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Biomedical subjects

S Dworkin

Publications and source records attributed to S Dworkin.

17 recordsLinked to original sources

Structural interventions: concepts, challenges and opportunities for research.

Structural interventions refer to public health interventions that promote health by altering the structural context within which health is produced and reproduced. They draw on concepts from multiple disciplines, including public health, psychiatry, and psychology, in which attention to interventions is common, and sociology and political economy, where structure is a familiar, if contested, concept. This has meant that even as discussions of structural interventions bring together researchers from various fields, they can get stalled in debates over definitions. In this paper, we seek to move these discussions forward by highlighting a number of critical issues raised by structural interventions, and the subsequent implications of these for research.

Acquired Immunodeficiency Syndrome↗

Systemic AA amyloidosis in the common marmoset.

The common marmoset (Callithrix jacchus) is a small New World primate native to Brazil that has been used extensively in biomedical research. A retrospective analysis of archived hematoxylin and eosin-stained tissue sections and clinical records was conducted at the New England Primate Research Center on 86 marmosets more than 1 year of age that were euthanized during the past decade because of morbidity and failure to thrive. Approximately 17% (15 of 86) were found to have amyloid deposits in one or more organs, including the liver, adrenal glands, kidneys, and intestine. This material was shown by amino acid sequence analysis to be composed of serum amyloid A (SAA)-related protein. This type of amyloidosis, designated AA or "secondary," is associated typically with an inflammatory process that induces elevated levels of the SAA amyloidogenic precursor molecule. Notably, there were no significant pathologic differences or other distinguishing features in animals with amyloid versus those without; furthermore, on the basis of the limited number of serum specimens available for analysis, the SAA concentrations in the two groups were comparable, thus suggesting the possible inheritable nature of the disorder. In this respect, the common marmoset provides a unique experimental model for study of the pathogenesis and treatment of AA and other forms of systemic amyloidosis.

Amino Acid Sequence↗

Temporomandibular disorders in adults with repaired cleft lip and palate: a comparison with controls.

The purpose of this study was to investigate the prevalence of temporomandibular disorders (TMD), and assess psycho-social distress in adult subjects with repaired complete cleft lip and palate (CLP). Sixty-three adults (42 males and 21 females, mean age 24.2 years, range 19.5-29.2) with repaired CLP (CLP group) were compared with a group of 66 adults without cleft (non-cleft group, 49 males and 17 females, mean age 25.5 years, range 20.2-29.9). All subjects underwent a clinical TMD examination, which followed the guidelines in the Research Diagnostic Criteria for TMD (RDC/TMD). Jaw function was assessed by evaluating answers to the mandibular function impairment questionnaire (MFIQ). Tension-type headache was diagnosed according to the International Headache Society (IHS) classification. Psychological status was assessed using the depression score and the non-specific physical symptom score with subscales of the Revised Symptom Checklist-90 (SCL-90-R). The prevalence of reported pain in the face, jaws and/or TMJs was 14 and 9 per cent for the CLP and non-cleft group, respectively, and did not differ significantly between the groups. The CLP group exhibited a significantly reduced jaw-opening pattern (P < 0.001) and a higher frequency of crossbites (P < 0.05) compared with the non-cleft group. Whilst jaw function was similar in both groups, a few items, e.g. speech and drinking, were significantly more impaired (P < 0.01) in the CLP group than in the non-cleft group. There were no significant differences between the two groups concerning tension-type headache or psycho-social distress. The study found that overall TMD pain or psycho-social distress was not more common in this CLP group than in a non-cleft group.

Adult↗

Carotid and aortic baroreflexes of the rat: I. Open-loop steady-state properties and blood pressure variability.

To characterize the baroreflex in central nervous system-intact neuromuscular-blocked rats, we measured the vascular and cardiac responses and compared direct stimulation of the aortic depressor nerve (ADN) with a capacitance electrode (differentially activating either A or A + C fibers) to carotid sinus pressure with a micro-balloon (SINUS). One-thousand-two-hundred-ninety-seven open-loop measurements of systolic blood pressure (SBP), heart rate, venous pressure (VBP), and mesenteric (msBF), femoral (fmBF), and skin (skBF) blood flow were completed; the linear range of the effects was determined for each response and stimulus mode. The rats were sinoaortic denervated (SAD). The open-loop stimulation effect was very stable; e.g., the mean effect of 790 ADN stimulations during >7 days was -9.8 mmHg, with an average drift of +0.001 mmHg/h. In contrast, there was large variability of the SBP baseline (e.g., SD = +/-10.9), which was due to SAD (+/-6.3 to +/-16.3 mmHg, t = -13. 9, df = 4, P < 0.0002) and was reversed by ganglionic block (+/-10.8 to +/- 2.9 mmHg, t = -12.9, df = 3, P < 0.001). The ADN stimuli produced larger depressor responses than sinus stimuli (-66 vs. -45 mmHg); all component responses paralleled the magnitude of the SBP effect, except interbeat interval (IBI), for which the ADN DeltaIBI was approximately 10 times that of SINUS. For all stimuli, fmBF increased and msBF did not. Mesenteric and femoral vascular conductance both increased, whereas VBP decreased and skBF followed SBP. We found that for all baroreflex response components, with the exception of SINUS-elicited DeltaIBI, there was an orderly, substantially linear, relationship between stimulus strength and response magnitude.

