AHEC students "try on" rural practice.
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Area Health Education Centers↗
Biomedical subjects
M Miller
Publications and source records attributed to M Miller.
Hematomas and limb skeletal malformations in chicken embryos following exposure to 5-fluoro-2-deoxyuridine.
Vascular injury or interruption may play a role in vertebrate limb teratogenesis. Since 5-fluoro-2'-deoxyuridine (FdU) can cause vascular injury in the murine limb and skull prior to the appearance of skeletal malformations in these structures, we studied the effects of this chemical on skeletal development in the chick embryo and noted any vascular injury. The yolk sacs of day three chick embryos (Hamburger and Hamilton states 17-19) were injected with solutions of vary concentrations of FdU in saline. The embryos developed until the 10th day of incubation when they were fixed for study. Uninjected, saline injected, and sham injected control embryos were similarly fixed. Upon gross inspection, frequent diffuse and saccular hematomas, as well as fluid-filled blisters, were noted in the limbs of embryos treated with FdU. After the embryos were fixed and cleared, and the skeletons stained, significant skeletal malformations were observed in these limbs. Bony elements of both the upper and lower limbs were affected in at least some of the embryos. The combination of FdU-induced hematomas and blisters with associated skeletal malformations in the same regions of some embryos suggests a relationship between these phenomena.
Abnormalities, Drug-Induced↗
[Evaluation of diagnostic and therapeutic management in patients with bacteriologically negative pulmonary tuberculosis].
The study aimed at assessing the frequency and type of errors in the diagnosis and management of newly registered bacteriologically negative cases of pulmonary tuberculosis. Random sample of 560 out of 7272 such patients registered in 1993 was subject of detailed analysis of all available medical documentation. The analysis was performed by an independent team of three specialists: pulmonologist, radiologist and epidemiologist. The results of the analysis indicate insufficient utilization of modern available diagnostic methods. Apart from clinical assessment the main basis for diagnosis of tuberculosis was A-P radiography. Tomography examination was performed in 35.5% of patient only, bronchoscopic in 19.8% and cytologic examination of sputum in 15.9%. Bacteriological examinations during the first phase of diagnosis, usually in hospitals, were satisfactory. Error in diagnosis was found in 63 patients, i.e. 11.3% of cases. The treatment in patients considered as correctly diagnosed, was in the intensive phase correct, but in the continuation phase--too long.
Biopsy↗
Hyponatremia: age-related risk factors and therapy decisions.
Normal aging is accompanied by many changes in the regulatory systems that control sodium and water balance, as well as diminished capacity to withstand the challenges of illness, drugs, and physiologic stresses. Consequently, the older person is at an increased risk for clinically significant alterations in sodium and water balance, especially hyponatremia. Awareness of these risk factors allows the physician to anticipate the impact of illnesses and drugs on volume and electrolyte status of the older patient and to implement a rational approach to therapeutic intervention and management.
Acute Disease↗
The case study as a scientific method for researching alternative therapies.
This article argues that the case study design is a research method capable of providing valuable data and insight into alternative therapies. The background and roots of the case study in medicine and clinical practice are covered, and the status of the case study as a scientific method is examined. The highly regarded randomized controlled clinical trial--though often powerful and useful--is neither feasible nor ideal for understanding the effects of many unconventional treatment approaches. Given the complexity of the factors involved in unconventional therapeutic applications--health beliefs, changing health paradigms, patient/practitioner interactions, multiple treatment modalities, multiple symptom profiles--the case study approach offers an alternative methodological route for investigating and generating findings in this arena. Reliability and validity of data collection, data reduction, and interpretation can be enhanced through steps discussed in this article. As it continues to work with evidence that is currently unorganized, the field of alternative medicine can benefit both in clinical prowess and scientific stature from additional, carefully conducted case studies.
Complementary Therapies↗
Diet and psychological health: a case study.
This article presents an example of the case study as a valuable methodological option for researching alternative and complementary therapies. This case study investigated the experiences of an individual in recovery from substance abuse who reported improvements in psychological symptoms following dietary changes. The underlying premise explored was that dietary or nutritional components can have a significant effect on psychological health and should therefore be used with other biopsychosocial approaches for the prevention and treatment of mental disorders. Until there is a shift in research priorities to encourage medical-cultural recognition of the impact of diet on psychological and physical health, smaller studies that rigorously investigate case reports can provide useful information to practitioners as well as laypeople.
Diet↗
Is hypertriglyceridaemia an independent risk factor for coronary heart disease? The epidemiological evidence.
