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Biomedical subjects

R L Goldberg

Publications and source records attributed to R L Goldberg.

At least 19 recordsLinked to original sources

Changes in cochlear mechanics during vocalization: evidence for a phasic medial efferent effect.

The mustached bat, Pteronotus p. parnellii, has a finely tuned cochlea that rings at its resonant frequency in response to an acoustic tone pip. The decay time (DT) and frequency of these damped oscillations can be measured from the cochlear microphonic potential (CM) to study changes in cochlear mechanics. In this report, we describe phasic changes that occur in synchrony with communication sound vocalizations of the bat. Three animals with chronically implanted electrodes were studied. During the experiments, 1-2 ms tone pips were emitted from a speaker every 200 ms. This triggered a computer analysis of the resulting CM to determine the DT and cochlear resonance frequency (CRF) of the ringing. The time relative to vocalizations was determined by monitoring the output of a microphone placed near a bat's mouth. Similar results were obtained from all three bats tested. In a representative case, the average DT was 2.33 +/- 0.25 ms while the bat was quiet, but it decreased by 46% to 1.26 +/- 0.75 during vocalizations, which indicates a greater damping of the cochlear partition. Sometimes, DT started decreasing immediately before the bat vocalized. After the end of a vocalization, the return to baseline values varied from rapid (milliseconds) to gradual (1-2 seconds). The CRF also changed from baseline values during vocalization, although the amount and direction of change were not predictable. When gentamicin was administered to block the action of medial olivocochlear (MOC) efferents, DT reduction was still evident during vocalization but less pronounced. We conclude that phasic changes in damping occur in synchrony with vocalization, and that the MOC system plays a role in causing suppression. Since suppression can begin prior to vocalization, this may be a synkinetic effect, mediated by neural outflow to the ear in synchrony with neural outflow to the middle ear muscles and the muscles used for vocalization.

Acoustic Stimulation

Serum calcitonin precursors in sepsis and systemic inflammation.

High serum levels of the calcitonin (CT) prohormone, procalcitonin (pro-CT), and its component peptides occur in systemic inflammation and sepsis. Using two different assays, we undertook a prospective study to determine the utility of serum precalcitonin peptides (pre-CT) as markers in this condition. Twenty-nine patients meeting criteria for the systemic inflammatory response syndrome were studied daily in two intensive care units. Sera were collected, and APACHE II scores were determined until recovery or death. All patients had markedly elevated serum pre-CT. Prognostically, peak values were the most important. The highest values portended mortality, and a lower level could be ascertained below which all patients survived. Peak pre-CT levels were significantly higher in patients with infection documented by blood cultures than in those patients with no documented infection from any source (P < 0.05). Mature CT remained normal or only moderately elevated. Compared with the serum pre-CT levels, receiver operating characteristic curve analysis revealed that the APACHE II scores, although more cumbersome, were better overall predictors of mortality. Thus, pre-CT is an important serum marker for systemic inflammatory response syndrome and is predictive of outcome. It also provides data concerning the presence of severe infection and may prove to be clinically useful for proactive patient care.

Adult

Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits.

Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.

Administration, Oral

Escalation of a fetish: coprophagia in a nonpsychotic adult of normal intelligence.

A 47-year-old man is described whose fetish of fecal smearing, coprophilia, escalated to coprophagia in a setting of depression and alcohol abuse. The case is the first described in a nonpsychotic adult of normal intelligence. Treatment focused upon the depression and substance abuse as well as on the psychodynamic issues that fostered his despair and allowed the fetish to evolve into coprophagia.

Age of Onset

Optimization of signal-to-noise ratio for multilayer PZT transducers.

