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PubMed1992

The new immunology.

Among the biomedical sciences, immunology stands out as a discipline in which knowledge emanating from fundamental research has rapidly been transferred to the clinical paradigm, with consequent improvement in human health. Virtually all medical subspecialties have benefitted from diagnostic reagents and technologies provided by basic immunology. In terms of numbers of lives saved, immunologic-based therapeutic strategies, most notably vaccination, rank among the most effective measures ever achieved by medical intervention. Yet, despite immunology's profound impact on medicine and the longstanding recognition of many of the general principles and cellular components involved in immunity, until relatively recently, the operational workings of the immune system eluded precise definition. The abstract nature of the immune system rendered the field intangible or, at the very least, confusing, to the nonimmunologic medical community. However, in recent years, this situation has changed radically, as cell cloning, hybridoma, and recombinant DNA technologies have provided the means to delineate the precise immunologic cellular structures and interactions. The purpose of this review is to highlight a few of the most significant advances in immunology during the past decade, and to show how they have made possible the translation of abstract concepts of classical immunology into tangible, structural information. Striking gains in the understanding of antigen recognition, one of the most fundamental aspects of immunity, are described as an illustrative case.

Antibodies, Monoclonal↗

PubMed2003

Surgical simulators.

The use of emerging virtual reality technology for surgical skill training has recently attracted a lot of attention. Computerized surgical simulators offer a significant potential for providing a realistic and configurable training environment that bridges the gap between basic training and performing the actual interventions on patients. This paper summarizes the current state of this rapidly developing field and analyses the major problems to be addressed in order to make this technology an indispensable tool for routine clinical training and education.

Journal Article↗

PubMed2004

Anti-aging medicine and research: a realm of conflict and profound societal implications.

Biogerontologists have recently launched a war of words on anti-aging medicine. They seek to discredit what they judge to be fraudulent and harmful products and therapies, and to distinguish their own research from what they regard as the pseudoscience of anti-aging injections, special mineral waters, and other services and products. Yet, many of these biogerontologists are themselves trying to develop interventions that will actually slow or arrest the fundamental processes of human aging and substantially extend average life expectancy and maximum life span. Achievement of these biogerontological goals would drastically alter the nature of individual and collective life, radically transforming virtually every social institution and norm. Biogerontologists who are engaged in anti-aging research need to undertake more active leadership in helping the public to understand their goals, to deliberately consider the implications of their fulfillment, and to begin thinking about ways to shape those ramifications in constructive fashions.

Aged↗

PubMedDate not supplied

Advanced virtual endoscopic pituitary surgery.

Endoscopy has recently been introduced to endonasal transsphenoidal pituitary surgery as a minimally invasive procedure for the removal of various kinds of pituitary tumors. To reduce morbidity and mortality with this new technique, the surgeon must be well-trained and well-prepared. Virtual endoscopy can be beneficial as a tool for training, preoperative planning, and intraoperative support. This paper introduces STEPS, a virtual endoscopy system designed to aid surgeons in getting acquainted with the endoscopic view of the anatomy, the handling of instruments, the transsphenoidal approach, and challenges associated with the procedure. STEPS also assists experienced surgeons in planning a real endoscopic intervention by getting familiar with the individual patient anatomy, identifying landmarks, planning the approach, and deciding upon the ideal target position of the actual surgical activity. The application provides interactive visualization, navigation, and perception aids and the possibility of simulating the procedure, including haptic feedback and simulation of surgical instruments.

Algorithms↗

PubMed2003

Socioeconomic gradients and low birth-weight: empirical and policy considerations.

