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Biomedical subjects

S M Johnson

Publications and source records attributed to S M Johnson.

At least 19 recordsLinked to original sources

D-dimers in the diagnosis of pulmonary embolism.

The aim of this study was to determine if the absence of circulating D-dimers, as determined by latex agglutination assays, can correctly exclude the presence of pulmonary embolism using pulmonary angiography as the diagnostic endpoint. Blood samples were obtained prospectively at the time of angiography for suspicion of acute pulmonary embolism. Plasma was assayed for D-dimer by five different latex agglutination assays. Angiographic evidence of pulmonary emboli was found in 34% (35/ 103) of patients. The latex agglutination assays had sensitivities of 97 to 100% and specificities of 19 to 29%. The negative predictive value was 94 to 100%. However, a negative D-dimer was rare in patients with recent surgery, malignancy, or total bilirubin > 34 micromol/L (> 2 mg/dl). In 31 patients suspected of pulmonary emboli but without these confounding factors, the five D-dimer assays were negative in 46 to 55% of patients with normal pulmonary angiograms. The negative predictive value in these patients was 100% by all five latex agglutination assays tested. The latex agglutination assays for D-dimer, when the pulmonary angiogram is used as the diagnostic endpoint and in the absence of recent surgery, malignancy, or liver disease, appears to be a clinically useful test in the diagnosis of acute pulmonary embolism.

Aged

Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients.

Hepatitis C virus (HCV) infection has been associated with de novo or recurrent membranoproliferative glomerulonephritis and acute transplant glomerulopathy in transplanted kidneys. Recently, anticardiolipin antibodies (ACA) have been linked with chronic HCV infection. A few reports have suggested an association between ACA and renal allograft thrombosis. This study examines the clinical and pathologic features of HCV-positive renal allograft recipients at our institution. From 1990 to 1996, 379 kidney transplants were performed. We identified 18 recipients (4.8%) with HCV-positive serology pretransplant. Determination of IgG and IgM ACA was performed by enzyme-linked immunosorbent assay, using pretransplant sera. Among the 18 patients, five patients presented with biopsy-proven de novo renal thrombotic microangiopathy (RTMA), occurring 5 to 120 d (median, 14 d) after transplant. No differences in pretransplant characteristics were observed between patients with (n = 5) or without (n = 13) RTMA. All five patients had a positive ACA test (either IgG or IgM titer > 2 SD above normal), compared with only one of 13 patients without RTMA. The mean value for IgG ACA was significantly higher in the RTMA patients than in patients without RTMA (22.9 +/- 14.1 versus 6.9 +/- 4.9 IgG phospholipid units, P = 0.02); however, there were no significant differences in IgM ACA titers. Rheumatoid factor and complement C4 levels were normal in pretransplant sera of patients with RTMA. Patients with RTMA had their cyclosporine withdrawn (four of five) or the dose was decreased (one of five), and one of five underwent plasmapheresis. Four of five patients died within 5 yr after transplant, compared with no deaths in the other 13 patients. Finally, as a control group, seven HCV-negative renal allograft recipients who presented with RTMA/hemolytic uremic syndrome during the same time period were found to have normal ACA values (IgG or IgM). RTMA associated with ACA in HCV-positive renal allograft recipients may represent a new clinical entity. The occurrence of this syndrome may have deleterious consequences for patient and graft survival.

Adult

Ovarian ablation alone promotes aortic intimal hyperplasia and accumulation of fibroblast growth factor.

