practice and vaccination), and mortality among siblings with night blindness. A total of 5,420 children were enrolled in a cross-sectional study from 2,101 households in the northern part of Bangladesh, a high risk area for night blindness. One hundred twenty-four children were reported by parents to have night blindness. Our results indicated that environmental factors, health behavior, and the death of siblings were significantly associated with the occurrence of night blindness in crude analyses, as well as in analyses with adjustment for a number of potential confounding variables. The strongest association was noted for sibling death. The findings support the notion that night blindness should not be viewed as an isolated health problem and that approaches aimed at improving vitamin A status should also include interventions directed to environmental and health-associated behavioral factors.
Radical maxillectomy is indicated for stage III and IV antroethmoidal carcinoma. In those cases where the anterior bony wall of maxillary antrum or the anterior facial soft tissue is involved or a previous Caldwell-Luc antrostomy was performed, a generous amount of cheek soft tissue has to be resected with the surgical specimen in order to achieve tumour-free margins. In such cases survival of the cheek flap is in jeopardy. Following orbital exenteration the resultant defect requires covering to promote healing and to protect the underlying bone. Traditionally, a skin graft has been used to line the orbital defect and the cheek flap. The pedicled temporoparietal galeal myofascial flap offers well-vascularized, reliable, supple and plentiful tissue which can be used to line both the orbit and the cheek, thus covering both sites with one flap. Such a case is presented and the surgical anatomy and technique are described.
Three differently sized mRNAs are expressed from each of two DHFR (encoding dihydrofolate reductase) alleles present in the Chinese hamster lung (CHL) cell line, DC-3F. The relative abundancy of the transcripts produced from each allele differs dramatically as a result of differential utilization of the multiple poly(A) sites present in the DHFR DHFR gene and a genetic polymorphism located within the third poly(A) signal of one allele. We sought to determine whether such differences in polyadenylation affect the steady-state levels of DHFR and mRNAs expressed from either allele and, in a more general sense, to ask whether differences in 3' end RNA processing in a gene containing multiple poly(A) sites affects the final level of gene expression. An SV40 promoter-based transient expression system producing chimeric cat::DHFR transcripts was developed to regenerate the in vivo mRNA polyadenylation patterns associated with each of the two DHFR alleles. The results demonstrate that the total amount of polyadenylated RNA expressed from each of these constructs in vitro is the same regardless of the differential utilization of the poly(A) signals that occurs between them. Moreover, measurement of the individual turnover rates of the DHFR mRNAs expressed in vivo from each allele, as determined by pulse-chase labeling and actinomycin D inhibition studies, revealed no significant allele-specific differences in transcript half-lives. Finally, measuring the steady-state levels of DHFR poly(A)+ mRNA in parental DC-3F cells demonstrated that both alleles are expressed to the same extent during normal growth. Thus, even though dramatic allele-specific differences in 3' end processing of DHFR transcripts occur in vivo, such differences do not appear to influence the steady-state levels of DHFR gene expression.
Thapsigargin (TG), a specific inhibitor of intracellular Ca2+ transport ATPases (SERCA), inhibits cell proliferation when added to culture media in the nanomolar concentration range. However, long term exposure to gradually increasing concentrations of TG induces resistance to TG inhibition in both the parental Chinese hamster lung fibroblast DC-3F and a subline derived from it via transfection and stable expression of a full-length cDNA encoding avian SERCA1 ATPase (DC-3F/Ca cells). TG resistance develops in parallel with selection of cells expressing higher levels of the endogenous SERCA2 as well as of the exogenous transfected SERCA1 ATPase, whose Ca2+ transport function can be studied in situ by imaging techniques and following isolation in microsomal fractions. Microsomes isolated from resistant cells contain two functionally distinct populations of ATPases: a population that is inhibited by stoichiometric titration with TG, and a population displaying resistance to inhibition even when TG exceeds the enzyme stoichiometry. It is apparent that resistance to TG develops in parallel with (a) selection of cells expressing high levels of SERCA ATPases, and (b) selection of an ATPase that is resistant to TG.
A detailed description of pulled elbow is missing from standard orthopaedic text books. Recently it has been reported that the prevalence of hypermobility among children with pulled elbow is higher than that in the normal population and that pulled elbow can be considered to be a consequence of joint hypermobility. Two hundred children with pulled elbow comprising 106 girls and 94 boys (age range 3-84 months, mean age 24 months) were treated and evaluated for signs of hypermobility in a prospective study. Hypermobility of joints was noted in 17 (8.5 per cent) of children who had a pulled elbow while in the 71 children in whom there had been more than one episode, the rate of hypermobility was 8.4 per cent. Comparison of these results with a control group of 100 normal children, in whom 10 (10 per cent) exhibited hypermobility, showed no association between joint hypermobility and an increased incidence of pulled elbow. The anatomical construction of the radial head, relative plasticity of the cartilage and the immature annular ligament in young children possibly predisposes them to pulled elbow, the incidence of which is increasing in our modern physically competitive society where children are participating in a wide range of physically demanding sports activities. Pulled elbows can also occur in children with hypermobility of joints, but there is no evidence that the incidence has increased.
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We conducted a prospective, blind study to determine whether a difficult endotracheal intubation could be predicted preoperatively by evaluation of one or more anatomic features of the head. In 471 adults presenting for elective surgery, the size of the tongue relative to the oral cavity was assessed according to the Mallampati classification (oropharyngeal class), and the distance between the chin and thyroid cartilage (thyromental distance) and the angle at full extension of the head (head extension) were measured. At laryngoscopy, the difficulty in visualizing the larynx was determined by a different observer. Assignment to oropharyngeal Class 3, a thyromental distance < or = 7 cm, and a head extension < or = 80 degrees, considered either alone or in various combinations, had low sensitivity and positive predictive values in identifying patients with airways that were difficult to intubate, but high specificity and negative predictive values. We conclude that these three tests are of little value in predicting difficult intubation in adults, although the likelihood of an easy endotracheal intubation is high when they yield negative results.
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