Becoming real: from model programs to implemented services.
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Biomedical subjects
Publications and source records attributed to V Miller.
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This clinical report emphasizes that comprehensive treatment planning, whether simple or complex, requires interdisciplinary knowledge. Conservative treatment was implemented for this patient, a 29-year-old woman with a posttraumatic anterior open occlusal relationship, crowding, and a shifted midline. The treatment plan involved selective occlusal grinding, adjunctive orthodontics, periodontal surgery, and cosmetic dentistry and proved to be highly successful.
BACKGROUND: Chronic constipation is a common problem in children. We observed the effects of cisapride in the management of idiopathic constipation in children. METHODS: Thirty-seven children with a history of constipation (i.e., pain and difficulty or delay in defecation for > 3 months) were recruited and randomly assigned to 8 weeks of treatment with either cisapride, 0.2 mg/kg three times daily, or matching placebo after a 2-week run-in period in a double-blind, parallel-group study design. In phase 1 (2 weeks), patients had plain abdominal radiographs to assess degree of faecal load, and those with impaction were given laxatives. After satisfactory clearance of faeces, total gastrointestinal transit time and orocaecal transit time were measured. In phase 2, after 8 weeks of treatment with either cisapride or placebo (0.2 mg/kg t.d.s.), the transit studies were repeated. RESULTS: Compared with placebo, cisapride did not improve either stool frequency or transit time in this study population. CONCLUSION: This study did not demonstrate a clinical role for the use of cisapride in the treatment of idiopathic constipation in children.
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The serum levels of the beta-chemokine RANTES and, albeit less, MIP-1 beta were found to be increased in 37 HIV-1 infected compared to seronegative individuals. In contrast the serum levels of IL-16 were only sporadically elevated in seropositives as well as in seronegatives. Concomitantly, the RANTES gene expression increased about tenfold in seropositives, whereas the MIP-1 beta and IL-16 mRNA levels were not elevated. No correlation between the increase of the MIP-1 beta and RANTES serum concentrations and the plasma virus load, the number of the peripheral CD4+ T cells or the therapy status of the patients was found. However, the increased proportion of activated CD8+CD38+ T cells in the peripheral blood of all seropositives paralleled the increased RANTES serum levels detected indicating that immune activation in HIV-1-infected individuals may contribute to increased RANTES serum levels.
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In mammals, there are seven classes of beta-tubulin genes, one of which, class III, is neuron specific. Using class-specific monoclonal antibodies, class III beta-tubulin protein could not be detected in frog embryos or in adults with either Western blotting or immunohistochemical techniques. In contrast, the class II beta-tubulin protein, which is predominant in mammalian brain but is also expressed in other tissues, is expressed only in neurons in frog embryos. Protein was detected only in neurons from late stages of neural tube closure through premetamorphic stages. At stages 21-28, the pioneering axons of Rohon-Beard, commissural, primary motor, and trigeminal ganglion neurons were distinctly stained in the axon scaffolds that they formed in the embryonic brain and the peripheral mesenchyme. Nonneuronal cells, both outside the nervous system and within it (e.g., radial glia, Müller glia, roof plate, and floor plate cells) were not immunoreactive. Throughout swimming and premetamorphic stages, neuronal cells in all brain regions became immunoreactive as they differentiated and extended axons. Whereas many embryonic neurons became postmitotic during gastrulation stages, neurons expressed detectable levels of class II beta-tubulin protein only beginning at the onset of overt axon outgrowth. These observations demonstrate that the neuron-specific beta-tubulin in frog is a different gene from that in mammals, and its protein product is detectable at the time of axonogenesis rather than neurogenesis.
Consistency is evaluated by an initial flow test that allows the clinician to select the material of choice for relining procedures according to the size and shape of the ridge and the condition of the soft tissue. In this study, the consistency of four autopolymerized soft liners was compared and tested to determine whether they meet the new International Standards Organization (ISO) 10139-1 specifications. Softness, assessed with a Shore A durometer, was compared with that of two heat-cured silicone soft liners, because the latter are known for their steady softness over long periods of time. The consistencies of all four autopolymerized soft liners complied with ISO specifications and their disk diameter ranged from 41.3 to 72.2 mm. The softness of all four soft liners changed with time, unlike the silicones whose softness remained consistent. Softness readings varied significantly with sample thickness and indicated the need to develop criteria for measuring softness properties and determining the minimal thickness required for clinical performance.