There has been considerable controversy over whether elevated levels of triglycerides, or hypertriglyceridaemia, is an independent risk factor in coronary heart disease (CHD). Discrepancies between findings of univariate and multivariate statistical analyses are likely to be due to the strong inverse correlation between plasma triglyceride levels and high density lipoprotein cholesterol. Convincing evidence of a link between elevated triglyceride levels and CHD has been reported in a meta-analysis of patients whose plasma triglyceride levels were measured in the fasting state. Further evidence has come from several angiographic studies that have examined the relationship between plasma triglyceride levels and the progression of coronary artery disease (CAD). It is critical that the threshold of placebo triglyceride, above which hypertriglyceridaemia is recognized, is set at an appropriate level. This will ensure that patients at potential risk of CHD receive appropriate lipid-lowering treatment. In an 18-year follow-up study, incidence and severity of stenosis correlated with plasma triglyceride level. At a triglyceride level of 100 mg. dl-1, which current guidelines would consider to be low risk, patients had a reduced chance of survival from coronary events. These findings suggest that the present classification of triglyceride levels in the assessment of CAD risk may need to be redefined.
Cholesterol, HDL↗
Structure of monellin refined to 2.3 a resolution in the orthorhombic crystal form.
The structure of orthorhombic crystals of monellin, a sweet protein extracted from African serendipity berries, has been solved by molecular replacement and refined to 2.3 A resolution. The final R factor was 0.150 for a model with excellent geometry. A monellin molecule consists of two peptides that are non-covalently bound, with chain A composed of three beta-strands interconnected by loop regions and chain B composed of two beta-strands interconnected by an alpha-helix. The N terminus of chain A is in close proximity to the C terminus of chain B. The two molecules in the asymmetric unit are related by a non-crystallographic twofold axis and form a dimer, similar to those previously observed in other crystal forms of both natural and single-chain monellin. The r.m.s, deviation between the Calpha atoms in the two independent molecules is 0.60 A, while the deviations from the individual molecules in the previously reported monoclinic crystals are 0.50-0.57 A. This result proves that the structure of monellin is not significantly influenced by crystal packing forces.
Journal Article↗
Clean lungs at a price. Do smoking-related deaths save the nation money?
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Cost of Illness↗
Results of directional coronary atherectomy in Northern New England. Northern New England Cardiovascular Disease Study Group.
The role of directional coronary atherectomy (DCA) in interventional cardiology remains uncertain. We report the Northern New England regional experience with DCA from 1991 to 1994. Data were collected on 11,178 patients having had an intervention on a single lesion in a single vessel (798 DCAs; 10,380 percutaneous transluminal angioplasties [PTCA]). The use of DCA increased from 1.8% of interventions in 1991 to 10% in 1994. Compared with PTCA, DCA patients were younger, more often men, had more 1-vessel disease and more coronary artery bypass surgery (CABG). DCA was more often used in the left anterior descending artery, in vein grafts, for restenoses, for subtotal occlusions, and with type A lesions. Angiographic success (96.7%) and clinical success (93%) were good. Adverse events were rare: mortality 0.9%, emergent CABG 2.2%, nonfatal myocardial infarction 2.8%. After adjusting for case-mix, there was no difference between DCA and PTCA for in-hospital mortality (odds ratio [OR] = 1.03, 95% confidence interval [CI] 0.44 to 2.43, p = 0.95) or need for emergent CABG (OR = 1.27, 95% CI 0.77 to 2.10, p = 0.34). Atherectomy patients were more likely to have a nonfatal myocardial infarction (OR = 2.0, 95% CI 1.26 to 3.20, p <0.01), to sustain an injury to the femoral or brachial artery (OR = 2.89, 95% CI 1.52 to 5.51, p <0.01), and to have a clinically successful procedure (OR = 1.37, 95% CI 1.01 to 1.88, p = 0.05). Our results support the relative safety and effectiveness of DCA as its use disseminated into the region.
Aged↗
Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 3, 5, 15, 16, 17, and 22.
As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16,17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (theta) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage.
Alleles↗
Alternative splicing in lecithin:cholesterol acyltransferase mRNA: an evolutionary paradigm in humans and great apes.