Animals↗

Carotid and aortic baroreflexes of the rat: II. Open-loop frequency response and the blood pressure spectrum.

To determine the relationship between blood pressure (BP) variability and the open-loop frequency domain transfer function (TF) of the baroreflexes, we measured the pre- and postsinoaortic denervation (SAD) spectra and the effects of periodic and step inputs to the aortic depressor nerve and isolated carotid sinus of central nervous system-intact, neuromuscular-blocked (NMB) rats. Similar to previous results in freely moving rats, SAD greatly increased very low frequency (VLF) (0.01-0.2 Hz) systolic blood pressure (SBP) noise power. Step response-frequency measurements for SBP; interbeat interval (IBI); venous pressure; mesenteric, femoral, and skin blood flow; and direct modulation analyses of SBP showed that only VLF variability could be substantially attenuated by an intact baroreflex. The -3-dB frequency for SBP is 0.035-0.056 Hz; femoral vascular conductance is similar to SBP, but mesenteric vascular conductance has a reliably lower and IBI has a reliably higher -3-dB point. The overall open-loop transportation lag, of which </=0.1 s is neural, is approximately 1.07 s. Constrained algebraic solution, over a range of frequencies, of the pre- and postSAD endogenous noise spectra and the independently determined relative frequency and absolute lag measurements was used to calculate the absolute gain for the open-loop TF. The average gain at 0.02 Hz, the frequency of maximum sensitivity, was 1.47 (95% confidence interval = +/-0.48), which agrees well with estimates for the dog reversible sinus. We found that, in the NMB rat, the effects of SAD on the BP noise spectrum were accounted for by the open-loop properties of the baroreflex.

Animals↗

Learning of physiological responses: II. Classical conditioning of the baroreflex.

The baroreflex can be classically conditioned. In neuromuscular blocked (NMB) rats, electrical stimulation of the aortic depressor nerve (ADN) and dopamine-produced blood pressure rise were effective unconditioned stimuli (UCS) for auditory discriminative classical conditioning. The conditioned response (CR) pattern (bradycardia, vasodilatation, and hypotension > 10 torr) closely resembled that of the unconditioned baroreflex. Conditioned stimulus (CS) specificity was demonstrated by discrimination of baroreflex-associated and nonassociated auditory stimuli, and also by elaborating depressor and pressor CRs to auditory CSs, which respectively had been associated with either baro-afferent (depressor) or tail-shock (pressor) UCSs. The conditioned-baroreflex-magnitude increased with trials. These findings support quantitative models in which CRs interact with and calibrate the gain and dynamic properties of natural reflexes.

Acoustic Stimulation↗

Verification of skeletal activity in tibial nerve recordings: a reply to Roberts (1991).

In Dworkin and Dworkin (1990), we described classically conditioned tibial nerve responses that were uncorrelated with vasomotor responses in the same limb. We pointed out that this finding conflicted with the persisting idea that skeletal and autonomic responses are permanently locked into fixed action patterns that can not be reorganized by learning (Cohen & Obrist, 1975). Roberts (1991) has doubted our interpretation. In this reply, we rebut his arguments and also describe new pharmacological and other recent data showing unambiguously that the nerve activity we measured was not of postganglionic sympathetic origin. We conclude that the nerve activity was most probably due to motoneurons and reiterate that the results of our experiment specifically failed to support a general assertion of obligatory central coupling between skeletal and autonomic mechanisms.

Animals↗

Learning of physiological responses: I. Habituation, sensitization, and classical conditioning.

Rats with chronic neuromuscular block (NMB) maintained by continuous infusion of alpha-bungarotoxin were classically conditioned. All rats showed reliable discriminative-conditioned tibial nerve firing, hind limb vasoconstriction, hypertension, bradycardia, and electroencephalographic (EEG) desynchronization. A regression analysis indicated that the conditioned vasoconstriction was neither centrally mediated by, nor inextricably linked to, skeletal (tibial) nerve firing. Throughout the experiment there were normal blood gases, pH, Na, serum protein, hematocrit, blood pressure, heart rate, vasomotor tone, and tibial nerve activity. The vital signs, EEG spectra, and cortical evoked potentials reflected regular sleep-wakefulness cycles and responsiveness to mild stimuli. The NMB rat preparation with its stable physiological state and fully intact central nervous system may be a useful model for a variety of physiological, medical, and neurobehavioral studies.

