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Biomedical subjects

A Keller

Publications and source records attributed to A Keller.

At least 19 recordsLinked to original sources

Variations in resource utilization among medical specialties and systems of care. Results from the medical outcomes study.

OBJECTIVE: To examine whether specialty and system of care exert independent effects on resource utilization. STUDY DESIGN: Cross-sectional analysis of just over 20,000 patients (greater than or equal to 18 years of age) who visited providers' offices during 9-day periods in 1986. Patient- and physician-provided information was obtained by self-administered questionnaires. SETTING: Offices of 349 physicians practicing family medicine, internal medicine, endocrinology, and cardiology within health maintenance organizations, large multispecialty groups, and solo practices or small single-specialty group practices in three major US cities. OUTCOME MEASURES: Indicators of the intensity of resource utilization were examined among four medical specialties (family practice, general internal medicine, cardiology, and endocrinology) and five systems of care (health maintenance organization, multispecialty group-fee-for-service, multispecialty group-prepaid; solo practice and single-specialty group-fee-for-service, and solo practice and single-specialty group-prepaid) before and after controlling for the mix of patients seen in these offices. The indicators of resource utilization were hospitalizations, annual office visits, prescription drugs, and common tests and procedures, with rates estimated on both a per-visit and per-year basis. RESULTS: Variation in patient mix was a major determinant of the large variations in resource use. However, increased utilization was also independently related to specialty (cardiology and endocrinology), fee-for-service payment plan, and solo and single-specialty group practice arrangements. After adjusting for patient mix, solo practice/single-specialty groups-fee-for-service had 41% more hospitalizations than health maintenance organizations. General internists had utilization rates somewhat greater than family physicians on some indicators. CONCLUSION: Although variations in patient mix should be a major determinant of variations in resource use, the independent effects of specialty training, payment system, and practice organization on utilization rates need further explication. The 2- and 4-year outcomes now being analyzed will provide information critical to interpretation of the variations reported herein.

Adult

Cancer: improving early detection and prevention. A community practice randomised trial.

OBJECTIVE: To test the impact of physician education and facilitator assisted office system interventions on cancer early detection and preventive services. DESIGN: A randomised trial of two interventions alone and in combination. SETTING AND SUBJECTS: Physicians in 98 ambulatory care practices in the United States. INTERVENTIONS: The education intervention consisted of a day long physician meeting directed at improving knowledge, attitudes, and skills relevant to cancer prevention and early detection. The office system intervention consisted of assistance from a project facilitator in establishing routines for providing needed services. These routines included division of responsibilities for providing services among physicians and their staff and the use of medical record flow sheets. MAIN OUTCOME MEASURES: The proportions of patients provided the cancer prevention and early detection services indicated annually according to the US National Cancer Institute. RESULTS: Based on cross sectional patient surveys, the office system intervention was associated with an increase in mammography, the recommendation to do breast self examination, clinical breast examination, faecal occult blood testing, advice to quit smoking, and the recommendation to decrease dietary fat. Education was associated only with an increase in mammography. Record review for a patient cohort confirmed cross sectional survey findings regarding the office system for mammography and faecal occult blood testing. CONCLUSION: Community practices assisted by a facilitator in the development and implementation of an office system can substantially improve provision of cancer early detection and preventive services.

Adult

The short-term effect of patient health status assessment in a health maintenance organization.

This study was designed to test the short-term effects of health assessment on the process of care and patient satisfaction. The 29 Chart physicians used the Dartmouth COOP Charts to measure their adult patients' health status during a single clinical encounter; the 27 control clinicians used no measure of health status. We compared the change between baseline and post-intervention information for a sample of all study clinicians' patients. Most of the patients were female (67%), well educated (70% had at least a college education) and young (approximately 90% were aged 59 years or younger). We found that the ordering of tests and procedures for women was increased by exposure to the COOP Charts (52% vs. 35%; p < 0.01); the effect in men was not as significant (37% vs. 23%: p = 0.06). Although women reported no change in satisfaction with care, men claimed that the clinician helped in the management of pain (p = 0.02). We conclude that the use of health status measures during a single clinical encounter in an HMO changes clinician test ordering behaviour and may improve the help male patients receive for pain conditions. The long-term impact of these management changes is not known.

