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Biomedical subjects

J A Clark

Publications and source records attributed to J A Clark.

At least 19 recordsLinked to original sources
PubMed1992

Pain and cyanosis associated with alpha 1-proteinase inhibitor.

PURPOSE: The purpose of this study was to investigate adverse reaction reports of pain and/or cyanosis attributed to alpha 1-proteinase inhibitor (A1PI), a plasma alpha-globulin protein used to treat A1PI deficiency. PATIENTS AND METHODS: The Food and Drug Administration's (FDA) Spontaneous Reporting System for the collection and analysis of suspected adverse reactions to drugs and biologics was searched for all reports with dates from January 1, 1988, through October 31, 1989, in which A1PI was named as the suspect biologic. A case of pain and/or cyanosis was defined and characteristics of cases were compared with all other reactions. Information about the production of A1PI and results from animal studies conducted by the manufacturer were also gathered. RESULTS: Fourteen cases of acute chest pain, back pain, and/or cyanosis among patients receiving A1PI infusions were reported to the FDA. The clinical aspects of reported cases were consistent with a rapidly acting, nonallergic mechanism and were easily distinguished from other reactions associated with A1PI. The characteristics of reported cases, the epidemic curve, and lot-specific analyses suggested a point source and strongly implicated two A1PI lots. Information about the production of A1PI and results from animal studies further implicated high-molecular-weight polysaccharides associated with sucrose stabilization of the suspect lots. CONCLUSION: These cases resemble adverse reactions attributed to complexes of protamine and heparin (a mucopolysaccharide). Similar vasoactive mechanisms are suggested. Research is needed to further define the pathophysiology associated with polysaccharide moieties.

Adult↗
PubMed1992

Ends of the line: diversity among chronic pain centers.

Chronic pain may cause an endless search for care for its sufferers, while presenting a persistently intractable problem for physicians and disability administrators faced with an illness that defies both conventional medical thinking and established disability compensation mechanisms. In the past 15 years pain centers have mushroomed. Some pain specialists, who are typically based on these centers, have claimed to provide comprehensive treatment for chronic pain and definitive solutions to problems of disability policy. However, pain control is not yet a unified field. Approaches to treatment vary and the definitions of the objects of treatment, i.e. chronic pain syndromes, differ. This paper describes the lines of diversity which characterize this emerging field of health care through an explanatory, cross-sectional survey of 25 pain treatment facilities operating in a single urban community. Pain centers were found to vary with respect to the following dimensions: institutional affiliation, professional background of the staff, treatment modalities offered, populations served, patient selection criteria, types of pain condition treated, and diagnostic and etiologic frames of reference. Pain centers may present a diverse array of options in a pain sufferer's search for care. In addition, the reliance on pain specialists for a resolution of complex problems of disability policy may be premature.

Ambulatory Care Facilities↗
PubMed1992

Serial magnetic resonance study assessing the effects of impingement on the MR image of the patellar tendon graft.

This study was designed to serially analyze the magnetic resonance (MR) appearance of patella tendon grafts during the first year of implantation, and to determine if the sagittal location of the tibial tunnel affects the MR appearance of the graft. An additional goal was to analyze the effect of the sagittal placement of the tibial tunnel placement on knee extension and stability. Two groups were defined by comparing the sagittal relationship of the tibial tunnel to the slope of the intercondylar roof from a lateral roentgenogram of the knee in full extension. The roof impinged group consisted of nine patients who had the tibial tunnel placed anterior to the tibial intersection of the slope of the intercondylar roof. The unimpinged group was composed of eleven patients who had the tibial tunnel placed posterior and parallel to the slope of the intercondylar roof. MR scans were obtained at 0-2, 12, 24, 36, and greater than 48 weeks postoperatively. The signal intensities of grafts in both groups were identical at 1 week, but increased in the impinged group by 3 months and remained increased at 12 months postoperatively (p less than 0.01). In contrast, the MR signal of grafts in the unimpinged group remained unchanged during the first year. Knees with impinged grafts had extension deficits but remained stable. Roof impingement was impossible to view directly with the knee in full extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Functional expression and CNS distribution of a beta-alanine-sensitive neuronal GABA transporter.