In medical ultrasound imaging, two-dimensional (2-D) array transducers are desirable to implement dynamic focusing and phase aberration correction in two dimensions as well as volumetric imaging. Unfortunately, the small size of a 2-D array element results in a small clamped capacitance and a large electrical impedance near the resonance frequency. This results in poor signal-to-noise ratio (SNR) of the array elements. It has previously been demonstrated that transducers made from multilayer PZT ceramics have lower electrical impedance and greater SNR than comparable single layer elements. A simplified circuit model has been developed to optimize the SNR for multilayer ceramic (MLC) transducers. In this model, an electronic transmitter excites the array element and in the receive mode, the element drives a coaxial cable load terminated by a high impedance preamplifier. The transducer impedance is Zt/N2, where N is the number of piezoelectric layers. Maximum transmit signal is obtained when N = Ntx such that the transducer impedance, Zt/Ntx2, is matched to the source impedance. Maximum receive signal is obtained when N = Nrx such that the transducer impedance, Zt/Nrx2, is matched to the coaxial cable reactance. For maximum pulse-echo signal, the transducer should be designed with N = square root of Ntx Nrx, the geometric mean of Ntx and Nrx. Using this optimization technique, a 1.5-D array was designed with 3 layers for maximum pulse-echo SNR. Results of simulations from the simplified circuit analysis were consistent with those of the KLM model. The 3 layer array was fabricated as well as a single layer control array. The measured transmit signal and receive signal agreed with the simulation results.

Ceramics

A program to develop residents as teachers.

Residents are recognized as important and influential teachers of medical students. Although they are expected to teach and evaluate students, few residents have been taught how, and most would like to receive training to develop and improve their skills as teachers. We developed a "Residents as Teachers" retreat based on our faculty development program for clinical preceptors. We focused on clinical precepting skills, including evaluation/feedback, and the ability to prepare and deliver a brief presentation. The program increased knowledge and skills and improved attitudes about teaching, as reflected in self-reports, observed performance, and medical student ratings. The retreat also provided a valuable social experience for residents. The program has been considered beneficial by residents, program faculty members, medical students, the student clerkship director, and the residents' primary care preceptors. The retreats form the centerpiece of our curriculum for residents as teachers and have become an annual tradition in the residency program.

Attitude of Health Personnel

A stromelysin assay for the assessment of metalloprotease inhibitors on human aggregated proteoglycan.

Human proteoglycan was aggregated to an immobilized hyaluronan solid phase on a 96-well ELISA plate. This complex was then degraded by recombinant human stromelysin. The remaining proteoglycan fragments were detected using a monoclonal antibody probe directed against the chondroitin sulfate (CS) region of the core protein. Stromelysin degraded the aggregate in a time and dose dependent manner as reflected by the loss of the CS epitope. Assay sensitivity was 0.125 U/well with total loss of the CS epitope occurring at 4 U/well. o-phenanthroline (IC50 = 52 microM) and U24522 (IC50 = 9 microM) inhibited degradation, while phosphoramidon did not. Serine and cysteine protease inhibitors had no effect. A comparative analysis of this assay with a reference method, substance P assay, gave similar inhibitor profiles. The use of aggregated human proteoglycan (native conformation) as a substrate, may better reflect how stromelysin inhibitors behave in the presence of complex substrates such as cartilage matrix.

Animals

Comparison of magnetic resonance imaging (MRI) and histopathology in rabbit models of osteoarthritis and immune arthritis.

Osteoarthritis was surgically induced in mature male Dutch Belted rabbits by sectioning the fibular collateral and sesamoid ligaments and removal of the anterior horn of the lateral meniscus. The site of surgical intervention was detectable by MRI. Histopathologic analysis revealed severe focal cartilage lesions on opposing surfaces of the tibia and femur. Histology of cartilage adjacent to the osteoarthritic lesions appeared normal. In another animal model, arthritis was induced by immunization against ovalbumin followed by intra-articular injection of ovalbumin. MRI of immune arthritic rabbit knees showed accumulation of synovial fluid and cartilage degradation. Histopathology was characterized by vascular necrosis of the synovium and depletion of cartilage proteoglycan. MRI can be used to non-invasively follow the therapeutic effects of drug treatment on synovial inflammation and cartilage degradation in rabbit knees.

