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Biomedical subjects

L Goodman

Publications and source records attributed to L Goodman.

At least 19 recordsLinked to original sources

No deterioration after 13 years in a stability study of a rabbit brain, plain, thromboplastin, RBT 1010, in rubber-stoppered ampoules.

RBT 1010, a rabbit brain thromboplastin, plain, was prepared at the Thrombosis Reference Centre, Withington Hospital, Manchester, in 1989. The batch has been stored at -20 degrees C, in rubber-stoppered ampoules, for 13 years. The material was unchanged after this time. This was confirmed in a stability study, in which the reagent was used to test the prothrombin times of a panel of plasmas stored in liquid nitrogen, one from a normal volunteer and two from stable anticoagulated patients. RBT 1010 was also tested in calibrations, according to World Health Organization recommendations, against the reference thromboplastin preparations CRM 149S and RBT 90.

Animals↗

Hyperconjugation not steric repulsion leads to the staggered structure of ethane.

Many molecules can rotate internally around one or more of their bonds so that during a full 360 degrees rotation, they will change between unstable and relatively stable conformations. Ethane is the textbook example of a molecule exhibiting such behaviour: as one of its two methyl (CH3) groups rotates once around the central carbon-carbon bond, the molecule will alternate three times between an unstable eclipsed conformation and the preferred staggered conformation. This structural preference is usually attributed to steric effects; that is, while ethane rotates towards an eclipsed structure, the electrons in C-H bonds on the different C atoms are drawing closer to each other and therefore experience increased repulsion, introducing a rotation barrier that destabilizes the eclipsed structure. Stabilization of the staggered structure through rotation-induced weakening of the central C-C bond and hyperconjugation has been considered to be involved, but evaluation of the contributions of these effects to ethane's internal rotation barrier and conformational preference remains difficult. Here we report a series of ethane structure optimizations, where successive removal of different interactions indicates that ethane's staggered conformation is the result of preferential stabilization through hyperconjugation. Removal of hyperconjugation interactions yields the eclipsed structure as the preferred conformation, whereas repulsive forces, either present or absent, have no influence on the preference for a staggered conformation.

Journal Article↗

Development and validation of the ITG Health-Related Quality-of-Life Short-Form measure for use in patients with coronary artery disease. Integrated Therapeutics Group.

BACKGROUND: Available coronary artery disease (CAD)-specific health-related quality-of-life (HRQL) measures are not ideally suited for routine clinical practice. We report development of a valid and reliable CAD-specific short-form measure. HYPOTHESIS: The Integrated Therapeutics Group (ITG) CAD-specific short-form HRQL measure is reliable and valid for assessing the health status of patients with CAD. METHODS: In all, 409 patients (mean age 62.4 years) completed the 24-item CAD-specific HRQL questionnaire. Factor analysis was used to identify the scaling of the 24 CAD-specific items. Analysis of variance was used to reduce the number of items within each scale, and reliability (Cronbach's alpha), discriminant validity, and ceiling and floor effects of short-form scales were evaluated. Short-form scales were compared with the longer scales using relative validity coefficients. The CAD severity was assessed using New York Heart Association criteria, physician assessment, electrocardiogram results, the number of myocardial infarctions, and the number of CAD-specific medications. Clinical validity of short-form scales was then assessed based on their ability to discriminate across severity levels of these clinical criteria. RESULTS: Four scales were identified: Extent of Chest Pain, Functioning and Well-Being, Activities Level-Physical, and Activities Level-Social. The 24-item questionnaire was reduced to a 13-item short form, with reliability exceeding 0.70 for all four scales. Relative validity estimates comparing short-form to original scales ranged from 0.68 to 2.58. Mean scores varied significantly (p < 0.05) by clinical severity, supporting the discriminant validity of the ITG CAD short-form scales. CONCLUSIONS: The ITG CAD short form (used alone or with a general HRQL measure) is valid and practical for assessing patients with CAD.

Aged↗

Etiology and pathophysiology of autistic behavior: clues from two cases with an unusual variant of neuroaxonal dystrophy.

