Counseling services: practice builders for the '90s.
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Biomedical subjects
Publications and source records attributed to M Miller.
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Decreased trends of tuberculosis incidence have been observed in Poland. A rate of decreased incidence has been hesitated from about 1% to above 12% per year. In 1989 year 16,185 (42.8%/100,000) cases with active pulmonary tuberculosis have been registered and about half of them have been bacteriologically supported. Analyzed epidemiological parameters for tuberculosis are twice higher in Poland than in Europe. Using relation between an incidence of active tuberculosis bacteriologically supported and annual risk of infection it was documented that an annual risk of tubercule bacillus infection was 10-times higher in Poland in comparison with other countries characterized by the lowest incidence of tuberculosis (Norway, Holland).
An analysis was carried out on 850 self-report questionnaires sent to Polish pulmonologists on their knowledge and attitude toward smoking. In the sampled population 38% of the males and 29% of females smoked. Smoking was dated as first among various noxious factors in human pathology. The knowledge of harmful effect of smoking was restricted to the cardio-respiratory system. Part of the responders, mainly smokers believe that smoking less than 15 cigarettes is harmless. ++Ex-smokers were most active in smoking cessation programs. Knowledge of harmful effect of smoking and cessation programs by physicians is unsatisfactory and teaching programs concerning this problem is mandatory.
Daily administration of either phenobarbital (60 mg/kg) or yin zhi huang (YZH, 30-60 ml/kg) for 5 days to rats similarly accelerated the clearance and conjugation of intravenously infused bilirubin. However, the two drugs had quite different effects on liver enzyme activities associated with xenobiotic metabolism and with bilirubin metabolism. Phenobarbital markedly increased cytochrome P-450 levels and the cytochrome-P-450-mediated formation of 4-hydroxybiphenyl whereas YZH had a slightly depressive effect on this enzyme system. Both drugs increased glucuronyl transferase activity using bilirubin and alpha-naphthol as substrates. Bilirubin conjugation in microsomes activated by uridine diphosphate-N-acetylglucosamine (NAG) was greater in YZH- than in phenobarbital-treated rats whereas phenobarbital was a more effective inducer in digitonin-activated enzyme. When alpha-naphthol was used as substrate (NAG-activated glucuronyl transferase), pretreatment with phenobarbital produced a greater increase in activity than did YZH. Glutathione-S-transferase activity (using chlorodinitrobenzene as substrate) was increased more than 2-fold by phenobarbital but only slightly (1.29 X) by YZH. In contrast, YZH (60 ml/kg) was more effective than phenobarbital in increasing glutathione peroxidase activity using cumene hydroperoxide as substrate. YZH appears to be a relatively specific inducer of enzymes involved in bilirubin metabolism.
The sleep of thirty elderly patients with recurrent unipolar depression was examined at baseline (before acute treatment of the index episode) and again in a state of symptomatic remission with nortriptyline (mean steady-state level: 82.1 ng/ml). Continuation therapy with nortriptyline was associated with improvement of polysomnographic sleep maintenance (mainly in the third and fourth sleep cycles, to a level similar to that of controls), prolongation of rapid-eye-movement (REM) sleep latency (exceeding that of controls), and potentiation of slow-wave activity during the first non-REM (NREM) sleep period. Clinical improvement, as measured by the Hamilton Depression Rating Scale, was significantly associated with shift of delta activity toward sleep onset (p less than 0.002), prolongation of REM sleep latency (p less than 0.0001), and improvement in sleep maintenance (p less than 0.0002). Multiple regression analysis showed that the single best correlate of clinical change was prolongation of REM sleep latency (i.e., prolongation of first NREM period). Perceived sleep quality improved significantly during early continuation therapy with nortriptyline, but not to the level reported by a group of 30 age- and sex-matched healthy controls. The findings are consistent with the concept that anti-depressant drug efficacy may depend upon strengthening of the homeostatic regulation of sleep and upon changes in the REM-sleep regulation.
