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Biomedical subjects

W J Williams

Publications and source records attributed to W J Williams.

At least 19 recordsLinked to original sources

Vitamin B12 deficiency: underdiagnosed, overtreated?

Neurologic damage may become permanent when the disorder is mistaken for multiple sclerosis or diabetic neuropathy--hence the need for prompt parenteral B12 in patients with pernicious anemia. The need for B12 injections is questionable for patients with achlorhydria and for those with a marginal or low serum B12 level but no signs or symptoms of deficiency.

Achlorhydria

Changes in sympathoadrenal response to standing in humans after spaceflight.

Plasma catecholamine levels and cardiovascular responses to standing were determined in astronauts before and after several Space Shuttle missions. Blood pressure, heart rate, and cardiac output were measured and blood samples for catecholamine analyses were drawn at the end of the supine and standing periods. Supine plasma norepinephrine and epinephrine concentrations increased 34 and 65%, respectively, on landing day compared with before flight. Standing on landing day resulted in a 65 and 91% increase in plasma norepinephrine and epinephrine, respectively. Supine and standing norepinephrine levels remained elevated 3 days after landing while epinephrine levels returned to preflight levels. On landing day, supine heart rate and systolic blood pressure increased 18 and 8.9%, respectively, and standing heart rate and diastolic blood pressure were elevated by 38 and 19%, respectively. On standing, stroke volume was decreased by 26% on landing day compared with before flight. Collectively, these data indicate that the decreased orthostatic function after spaceflight results largely from the decreased stroke volume. Possible mechanisms contributing to this condition are discussed.

Adrenal Glands

Isolation and purification of a vascular hyperreactivity factor from rabbit kidney cortex.

A compound capable of amplifying the threshold pressor response to norepinephrine (NE) was obtained from rabbit kidney cortex. This compound was purified and characterized using a series of techniques including gel filtration, ion exchange chromatography, preparative electrofocusing, HPLC, FAB mass spectrometry (FAB-MS), and Fourier transform infrared spectrometry. From this, an acid/heat stable (6N HC1, 160 degrees C, 24 hours), low molecular weight (ca 147) compound with a strong (+) charge density (Pi greater than 10) was identified. When injected into assay rats (i.v.), this compound amplified the pressor response to fixed doses of NE. Taken together, this compound exhibits nearly identical characteristics (i.e. acid/heat stability, structure, charge and biologic activity to the naturally occurring polyamine spermidine (SPD-145.6 daltons). Moreover, bolus injections of SPD (10 micrograms, i.v.) amplified the pressor response to NE over a range of doses from 5-25 ng.

Animals

CD4 lymphocyte decline and survival in human immunodeficiency virus infection. The Military Medical Consortium for Applied Retroviral Research.

The loss of the CD4 lymphocyte is the central pathophysiologic event in the progression of human immunodeficiency virus (HIV) infection. This retrospective study, based on review of data from deceased HIV patients followed in a single HIV clinic, was conducted to determine if the rate of CD4 lymphocyte decline was predictive of survival. Forty of 172 patients met defined criteria for inclusion in this study. For each patient, CD4-cell counts showed approximate exponential decline over time. A Cox regression analysis was used to assess the association of CD4 cell decline (half-life), race, age, gender, initial CD4-cell count, and treatment (anti-Pneumocystis carinii pneumonia prophylaxis and/or zidovudine vs. no therapy) on total survival (from initial CD4 cell count) and on remaining survival time after reaching a CD4 cell count of 100 (estimated). For all patients, the rate of CD4 cell decline was predictive of total survival (p = .009) but not for survival after reaching a count of 100 (p = .6). For patients who had never received therapy (6 patients), however, the CD4 half-life remained associated with survival time from 100 CD4 cells (p < .05) as opposed to the treated patients. Therapy was the single variable most predictive of both survival endpoints, resulting in an increase in median total survival of 27.2 mo (p < .00001) and of 15.4 mo from a CD4 cell count of 100 (p < .00004). Nonwhites had a slight survival disadvantage compared to whites (p = .08 overall; p = .02 from CD4 cell count of 100).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

An information flow technique for category related evoked potentials.

We report a technique for studying interactions among many subsystems of a biological system. A general mathematical technique is developed for information flow among various subsystems of a system when two or more classes of stimuli are presented to the system. The technique is validated by various simulation studies and then applied to a brain system. The usefulness of the technique is demonstrated for visual event related potentials (ERP's) obtained from human subjects suffering from phobias. The stimuli are briefly flashed words and phrases. The word classes are pleasant, unpleasant, conscious, and unconscious. The conscious class consists of words known by the patient to relate to the problem, whereas the unconscious class of words consists of words related to deep conflicts which are not recognized by the patient. It is demonstrated that information flow is suppressed under supraliminal presentation of the unconscious class, but is strong under subliminal presentation. The technique has the potential of being an objective indicator of conflictual relationships in these patients. The principle of the technique can be applied to any system in which interactions among subsystems are to be analyzed.

Awareness

Time-frequency representation of electrocorticograms in temporal lobe epilepsy.