Episode of Care

Activation of the gene encoding the glycolytic enzyme beta-enolase during early myogenesis precedes an increased expression during fetal muscle development.

We define the spatial and temporal patterns of expression of the gene encoding the glycolytic enzyme, beta-enolase, during mouse ontogenesis. Transcripts were detected by in situ hybridization using 35S labelled cRNA probes. The beta-enolase gene is expressed only in striated muscles. It is first detected in the embryo, in the cardiac tube and in newly formed myotomes. In the muscle masses of the limb, beta gene expression occurs at a low level in primary fibers, and subsequently greatly increases at a time which corresponds to the onset of innervation and secondary fiber formation. Later in development, it becomes undetectable in slow-twitch fibers. Our results demonstrate the multistep regulation of the beta-enolase gene. The regulation of this muscle-specific gene in somites is discussed in terms of the myogenic sequences of the MyoD family shown to be present when it is activated.

Animals

[Risk of osteoporosis in long-term heparin therapy of thromboembolic diseases in pregnancy: attempted prevention with ossein-hydroxyapatite].

Generalized idiopathic osteoporosis and transient osteoporosis of the hip are both rare complications of pregnancy. More frequently, long-term heparin administration to treat deep thrombosis in the legs or pelvis may lead to substantial decreases in bone mass and consequently increased risk of osteoporosis. Therapeutic studies with the aim to counteract the osteoporosis inducing effect of heparins, have not been published to date. In the special situation of pregnancy, most medications used for osteoporosis are contraindicated. In our open randomised study, 9 women on heparin-treatment received daily 6.46 g of the bone preparation OHC (ossein-hydroxyapatite-compound) over a period of 6 months and were compared to 11 women without bone protective treatment. In the OHC-group, good compliance was observed with no side effects and reduced back pain. Bone mass did not change significantly, whilst it dropped significantly statistically in the controls.

Adult

Benefits and obstacles of health status assessment in ambulatory settings. The clinician's point of view. The Dartmouth Primary Care COOP Project.

In the past decade physicians have identified the need to expand patient assessment to include global function and quality of life. During the same period, the busy clinic has evolved into the location where this assessment seems most appropriate. Integrating functional health assessment into a busy clinical practice is difficult because the necessary steps require time, thought, recording, and follow-up. Attention to the office ecosystem is very important before any patient care management method is introduced. The clinician must transform the results of health status screening into a specific functional diagnosis. The clinician has to understand the sensitivity, specificity, and predictive value of the measure for a preliminary diagnosis to be made. Often, additional measurements must be taken to establish a specific diagnosis. These steps encompass assessment linkage. Once the specific cause for the dysfunction is recognized, the clinician then has to determine the need for special resources. This is called the resource linkage. By following the steps outlined in this paper, the clinician should be able to overcome many obstacles for functional health status assessment in busy ambulatory settings.

Activities of Daily Living

Modulation of embryonic and muscle-specific enolase gene products in the developing mouse hindlimb.

During striated muscle development, the glycolytic enzyme enolase (EC 4.2.1.11) undergoes an isozymic transition, from the embryonic alpha alpha form towards the muscle-specific forms alpha beta and beta beta. The regulation of this transition was analyzed in mouse hindlimb muscles from embryonic day 15 (E15) to the adult stage. The quantitative modulations of the levels of the transcripts and subunits of alpha and beta enolase genes were determined. The absolute amounts of alpha and beta enolase mRNAs were estimated using in vitro synthesized transcripts as calibration standards, thus allowing an evaluation of their relative contribution at each stage examined. The muscle-specific beta enolase mRNA is already present at E15. Its level then increases and, from E17, this transcript becomes predominant. This accumulation is biphasic: a steep prenatal rise, corresponding to a net increase per fiber, accompanies the formation of secondary myofibers and the development of innervation; a second rise, beginning at postnatal day 5, is temporally correlated with the definitive specialization of the myofibers. Most of the decrease in alpha mRNA level occurs postnatally. No temporal or quantitative correlation between the up-regulation of beta mRNA and the down-regulation of alpha mRNA levels is observed throughout hindlimb muscle development. Quantitative immunoblotting analyses carried out in parallel show that the enolase isozymic transition is mainly controlled at the mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Evaluation of a commercially available complement fixation test for diagnosis of Helicobacter pylori infection and for follow-up after antimicrobial therapy.