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Hyperapobetalipoproteinemia (hyperapoB), a familial lipoprotein disorder characterized by an increase in small, dense, low-density lipoprotein (LDL) particles, is strongly associated with coronary artery disease. There are two metabolic defects in hyperapoB: an increased synthesis of a very-low-density lipoprotein in liver, resulting in an overproduction of LDL, and a delayed clearance of post-prandial triglyceride and free fatty acids. To date, defects in the apolipoprotein B gene do not appear to explain the hyperapoB phenotype. Defect(s) in the uptake or intracellular metabolism of free fatty acids have been found in cells from hyperapoB patients. Three basic proteins (BPs)--BP I (Mr 14,000, pI 9.10), BP II (Mr 27,500, pI 8.48), and BP III (Mr 55,000, pI 8.73)--were isolated from normal human serum. Compared with normal fibroblasts, cultured hyperapoB fibroblasts incubated with BP I, which appears to be the same protein as acylation-stimulating protein (ASP), showed 50% less stimulation of triglyceride acylation and cholesterol esterification, whereas BP II markedly stimulated cholesteryl ester formation, and BP III caused no difference in response vs normal fibroblasts. However, in cultured normal human monocyte macrophages, BP III, but not BP I or BP II, stimulated cholesteryl esterification two- to threefold. BP I, BP II, and BP III may provide new insights into normal metabolism of lipids, lipoproteins, and free fatty acids and the pathophysiology of hyperapoB.
Coronary heart disease (CHD) is the major cause of mortality in the elderly. Important risk factors include hypercholesterolemia, systolic and diastolic hypertension, cigarette smoking, hyperglycemia, and obesity. Elderly patients with existing CHD should be treated aggressively to control these risk factors, along with other medical therapies to treat myocardial ischemia. For elderly patients without recognized CHD, however, a more conservative approach is recommended and includes behavioral interventions when appropriate and pharmacologic therapy for higher risk patients with persistent, uncontrolled risk factors.
A retrospective study involving 720 dogs and cats that underwent a variety of elective surgical procedures was done to compare the effectiveness of reusable cotton barrier materials with that of a commercially available disposable barrier system for prevention of wound infection. The overall wound infection rate, using cotton barrier materials, was 3.1% and for disposable materials, was 4.4%. The difference between groups was not significant.
An outbreak of Pontiac fever occurred among 34 of 56 people attending conferences at a hotel in Santa Clara County, California, in 1988. Two groups had an acute febrile upper respiratory illness, with a mean attack rate of 82% and a mean incubation period of 56 hours. Symptoms resolved spontaneously within 5 days. Legionella anisa, which had not previously been associated with outbreaks of Pontiac fever or legionnaires' disease, was isolated from a decorative fountain in the hotel lobby. In addition, 5 of 8 pairs of serum samples from cases showed a more than fourfold rise in antibody titre to the L anisa recovered from the fountain. 42% of hotel employees had titres greater than or equal to 256 against L anisa, whereas none of 48 serum samples from matched controls had titres greater than or equal to 128. The findings raise concern about water treatment protocols for extent of disease that might be caused by exposure to aerosols containing L anisa and other Legionella species.