OBJECTIVE: To examine whether socioeconomic status (SES) gradients emerge in health outcomes as early as birth and to examine the magnitude, potential sources, and explanations of any observed SES gradients. DATA SOURCES: The National Maternal and Infant Health Survey conducted in 1988. STUDY DESIGN: A multinomial logistic regression of trichotomized birth-weight categories was conducted for normal birth-weight (2,500-5,500 grams), low birth-weight (LBWT; < 2,500 grams), and heavy birth-weight (> 5,500 grams). Key variables included income, education, occupational grade, state-level income inequality, and length of participation in Women-Infants-Children (WIC) for pregnant mothers. PRINCIPAL FINDINGS: A socioeconomic gradient for low birth-weight was discovered for an adjusted household income measure, net of all covariates in the unrestricted models. A gross effect of maternal education was explained by maternal smoking behaviors, while no effect of occupational grade was observed, net of household income. There were no significant state-level income inequality effects (Gini coefficient) for any of the models. In addition, participation in WIC was discovered to substantially flatten income gradients for short-term participants and virtually eliminate an income gradient among long-term participants. CONCLUSIONS: Although a materialist explanation for early-life SES gradients seems the most plausible (vis-à-vis psychosocial and occupational explanations), more research is needed to discover potential interventions. In addition, the notion of a monotonic gradient in which income is salutary across the full range of the distribution is challenged by these data such that income may cease to be beneficial after a given threshold. Finally, the success of WIC participation in flattening SES gradients argues for either: (a) the experimental efficacy of WIC, or (b) the biasing selection characteristics of WIC participants; either conclusion suggests that interventions or characteristics of participants deserves further study as a potential remedy for socioeconomic disparities in early-life health outcomes such as LBWT.

Educational Status↗

PubMed1988

Pressure-volume relation around zero transmural pressure in excised cross-circulated dog left ventricle.

Left ventricular (LV) pressure-volume (PV) relations of quasi-isobaric contractions around zero transmural pressure were studied with a new volumetric method. Left ventricles of isolated cross-circulated dog hearts were connected to a large air tank through the mitral annulus. The volume of the air space was changed with a volume servo pump to oscillate the transmural pressure (P) around zero. Instantaneous LV volume (V) was computed from P by Boyle's law (P.V = constant) to draw the PV trajectories of the isobaric contractions. The end-systolic PV relation (ESPVR) and end-diastolic PV relation (EDPVR) curves intercepted the volume axis at two different volumes (Vo and Vu, respectively). The slopes of both ESPVR and EDPVR curves as well as Vo and Vu were variably influenced by positive and negative inotropic states, heart rate changes, arrhythmias, ischemia, and rigor. In control before any interventions, LV stroke and suction volume (delta V = Vu - Vo) at zero P was 7.5 +/- 2.5 (SD) ml/100 g left ventricle, which changed with the changes in Vo and Vu. delta V decreased with decreases in P from zero and virtually vanished at a pressure (Pn) of -9.5 +/- 2.0 mm Hg. Directly measured LV dead volume (Vd) at Pn was 4.1 +/- 1.3 ml/100 g. The results seem essential for evaluation of LV filling and suction during diastole.

Animals↗

PubMed1985

Regulation and consultation in community care facilities.

Residential community care facilities for deinstitutionalized patients are severely criticized for providing poor-quality care. Yet deinstitutionalization occurred without adequate planning or funding, and facility administrators were left on their own with virtually no regulation and no involvement with the mental health profession. Mental health professionals must focus on improving their understanding of the problems experienced by the community care industry, build alliances with facility administrators, and collaboratively design regulatory and consultative interventions that will help administrators reintegrate the mentally ill into the community. The author uses regulatory and consultative approaches implemented in California and Virginia as case examples.

California↗

PubMed1997

The potential role of topotecan in the treatment of advanced breast cancer.

Despite the rational use of hormonal, surgical, radiotherapeutic, and chemotherapeutic interventions, metastatic breast cancer represents a historically incurable disease and is currently one of the leading causes of cancer-related death in women. Survival rates in patients with metastatic breast cancer vary with location and type of metastasis, but virtually all will relapse. Standard cytotoxic therapies for the treatment of metastatic breast cancer remain unsatisfactory; thus, new active agents can be a valuable option for many patients. Topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor, currently is being assessed in the treatment of metastatic breast cancer. Preliminary results from preclinical and phase I trials suggest topotecan is active against breast cancer. Results of ongoing phase II trials thus far suggest that topotecan may be effective in stabilizing disease and prolonging time to relapse. Further studies are needed to determine whether topotecan will prove to be a valuable new option in the treatment of metastatic breast cancer.