The synaptic action of gamma-aminobutyric acid (GABA) is terminated by high affinity, Na(+)-dependent transport processes in both neurons and glia. We have isolated a novel GABA transporter cDNA, GAT-B, which encodes a high affinity (Km = 2.3 microM), Na(+)- and Cl(-)-dependent GABA transport protein that is potently blocked by beta-alanine, a compound generally considered a selective inhibitor of glial transport. However, in situ hybridization studies indicate that GAT-B mRNA is expressed predominantly within neurons. These data indicate that the neuronal-glial distinction of GABA transporters based on inhibitor sensitivities must be reconsidered and suggest a greater diversity of GABA transporters than has been predicted by previous pharmacologic studies.

Amino Acid Sequence↗
PubMed1992

Conservative management of a pulmonary artery bullet embolism: case report and review of the literature.

A case of pulmonary artery bullet embolism managed by observation with no complications at 9-month follow-up prompted a review of the literature. We found a total of 32 cases reported since 1966, with no deaths. Fourteen of the patients were managed by observation and five patients were followed with no resulting complications noted. Conservative management of selected cases of pulmonary artery bullet emboli may be warranted in light of the risks of extraction. These cases should continue to be reported with follow-up.

Adult↗
PubMed1992

Tibial tunnel placement in anterior cruciate ligament reconstructions and graft impingement.

Fifty-six anterior cruciate ligament (ACL) reconstructions had a magnetic resonance scan of the ACL graft six months after operation. The impingement-free grafts (n = 26) had a low magnetic resonance signal from origin to insertion. Impinged grafts (n = 30) had an increased magnetic resonance signal confined to the distal two thirds of the graft. The location of the tibial tunnel (TT) was determined from a lateral roentgenogram. Positioning the center of the TT 12-23 mm from the anterior edge of the tibia consistently produced graft impingement and flexion contractures. Roof impingement was avoided and hyperextension was regained when the TT was centered more posteriorly within a 6-mm impingement-free zone (22-28 mm from the anterior edge of the tibia). Stability and knee extension were significantly better when the center of the TT was 2-3 mm posterior to the center of the normal ACL insertion.

Adult↗
PubMed1992

Evaluation of Telazol-xylazine as an anesthetic combination for use in Syrian hamsters.

The availability of safe parenteral anesthetics for use in Syrian hamsters is limited. We evaluated the effects of Telazol-xylazine (TZX) combinations with respect to anesthetic efficacy and potential for tissue damage. Two dose levels of the combination were administered by both the intraperitoneal (IP) and intramuscular (IM) routes. TZX by the IM route failed to consistently produce anesthesia and caused gross and histopathologic muscle lesions. IP administration of 20 mg/kg Telazol combined with 10 mg/kg xylazine was adequate for restraint purposes. IP administration of 30 mg/kg Telazol combined with 10 mg/kg xylazine produced a safe, reliable level of surgical anesthesia without evidence of gross or histopathologic lesions. There was no nephrotoxicity at either concentration of the anesthetic. A dose level of TZX that provides safe parenteral anesthesia in Syrian hamsters was determined.

Anesthesia, General↗
PubMed1992

One-day hospitalization following modified radical mastectomy.

Postoperative management of patients following modified radical mastectomy has changed dramatically in recent years. Historically, patients usually remained in the hospital with closed suction drainage until the amount of drainage had decreased sufficiently for them to be removed. The feasibility of early discharge on the day following surgery was studied in a prospective manner in 29 consecutive breast cancer patients; 27 underwent unilateral modified radical mastectomy and 2 bilateral mastectomies by a single surgeon. All patients were instructed before surgery about planned early discharge and drain care. Twenty-seven of 29 patients (93.3%) were discharged the day following surgery. However, 2 patients refused discharge and were discharged on postoperative Day Two, and one patient was readmitted for confusion. Drains were removed in the office an average of 5.07 days after surgery. Forty-five per cent of patients developed a seroma that required aspiration at least once. No significant long-term sequela were experienced as a result of early discharge. The average hospital cost was reduced by $2,474.00 or 36 per cent (P less than 0.001) as compared to other surgeons in the same medical center who held to traditional postoperative care. The authors conclude that discharge on the day following surgery for patients undergoing a modified radical mastectomy is safe and cost effective.

