Drinking water quality: new challenges for an old problem.
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Animals↗
Biomedical subjects
J McNeil
Publications and source records attributed to J McNeil.
Summary of track A: basic science.
AIM: To review Track A, which is organized into five broad areas of emphasis. TOOLS: A variety of new virologic tools are allowing researchers to more effectively evaluate many aspects of HIV, from various therapies and vaccine candidates to the recombination and international spread of genotypes. PATHOGENESIS: The recent understandings of HIV-1 pathogenesis have led to potential new treatment strategies of early aggressive treatment with combination drugs and the potential for biologic or immunologic therapy directed to blocking viral entry through second receptors. TREATMENT: HIV treatment focused on chemical/drug advances and treatment, and immunologic/genetic advances. Some areas of development include optimizing combination therapies using the oncology model; continued work on new preclinical compounds (e.g. integrase and tat/rev inhibitors); evaluation of viral reduction in all compartments; and resistance surveillance and prevention. Biologics, including fusin/CC-CKR5 inhibitors and CD8 HIV-1 suppressor factors, ex vivo expansion of T cells and in vivo expansion of effector CD8 cells continue to be developed as possible future treatments. VACCINES: In order to obtain worldwide control over HIV, we must have a universally effective vaccine. The question remains as to what specifically is required for a protective response. Mechanisms of CD8 suppression, and cellular and antibody correlates of protection were discussed as areas of research that may shed light on the critical protective immune response. GENOTYPES: Discussion of HIV genotypes focused on international subtypes, correlates of diversity, and HIV-1 recombination. Numerous groups have shown an international intermixing of HIV-1 strains. Recombination during transcription was found to lead to extensive genomic shift and increased diversity, which may also increase HIV-1 fitness and enhance transmission. CONCLUSIONS: The spread and adaptation of HIV-1 is occurring independently of borders. Therefore, HIV-1 research must be global; vaccine development must be international in concept and application; collaboration in all areas is essential for success in combating HIV; and finally, the challenge for the future will be to actively involve all basic scientists in the science of the international epidemics.
AIDS Vaccines↗
Oral yeast colonization of HIV-infected outpatients.
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AIDS-Related Opportunistic Infections↗
Cytogenetic and fluorescence in situ hybridization studies on sporadic and hereditary tumors associated with von Hippel-Lindau syndrome (VHL).
We performed cytogenetic and fluorescence in situ hybridization (FISH) studies on 29 sporadic or familial tumors associated with von Hippel-Lindau [correction of Landau] disease. Four of five renal cell carcinomas with detectable alterations showed clones with chromosome 3 alterations. These changes led to loss of genetic material visible with cytogenetic resolution: either an unbalanced translocation involving 3p or loss of a whole homolog 3, resulting in monosomy of 3p. We have previously mapped the VHL gene to chromosomal region 3p25-p26. We applied FISH using the single copy probes cA233 and cA479, sequences close to the VHL gene, in a search for submicroscopic deletions of 3p. Use of FISH with differentially labeled probes indicated cA479 to be distal to cA233, but both were located within bands 3p25-26. FISH with single copy probes for interphase cytogenetics detected four subclones with deletions in the VHL region in 8/22 tumors, including four tumors which appeared cytogenetically normal. FISH proved to be a powerful tool in tumor genetic studies, especially helpful in detecting tumor subclones in benign and slowly growing tumors.
Adrenal Gland Neoplasms↗
A placebo-controlled study of three clonidine doses for smoking cessation.