Lecithin:cholesterol acyltransferase (LCAT), an important enzyme affecting reverse cholesterol transport, is expressed in liver and cultured fibroblasts. Sequencing of LCAT cDNA clones demonstrated the coexistence of two mRNA products. In addition to the normal transcript, we identified an alternate message with a splice-mediated insertion of a 95 bp Alu cassette at the junction of exons 5 and 6. In humans, the alternate transcript represents 5-20% of the complete LCAT message in cultured fibroblasts and liver. It is present in humans and the great apes but not in lesser apes (gibbon, siamang) or lower-order primates (e.g., old or new world monkeys). Sequencing of intron 5 of the LCAT locus in several primates revealed a G-->A transition at the splice donor recognition site in the Alu repeat of the gibbon and a G-->A substitution in the last position of the 95 bp Alu sequence of the rhesus monkey, an old world monkey. Both substitutions have been associated with exon skipping in other genes. These results demonstrate that alternative splicing of LCAT mRNA is variant among primates and suggest a potential role of Alu elements in the evolutionary diversity of proteins.
Alternative Splicing↗
Alteration of local cerebral glucose utilization following intravenous administration of heroin in Fischer 344 rats.
The 2-deoxyglucose method was used to study the effects of acute administration of small intravenous doses of heroin on rates of glucose utilization in rat brain to identify small brain regions that may be involved in the acute behavioral effects of heroin. In contrast to previous studies which have used relatively large doses, the doses of heroin used in this study have been shown to be self-administered [Martin, T.J., Dworkin, S.I. and Smith, J.E., Alkylation of mu-opioid receptors by beta-funaltrexamine in vivo: comparison of the effects on in situ binding and heroin self-administration in rats., J. Pharmacol. Exp. Ther., 272 (1995) 1135-1140.]. Administration of 18 microg/kg of heroin resulted in higher rates of glucose utilization in the medial olfactory tubercle, anterior nucleus accumbens and dorsolateral caudate while having no other effects on limbic structures compared to saline-treated animals. Conversely, the rate of glucose utilization was lower than control in the habenula, dorsal raphe, and central gray following adminstration of 18 microg/kg of heroin. Administration of two higher doses (60 and 100 microg/kg) resulted in lower rates of glucose utilization in the thalamus, habenula, inferior colliculus, dorsal raphe and central gray compared to saline. The higher rates of glucose utilization in the limbic areas were specific for the lowest dose of heroin, whereas the effect of lowering the rate of glucose utilization compared to control in the thalamus and inferior colliculus were an increasing function of dose. In the habenula and dorsal raphe, however, the dose-effect function was inverted. These data indicate that the alterations of glucose utilization in rat brain by heroin are site-specific and the systems involved as well as the nature of the alteration differs for individual doses of heroin.
Analgesics, Opioid↗
A practical guide for the diagnosis and treatment of acute sinusitis.
OBJECTIVE: To develop guidelines for the diagnosis and management of acute sinusitis. OPTIONS: Diagnostic clinical criteria and imaging techniques, the role of antimicrobial therapy and duration of treatment, and the role of adjunct therapy, including decongestants, glucocorticosteroids and nasal irrigation. OUTCOMES: Improved accuracy of clinical diagnosis, better utilization of imaging techniques and rational use of antimicrobial therapy. EVIDENCE: A MEDLINE search for relevant articles published from 1980 to 1996 using the MeSH terms "sinusitis," "acute sinusitis," "respiratory infections," "upper respiratory infections," "sinusitis" and "diagnosis," "sinusitis" and "therapy," "sinusitis" and "etiology," and "antimicrobial resistance" and search for additional articles from the reference lists of retrieved articles. Papers referring to chronic sinusitis, sinusitis in compromised patients and documented nonbacterial sinusitis were excluded. The evidence was evaluated by participants at the Canadian Sinusitis Symposium, field in Toronto on April 26-27, 1996. VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. Strategies were identified to deal with problems for which no adequate clinical data were available. Recommendations arrived at by consensus of the symposium participants were included. BENEFITS, HARMS AND COSTS: Increased awareness of acute sinusitis, accurate diagnosis and prompt treatment should reduce costs related to unnecessary investigations, time lost from work and complications due to inappropriate treatment. As well, physicians will be better able to decide which patients will not require antimicrobial therapy, thus saving the patient the cost and potential side effects of treatment. RECOMMENDATIONS: Clinical diagnosis can usually be made from the patient's history and findings on physical examination only. Five clinical findings comprising 3 symptoms (maxillary toothache, poor response to decongestants and a history of coloured nasal discharge) and 2 signs (purulent nasal secretion and abnormal transillumination result) are the best predictors of acute bacterial sinusitis (level I evidence). Transillumination is a useful technique in the hands of experienced personnel, but only negative findings are useful (level III evidence). Radiography is not warranted when the likelihood of acute sinusitis is high or low but is useful when the diagnosis is in doubt (level III evidence). First-line therapy should be a 10-day course of amoxicillin (trimethoprim-sulfamethoxazole should be given to patients allergic to penicillin) (level I evidence) and a decongestant (level III evidence). Patients allergic to amoxicillin and those not responding to first-line therapy should be switched to a second-line agent. As well, patients with recurrent episodes of acute sinusitis who have been assessed and found not to have anatomic anomalies may also benefit from second-line therapy (level III evidence). VALIDATION: The recommendations are based on consensus of Canadian and American experts in infectious diseases, microbiology, otolaryngology and family medicine. The guidelines were reviewed independently for the advisory committee by 2 external experts. Previous guidelines did not exist in Canada.