Adult↗
PubMed1991

Vaccinia-T7 RNA polymerase expression system: evaluation for the expression cloning of plasma membrane transporters.

The vaccinia/T7 transient expression system, which results in rapid, high-level expression of proteins encoded by plasmids bearing T7 promoters, provides a powerful strategy for the expression cloning of membrane transporters. To test the feasibility of this approach, we introduced the rabbit Na+/glucose transporter by liposome-mediated transfection into vaccinia infected HeLa cells and determined the characteristics and sensitivity of induced [14C]alpha-methyl D-glucopyranoside uptake. We observed a rapid (4-12 h) expression of saturable (Kt = 342 microM) [14C]alpha-methyl D-glucopyranoside uptake following transfection, with substrate and inhibitor sensitivities of the native carrier, including Na+ and temperature dependence and appropriate phloridzin sensitivity (KI = 9.1 microM). The time-dependent increase in alpha-methyl D-glucopyranoside uptake coincided with a decline in endogenous Na+/D-aspartate transport. Maximal levels of expression achieved were nearly 10-fold higher than that reported for transient expression of Na+/glucose transporters in the COS cell system. Rate and dilution estimates demonstrates a sensitivity of detection of single clones diluted several thousand fold by nonspecific plasmid DNA. A further 3-fold increase in transport sensitivity was achieved after transfection of plasmid constructs bearing additional 5'-T7 stem-loop and 3'-T7 termination signals. When cell lines with low endogenous transport were coupled with substrates of high specific activity, as with measurements of induced [3H]gamma-aminobutyric acid uptake, we were able to detect expression from transporter bearing plasmids diluted as much as 10,000-fold by non-specific plasmid DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Bringing social structure back into clinical decision making.

Although research in the past twenty years has resulted in an increasingly sophisticated understanding of clinical decision making processes, the dominant approach in this area of inquiry remains limited. Most studies emphasize normative models of how decisions ought to be made, others attempt to describe physicians' thinking, but few take the social context of decision making systematically into account. Research models typically assume that physicians are autonomous professionals practicing in socially insular clinical settings--an approach that is consistent with classic formulations of the social structure of medical practice, but they ignore 30 years of sociological research on research on patient-physician relationships and major historical changes in the structure of medical practice. Eisenberg's still timely advice to students of clinical decision making--that they need to describe decision making in the context of 'sociologic influences' (including patient, physician and practice setting characteristics)--is expanded in the present discussion. Recent studies are reviewed, highlighting important dimensions of social structure impinging on physicians' decision making. Findings indicate that the process of clinical decision making is likely influenced by patients' age, gender, socioeconomic status, and race, physicians' professional training and experience, as well as by larger structural features of organized clinical settings. Our review of these studies on the social context of clinical decision making, however, reveals major methodological limitations including those inherently imposed by secondary data analysis, normative approaches, written case vignettes, small, non-random samples and the inadequate control of confounding influences. We present a feasible, alternative research strategy, built on a factorial experimental design. Illustrative findings indicate how complex social structural influence on clinical decision making may be disentangled in an unconfounded manner.

Age Factors↗
PubMed1991

Distinct, developmentally regulated brain mRNAs direct the synthesis of neurotransmitter transporters.