BACKGROUND: Estrogen-mediated cardiovascular protection is incompletely explained by its beneficial lipid-modifying effects. Previous studies interrogating direct vascular effects of estrogens have used models of either diet- or injury-induced atherosclerosis. The purpose of this study was to determine the influence of ovarian ablation alone on vascular remodeling. We hypothesized that estrogens are atheroprotective, independent of their influence on lipid metabolism, by directly influencing the production and effects of a prototypical atherogenic mediator, basic fibroblast growth factor (bFGF). METHODS AND RESULTS: Twenty-five female sheep were randomized to sham operation, ovariectomy, or ovariectomy plus 17beta-estradiol replacement. Serum cholesterol and triglyceride levels were serially measured for 1 year and were similar among groups and in the normal range (30 to 60 mg/dL). At 6, 9, and 12 months, ovariectomy resulted in aortoiliac intimal hyperplasia compared with sham (P<0.01) and hormone replacement (P<0.01) groups. The neointima of ovariectomized animals was characterized immunohistochemically by increased vascular smooth muscle cells (VSMCs). Levels of bFGF protein were determined in adjacent aortic segments. Ovariectomized sheep had 2-fold more FGF than sham or ovariectomized sheep that received hormone replacement. In vitro, estradiol inhibited the mitogenic effect of bFGF on human aortic VSMCs. CONCLUSIONS: Without dietary manipulation, ovarian ablation alone induces aortic intimal hyperplasia in the ewe. Estradiol abrogates this response independently of its effects on serum lipids. Hormone replacement decreases the accumulation of the atherogenic peptide bFGF in vivo and inhibits the mitogenic response of VSMCs to bFGF in vitro. These results suggest that estrogens may provide atheroprotection both by modulating local production and by attenuating the influence of bFGF on VSMC growth.

Animals

Problem-based learning: its rationale and efficacy.

Problem-based learning (PBL) in medical education uses clinical cases as the context for students to study basic and clinical sciences. Its possible advantages over traditional approaches include its greater relevance to the practice of medicine, its ability to promote retention and application of knowledge, and its encouragement of self-directed life-long learning. Possible disadvantages include higher costs, both in resources and staff time. Although its efficacy is difficult to evaluate, the current enthusiasm for PBL seems justified and its use is likely to increase further.

Australia

Degeneration of the dendritic arbor as an index of neurotoxicity in identified catecholamine neurons in rat brain slices.

Although catecholamine neurons are vulnerable targets for neurotoxins and degenerative disease, few in vitro studies have investigated the mechanisms of neurodegeneration in these cells. We therefore developed a brain slice preparation for this purpose. Rats were killed by cervical dislocation and 400-microm-thick horizontal slices containing midbrain catecholamine neurons were incubated for 2 h in the presence or absence of kainic acid (KA, 50 microM). After fixation, the slices were recut by a technique that provided thin (40 microm) sections in the same plane as the parent slice. Catecholamine neurons in these coplanar sections were labeled by immunostaining for tyrosine hydroxylase (TH) coupled with diaminobenzidine. The topographical organization of the horizontal plane of the brain was retained in the coplanar sections, enabling precise identification of catecholamine neurons in the thin sections, by reference to an atlas in the horizontal plane. In this study we examined neurons in the substantia nigra (SN). A key feature of the immunostaining was that it revealed both the cell body and also the extensive dendritic projections of SN neurons in the horizontal plane. After treatment with KA, cell bodies remained intact but the dendrites were truncated or fragmented. The loss of dendrites is a sensitive and readily quantifiable indicator of damage. KA caused significant reductions in the proportion of SN neurons with intact dendrites and in the total length of the dendrites, measured using a computer program. The sensitive index of damage and the facility to clearly distinguish catecholamine groups that are topographically close yet functionally distinct are the principal features of the experimental approach that we have developed. The preparation offers major advantages for investigating the selective vulnerability or resistance of particular types of catecholamine neurons to damage.

Animals

Excitatory amino acid-induced degeneration of dendrites of catecholamine neurons in rat substantia nigra.