Animals↗

PubMedDate not supplied

Screening to identify patients at risk: profiles of psychological risk factors for early intervention.

There is a serious need to provide effective early interventions that prevent the development of persistent pain and disability. Identifying patients at risk for this development is an important step. Our aim was to explore whether distinct subgroups of individuals with similar response patterns on a screening questionnaire exist. Moreover, the objective was to then relate these groups to future outcomes, for example, sick leave as an impetus for developing tailored interventions that might better prevent chronic problems. A total of 363 patients seeking primary care for acute or subacute spinal pain completed the Orebro Musculoskeletal Pain Screening Questionnaire and were then followed to determine outcome. Cluster analysis was used to identify subgroups. Validity was tested using 3 methods including the split-half technique. The subgroups were compared prospectively on outcome measures obtained 1 year later. Using pain intensity, fear-avoidance beliefs, function, and mood, we found 4 distinct profiles: Fear-Avoidant, Distressed Fear-Avoidant, Low Risk, and Low Risk-Depressed Mood. These 4 subgroups were also robust in all 3 of the validity procedures. The 4 subgroups were clearly related to outcome. Although the low risk profiles had virtually no one developing long-term sick leave, the Fear-Avoidant profile had 35% and the Distressed Fear-Avoidant profile 62% developing long-term sick leave. Our results suggest that fear-avoidance and distress are important factors in the development of pain-related disability and may serve as a key for early identification. Providing interventions specific to the factors isolated in the profiles should enhance the prevention of persistent pain and disability.

Adult↗

PubMed2004

Percutaneous management of bile duct strictures and injuries associated with laparoscopic cholecystectomy: a decade of experience.

BACKGROUND: The 1990s were associated with a dramatic increase in bile duct injuries with the widespread use of laparoscopic cholecystectomy (LC). Interventional radiology has an integral role in diagnosing and managing these injuries. Definitive percutaneous management with balloon dilatation might be possible in select patients with intact biliary-enteric continuity, but longterm data are limited. STUDY DESIGN: Data were collected prospectively on 51 consecutive patients with major bile duct stricture or injury associated with LC, treated with percutaneous management, January 1, 1990, to December 31, 1999. Percutaneous transhepatic cholangiography and biliary catheter placement were followed by balloon dilatation and stenting. Outcomes were assessed with direct patient contact or hospital records. RESULTS: All patients completed treatment, and 50 (98%) were stent free at mean followup of 76 months. The success rate of percutaneous management was 58.8%, without need for subsequent intervention. Presenting symptoms, level of injury, and number of stents or dilatations did not predict outcomes. Percutaneous treatment was more likely to fail in patients stented for less than 4 months (p < 0.001). Operative repair at Hopkins before percutaneous management was predictive of a successful outcome (p < 0.05). Including subsequent operations or percutaneous management, successful outcomes were achieved in 98% of patients. CONCLUSIONS: Major bile duct injuries after LC remain a clinical challenge. Although surgical reconstruction is the treatment cornerstone, selected patients with biliary-enteric continuity can achieve successful long-term results with definitive percutaneous management. The combination of percutaneous management and surgical reconstruction results in successful outcomes in virtually all patients.

Adult↗

PubMedDate not supplied

Effect of a computer-based intervention on social support for chronically ill rural women.

Social support is a key factor in illness management. Despite the positive effects of support groups, there are barriers to participation by rural dwellers in face-to-face groups. To address these barriers, a computer-based support group intervention, the Women to Women Project, was designed to provide peer support and health information through a computer-based intervention. Data from three groups (intervention, information, comparison) of woman who participated in the program were analyzed. The pattern of improvement in social support was in the anticipated direction, but not significant in the main analysis. Exploratory analysis was conducted on a vulnerable subsample of women reporting low social support and high psychosocial distress. Results suggest that improvement in social support, based on the intervention, was greater for the vulnerable subsample as compared with the sample as a whole. An effective and efficient means of providing social support and facilitating the mobilization of this support is through self-help groups; this study demonstrates that virtual support groups can increase perceived social support.

Adult↗

PubMed2003

Influence of glucose control, lipoproteins, and haemostasis function on brachial endothelial reactivity and carotid intima-media area, stiffness and diameter in Type 1 diabetes mellitus patients.