Animals

A comparison of chondrocyte proteoglycan metabolism in monolayer and agarose cultures.

Bovine chondrocyte cultures were established in agarose and in monolayers to compare the effects of cytokines and drugs on matrix metabolism. The production of sulfated glycosaminoglycans (S-GAG) from the medium and cell surface compartments were measured by a dimethylmethylene blue assay. In the agarose cultures most of the proteoglycan remained in the agar, but was continuously released into the medium for more than 50 days. In the monolayers, the cell surface compartment became saturated with S-GAG in 5-6 days. Then a time-dependent decrease of accumulation occurred in the medium after 8-10 days. The anabolic effects of insulin-like growth factor (IGF) and a protein kinase C activator (PMA) were measured in these cultures. IGF and PMA increased S-GAG accumulation in the medium from monolayers but not from agarose cultures. In the agarose cultures, S-GAG was released into the medium after these cultures were changed to serum-free test conditions. This release overshadowed any increase in S-GAG synthesis. The catabolic effect of IL-1 was more evident in the monolayers than in the agarose cultures. Agarose cultures maintain the chondrocyte phenotype longer than monolayers but for initial drug studies monolayer cultures appear to be more appropriate.

Animals

Release of cell surface proteoglycan from chondrocytes by interleukin-1.

A cell culture model was developed to assess factors that can protect cartilage from recombinant human interleukin-1 alpha (IL-1)-induced breakdown. IL-1 (0.01-10 ng/ml) caused a dose-dependent release of cell surface proteoglycan into the medium of bovine and rabbit articular chondrocytes. Sulfated glycosaminoglycan (S-GAG) was detected in the medium and on the cell surface by a dimethlymethylene blue assay. The redistribution of the cell surface S-GAG to the medium compartment required protein synthesis because it was inhibited by cycloheximide and was time-dependent (> 5 h). Although the release was most likely due to de novo synthesis of proteases, standard protease inhibitors failed to prevent the release even when used in combination. TGF-beta and IGF-I increased the amount of S-GAG in both the medium and cell surface compartments, but did not protect from IL-1-induced release. This method has an advantage over a cartilage model of IL-1-induced matrix release because the drug and cytokine exposure time is reduced and the variability is less.

Animals

Professionally-led support groups for cancer patients: an intervention in search of a model.

OBJECTIVE: The objective of this review was to evaluate the clinical and research literature on professionally-led support groups for cancer patients and to propose an approach that would address patients' needs from diagnosis through survivorship. METHOD: Computerized and manual searches, including Medline and Psychlit searches, were completed for reviews of the literature. Twelve research studies were identified that met our criteria for in-depth review. A clinical model emerged from discussions of an oncology study group based on theoretical formulations and clinical experience with oncology patients. RESULTS: We found that recent research suggests that professionally-led support groups are increasing in number and that participation in such groups seems to enhance patients' quality, and possibly even quantity, of survival. Despite this, little effort has been made to determine what type of group may be appropriate for which patients and when in their course of care. CONCLUSIONS: If psychosocial intervention, in the form of professionally-led support groups for cancer patients, is to be more effective, it should be guided by a model which takes into consideration the changing needs and concerns of patients over the course of illness and, in many cases, recovery. The authors present an outline delineating what such a model might entail.

Adaptation, Psychological

Developing community faculty. Principles, practice, and evaluation.

Medical education is increasingly emphasizing outpatient experiences in community settings, and, concurrently, the development and assessment of the teaching skills of community faculty. These skills can be addressed through a faculty development program focusing on (1) issues relevant to community education, (2) adult learning principles, and (3) logistics that facilitate the participation of community medical faculty. Using a series of 1- to 3-day seminars, the program described focused on clinical precepting and brief presentations, used interactional teaching and practicums, and actively involved participants in the evaluation and planning fo the seminars. Evaluation of the program suggested that it was successful in increasing participants' knowledge and application of educational principles taught. Such programs can result in the development of an effective and potentially abundant resource of faculty members for the medical education of students and residents.

Clinical Competence