Two unrelated individuals with autistic behavior had numerous swollen axon terminals (spheroids) located in specific brain regions relevant to their behavioral symptoms. Spheroids are characteristic of neuroaxonal dystrophy, but the clinical profile and anatomic distribution of the lesions in these two patients differed from those of previously described patients with neuroaxonal dystrophy. Spheroids were numerous in the sensory nuclei of the spinal cord and medulla, specific nuclei and the reticular formation of the brainstem tegmentum, hypothalamus, anterior and dorsomedial thalamus, hippocampus, and cingulate and orbitofrontal cortices. Spheroids were sparse in the primary and association cortices and basal ganglia and absent in the hemispheric white matter. Cerebellar atrophy was present in both cases but associated with spheroids in only one case. These cases represent a new variant of neuroaxonal dystrophy in which behavioral symptoms characteristic of autism dominated the clinical picture. Neuroaxonal dystrophy should be included in the list of diseases that may be found in persons with autism.

Adult↗

Advantages of rhythmic movements at resonance: minimal active degrees of freedom, minimal noise, and maximal predictability.

Using time delay embedding, the authors applied phase space reconstruction to the time series of rhythmic movements of a hand-held pendulum. Subjects (N = 6) produced the manual oscillations about the wrist at the pendulum's resonant frequency and at a higher and a lower frequency. The number of active degrees of freedom required to capture the dynamics of the rhythmic behavior was 3 for the resonant frequency and 4 for each of the nonresonant frequencies. The residual high-dimensional noise was similarly lowest for the resonant frequency. Whereas 33% and 20%, respectively, of the vectors in the phase spaces of the dynamics higher and lower than resonance were unpredictable, only 12% were unpredictable at resonance. Finally, the predictability of the evolving dynamics extended farther into the future for oscillations at the resonant frequency. At resonance, the prediction horizon was 5 times farther than the prediction horizon for the higher than resonance behavior and 2.5 times farther than that for the lower than resonance behavior. The results suggest that, in pendular oscillations of a limb or limb segment, attunement of the central nervous system to the resonant frequency minimizes the variables to be controlled and maximizes the predictability of the rhythmic movement's chaotic dynamics.

Forecasting↗

First glimpses

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Journal Article↗

Infectious diarrhea.

Infectious diarrhea is an extremely common illness that affects millions of Americans annually. For most patients, the illness is a self-limited one. Its major risk is dehydration. However, for some patients, diarrhea can lead to severe dehydration or be associated with bacteremia and metastatic infection. Patients with these conditions require prompt treatment. A large number of organisms have been associated with diarrhea in humans, and most laboratories routinely screen for Salmonella, Shigella, and Campylobacter. Other bacteria, parasites, and viruses account for a significant percentage of diarrhea cases and frequently go undetected. This article summarizes many of these pathogens and describes the settings in which they can be acquired. Food distribution networks have made the delivery of previously rare foods to remote areas a commonplace occurrence; this has also led to new challenges in the diagnosis and prevention of food-borne illnesses. Outbreaks of diarrhea now frequently extend across many states. The identification of a rare strain of a bacterial pathogen or changes in the isolation rate of common pathogens may be early clues to the cause of such an ongoing outbreak. Most enteric pathogens cause disease by either stimulating the secretion of fluids at the level of the small bowel or by irritating and invading the colon. Organisms that cause disease by the latter mechanism have the potential to invade the blood stream and spread to other parts of the body, including the bones and the central nervous system. Several organisms have been associated with specific postinfectious syndromes that are responsible for additional morbidity and mortality. The antibiotic resistance of bacterial pathogens has been increasing, and this has a limiting effect on the empiric treatment choices available for suspected bacterial diarrhea. Careful attention to local sensitivity patterns and appropriate testing of the patient's isolate are among the important factors that lead to successful treatment decisions.

Bacterial Infections↗

Tamoxifen and fenretinide in women with metastatic breast cancer.