The Xenopus laevis oocyte expression system was utilized to define developmental and structural properties of neurotransmitter transporter mRNAs and the pharmacological characteristics of encoded carriers independent of the complexities of brain tissue preparations. Poly(A)+ RNA from dissected brain regions of neonatal and adult rats was microinjected into Xenopus oocytes and the expression of Na(+)-dependent neurotransmitter transporters determined 48 h later. Transport studies conducted with oocytes injected with RNAs derived from juvenile rat tissues indicate a region- and transporter-specific, postnatal increase in mRNA abundance as a major factor in the developmental changes observed for brain high-affinity amino acid uptake systems. Both L-glutamic acid (Glu) and gamma-aminobutyric acid (GABA) uptake systems were detectable by day 3 in postnatal forebrain mRNA and became progressively enriched during the next 2 weeks of forebrain development. In contrast, brainstem Glu and GABA transporter enrichment was 60-70% of adult values by day 3 and exceeded adult levels by day 10. Parallel determinations of L-glutamic acid decarboxylase mRNA abundance during development argue for distinct regulatory influences on mRNAs directing transmitter synthesis and reuptake. Glycine uptake could not be detected at any point of forebrain development and exhibited a gradual postnatal rise to adult levels over the first 3 postnatal weeks of brainstem development. Uptake studies conducted with well-characterized inhibitors of Glu, GABA, dopamine, and choline transport (D-aspartate, nipecotic acid, nomifensine, and hemicholinium-3, respectively) revealed that oocyte transporters encoded by adult rat brain mRNAs retained antagonist sensitivities exhibited by in vitro brain preparations. In addition, a differential regional sensitivity to the Glu transport antagonist dihydrokainate (1 mM) was observed, lending support to previous reports of region-specific Glu transporter subtypes. To determine the structural diversity present among brain transporter mRNAs, poly(A)+ RNA was size-fractionated on linear (10-31%) sucrose density gradients prior to oocyte injection. These experiments revealed two mRNA size classes (2.4-3.0 kb, 4.0-4.5 kb) independently capable of directing the synthesis of Glu, GABA, and glycine transporters. In regions other than the cerebellum, Glu and GABA transporter activities migrated as single, yet distinct, peaks of 4.0-4.5 kb. In contrast, both Glu and GABA transporters exhibited major peaks of activity at 2.5-3.0 kb with size-fractionated cerebellar mRNA. Brainstem glycine uptake exhibited a broad sedimentation profile, with peaks apparent at 2.4 and 4.0 kb. Taken together, these findings indicate previously unappreciated complexity in mRNA structure and regulation which underlies the expression of amino acid neurotransmitter uptake systems in the rodent CNS.

Aging↗
PubMed1990

Labetalol hepatotoxicity.

The Food and Drug Administration has received 11 reports of cases (three fatal) in the United States in which hepatocellular damage was associated with labetalol. The temporal circumstances strongly implicate labetalol; the conditions of nine patients improved after cessation of labetalol therapy, and one patient had a recurrence after therapy was restarted. Follow-up with each reporting physician failed to provide historic or laboratory evidence for other viral, toxic, or drug-induced causes of hepatocellular damage, and the case series did not show the demographic and historic risk factors that would be expected if non-A, non-B hepatitis were the cause. Reports of microscopic liver examinations were available in the 5 cases in which they were done. The reported histologic changes were consistent with hepatocellular necrosis in four instances and chronic active hepatitis in one. The clinical presentation of the cases was most compatible with the mechanism of metabolic idiosyncracy, but other pathogenetic explanations could not be entirely excluded.

Adult↗
PubMed1990

Corticosterone regulates the expression of ADP-ribosylation factor messenger RNA and protein in rat cerebral cortex.

ADP-ribosylation factors (ARFs) comprise a family of small GTP-binding proteins found in brain and other tissues. Recent studies have demonstrated that the expression of the larger heterotrimeric guanine nucleotide binding proteins is under control by steroid hormones. Therefore, in the present study, we examined the influence of glucocorticoids on the expression of ARF mRNA and protein. using specific cDNA probes and antisera, respectively. Chronic administration of corticosterone (7 days) significantly increased levels of mRNA for ARF1 and ARF3, two subtypes of ARF, in rat cerebral cortex. Chronic administration of corticosterone was also found to increase levels of ARF immunoreactivity in this brain region. However, 1-day administration of corticosterone did not influence levels of mRNA for either ARF1 or ARF3. In contrast to corticosterone, bilateral adrenalectomy (7 days after surgery) was found to decrease ARF1 and ARF3 message relative to sham controls; this effect of adrenalectomy was reversed by corticosterone treatment. These results demonstrate that the expression of ARF is under hormonal control and may underlie aspects of glucocorticoid action on neuronal function.