BACKGROUND: The objectives of this study were to determine the influence of glucose control on lipoprotein and haemostasis variables in Type 1 diabetes mellitus patients and to evaluate the global impact of these metabolic risk factors on brachial artery reactivity and carotid artery atherosclerosis, stiffness and diameter. DESIGN: Follow up of Type 1 diabetes patients randomized to insulin-intensive conventional treatment (ICT, n = 29) or insulin-standard treatment (ST, n = 25) in the Stockholm Diabetes Intervention Study (SDIS) more than 14 years ago. RESULTS: The intensive conventional treatment patients had lower glycosylated haemoglobin (HbA1c) compared with the ST patients, i.e. 7.01 (SD 0.51) vs. 8.31 (0.97), while concentrations of the lipoprotein and haemostasis variables analyzed were virtually similar. The carotid artery intima-media area was associated with high HbA1c, high serum (S)-cholesterol levels, and low high-density lipoprotein (HDL)-cholesterol levels. Carotid artery stiffness was associated with high systolic blood pressure, high HbA1c, high fibrinogen, and high HDL-cholesterol. Brachial artery endothelial reactivity was higher for women and those with low S-cholesterol. CONCLUSION: In patients with Type 1 diabetes, glucose control appeared to have no effect on either lipoproteins or haemostasis variable concentrations. Poor glucose control, and high levels of S-cholesterol, systolic blood pressure and plasma fibrinogen were associated with development of atherosclerosis, thus emphasising the importance of global risk factor control in patients with Type 1 diabetes mellitus.

Adult↗

PubMed2002

Midbrain syndrome with eye movement disorder: dramatic improvement after cranioplasty.

BACKGROUND: Patients with skull defects sometimes develop neurological deficits, which have been grouped under "the syndrome of the trephined". The deficits are usually nonspecific or nonlocalizing, such as apathy or diffuse headaches. We report, to our knowledge, a first case of severe midbrain syndrome associated with a skull defect. Cranioplasty dramatically resolved the patient's symptoms. A midbrain syndrome represents the main manifestation of the syndrome of the trephined and can be corrected by cranioplasty. CLINICAL PRESENTATION: A 38-year-old man with head trauma and epidural hematoma initially had normal eye motility. He developed a skull defect after infection following cranioplasty. He presented with onset of neurological symptoms one year after head trauma with a skull defect, a small divergent and vertical strabismus, elevation deficit of both eyes, headaches and fatigue. Over several months he developed severe bilateral deficit of adduction, elevation, depression and convergence. He had neuropsychological deficits, fatigue, headaches and impaired coordination. Neuroimaging and lumbar puncture did not show evidence of increased intracranial pressure or hydrocephalus. INTERVENTION: Cranioplasty using Palacos was performed one-and-a-half years after trauma. Immediately after surgery, the patient noted remarkable improvement in his symptoms. Headaches and fatigue disappeared within two days. Two weeks after cranioplasty the patient had orthotropia and virtually normal ocular motility. Neurological symptoms completely disappeared. Recovery remained sustained for over 5 years after cranioplasty. CONCLUSION: To our knowledge, this represents the first case of the syndrome of the trephined in which the neurological deficits map primarily to the brainstem and show rapid improvement following cranioplasty. We show that cranioplasty in patients with large skull defects is indicated for more then cosmetic reasons and should be considered even after longer periods following a trauma.

Adult↗

PubMedDate not supplied

Reduction of physiological, behavioral, and self-report responses in type A behavior: a preliminary report.

Recent reports indicate that Type A Behavior may be reducible by behavioral and other psychotherapeutic methods. To date, however, there has been virtually no demonstration of reduction of the actual, observed behavior. Furthermore, the physiologic hyperresponsiveness that seems to characterize many Type A individuals when under stress, has received relatively little therapeutic attention. This preliminary, uncontrolled report describes a cognitive-behavioral group intervention program, before and after which patients underwent assessment on physiologic, behavioral, and self-report assessments. These included heart rate and blood pressure responsiveness under stressful conditions, trained observer ratings of Type A Behavior, and a variety of subjective measures of Type A Behavior and psychological distress and symptoms. Results showed limited improvement on most behavioral and self-report indices. Relatively greater reduction of Type A Behavior was associated with higher pre-treatment levels of Type A Behavior, with the absence of coronary artery disease and with male gender.