Three time-frequency distributions are evaluated in terms of their efficacy in representing nonstationary electrocorticograms (ECoG's) in human temporal lobe epilepsy. The results of a new method, the exponential distribution, are compared with those of the spectrogram and the Wigner distribution. It is shown that the exponential distribution represents a considerable improvement over the spectrogram in terms of resolution and markedly reduces cross-terms present in the Wigner distribution. Exponential distribution representations of ECoG's from different stages of an epileptic record are developed as contour maps. These high-resolution representations offer a lucid display of temporal-spectral features of the rapidly varying signals that constitute ECoG's recorded in temporal lobe epilepsy.

Adult

Time frequency distributions of TMJ sounds.

For analysis of time-varying signals such as the TMJ sounds, it is often desirable to know how the frequency components change with time, using methods of time-frequency analysis. The aim of this study was to compare two of the most familiar methods for energy density representation with a newly developed technique. The sounds were recorded with a microphone fastened to the subject's forehead, transformed to the time-frequency domain and displayed as 3D- and contour plots using spectrogram, Wigner distribution (WD), and the reduced interference distribution (RID) to display their time-frequency energy distributions. The spectrogram resolved only the low-frequency components. The WD provided higher resolution but also exhibited strong interference between components. The RID gave a detailed representation of the TMJ signals' relative energy distribution in the time and frequency domains, with a great reduction in the interference or cross terms. The RID therefore appears to be most useful in the application of time-frequency distributions in classification of TMJ sounds.

Analog-Digital Conversion

Kveim-Siltzbach test revisited.

The Kveim-Siltzbach (KS) skin test has been in use worldwide for fifty years. It is a safe, simple and specific out-patient technique to confirm the diagnosis of sarcoidosis and to provide evidence of activity of the disease. It is most helpful in delineating sarcoidosis as a cause of erythema nodosum, uveitis, liver granulomas, hypercalciuria and meningitis. It is the patient's preference when he is confronted with the choice between a skin test or alternatively bronchoscopy, lung biopsy or aspiration liver biopsy. It also creates considerable academic interest for it reflects granuloma formation vividly when viewed by modern immunopathology techniques. Its disadvantage is that it takes a month to provide a result; a critical month in which systemic steroids are avoided for this would suppress the test. The immunopathology of the KS test is similar to spontaneous sarcoid granuloma formation, and evolution of the KS granuloma may provide clues to the cause of sarcoidosis and other granulomatous disorders.

Humans

Caplan's syndrome.

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Caplan Syndrome

Phase space topography and the Lyapunov exponent of electrocorticograms in partial seizures.

Electrocorticograms (ECoG's) from 16 of 68 chronically implanted subdural electrodes, placed over the right temporal cortex in a patient with a right medial temporal focus, were analyzed using methods from nonlinear dynamics. A time series provides information about a large number of pertinent variables, which may be used to explore and characterize the system's dynamics. These variables and their evolution in time produce the phase portrait of the system. The phase spaces for each of 16 electrodes were constructed and from these the largest average Lyapunov exponents (L's), measures of chaoticity of the system (the larger the L, the more chaotic the system is), were estimated over time for every electrode before, in and after the epileptic seizure for three seizures of the same patient. The start of the seizure corresponds to a simultaneous drop in L values obtained at the electrodes nearest the focus. L values for the rest of the electrodes follow. The mean values of L for all electrodes in the postictal state are larger than the ones in the preictal state, denoting a more chaotic state postictally. The lowest values of L occur during the seizure but they are still positive denoting the presence of a chaotic attractor. Based on the procedure for the estimation of L we were able to develop a methodology for detecting prominent spikes in the ECoG. These measures (L*) calculated over a period of time (10 minutes before to 10 minutes after the seizure outburst) revealed a remarkable coherence of the abrupt transient drops of L* for the electrodes that showed the initial ictal onset. The L* values for the electrodes away from the focus exhibited less abrupt transient drops. These results indicate that the largest average Lyapunov exponent L can be useful in seizure detection as well as a discriminatory factor for focus localization in multielectrode analysis.

Brain Mapping

Silent sarcoidosis and clubbing.

We report a case of sarcoidosis which was not diagnosed in life for a variety of reasons. In particular the chest was silent despite extensive pulmonary damage, and florid finger clubbing developed within a very short time.

Female

Laser microprobe mass spectrometry (LAMMS) analysis of beryllium, sarcoidosis and other granulomatous diseases.

Beryllium was detected in the granulomas of all thirty-three cases of CBD examined and was absent in thirty cases of sarcoidosis. It was also found in association with coal dust in one of twelve normal lungs. Beryllium could also be detected in Schaumann bodies and hyalinized scars. Beryllium, though sometimes present in Kveim negative biopsies of CBD patients, was not found in any originating Kveim antigen. Rare earths (La, Ce, Pr and Nd) were unexpectedly found in two of the thirty sarcoid patients but not in any other samples. We have identified the crystalline component of Schaumann bodies as calcite and shown that they, as well as calispherules of microlithiasis, contain calcium phosphate. Al and Ti may be found in normal lungs but when associated with hypersensitivity granulomatous disease, their oxides were also present.

Berylliosis