The structure of Rous sarcoma virus protease has been solved by multiple isomorphous replacement in the crystal form belonging to space group P3(1)21, with unit-cell parameters a = 88.95 A and c = 78.90 A. The enzyme belongs to the family of aspartic proteases with two identical subunits composing the active homodimer. The noncrystallographic dyad relating these two subunits was identified after preliminary tracing in the MIR map and was used for phase improvement by electron-density averaging. Structure refinement resulted in a model that included 1772 protein atoms and 252 water molecules, with an R factor of 0.144 for data extending to 2 A. The secondary structure of a retroviral protease molecule closely resembles that of a single domain in pepsin-like aspartic proteases and consists of several beta-strands and of one well-defined and one distorted alpha-helix. The dimer interface is composed of the N- and C-terminal chains from both subunits which are intertwined to form a well-ordered four-stranded antiparallel beta-sheet. In each monomer, the catalytic triad (Asp-Ser-Gly) is located in a loop that forms a part of the psi-structure characteristic to all aspartic proteases. The position of a water molecule between the active-site aspartate residues and the general scheme of H bonding within the active site bear close resemblance to those in pepsin-like aspartic proteases and therefore suggest a similar enzymatic mechanism. The binding cleft over the active site is covered by two flap arms, one from each monomer, which are partially disordered. The retroviral protease dimer has been compared with several enzymes of cellular origin, with chains aligning to an rms deviation of 1.90 A or better.
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Parvovirus infection was confirmed by fluorescent antibody staining or viral culturing in 137 (22%) of 615 necropsy accessions from dogs at the Missouri Veterinary Medical Diagnostic Laboratory from Jan 1, 1987 through Sept 30, 1988. Septicemic colibacillosis was diagnosed in 88 (90%) of the 98 canine parvovirus-positive accessions in which liver or lung was cultured bacteriologically. Pulmonary edema or alveolitis similar to that seen in the human adult respiratory distress syndrome was observed in 63 (69%) of the 91 canine parvovirus-positive accessions in which the lungs were examined histologically.
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Crystal structures of two forms of ribonuclease A with deoxynucleosides covalently bound to respectively His 12 and His 119 have been solved. One form, T-H12-RNase, has a deoxythymidine bound to N epsilon 2 of His 12, while the other one, U-H119-RNase, has a deoxyuridine bound to N delta 1 of His 119. The two crystal forms are nearly isomorphous, with two molecules in the asymmetric unit. However, the modified ribonucleases differ both in their enzymatic activities and in the conformation of the catalytic site and of the deoxynucleoside-histidine moiety. T-H12-RNase is characterized by complete loss of enzymatic activity; in this form the deoxynucleoside completely blocks the catalytic site and forms intramolecular contacts with residues associated with both the B1 and B2 sites. U-H119-RNase retains 1% of the activity of the unmodified enzyme, and in this form His 119 adopts a different orientation, corresponding to the alternate conformation reported for this residue; the deoxynucleoside-histidine moiety points out of the active site and does not form any contacts with the rest of the protein, thus allowing partial access to the catalytic site. On the basis of these structures, we propose possible mechanisms for the reactions of bromoacetamido nucleosides with ribonuclease A.
The National Cholesterol Education Program treatment guidelines define a plasma total cholesterol of less than 200 mg/dl as "desirable" and recommend no further evaluation of plasma lipid or lipoprotein levels in patients with coronary artery disease (CAD). To determine the prevalence of dyslipidemias in the presence of coexistent CAD and total cholesterol less than or equal to 200 mg/dl, a retrospective case-control study of 1,000 patients who underwent diagnostic coronary angiography was performed. Of 351 patients with total cholesterol less than or equal to 200 mg/dl, 76% of the men (244) and 44% of the women (107) had angiographically demonstrated CAD. In men with CAD and total cholesterol less than or equal to 200 mg/dl, there was a significantly greater prevalence of low levels of high density lipoprotein (HDL) cholesterol (less than or equal to 35 mg/dl), age greater than 50 years, systemic hypertension and diabetes mellitus compared to non-CAD control subjects. In women with CAD and total cholesterol less than or equal to 200 mg/dl, HDL cholesterol less than or equal to 45 mg/dl and diabetes mellitus were also significantly prevalent. Multiple logistic regression analyses revealed that HDL cholesterol, hypertension and age in men and very low density lipoprotein cholesterol in women were significantly associated with CAD after adjustment for other risk factors. These results suggest that a complete lipid and lipoprotein analysis be obtained in all patients with CAD, irrespective of the plasma (or serum) total cholesterol level.