Acute Disease↗
Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators.
BACKGROUND: Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase. METHODS AND RESULTS: We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P = .006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P = .05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively). CONCLUSIONS: The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.
Adult↗
Selective hyperexpression of c-jun oncoprotein by glass fiber- and silica-transformed BALB/c-3T3 cells.
Mining and mineral processing are important industries in the United States. A large number of workers are potentially exposed to silica during mining and to glass fibers during manufacturing. There is a concern regarding lung cancer risk among workers exposed to silica and glass fibers. Our previous studies showed that both glass fibers and silica induced transformation of BALB/c-3T3 cells. In order to explore the relationship between silica and glass fiber-induced cell transformation and oncoprotein expression, the protein products of seven proto-oncogenes (c-K-ras, c-H-ras, c-sis, c-myc, c-myb, c-erb B1 and c-jun) and one tumor suppressor gene (p53) were examined in BALB/c-3T3 cells transformed by glass fibers or silica using immunoblotting with specific monoclonal or polyclonal antibodies. The results showed that all transformants, including eight induced by glass fibers and eight by silica (Min-U-Sil 5), were positive for c-jun protein expression; the level of c-jun protein was elevated 8-21-fold in these transformants. Other protooncogene proteins in transformed cells were either not detectable or not different from non-transformed cells. These results suggest that the overexpression of c-jun is common in BALB/c-3T3 transformed cells induced by glass fibers or silica. It seems, therefore, that the expression of c-jun may play an important role in the transformation process.
3T3 Cells↗
Analysis of the structure of chemically synthesized HIV-1 protease complexed with a hexapeptide inhibitor. Part I: Crystallographic refinement of 2 A data.
The structure of a complex between a hexapeptide-based inhibitor, MVT-101, and the chemically synthesized (Aba 67,95,167,195; Aba: L-alpha-amino-n-butyric acid) protease from the human immunodeficiency virus (HIV-1), reported previously at 2.3 A has now been refined to a crystallographic R factor of 15.4% at 2.0 A resolution. Root mean square deviations from ideality are 0.18 A for bond lengths and 2.4 degrees for the angles. The inhibitor can be fitted to the difference electron density map in two alternative orientations. Drastic differences are observed for positions and interactions at P3/S3 and P3'/S3' subsites of the two orientations due to different crystallographic environments.
Crystallography, X-Ray↗
Local cerebral metabolic effects of the novel cocaine analog, WF-31: comparisons to fluoxetine.
The effects of the acute administration of the selective serotonin uptake inhibitor, fluoxetine, on rates of local cerebral glucose utilization in rats were compared to those of the novel cocaine analog, [2beta-propanoyl-3beta-(4-isopropylphenyl)-tropane, WF-31, which has greater affinity for serotonin than dopamine transporters, using the quantitative autoradiographic 2-[14C]deoxyglucose method. Locomotor activity was assessed simultaneously. Fluoxetine administration resulted in dose-dependent decreases in locomotor behavior, as well as widespread reductions in rates of metabolic activity in brain areas including raphe nuclei, dorsal and ventral striatum, amygdala, hippocampus, limbic cortex, and thalamus. These effects were largely concentrated in brain regions containing high densities of serotonin transporters as revealed by in vitro autoradiography. In contrast, the acute administration of WF-31 produced more discrete changes in metabolic activity that were localized within the raphe nuclei and in portions of the hippocampal formation. Blockade of WF-31's dopaminergic effects by pretreatment with the antagonist, alpha-flupenthixol, resulted in a pattern of metabolic changes that closely resembled that observed with fluoxetine. These data suggest that the alterations in functional activity produced by both fluoxetine and WF-31 are largely the result of actions on serotonergic systems.
Animals↗