BACKGROUND: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. PATIENTS AND METHODS: Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. RESULTS: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. CONCLUSIONS: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.

Adult↗

Cervical dysplasia in women with HIV.

Prevention of cervical cancer in HIV-positive women is possible through regular cervical cytological screening for early detection and a variety of effective treatment options for dysplasia. Women with HIV infection continue to have an increased rate of CIN, and cervical dysplasia appears to recur more frequently and progress more rapidly in severely immunocompromised women with high-risk type HPV infection. The Pap test is an effective screening tool, but high rates of recurrence in immunocompromised women reinforce the need for more frequent screening in HIV-positive women with a history of abnormal smears and CD4 counts less than 200. Health care providers should be aware of the latest recommendations for cervical dysplasia evaluation and should apply these in their care of HIV-infected women. Early detection, prompt treatment, and meticulous follow-up are essential in the prevention of cervical dysplasia, as well as the morbidity and mortality associated with cervical cancer in women with HIV.

Aftercare↗

The effects of roll vs. pitch rotation in humans under orthostatic stress.

BACKGROUND: It has been known since 1953 that pre-exposure to less than +1 Gz will reduce subsequent +Gz-tolerance. With few exceptions, during operational flying, the transition from hypogravity to hypergravity involves roll as well as pitch rotation. We examined the effect of roll vs. pitch rotation while undergoing transition from hypogravity to +1 Gz on a tilt table. METHODS: Twelve subjects (28-47 yr old) were rotated at 45 degrees x s(-1) from head-up (HU) at 15 degrees relative to gravitational vertical to 135 degrees head-down (HD) and back to the HU position after different HD dwell times. HD dwell times were set at 7, 15, and 30 s. The subject was rotated about the interaural axis (pitch) and about the naso-occipital axis (roll). Both the HD dwell times and axes of rotation were randomized within and across subjects. BP and heart rate were recorded during the HU-HD-HU maneuver. RESULTS: Analysis of variance, repeated measure design revealed that the rate and magnitude of BP decrease induced by the HD to HU maneuver is significantly higher (p < 0.01) in roll than in pitch during all HD dwell times. The decrease of BP at 7s is significantly (p < 0.01) higher than at 15s and 30s. Heart rate increases significantly higher (p < 0.01) in pitch than in roll at 7s-dwell time. CONCLUSION: Our results suggest that the compensatory mechanism to orthostatic stress is more efficient in response to pitch than roll rotation. This is reflected from the findings that the mean magnitude of OH (orthostatic hypotension) and the rate of BP decrease induced by the HD-HU maneuver is significantly greater in roll rotation than pitch rotation. The mean HR increase post HD-HU rotation is significantly higher in the pitch than the roll rotation. The significant rate of BP decrease during HD-HU roll rotation could have important implications for maintaining G-tolerance and spatial orientation during subsequent exposure to hypergravity.

Adaptation, Physiological↗

Obstacles to victims' cooperation with the criminal prosecution of their abusers: the role of social support.

Over the last 20 years, diminishing tolerance for domestic violence has triggered significant criminal justice reforms designed to facilitate the prosecution of abusers. Prosecutors, for example, have adopted policies requiring that cases go forward even if the victim later has second thoughts. Although increasingly common, these "no drop" policies reflect a profound irony about domestic cases that is well known but little understood: the most formidable problem in prosecuting such cases is often the victim's own unwillingness to bring the abuser to justice. This prospective study explored a range of factors potentially predictive of domestic violence victims' cooperation with the prosecution of their abusers. Although the study focused on interpersonal and institutional social support, it also investigated the influence of violence severity, victim demographic factors, and victim mental health characteristics, including the presence of depressive symptoms, emotional dependence on the abuser, and substance abuse. Findings showed that tangible support, severity of violence in the relationship, and the presence of children in common with the abuser all significantly predicted victims' cooperation with the prosecution of their abusers. Substance abuse significantly predicted victims' noncooperation with prosecution. The research and policy implications of these findings are discussed.

Adolescent↗