Adult↗

PubMed1990

Behavioral risks for human immunodeficiency virus infection in adolescent medical patients.

This paper is an examination of the extent to which adolescents in primary care indicated behavioral risk for human immunodeficiency virus infection, and the degree to which their clinic records reflected either awareness of such conditions or interventions for them. Levels of risk were assigned to the youths based on known risk factors in adult populations and arbitrarily selected natural breaks in the frequency of sexual behaviors. Of the sample, 3% were at high risk for human immunodeficiency virus infection because the adolescents engaged in prostitution, injectable drug use, male homosexual behavior, or had a sexually transmitted disease associated with genital ulcers or sores; 16% were at moderate risk because the youths had more than six sexual partners in the year preceding the interview or had nonulcerative forms of sexually transmitted disease; and the remainder were at low risk. Fewer than half of the youths at risk for human immunodeficiency virus infection sought or received help for any of their problem behaviors, while virtually all sought and received help for sexually transmitted diseases. Because a high proportion of the youths engaging in risky behaviors had sexually transmitted diseases, the most promising approach for prevention of human immunodeficiency disease infection is through health clinics that treat sexually transmitted diseases. These clinics could screen the youths for associated behavioral risk factors, and then offer preventive or interventive services.

Adolescent↗

PubMed1996

Vitamin D receptor gene variants: implications for therapy.

Osteoporosis is a major health problem in virtually all societies where its incidence and impact have been studied in terms of cost, morbidity, mortality and quality of life. The major determinant of fracture risk is bone density and, presumably, bone strength. A large number of lifestyle influences and medical interventions modify bone density, but the variation and slowness of change in response to any intervention necessitates long-term follow up. The definition of genetic factors in the determination of bone mass, and possibly in the changes in bone density, over time offer important insights into the mechanisms of response to treatment. Most importantly, if genetic factors can determine response to therapy, the understanding of such factors could influence selection of optimum therapy.

Alleles↗

PubMed1992

Rapid complementation assay for anti-HIV-1 drug screening and analysis of envelope protein function.

A complementation assay is described that can be used with relative safety to quantitate rapidly inhibitory effects of potential anti-HIV-1 drugs on virtually any stage of the HIV-1 life cycle by measurements of chloramphenicol acetyltransferase (CAT) activity. Of particular interest is that this system is also capable of detecting inhibition of the viral trans-activator Rev, an important potential target for drug intervention. Other applications of the system may include studies to identify domains of the envelope glycoprotein that determine infectivity and tropism or that define epitopes recognized by neutralization antibodies.

Antiviral Agents↗

PubMed1998

Registration of real and CT-derived virtual bronchoscopic images to assist transbronchial biopsy.

This paper describes research work motivated by an innovative medical application: computer-assisted transbronchial biopsy. This project involves the registration, with no external localization device, of a preoperative three-dimensional (3-D) computed tomography (CT) scan of the thoracic cavity (showing a tumor that requires a needle biopsy), and an intraoperative endoscopic two-dimensional (2-D) image sequence, in order to provide assistance in transbronchial puncture of the tumor. Because of the specific difficulties resulting from the data being processed, a multilevel strategy was introduced. For each analysis level, the relevant information to process and the corresponding algorithms were defined. This multilevel strategy, thus, provides the best possible accuracy. Original image processing methods were elaborated, dealing with segmentation, registration and 3-D reconstruction of the bronchoscopic images. In particular, these methods involve adapted mathematical morphology tools, a "daemon-based" registration algorithm, and a model-based shape-from-shading algorithm. This pilot study presents the application of these algorithms to recorded bronchoscopic video sequences for five patients. The preliminary results presented here demonstrate that it is possible to precisely localize the endoscopic camera within the CT data coordinate system. The computer can thus synthesize in near real-time the CT-derived virtual view that corresponds to the actual endoscopic view.

Biopsy, Needle↗