Commercially available complement fixation test reagents (Institute Virion Ltd., Rüschlikon, Zurich, Switzerland) available in package format were evaluated for the serodiagnosis of Helicobacter pylori infection. The assay was compared with bacterial culture and histological Giemsa stain of gastric biopsy specimens obtained from 930 patients of different ages and from different ethnic groups, with a variety of upper gastrointestinal tract symptoms. The prevalence, sensitivity, specificity, and positive and negative predictive values, respectively, were 35, 71, 90, 80, and 85% for Belgian patients aged 40 years or younger, 50, 81, 93, 92, and 83% for Belgian patients older than 40 years, and 83, 83, 79, 95, and 48% for Mediterranean patients. Using 645 serum specimens from 226 patients, we also evaluated the complement fixation test for its ability to monitor the eradication of H. pylori following antimicrobial therapy. Overall, H. pylori was eradicated from 122 patients while 104 patients remained infected with the organism. A significant decrease in antibody levels was observed 3 to 6 months after the end of therapy in the group of patients from whom H. pylori was eradicated.

Adolescent

The Bel-1 protein of human foamy virus activates human immunodeficiency virus type 1 gene expression via a novel DNA target site.

The Bel-1 protein of human foamy virus can activate transcription directed by the long terminal repeat (LTR) promoter of human immunodeficiency virus type 1 (HIV-1). The target sequence for Bel-1 is shown to lie within the HIV-1 LTR U3 region but does not coincide with any previously described factor-binding site. Gene expression directed by an HIV-1 LTR lacking functional sites for the inducible cellular transcription factor NF-kappa B was activated over 100-fold by coexpression of Bel-1. These observations suggest that Bel-1 has the potential to significantly enhance the level of HIV-1 gene expression in cells dually infected with HIV-1 and human foamy virus.

Base Sequence

Synaptic proliferation in the motor cortex of adult cats after long-term thalamic stimulation.

1. One of the hypotheses for information storage in the CNS postulates the induction of structural changes in synaptic circuits. This postulate predicts that behavioral experiences produce changes in neural activity that subsequently induce synaptogenesis in the mature CNS. Available data indicate that the establishment of engrams for novel motor acts may involve alterations of synaptic interactions within the primary motor cortex. The present study examines the hypothesis that patterns of synaptic circuitry and of synaptic activation are rearranged after enhanced neural activity in pathways projecting to the motor cortex. 2. Electrodes implanted in the ventroposterolateral (VPL) nucleus of the thalamus were used for long-term stimulation (20 microA, 4 days) of afferents to the motor cortex in freely behaving, adult cats. This stimulation primarily affected corticocortical inputs from the somatosensory cortex (area 2) to area 4 gamma of the motor cortex. Electron microscopy and stereological procedures were used to compare the numerical density (Nv) of various types of synapses in layers II/III of the stimulated (experimental) motor cortex with the Nv of the corresponding synapses in the contralateral (control) hemisphere. 3. Long-term stimulation produced a significant increase (25.6%) in synaptic Nv in experimental motor cortex. This increase was due primarily to an increase in the Nv of asymmetrical synapses with dendritic spines. The numbers of symmetrical synapses, and of asymmetrical synapses with dendritic shafts, were not affected by long-term stimulation. 4. Synaptic active zones [calculated by measuring the lengths of postsynaptic densities (PSDs)] were significantly longer in experimental motor cortex. Lengthening of PSDs occurred selectively in asymmetrical synapses with dendritic shafts (28% increase). 5. The Nv of synapses having perforations in their PSDs (perforated synapses) was significantly higher in experimental hemispheres. Also increased was the incidence of synapse-associated polyribosomes, which are most commonly found at the base of dendritic spines. An increase in the number of perforated synapses and of polyribosomes are both morphological hallmarks of synaptogenesis. 6. The percentages of synapses having different curvatures (i.e., presynaptically concave, convex, or flat) were similar in experimental and in control motor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

[False rubella diagnosis in pregnancy by IgM enzyme immunoassay].