PURPOSE: Pharmacologic lysis or balloon thrombectomy are options to treat acute arterial thrombosis; however, little is known about their effects on functional changes in the arterial wall. The aim of this study was to determine function of the endothelium and smooth muscle in canine arteries revascularized after acute thrombosis with balloon thrombectomy or lytic therapy. METHODS: Acute thrombosis was obtained by bilateral proximal and distal ligation of 8-cm. segments of the femoral arteries in dogs. After 24 hours, the ties were removed and the arteries randomized to treatment groups: group 1, balloon thrombectomy (# 4 Fogarty balloon catheter at 60 grams linear shear x 1 pass, n = 7); group 2, untreated, tie removal only (n = 6); group 3, regional intra-arterial urokinase infusion (4000 U/min x 90 min, n = 6); group 4, regional intra-arterial carrier infusion (0.43 ml/min x 90 min, n = 6); group 5, unoperated normal vessels (n = 5). After treatment, the arteries were removed and endothelial and smooth muscle responses examined in organ chambers. Endothelial loss was graded with light microscopy of vessel rings from each animal by an observer blinded to the treatment group. Findings were confirmed with scanning electron microscopy. RESULTS: Treatment with urokinase did not alter endothelium-dependent relaxations or smooth muscle contractions compared with carrier infusion or untreated alone. Balloon catheter thrombectomy significantly reduced endothelium-dependent relaxations compared with all other groups in response to acetylcholine, bradykinin, and thrombin (p < 0.001). Contractions of smooth muscle in response to potassium chloride (60 mol/L) and phenylephrine (1 x 10-6 mol/L) were also reduced (p < 0.05). Rings from balloon thrombectomized arteries contracted in response to calcium ionophore A23187 (p < 0.001); these contractions were endothelium dependent and not reduced by indomethacin or blockade of endothelin A and B receptors. No significant differences in percentage of endothelial coverage between groups were assessed by light and electron microscopy. CONCLUSION: Thrombolysis with urokinase caused no or minimal abnormalities in endothelial and smooth muscle function. Endothelium present after balloon thrombectomy produces contractile factors. Although the duration and recovery of these abnormalities in function are unknown, these findings support preferential use of urokinase over balloon thrombectomy when possible in acute arterial thrombosis or embolism.
OBJECTIVE: To compare two antiretroviral regiments, loviride plus lamivudine (3TC) plus zidovudine (ZDV) (triple combination) and loviride plus ZDV (double combination) in terms of pharmacokinetic interactions, tolerability, safety, and immunological and virological efficacy. STUDY DESIGN: An open, case-controlled, pharmacokinetic and 24-week continuous treatment pilot study. PATIENTS: Twenty p24 antigen-positive patients, 10 per treatment group, were matched according to p24 antigenaemia less or more than 100 pg, CD4 count less or more than 150 x 10-(6)/l, and gender. Eight out of 10 cases and seven out of 10 controls had received previous antiretroviral therapy. RESULTS: No clinically relevant pharmacokinetic interactions were observed. Both treatment combinations were well tolerated. Median absolute and percentage CD4 count increases above baseline were more pronounced in the triple combination arm than in the double combination arm. Median p24-antigen and plasma viraemia level decreases below baseline were more pronounced in the triple combination arm. The M(184)I/V mutation was detected in all plasma samples of triple combination patients examined at week 12. Mutations conferring resistance to loviride and ZDV were found in a significant subset of patients in both treatment arms. CONCLUSIONS: Both combination regimens have an excellent safety/tolerability profile, but a higher level of in vivo efficacy is achieved by the triple combination, despite genotypic changes conferring resistance to one or all of these agents. The conclusions drawn are limited by small population size and the heterogenous pretreatment history. However, they support the validity of and strongly encourage a rationally designed multidrug combination approach to HIV therapy.