BACKGROUND AND OBJECTIVE: Clonidine in doses of 150 to 450 micrograms per day has been reported to reduce symptoms of craving associated with tobacco withdrawal and, in some cases, to improve long-term abstinence rates of smoking cessation programs. However, subjects frequently experienced symptoms of dry mouth and drowsiness. This study investigated the lower end of the effective dose range of clonidine for smoking cessation to identify the lowest useful dose and thus minimize the adverse effects of the drug. METHODS: A randomized, double-blind, four-way crossover design compared the effects of clonidine doses or placebo within individual subjects for 4 consecutive weeks. Smokers who were highly nicotine dependent were randomly assigned to different sequences of placebo and 300, 200, and 100 micrograms clonidine per day. Subjects were treated for 4 days of each treatment week and began smoking cessation from the end of day 2. Smokers recorded withdrawal symptoms on multiple visual analog scales during days 3 and 4 before resuming normal smoking until the next period of smoking cessation. RESULTS: A statistically significant dose-response effect was found for craving scores (dose-response gradient, -3.8/100 micrograms; 95% confidence interval [CI], -6.2 to -1.5; p = 0.002) but not for pooled tobacco withdrawal scores. The dose of 300 micrograms per day reduced mean craving scores significantly (-16%; 95% CI, -31% to -1%). Dosing with 200 micrograms approached statistical significance (-14%; 95% CI -30% to 1%) but dosing with 100 micrograms did not (-6%; 95% CI, -22% to 9%). Troublesome adverse experiences were reported by more than 67% of subjects during 200 and 300 micrograms dosing. CONCLUSIONS: This study showed a statistically significant dose-response effect of clonidine on tobacco withdrawal craving and a reduction in mean craving scores of 16% during 300 micrograms dosing. However, its clinical usefulness is doubtful because of frequently reported adverse experiences.
Adult↗
Measurement of surgical costs: a clinical analysis.
Because of reduced health care funding it is becoming necessary for surgeons to take a greater interest in the costs of individual operations. This study reports costs directly measurable to the patient, and also the indirect costs of hospital overheads, an operating suite and teaching, which were 37, 10 and 15%, respectively (62%), of hospital budget. A scheme has been developed which could give surgeons a standard to report direct costs. Pre-admission, ward, operating room, recovery, intensive care and post-admission are defined as cost periods and the modalities of staff, equipment (capital, maintenance and replacement), imaging, laboratory and consumables apply to each. This strategy was applied to assess open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) as an example. The direct costs for OC were $3706 and LC $2868, a difference of $838; the indirect and direct costs were OC $6004 and LC $4646, a difference of $1358. Thus indirect cost magnified the difference between the operations. Bed stay, density of nursing and use of disposable instruments were the major influence on direct costs. The individual cost advantage of a shorter bed stay may be countervailed by an increased hospital activity. The main patient benefit of new operations may be improved quality of life and more rapid return to work with prevention of salary losses. A method has been developed to define costs of a particular surgical operation with the purpose of stimulating surgeons' interest in this topic and developing a common style of reporting.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholecystectomy↗
Prevalence of HPV DNA in cervical specimens in women with renal transplants: a comparison with dialysis-dependent patients and patients with renal impairment.
The aim of this study was to assess the prevalence of human papillomavirus (HPV) DNA in women who had received a renal transplant and to compare this with two control groups. Women who had a functioning renal transplant for greater than 6 months (n = 69) were compared with women on maintenance dialysis (n = 89) and women with impaired renal function (creatinine 0.15-0.39 mmol/l) (n = 22). Women were excluded if they had had a hysterectomy, were older than 65 years, or were not yet sexually active. A questionnaire and cervical scrape were obtained from each participant. The cervical scrape was analysed for HPV DNA using PCR and the L1 consensus primers. The participation rate of transplant patients, dialysis patients and those with impaired renal function ('normal' group) was 69, 68, and 78% respectively. The characteristics of the three groups of women at enrollment were similar. No cytological abnormalities were present in the 'normal' population but 11 of 89 patients on maintenance dialysis and nine of 69 transplant patients had cytological abnormalities of atypia or greater (P = 0.08 and P = 0.07, for 'normal' compared to dialysis and transplant groups respectively). One (4.5%) of the 'normal' women had evidence of HPV DNA, while 18 (20%) of patients on maintenance dialysis and 15 (22%) of transplant patients were positive (P = 0.07 and P = 0.05, for 'normal' compared to dialysis and transplant groups respectively). This study suggests that not only transplant recipients but also dialysis patients may have a higher prevalence of risk factors (cytological abnormalities and HPV DNA) for the development of cervical cancer.
Adult↗
Attentional dyslexia: a single case study.
A single case study of an attentional dyslexic is reported. The patient B.A.L. was able to read single letters and single words presented in isolation without difficulty. However, his reading of prose was very disrupted and his ability to read rows of letters and words was significantly impaired. A "flanking" procedure, in which there was a single target item, flanked by other stimuli, was used in a series of experiments to analyse his dyslexic impairment. First it was established that his attentional deficit was specific to reading in so far as the patient did not have comparable difficulties with pictorial material. His performance in the flanking experiments was consistently impaired; and furthermore was unaffected by speed of presentation, the number of flanking stimuli, and the spatial arrangement of the flanking stimuli. The important exception was when the flanking stimuli were of a different category. There was no decrement in performance when target letters were flanked by words or when words were flanked by letters. This study both corroborates and extends the original account of attentional dyslexia (Shallice and Warrnington, Neuropsychologia 15, 31-41, 1977) in terms of a damaged "filter" mechanism controlling the transition from a parallel to a serial stage of reading processing. The categorical effects reported here indicate that such a filter must be post lexical and suggest further that there are multiple filters in the reading system.