On the basis of a case report of a false-positive rubella diagnosis in early pregnancy the interpretation of positive IgM is discussed. A primigravida at 14 weeks of gestation showed rubella-specific IgM in an enzyme immunoassay. This result could not be confirmed by an alternative method (hemagglutination-inhibiting test after separating the serum by density gradients into different immunoglobulin classes and removal of the IgG with protein A). The immunological status corresponded with a past rubella infection or with the status after vaccination (IgG-positive). It is therefore recommended to use an additional method in the presence of IgM, especially if an interruption of the pregnancy has to be considered. In the course of the examination a recent cytomegalovirus infection could be detected.

Adult

The C-terminal domain of the pulmonary surfactant protein C precursor contains signals for intracellular targeting.

We have studied the intracellular transport of the pulmonary surfactant SP-C precursor in vitro and in vivo. In order to monitor the route of the SP-C precursor, we constructed various C-terminally truncated forms of SP-C, which were tagged with a sequence derived from the C-terminus of the human c-myc gene (aa 409-419). Expression of these constructs under the control of the SV40 enhancer and the huMT-II promoter in stably transformed Chinese hamster ovary (CHO) cells revealed that the complete precursor molecule is localized mostly in vesicular structures, probably of lysosomal origin. The truncated precursor lacking the last 22 amino acids at the C-terminus (SP-C/Ctag), however, was restricted to the endoplasmic reticulum as shown by immunofluorescence, using antibodies directed against the tag-sequence, the lysosomal enzyme cathepsin D, the enzyme disulfide isomerase, and the Golgi zone. The intracellular localization was substantiated by subcellular fractionation analysis, suggesting that the last 22 amino acids are necessary for intracellular targeting. Furthermore, Triton X-114 extractions from CHO cells revealed a modification of the SP-C precursor. In vitro translation and pulse-chase experiments in the absence or presence of microsomes showed that the modification occurs post-translationally and in a time-dependent manner. Membrane association studies using an SP-C precursor lacking the mature peptide indicated that the modification is of hydrophobic nature but not a thioester-linked fatty acid.

Amino Acid Sequence

Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia.

PURPOSE: This multicenter, double-blind, randomized trial was performed to determine the efficacy and safety of pamidronate disodium (APD) in comparison to etidronate disodium (EHDP) in the treatment of cancer-related hypercalcemia. PATIENTS AND METHODS: Sixty-five male and female adult patients with cancer and corrected calcium levels of greater than or equal to 12.0 mg/dL after 24 hours of hydration were randomized to receive either 60 mg APD given as a single 24-hour infusion or 7.5 mg/kg EHDP given as a 2-hour infusion daily for 3 days. RESULTS: APD normalized corrected calcium levels in 70% (21 of 30) of patients, whereas EHDP did so in 41% (14 of 34) of patients (P = .026). The mean corrected serum calcium level decreased from 14.6 to 10.5 mg/dL in the APD-treated group and from 13.8 to 11.6 mg/dL in the EHDP-treated group within the first week of treatment. There was no difference in response to APD in patients without versus those with bone metastases (78% v 67%). Both drugs were well tolerated. CONCLUSION: This study demonstrated that a single 60-mg infusion of APD is safe and more effective than EHDP given at the dose of 7.5 mg/kg for 3 days in the treatment of cancer-related hypercalcemia.

Adult

Tools, teamwork, and tenacity: an office system for cancer prevention.

BACKGROUND: Despite national priorities in cancer control, the number of people with established ongoing medical care who do not receive indicated preventive services is substantial. Proven strategies to optimize preventive care in community practice are limited. METHODS: In the Cancer Prevention in Community Practice Project (CPCP), 50 primary care providers were randomly assigned to receive an "office system" intervention. The intervention led to reorganization of office operations based on four functional core components: identifying patients' needs for services; monitoring their status over time; providing positive reinforcement to patients; and establishing an internal feedback component consisting of a brief audit to assess how the system is operating. Implementation of the CPCP system in each practice was accomplished using trained facilitators, and involved incorporating one or more tools developed to meet the functional components of the practice. RESULTS: One hundred percent of the practices were successful in implementing some changes in their office operations that met CPCP office system functional criteria. All study practices implemented customized flow sheets, while use of other office system tools were incorporated at between 32% to 75% of study sites. Identifying patients in need of preventive services was performed most often by the clinical staff (39%), whereas monitoring patients' receipt of preventive services over time and reinforcing positive patient behavior were performed most often by physicians (63% and 46%, respectively). Changes made in practices were maintained for at least 12 months. CONCLUSIONS: Primary care practices in community settings can implement significant and lasting changes in their practice environment that will improve their performance of preventive activities. The functional components of the CPCP office system design proposed and tested here are applicable to a wide variety of practice settings.