We have recently established a rat substantia nigra (SN) slice preparation in which a sensitive index of excitatory amino acid (EAA) toxicity was degeneration of the dendritic arbor of catecholamine neurons labelled by immunostaining for tyrosine hydroxylase (TH). The present study examined the pharmacological characteristics of EAA-induced neurotoxicity. Rats were anesthetised by halothane inhalation and killed, the brain was rapidly removed, and 400-microm-thick SN slices cut in the horizontal plane on a vibratome. Slices were incubated in saline buffer at 35 degreesC for 15 min to 6 h in the presence or absence or absence of kainic acid (KA) or N-methyl-D-aspartate (NMDA) in concentrations ranging from 10 to 500 microM. The slices were then fixed and resectioned into 40-microm sections that were coplanar with the parent slice. Dopaminergic SN neurons were labeled using antibody to tyrosine hydroxylase (TH) coupled to diaminobenzidine. A feature of the immunostaining was that it labeled not only the cell body but also the prolific dendritic arborization of SN neurons. Dendritic damage was quantified by counting the proportion of neurons with intact dendrites after treatment with EAA. KA and NMDA caused loss of dendrites that was prevented by CNQX (20 microM) and MK-801 (20 microM), respectively, indicating that activation of either NMDA or non-NMDA receptors produces neurotoxicity. EAA-induced dendritic damage was observed within 2 h of treatment with a low concentration (10 microM) of KA and within 15 min if the concentration was increased to 500 microM. Thus the loss of dendrites occurs rapidly and precedes disintegration of the cell bodies. Furthermore, brief (15 min) exposure to EAA initiated damage in the dendrites which progressed after the EAA was removed from its receptor. The observations are consistent with the postulated role of EAAs in neurodegenerative diseases. Labeling the dendritic arbor provides a sensitive approach to investigating the cellular mechanisms of neurodegeneration of catecholamine neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione

Neurotrophic corneal defects after diode laser cycloablation.

PURPOSE: To report the occurrence of neurotrophic corneal defects after ciliary body ablation with the diode laser. METHODS: Case reports. RESULT: Neurotrophic keratitis, previously associated with cyclocryotherapy, may also be associated with ciliary body ablation with a contact diode laser. CONCLUSION: Practitioners who use the diode laser for ciliary body ablation should be aware of neurotrophic keratitis as a possible complication, especially because the patient population receiving this therapy may have diabetes, chronic eye inflammation, or other conditions predisposing to compromised corneal innervation, which is necessary for epithelial integrity.

Adult

An evaluation of the Weber classification of ankle fractures.

This retrospective study over a 3 year follow-up was designed to establish the significance of the Weber classification of ankle fractures with regards to functional and radiographic outcome. One hundred and seven patients were available for follow-up, of which 88 ankles could be classified with the Weber system. Medial malleolar fractures alone and pilon fractures could not be classified with this system. A correlation was found between the type of Weber fracture and the overall ankle score. This held true for unimalleolar fractures alone. More complex bimalleolar and trimalleolar fractures did not follow this convention. Logistical regression analysis was used to evaluate other predictors of outcome. Bimalleolar and trimalleolar fractures were statistically significant predictors of a poorer outcome (P = 0.033, P = 0.021). The initial degree of displacement was also determined to be a predictor of outcome (P = 0.0133) as was the operative reduction (P = 0.0113). Using linear regression, older age (> 62 years) was also established as a predictor of a poorer outcome (P < 0.05). The Weber classification was found to be a predictor of outcome in unimalleloar ankle fractures and not for multimalleolar fractures. We have identified further predictors of a poorer outcome in ankle fractures as the degree of initial injury, the number of malleoli fractured and older age. These factors were found to have greater significance in predicting outcome than the level of fibular fracture alone. We have identified a deficiency of the Weber system in excluding these criteria and have addressed this by modifying the existing system to include the number of malleoli involved, thus providing a more useful prognostic tool.

Adolescent

N-methyl-D-aspartate-mediated bulbospinal respiratory drive is pH/P(CO2)-insensitive in turtle brainstem-spinal cord.