Animals↗

Effects of 5,7-dihydroxytryptamine lesions of the nucleus accumbens in rats responding on a concurrent schedule of food, water and intravenous morphine self-administration.

The role of serotonergic innervations of the nucleus accumbens in the processes maintaining intravenous self-administration was assessed in rats responding on a concurrent schedule of food, water and morphine presentations. Five rats were trained on a concurrent fixed-ratio schedule of food and water presentation. They were then implanted with intravenous jugular catheters and bilateral injection guide cannulae into the central medial nucleus accumbens, made physically dependent on morphine and allowed to choose between intravenous morphine, food and water deliveries. A three-lever choice procedure provided almost continuous access to the three reinforcers. Dose-effect curves were determined by the substitution of the daily dose of morphine (3.3 mg/injection) with other doses (0.83-13.2 mg/injection) or eliminating drug injections (extinction) for 24 hour periods. The behavioral effects of 24 hour food extinction probes were also determined. The rats subsequently received bilateral microinjections of either the vehicle or 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus accumbens. Following the lesion, response independent infusions of morphine were delivered for 24 hours at the previous rate of self-injection. The animals were placed back on the concurrent schedule and morphine dose-effect curves were redetermined. The 5,7-DHT lesion resulted in a significant dose-related decrease in morphine self-administration, and little or no effect on responding maintained by food or water presentations. Serotonergic innervations of the nucleus accumbens appear to participate in the neuronal activity mediating intravenous morphine self-administration.

5,7-Dihydroxytryptamine↗

Temporomandibular disorders. Variation in clinical practice.

This research describes the extent of variability in diagnosis and treatment of temporomandibular disorders (TMD) and relates this variability to treatment outcomes. A health maintenance organization sequentially referred 145 patients with orofacial pain and dysfunction to two TMD clinics. The two clinics differed substantially in their use of tomography (applied to 28% vs. 64% of all patients), and varied moderately in diagnoses assigned to the patient groups. There was large variation in selection of treatments including appliances for bruxism (64% vs. 5%), mandibular repositioning (10% vs. 25%), and joint stabilization (3% vs. 30%); anti-inflammatory medications (44% vs. 19%) and analgesics (16% vs. 2%); and subsequent referral for dental or orthodontic treatment (1% vs. 42%). The differences in diagnostic and therapeutic practice that were found were not associated with important differences in patient-reported pain and dysfunction at 1-year follow-up. These data indicate the need for systematic approaches to identifying, evaluating, and modifying variation in health care practices for common presenting problems lacking reliable methods of evaluation and generally accepted clinical standards for choice of treatments.

Adult↗

Behavioral method for the treatment of idiopathic scoliosis.

Idiopathic scoliosis was treated by an automated portable posture-training device that incorporated precise behavioral principles and enabled therapeutic training to be given in the patients' normal environment throughout the entire day. Twenty-one patient-years of training were completed with a group of 12 adolescent girls selected as being imminently likely to require a brace because of the way their spinal curves had been progressing. As an alternative to conventional brace therapy, patients found the posture-training device considerably less physically restraining and more cosmetically acceptable. Most patients wore it 23 hr per day for at least 1 year and adapted well to the constant physical and psychological presence of the instrument. For 10 patients, the outcome was entirely successful; they were discharged from this pilot study as satisfactorily corrected. Progression of the scoliotic curve was arrested; in fact, there was an average slight improvement in the Cobb angle (a measure of spinal curvature) as measured by x-ray radiography.

Adolescent↗

Psychobiological markers in coexisting pain and depression: toward a unified theory.

Psychological and biological variables were examined in two groups of patients with both depression and pain. The relationship of these variables to severity of pain and to pain threshold was examined in a nontreatment evaluation group (N = 25), and their relationship to relief of pain and depression was examined n a doxepin-treated group (N = 16). Eighty-seven percent of the treatment group experienced some pain relief, and 56% experienced complete relief. In the nontreatment group, anxiety as measured on the Zung Anxiety Scale, depression as measured on the Hamilton Depression Scale, and urinary 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were all found to correlate significantly and positively with severity of pain as rated on the McGill Pain Questionnaire. Each of these variables was related to different dimensions of the pain experience as measured by the McGill-Melzack Pain subscales. Only anxiety correlated significantly with pain threshold. In the treatment group final pain relief was positively correlated with initial MHPG and anxiety and with improvement in depression. A theory unifying biological, psychological, and clinical experimental pain data is presented.

Anxiety Disorders↗