Biomedical subjects
Publications and source records attributed to G Clark.
Centralisation of viral diagnostic services offers the potential for cost saving in laboratories, but incurs costs for transporting specimens. In a trial of 326 paired specimens, isolation rates of viruses sent by overnight post and a more expensive same-day courier service were similar.
A major factor influencing whole blood cyclosporin A levels in young children with renal transplants is the variable absorption of Sandimmun (SIM). Neoral (NEO) is a new microemulsion of cyclosporin A (CYA) that has been reported to have better absorption characteristics. We compared the pharmacokinetics of SIM and NEO in nine renal transplant recipients aged less than 11 years (range 4.8-10.9 years) and observed clinical parameters during 6 months of NEO therapy. Median CYA dosage was 149 mg/m2 per day (range 98-226). We observed an increase in the maximum CYA concentration (Cmax) of 114%, an increase in area under the curve (AUC) of 71% and the time to reach Cmax was reduced from 1.75 h to 1.25 h with NEO, while 12-h trough levels (C12 h) did not change significantly. AUC correlated with C12 h for SIM (r2 = 0.833) and NEO (r2 = 0.699) and also C1.5 h for NEO (r2 = 0.775). During 24 weeks' follow-up, the coefficient of variation of CYA levels was lower for NEO (13%) than for SIM (20%). Although CYA dosages at the start and the end of 6 months on NEO were similar, only one patient was maintained on a constant dose. Four patients had acute reversible rises in plasma creatinine which responded to a 11% reduction in NEO dose; their increase in AUC was greater than those patients not showing a rise in plasma creatinine. Overall, median plasma creatinine was unchanged at the end of the study. NEO was well tolerated by the patients; temporary nausea and headache were experienced by three patients and one of them stopped NEO after 20 days. Other biochemical parameters were not significantly different on NEO.
Paclitaxel shows a broad clinical activity in ovarian, breast and non-small cell lung cancers. However, controversy remains about the respective effects of doses and schedules in paclitaxel cytotoxicity. This study was conducted to compare the cytotoxic activity of short-term (1 h) versus prolonged exposure (14 days) to paclitaxel in human cancer cells. A soft-agar cloning system assay was used to determine the in vitro effects of 0.025-25.0 microg/ml paclitaxel against cancer cells taken directly from patients. A decrease in tumor colony formation resulting from drug exposure was considered an in vitro response if survival of colonies was up to 50% of that in positive controls. Among 11 evaluable patients' biopsies, both short- and long-term exposure to paclitaxel had significant concentration-dependent effects on the growth inhibition of human cancer cells. With the 1 h exposure schedule, in vitro responses were observed in 9,18 and 64% of evaluable tumor specimens at final concentrations of 0.25, 2.5 and 25.0 microg/ml, respectively. With the prolonged exposure schedule, concentrations of 0.25, 2.5 and 25.0 microg/ml induced 27, 45 and 91 in vitro response rates, respectively. In those patients' biopsies prolonged exposure to paclitaxel induced significantly more in vitro tumor responses than 1 h administration (p < 0.01). Similar trends were observed in ovarian, breast and non-small cell lung cancers. Our data indicate that the duration of exposure to paclitaxel is an important factor in paclitaxel cytotoxicity in human tumors and suggest that long-term exposure may improve the antitumor activity of paclitaxel.
Most of the current welfare reform incentives make assumptions about the behavior of AFDC clients. Among these assumptions are that clients will seek to maximize their financial resources; that they understand the requirements of the welfare reform; and that they can control the behaviors targeted by the welfare reform effort. Using survey data gathered from AFDC clients involved in Maryland's welfare reform initiative, the authors suggest that the assumptions underlying these welfare reform initiatives may be too simplistic. For welfare reform to be effective, the authors argue that these initiatives must reflect the complexity of the problems and concerns faced by the AFDC client.
This paper discusses the efforts of the Health Resources and Services Administration (HRSA) to work with a broad constituency to combat and ultimately prevent family violence. In partnership with states and communities, HRSA implements programs to strengthen health care infrastructure, support direct community-based service delivery, and educate health care providers. Soliciting and incorporating community input are critical steps in designing innovative training approaches to deal with pressing health concerns, such as the efforts of family violence in a community. This type of collaboration is evident in HRSA's programs such as the Area Health Education Centers, the Geriatric Education Centers, and the AIDS Education and Training Centers. Health care delivery systems and special health interventions must respond to the far-reaching effects of family violence. HRSA is devising a comprehensive strategy to guide program development in violence intervention. This strategy would build on successful models of education, prevention, and service delivery, as well as identification of critical areas for collaboration between community activists, researchers, epidemiologists, health care providers, policymakers, academicians, survivors, philanthropists, representatives from state and local government, and the faith community.
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Nephrotic syndrome presenting in the 1st year of life is often associated with a very poor prognosis for normal renal function. A small proportion of patients, particularly boys, presenting after the first 3 months of life with idiopathic-type, steroid-sensitive nephrosis, have a much better prognosis and may achieve sustained remission. We describe three boys with infantile idiopathic nephrotic syndrome of the mesangial proliferative glomerulonephritis type who went into complete remission. The patients, their first-degree relatives or both suffered from atopy (eczema, asthma or hayfever). This is the first report linking infantile nephrotic syndrome and atopy. The literature linking idiopathic nephrotic syndrome and atopy is reviewed, and the implications of our findings discussed.