In a 10-week randomised cross-sectional study we used an 88-item questionnaire to assess the quality of life in 16 children (ages 8-17 years) with Crohn's disease and their families. The questionnaire covered six domains of health-related quality of life, including disease and its treatment, social, emotional, family, education, and future aspects. Crohn's disease affected education, with absenteeism in 12 and distraction during school work in six. Three children had had a home tutor, and five stated their need for one. Engaging in sports was a problem for eight children, mainly because of a lack of energy in five and the presence of a stoma in three children. Three children had missed every PE lesson in 1 year. Five children cited the social problem of being unable to stay over at friends' houses. Bullying concerned parents more than the children. Holiday difficulties included long distance traveling or lack of toilet facilities during school trips. Elemental diet was the preferred treatment, although the majority complained about the taste. Surgery was the most effective method of symptom control, though the resulting stoma was upsetting and restricted sports activities. Children on steroids had more depressive symptoms. Using the Rutter A Questionnaire, five children were designated "neurotic." Parents' views of the severity of symptoms significantly correlated with their children's views regarding rectal bleeding, poor growth, lack of energy, and poor appetite (p < 0.01). The main parental concerns were the side effects of medications and issues concerning their children's future, including schooling, job prospects, and marriage. The parents of 11 children cited problems with children's behaviour. The parents of seven cited disruption of work, and those of six named taking holidays. Crohn's disease in children, in addition to being a symptomatically disabling condition, has a great impact on the health-related quality of life of both sufferers and their parents. The questionnaire was a useful instrument, and with some adjustment it can be used again in large group studies.
Seven children with intractable diarrhoea of infancy seen between 1990 and 1993 developed endoscopically established inflammatory bowel disease unrelated to bacterial infection and not responsive to whole protein exclusion. Mouth ulcers were present in two patients, endoscopic upper-gastrointestinal-tract inflammation in two, villous atrophy in six, and chronic nonspecific colitis in all seven. There was considerable clinical and histological heterogeneity. All patients required parenteral nutrition. Steroid therapy was completely successful in only one child, while two underwent colectomy, and two died. Previously described cases other than those due to infection or milk intolerance have been rare and sporadic. The prevalence of inflammatory bowel disease in infancy is unknown but appears to be increasing.
Present methods to screen for alcohol abuse are generally obtrusive and result in referral to services that deal mainly with alcoholics. These factors deter physicians from identifying alcohol abuse patients at an early stage. In the present study, 81% of all primary care physicians of a single city evaluated (i) the efficiency and the acceptability of a nonobtrusive screening method for the identification of problem drinkers and (ii) the effectiveness of brief cognitive behavioral counseling given by a nurse in a lifestyle context. Patients (n = 15,686) attending the private practices of 42 primary-care physicians were asked four alcohol-neutral trauma questions in the reception area. Physicians asked about alcohol use and alcohol-related problems only to patients with previous trauma. Problem drinkers by defined criteria were offered an appointment with a nurse who, by random assignment, gave either 3-hr of cognitive behavioral counseling over 1 year or simply advised patients to reduce their alcohol intake. The screening method identified 62-85% of expected number of problem drinkers in this population. Following the application of exclusion criteria, 105 problem drinkers were entered in the intervention part of the study. After 1 year, patients who received counseling showed significant reductions in reported alcohol consumption (-70%; p < 0.001), psychosocial problems (-85%; p < 0.001) and serum gamma glutamyl transferase (-32% to -58%; p < 0.02). Physician visits were reduced (-34%; p < 0.02) following counseling. Patients receiving only advice showed neither reductions in psychosocial problems nor in serum gamma glutamyl transferase or physician visits, but reported a 46% reduction (p < 0.01) in alcohol consumption. Data indicate that asking patients about recent trauma is efficient and is well accepted as the first screening instrument in the identification of the problem drinker. Cost of screening per patient is under one dollar. Counseling of 3 hr given by a nurse is markedly superior (p < 0.05) to simple advice in reducing alcohol consumption, objective indicators of alcohol-related morbidity, and the frequency of physician visits.
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BACKGROUND: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia. METHODS: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio. RESULTS: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%. CONCLUSION: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.