ADP-Ribosylation Factor 1↗
PubMed1990

Integration of stereoscopic DSA with three-dimensional image reconstruction for stereotactic planning.

Following 4 years of experience using a microcomputer-based system for the planning of stereotactic neurosurgery, we have now developed a workstation with the capability of displaying and analyzing three-dimensional images for this purpose. In addition to viewing volumetrically rendered three-dimensional computer tomograms and magnetic resonance images, we may directly view and analyze stereoscopic digital angiograms. In addition to each set of images being viewed in isolation, we may also combine the three-dimensional anatomical images with the stereoscopic angiograms. This new system is based on a computer equipped with a light polarization switched screen capable of displaying stereoscopic images directly to the observer, thus permitting him to interact with the three-dimensional volume directly, determining coordinates and positioning probe trajectories.

Angiography, Digital Subtraction↗
PubMed1990

Sudden death in rheumatoid arthritis from vertical subluxation of the odontoid process.

Rheumatoid arthritis is a chronic, multisystem disease that causes significant morbidity and early mortality. A common source of morbidity in severe rheumatoid arthritis is involvement of the cervical spine. Sudden death due to subluxation of the odontoid process into the medulla oblongata is a dramatic but rare complication. We report the case of a patient who died suddenly. Computerized tomography scan, autopsy, and clinical findings were correlated. Studies of cervical involvement in rheumatoid arthritis were analyzed for cases of vertical subluxation. The case reports of sudden deaths and patients treated for vertical subluxation were reviewed; they revealed a trend toward surgery in patients with neurological abnormalities. However, a comparison of clinical outcome does not demonstrate improved survival with surgical intervention. Randomized trials comparing surgical with nonsurgical therapy are needed.

Aged↗
PubMed1989

Stereotactic neurosurgery planning on a personal-computer-based work station.

Stereotactic surgery requires knowledge of cerebral structures derived from more than one image source. We have developed a PC-AT-based workstation that accepts patient images, made with the stereotactic frame in place, from CT, MRI, and DSA modalities. Reference markers on the frame are identified in the images to establish the coordinate geometry for each modality. Target points may be identified on each image type and trajectories of probe paths to these points defined. Targets identified on one set of images may be transferred automatically to other images of the same patient in order to guarantee a vessel-free path of approach to a target point deep within the brain. To date several hundred patients have had stereotactic surgery performed on the basis of plans using this system. Procedures included biopsy and aspiration of lesions, implantation of electrodes for the recording of deep EEG signals, and radiosurgical techniques. We present clinical examples of the use of this system in typical stereotactic neurosurgery procedures, address stereoscopic applications, and discuss the results of intermodality tests to establish the accuracy of the technique.

Angiography, Digital Subtraction↗
PubMed1989

Blood and component wastage report. A quality assurance function of the hospital transfusion committee.

The transfusion service of a regional referral medical center issues a monthly blood and component wastage report to the Hospital Transfusion Committee. The report includes the amount and type of units wasted, who is responsible, and the cost incurred by the wastage. The individuals responsible for wastage include physicians, nurses, and laboratory personnel. Physicians are responsible for most wastage, principally by failing to administer thawed or pooled blood products. The Hospital Transfusion Committee initiated a wastage-reduction program that included a letter to physicians indicating the patient's name and the type of blood and/or components that the addressed physicians was responsible for wasting. Simple corrective actions results in a 73 percent reduction in our blood and component wastage. Monitoring of blood and component wastage should be routine quality assurance function of the Hospital Transfusion Committee.

Blood Transfusion↗