Intron lariat formation between the 5' end of an intron and a branchpoint adenosine is a fundamental aspect of the first step in animal and yeast nuclear pre-mRNA splicing. Despite similarities in intron sequence requirements and the components of splicing, differences exist between the splicing of plant and vertebrate introns. The identification of AU-rich sequences as major functional elements in plant introns and the demonstration that a branchpoint consensus sequence was not required for splicing have led to the suggestion that the transition from AU-rich intron to GC-rich exon is a major potential signal by which plant pre-mRNA splice sites are recognized. The role of putative branchpoint sequences as an internal signal in plant intron recognition/definition has been re-examined. Single nucleotide mutations in putative branchpoint adenosines contained within CUNAN sequences in four different plant introns all significantly reduced splicing efficiency. These results provide the most direct evidence to date for preferred branchpoint sequences being required for the efficient splicing of at least some plant introns in addition to the important role played by AU sequences in dicot intron recognition. The observed patterns of 3' splice site selection in the introns studied are consistent with the scanning model described for animal intron 3' splice site selection. It is suggested that, despite the clear importance of AU sequences for plant intron splicing, the fundamental processes of splice site selection and splicing in plants are similar to those in animals.
Starting from Jung's hypothesis of 'the psychoid', the author suggests that the concept can be extended and understood as a dynamic, relational and interpersonal experience-especially in regressed analytic relations. The author then defines his use of the term 'animating body' as having to do with primitive animal imagery and with psychosomatic symptoms stemming from disturbed pre-verbal and pre-whole-object stages of development. A case of a borderline patient is presented, whose projective identifications into the analyst infected him with her psychosomatic disorder, with her internalized Oedipal confusion and necessarily induced a mutually similar animal dream symbolism. If these embodied countertransference experiences (of desperate merging and sickening identification) can be lived through (tolerated and survived), thought through and interpreted, then they can actually become enlivening and lead to a therapeutic psychosomatic co-ordination.
BACKGROUND: The aim of this study was to determine whether significant differences exist in lung bioavailability between generic (Salamol, Salbulin) and innovator (Ventolin) formulations of inhaled salbutamol given by metered dose inhalers. METHODS: Ten healthy volunteers of mean age 20.5 years with a forced expiratory volume in one second (FEV1) of 112.1% predicted were studied in a randomised double blind single dosing crossover study. Salbutamol, 1200 micrograms, was given with mouth rinsing and lung bioavailability was assessed by measuring plasma salbutamol levels and urine excretion of salbutamol. RESULTS: No differences were seen between innovator and generic salbutamol metered dose inhalers in plasma salbutamol levels, urinary salbutamol excretion, or extrapulmonary beta 2 activity. The maximum plasma salbutamol concentration (mean Cmax) and time to maximum concentration (median Tmax) were: Ventolin (2.93 ng/ml, 10 minutes), Salbulin (3.01 ng/ml, 10 minutes), Salamol (3.33 ng/ml, 10 minutes). The geometric mean ratio and 95% confidence interval for Cmax were: Salbulin/Ventolin 1.02 (0.69 to 1.41) and Salamol/Ventolin 1.13 (0.94 to 1.35). CONCLUSIONS: No differences are apparent between the two generic and innovator formulations of salbutamol metered dose inhaler in terms of lung bioavailability.
An in vitro cleavage system was established to measure HCV NS3 protease trans-processing activity. This system utilizes purified NS3-4A protein from baculovirus, purified substrates expressed by in vitro transcription and translation and defined buffer components. The 41-residue substrates, 5A/5B and 4A/4B, were processed efficiently in trans by wild-type NS3 but not by a catalytically inactive mutant protease; radiolabel sequencing confirmed that NS3-mediated cleavage occurred at the correct cysteine/serine sites, thereby authenticating this system. Two striking features of this in vitro assay are: (1) analogous 4B/5A and 3/4A substrates cannot be processed in trans under the same conditions, and (2) in vitro cleavage of the 5A/5B and 4A/4B sites is highly dependent on the presence of NS4A, which we show is not the case in vivo.
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This study assessed speech perception benefits for three congenitally deaf adolescents who used an electrotactile speech processor (Tickle Talker(TM)) and subsequently went on to use a Nucleus Minisystem 22 cochlear implant. Both devices provided significant and comparable benefits for all children in the device plus lipreading condition. All children benefited from the additional information provided by either the Tickle Talker(TM) or the cochlear implant, and were able to perceive speech information with these devices that was not available through either aided residual hearing or lipreading. None of the three children were able to understand open-set words or sentences using either hearing aids alone or Tickle Talker(TM) alone, without the aid of lipreading. Two of the children showed significant open-set speech perception benefits while using their cochlear implant alone.
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This article reports on the use of a Visual Inspection Protocol (VIP) to measure observable characteristics of syringes deposited at the San Francisco needle exchange program. Syringes received by the program were evaluated by several inspectors using the VIP, and interrater reliability was assessed for each item. In Study I, syringes bearing individual markings made by the user (n = 568) were more likely to be capped at the point end and plunger end, and more often were new in appearance when compared with unmarked syringes (n = 2,820). In Study II, syringes with a short street life (n = 250) were more often new in appearance and were less likely to contain blood than syringes with a long street life (n = 246). Syringes having individual markings also show signs of more careful use, and marking syringes may represent an ad hoc HIV prevention strategy for some injection drug users.
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