A split-bath in vitro brainstem-spinal cord preparation from adult turtles (Pseudemys scripta) was used to test the hypotheses that: (1) bulbospinal respiratory synaptic transmission is mediated, at least in part, by N-methyl-D-aspartate (NMDA) glutamatergic receptors, and (2) this transmission is suppressed by low spinal pH (induced by hypercapnea). Recordings from intact pectoralis (expiratory) and serratus (inspiratory) nerves showed that the in vitro turtle brainstem-spinal cord preparation produces phasic expiratory and inspiratory bursts of activity similar to that produced by intact turtles. Bath application of AP-5 [(+/-)-2-amino-5-phosphonopentanoic acid, a noncompetitive NMDA receptor antagonist] to the spinal cord reversibly reduced pectoralis and serratus burst amplitude. In contrast, lowering the pH from 8.04 to 6.94 did not alter burst amplitude in either pectoralis or serratus nerves. These data suggest that spinal NMDA receptors: (1) mediate part of the bulbospinal respiratory synaptic transmission, and (2) are pH/P(CO2)-insensitive. The pH/P(CO2)-insensitivity of NMDA-dependent bulbospinal respiratory synaptic transmission may represent an important adaptation in turtles.

Animals

CO2 and heat have different effects on directed ventilation behavior of grasshoppers Melanoplus differentialis.

We tested the hypothesis that CO2 and heat have different effects on the ventilatory pattern of grasshoppers Melanoplus differentialis. Eight grasshoppers were sealed between rostral (inspiratory) and caudal (expiratory) spiracles in separated, airtight, chambers and pressure changes were measured. Normal breathing patterns decreased pressure in the rostral chamber and increased pressure in the caudal chamber (i.e. unidirectional pumping rostral to caudal). Insects exposed to ventilatory stimulation by CO2 or heat significantly increased pumping frequency from 26+/-2 (+/-S.E.M.) at 0% CO2 to 54+/-6 breaths/min at 8% CO2 (at 30 degrees C), and from 27+/-3 at 30 degrees C to 44+/-4 breaths/min at 45 degrees C. Unidirectional pumping failed to change with increased CO2 concentration and increased significantly with heat exposure. Thus, while CO2 only increased pumping frequency, heat increased pumping frequency and unidirectional pumping.

Air Pressure

Creating healing relationships for couples dealing with trauma: the use of emotionally focused marital therapy.

Emotionally focused marital therapy (EFT), a marital therapy that particularly focuses on the creation of secure attachment, has proven in empirical studies to be effective for distressed couples. This paper discusses the application of EFT in couples where one or both of the partners have experienced significant trauma. EFT, in this context of trauma, incorporates the nine steps of conventional EFT and also encompasses the three stages of the "constructivist" self development theory of trauma treatment. This paper illustrates how the integration of EFT and trauma treatment can prove effective in treating not only relationship distress but also the individual symptoms of posttraumatic stress disorder (PTSD).

Affect

Protection against lethal murine coccidioidomycosis by a soluble vaccine from spherules.

The formaldehyde-killed, whole-spherule vaccine, which is protective against lethal challenge of laboratory animals with Coccidioides immitis, was fractionated. It yielded a soluble, multicomponent, subcellular fraction termed the 27K vaccine. This vaccine, when it was accompanied by adjuvant, protected mice against lethal intranasal and intravenous challenge with C. immitis.

Animals

Molecular cloning, expression, and immunogenicity of MTB12, a novel low-molecular-weight antigen secreted by Mycobacterium tuberculosis.

Proteins secreted into the culture medium by Mycobacterium tuberculosis are thought to play an important role in the development of protective immune responses. In this report, we describe the molecular cloning of a novel, low-molecular-weight antigen (MTB12) secreted by M. tuberculosis. Sequence analysis of the MTB12 gene indicates that the protein is initially synthesized as a 16.6-kDa precursor protein containing a 48-amino-acid hydrophobic leader sequence. The mature, fully processed form of MTB12 protein found in culture filtrates has a molecular mass of 12. 5 kDa. MTB12 protein constitutes a major component of the M. tuberculosis culture supernatant and appears to be at least as abundant as several other well-characterized culture filtrate proteins, including members of the 85B complex. MTB12 is encoded by a single-copy gene which is present in both virulent and avirulent strains of the M. tuberculosis complex, the BCG strain of M. bovis, and M. leprae. Recombinant MTB12 containing an N-terminal six-histidine tag was expressed in Escherichia coli and purified by affinity chromatography. Recombinant MTB12 protein elicited in vitro proliferative responses from the peripheral blood mononuclear cells of a number of purified protein derivative-positive (PPD+) human donors but not from PPD- donors.