Attention↗
Aortic distensibility and left ventricular structure and function in isolated systolic hypertension.
Aortic mechanical properties were assessed in a group of elderly subjects with untreated isolated systolic hypertension using two-dimensional echocardiography. Echocardiographic (two-dimensional and Doppler) assessment of left ventricular structure and function was also made. Ten subjects (mean age 71.7 +/- 1.9 years, 20% male, mean clinic blood pressure 163.6/79.2 +/- 1.2/2.0 mmHg) were compared with 16 normotensive subjects of similar age (69.4 +/- 1.6 years, 38% male, mean clinic blood pressure 129.8/78.2 +/- 3.2/2.9 mmHg). Aortic distensibility at the level of the transverse aortic arch was significantly reduced among subjects with isolated systolic hypertension. The thickness of the interventricular septum was approximately 20% greater in the hypertensive subjects (P < 0.01) and the average wall thickness to radius ratio was increased by 30%. Patterns of transmitral diastolic flow were also different in subjects with isolated systolic hypertension. Deceleration time was significantly greater (P < 0.01) and the ratio of early to late transmitral diastolic peak flow velocities was significantly less in the hypertensive (P < 0.05) than in the normotensive group. Left ventricular systolic function was well preserved. These findings are consistent with the suggestion that isolated systolic hypertension represents a state of increased aortic stiffness which may contribute to the development of left ventricular hypertrophy. Whether this increase in aortic stiffness is the cause or effect of the elevated systolic blood pressure remains unresolved.
Aged↗
Unilateral frontal lobectomy can produce strategy application disorder.
Following a 5 cm left frontal lobectomy for the removal of a mixed astrocytoma-oligodendroglioma, a 51 year old right handed man showed a marked dissociation between his performance on standard neuropsychological tests and his everyday behaviour. In contrast to his intact neuropsychological test performance, he was impaired on a test of "strategy application" which requires goal articulation, plan specification, self-monitoring, and evaluation of outcomes, as well as the establishment of mental "markers" to trigger specific behaviour. Strategy application disorder can therefore be produced by a unilateral circumscribed frontal lobe lesions.
Anger↗
Treatment of acute idiopathic thrombocytopenic purpura with high-dose methylprednisolone and immunoglobulin.
In childhood idiopathic thrombocytopenic purpura (ITP), both intravenous high-dose steroids and immunoglobulin treatments have been demonstrated to raise platelet counts reliably and in most cases within 72 h, when used as separate therapeutic modalities. However, until now, the preferred emergency management of life-threatening complications in children with ITP has been immediate splenectomy. Since steroids and immunoglobulin create a partial splenic dysfunction, through different mechanisms, we investigated whether combined treatment with both drugs could produce a rapid platelet count increase comparable to that of splenectomy. Eleven patients, ages 4 months to 6 years, with a diagnosis of acute ITP were entered into this pilot study. Treatment consisted of intravenous high-dose methylprednisolone (20 mg/kg in 30 min) followed by intravenous gamma globulin (Gamimune-N, 1 g/kg over 5 h). The combined therapy resulted in rapid increments in the platelet counts of all patients within the 24-hour period. At 12-h, in particular, 9/11 patients had platelet counts of 30 x 10(9)l or more. We conclude that this combined therapy provides a prompt rise in platelet counts to a safe and hemostatic level and may offer a viable alternative for emergency splenectomy and its associated morbidity/mortality in many cases of childhood ITP.
Child, Preschool↗
Differences in the acute and chronic antihypertensive effects of lisinopril and enalapril assessed by ambulatory blood pressure monitoring.