Adult

[Conventional roentgen functional diagnosis--videodensitometry. 1. Densitometric and topometric measurements of roentgen video images: technique and method of measuring].

It is possible to measure movements in the human body with the help of X-ray television systems. A great number of different techniques has been published in the scientific literature. They all based on only two principles with qualitative differences in signal acquisition. The densitometric and topometric measurements are assessed and compared. Neither the densitometric nor the topometric principle seems to be superior. To support the experimental work the videoanalyser VIANA MP was developed on the Ilmenau Institute of Technology.

Computer Systems

[Conventional roentgen functional diagnosis--videodensitometry. 2. Clinical imaging site for noninvasive diagnosis of organ motion].

By means of the described system it is possible to measure and as well analog as digital process the organ movement, needing a X-ray television system for flouroscopy and a videotape for continuously recording. Using the densitometric principle measurements of time and a quantitative form analysis of the curves are performed. After border recognition and using the topometric principle, the local organ motion can be evaluated. The levels of signal and noise in the measured curves are computed by a fourier transformation. In the field of functional cardiology the video signal is recorded and processed synchronously with the electrocardiogram.

Computer Systems

Microvasculopathy in the ocular fundus after bone marrow transplantation.

OBJECTIVE: To determine the incidence and time course of retinal and optic-disk ischemia after bone marrow transplantation and to describe the clinical, fluorescein-angiographic, and histologic findings in patients with these ischemic fundus lesions. DESIGN: Prospective cohort study; standardized clinical and ophthalmologic evaluation of all patients before bone marrow transplantation and 3, 6, and 12 months after transplantation (and when indicated). SETTING: University hospitals in Basel, Switzerland. PATIENTS: Consecutive patients (127) treated with allogeneic or autologous bone marrow grafts. MAIN RESULTS: Thirteen of the 127 patients (10%; 95% Cl, 5% to 15%) had lesions of the ocular microcirculation. All patients had cotton-wool spots in the fundus of both eyes, and three patients also had bilateral optic-disk edema. Secondary changes included retinal hemorrhages and lipid deposits. The ischemic fundus lesions appeared during the first 6 months after transplantation and were reversible in 9 of the 13 patients. The lesions occurred only in patients who were treated with total body irradiation and were given cyclosporin A as prophylaxis for graft-versus-host disease. CONCLUSIONS: Ischemic fundus lesions are a frequent complication after bone marrow transplantation. They were only observed in patients treated with total body irradiation and cyclosporin A. This combination of therapy appears to have an additive effect on the development of ocular and possibly generalized microvascular lesions.

Adolescent

Prediction of hepatitis C virus infectivity in seropositive Australian blood donors by supplemental immunoassays and detection of viral RNA.

The prevalence of anti-hepatitis C virus (HCV) enzyme immunoassay (EIA)-positive in 167,511 Australian volunteer blood donors from Adelaide, Melbourne, Perth, and Sydney was 0.78%. One thousand two-hundred and eighteen EIA-positive serum samples were assessed by supplemental tests including a blocking EIA and two peptide EIAs corresponding to major epitopes of the HCV C-100-3 antigen. Seven hundred and eighteen samples (59%) were negative by supplemental testing; no evidence of reactivity with other HCV gene products or HCV RNA detected by cDNA polymerase chain reaction was found in selected samples from this group. In contrast, of 43 samples randomly selected from 400 samples (32.8%) positive by supplemental testing, 88% were reactive with HCV 33-C or core antigens and 52% contained HCV RNA, suggesting contact with HCV and infectivity of most donors in this group. Most samples equivocal by supplemental testing reacted only with C-100 and not with other HCV antigens when tested by dot immunoblot assay. Only 21% had detectable HCV RNA. The battery of assays used in this study indicated that approximately 32% of HCV EIA repeatably reactive serum samples were serologically related to HCV, corresponding to a 0.25% prevalence of potentially infectious donors.

Adult