Amino Acid Sequence

Hypoxia, temperature, and pH/CO2 effects on respiratory discharge from a turtle brain stem preparation.

An in vitro brain stem preparation from adult turtles (Chrysemys picta) was used to examine the effects of anoxia and increased temperature and pH/CO2 on respiration-related motor output. At pH approximately 7.45, hypoglossal (XII) nerve roots produced patterns of rhythmic bursts (peaks) of discharge (O.74 +/- 0.07 peaks/min 10.0 +/- 0.6 s duration) that were quantitatively similar to literature reports of respiratory activity in conscious, vagotomized turtles. Respiratory discharge was stable for 6 h at 22 degrees C; at 32 degrees C, peak amplitude and frequency progressively and reversibly decreased with time. Two hours of hypoxia had no effect on respiratory discharge. Acutely increasing bath temperature from 22 to 32 degrees C decreased episode and peak duration and increased peak frequency. Changes in pH/CO2 increased peak frequency from zero at pH 8.00-8.10 to maxima of 0.81 +/- 0.01 and 1.44 +/- 0.02 peaks/min at 22 degrees C (pH 7.32) and 32 degrees C (pH 7.46), respectively; pH/CO2 sensitivity was similar at both temperatures. We conclude that 1) insensitivity to hypoxia indicates that rhythmic discharge does not reflect gasping behavior, 2) increased temperature alters respiratory discharge, and 3) central pH/CO2 sensitivity is unaffected by temperature in this preparation (i.e., Q10 approximately 1.0).

Animals

Catecholaminergic modulation of respiratory rhythm in an in vitro turtle brain stem preparation.

An in vitro brain stem preparation from adult turtles was used to determine effects of dopamine (DA) and norepinephrine (NE) on the pattern of respiratory motor output recorded from hypoglossal nerve roots (XII). Bath-applied DA (10-200 microM) increased the frequency of respiratory bursts (peaks) from 0.9 +/- 0.2 to 2.4 +/- 0.3 (SE) peaks/min, resulting in a 99 +/- 9% increase in neural minute activity. R[+]-SCH-23390 (10 microM, D1 antagonist) and eticlopride (20 microM, D2 antagonist) attenuated the DA-mediated increase in peak frequency by 52 and 59%, respectively. On the other hand, the DA-receptor agonists apomorphine (D1, D2), quinelorane (D2), and SKF-38393 (D1) had no effect on peak frequency. Prazosin, an alpha1-adrenergic antagonist (250 nM) abolished the DA-mediated frequency increase. Although NE (10-200 microM) and phenylephrine (10-200 microM, alpha1-adrenergic agonist) increased peak frequency from 0.5 +/- 0.1 to 1.2 +/- 0.3 peaks/min and from 0.6 +/- 0.1 to 1. 0 +/- 0.2 peaks/min, respectively, these effects were not as large as that with DA alone. The data suggest that both dopaminergic and adrenergic receptor activation in the brain stem increase respiratory frequency in turtles, but the DA receptor-mediated increase is dependent on coactivation of alpha1-adrenergic receptors.

Adrenergic Agonists

Professional identity: key to the future of the osteopathic medical profession in the United States.

The authors have been professionally and personally associated with osteopathic medicine since 1972. During this period, they have observed, from several perspectives, the processes by which trainees and osteopathic physicians inculcate their unique professional identity. Yet, increasingly, the philosophic and practical components that have historically defined osteopathic medicine as a distinctive approach to medical practice are rapidly eroding. Powerful forces associated with such things as professional prestige, public acceptance, professional collaboration with allopathic physicians, as well as changing trainee expectations, are rapidly reshaping the osteopathic medical profession. The degree to which osteopathic medical practitioners embrace the philosophic and clinical components unique to their profession will determine whether the profession retains its identity as a separate medical entity. If the current de-emphasis of these identifying characteristics continues, little more than a name will distinguish osteopathic medicine from the allopathic medical profession.

Attitude of Health Personnel