Although lisinopril and enalapril are equipotent angiotensin converting enzyme (ACE) inhibitors lisinopril has been reported to produce greater inhibition of plasma ACE 24 hours after single doses. This study compared the antihypertensive effects of once daily 10mg doses of the drugs using a randomised, double-blind, two period cross-over design with ambulatory blood pressure monitoring. Lisinopril lowered mean 24 hour systolic blood pressure significantly more than enalapril after 4 weeks of treatment (14/7 +/- 2/1mmHg & 9/6 +/- 2/1mmHg, respectively, adjusted SBP difference 4.8mmHg, P < 0.01). This difference was confined to the second 12 hours of the daily dosage interval (adjusted SBP difference 13-24 hours after dosing 9.9mmHg, P < 0.001). The diastolic pressure showed a similar trend but this was not statistically significant. The side effects of each agent were minor. We conclude that chronic, once daily therapy with 10mg of lisinopril reduces systolic blood pressure more effectively than an equal dose of enalapril due to its greater effect in the latter half of the 24 hour dosage interval.
Adult↗
Reversible splenic hypofunction in hypertransfused children with homozygous sickle cell disease.
Functional hyposplenism, as documented by technetium 99 metastable sulfur colloid spleen scan and increased pocked erythrocyte count (also known as a pit count), is well described in children under 2 years of age with homozygous sickle cell anemia. We evaluated the clinical course and splenic function of 16 patients with sickle cell anemia (ages 3 to 20 years) on a hypertransfusion program for more than 6 months following a cerebrovascular accident. Patients were followed with simultaneous spleen scan and pitted erythrocyte count using direct interference contrast microscopy. Pit counts were taken prior to each transfusion and hemoglobin S level maintained at less than 20%. With the exception of two patients, splenic function was recovered only in those patients who were younger than 10 years of age at the time transfusion was initiated. There were no serious bacterial infections or other complications of sickle cell anemia documented in the hypertransfused group. Based on our results and the literature review, we conclude that some patients with sickle cell anemia receiving intensive hypertransfusion therapy for a cerebrovascular accident recover a normal splenic phagocytic function. Age and level at which the hemoglobin S is maintained are important factors in reestablishing splenic phagocytic function.
Adolescent↗
Bone marrow transplant in Shwachman Diamond syndrome.
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Adolescent↗
Ginger root--a new antiemetic. The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery.
The effectiveness of ginger (Zingiber officinale) as an antiemetic agent was compared with placebo and metoclopramide in 60 women who had major gynaecological surgery in a double-blind, randomised study. There were statistically significantly fewer recorded incidences of nausea in the group that received ginger root compared with placebo (p less than 0.05). The number of incidences of nausea in the groups that received either ginger root or metoclopramide were similar. The administration of antiemetic after operation was significantly greater in the placebo group compared to the other two groups (p less than 0.05).
Adolescent↗
Clinical competencies for community health nursing.
Cost-containment strategies initiated in the early 1980s caused a major shift in site of care delivery for persons needing nursing care. Where once the majority of clients were cared for in the acute-care setting until they were self-sufficient, now most are discharged to the home environment still requiring acute-care nursing interventions as well as community health nursing skills. This rapid shift in practice sites has placed severe strain on community health nursing agencies. Not only are more nurses required to fill the increased demand for services, but the demand comes at a time when we are experiencing a severe nursing shortage. This has forced many agencies to hire acute care nurses who have little or no community health nursing experience. These nurses come to community health nursing expecting to use the same set of skills and knowledge base used in their acute-care practice; however, the skill levels and concepts required for community health nursing are quite different from the acute care setting. Educational preparation has not kept pace with this shift in practice. Consequently, many nurses are not adequately prepared to enter community health nursing. Preparation must include theoretical and experiential components that focus on assessment skills (of the community and individual), decision making, case management, health systems management, teaching, and leadership. Collaborative efforts between community health organizations and educational institutions would seem to be one solution that would ensure adequately prepared nurses for community health nursing. The establishment and maintenance of strong staff-development programs within community health nursing agencies are also required.
Clinical Competence↗
Human type II collagen gene (COL2A1) assigned to chromosome 12q13.1-q13.2 by in situ hybridization with biotinylated DNA probe.
We have made a regional assignment of the type II collagen gene (COL2A1) on human chromosome 12 by means of an in situ hybridization technique with a biotinylated DNA probe. The precise localization of the signal was mapped to the band 12q13.1-q13.2. This result was in agreement with the previous mapping by isotopic in situ hybridization technique (12q13.1-q13.2), but not with the result of Southern hybridization analysis using somatic cell hybrids (12q14.3).
Chromosome Banding↗