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Biomedical subjects

R Baron

Publications and source records attributed to R Baron.

At least 163 records · Page 9Linked to original sources
PubMed1996

Postganglionic cholinergic dysautonomia with incomplete recovery: a clinical, neurophysiological and immunological case study.

A 26-year-old man presented with signs and symptoms of marked postganglionic cholinergic autonomic dysfunction manifested by non-reacting dilated pupils, paresis of accommodation, decreased salivation, dry skin, atony of the bladder, erectile impotence and complete gastrointestinal paresis. Standard neurophysiological tests for myelinated sensory and motor fibre function and quantitative methods to examine unmyelinated parasympathetic, sympathetic and afferent fibres were performed: parasympathetic function was measured by heart rate variation tests. Sympathetic cutaneous vasoconstrictor responses induced by deep inspiration were examined with laser Doppler flowmetry. Cutaneous nociceptive C-fibre function was assessed by measurement of axon reflex vasodilatation and flare size induced by histamine iontophoresis. The findings confirmed that the abnormalities were restricted exclusively to the cholinergic postganglionic autonomic systems. All other functions were completely preserved. Modern neurophysiological methods of testing sympathetic and afferent small fibre function might help in the diagnosis of cholinergic postganglionic dysautonomia in the early stages. The specificity of the dysfunction argues in favour of an immunological pathogenesis. However, antibody screening including acetylcholine receptor antibodies and voltage-gated calcium channel antibodies gave negative results. Whatever autoimmunological mechanism might be involved, the postulated antibodies act highly specifically on unknown structures of the cholinergic postganglionic autonomic neurons.

Adult↗
PubMed1996

Reflex sympathetic dystrophy: skin blood flow, sympathetic vasoconstrictor reflexes and pain before and after surgical sympathectomy.

To examine the pathophysiological mechanisms of vascular disturbances and to assess the role of the sympathetic nervous system, 12 patients with reflex sympathetic dystrophy (RSD) of the hand were studied using laser Doppler flowmetry. Cutaneous blood flow, skin resistance and skin temperature were measured at the affected and contralateral hands. Sympathetic vasoconstrictor reflexes were induced bilaterally by deep inspiration. Four patients were treated with unilateral surgical sympathectomy and pain and vascular changes were documented in follow-up investigations. (1) After acclimatization in cold environment (< or = 18 degrees C) blood flow and skin temperature were considerably lower on the affected side in 10 patients. No additional vasoconstrictor reflexes could be elicited. (2) After acclimatization in warm environment (22-24 degrees C) blood flow and skin temperature demonstrated no side differences in all cases. Vasoconstrictor responses were the same on both sides. (3) After sympathectomy vasoconstrictor reflexes were absent. Skin resistance was considerably higher on the affected side. In the first 4 weeks the affected hand was warmer and blood flow was higher compared with the healthy side. Thereafter, skin temperature and perfusion slowly decreased and the affected hand turned from warm to cold. Very regular high amplitude vasomotion waves occurred unilaterally. There were no signs of reinnervation. Two patients had long-term pain relief. We conclude as follows. (1) Side differences in skin temperature and blood flow are no static descriptors in RSD. They are dynamic values depending critically on environmental temperature. Therefore, they have to be interpreted with care when defining reliable diagnostic criteria. (2) Vascular disturbances in RSD are not due to constant overactivity of sympathetic vasoconstrictor neurons. Changes in vascular sensitivity to cold temperature and circulating catecholamines may be responsible for vascular abnormalities. Alternatively, RSD may be associated with an abnormal (side different) reflex pattern of sympathetic vasoconstrictor neurons due to thermoregulatory and emotional stimuli generated in the central nervous system. (3) After sympathectomy, denervation supersensitivity of blood vessels and intense vasomotion may be associated with recurrence of pain in some patients.

Adult↗
PubMed1996

[Nosocomial infections due to syncytial respiratory virus: which hygienic measures].

Nosocomial respiratory tract infections due to respiratory syncytial virus are common among hospitalized children. The overall prevention is based on 3 points: prevention of person-to-person viral transmission, infection surveillance and staff education. Handwashing is the main protective attitude. Other measures such as gloving, gowning and wearing masks and goggles are discussed. Changes in hospital organisation during epidemic periodes must also be considered.

Adolescent↗
PubMed1996

An outbreak of cholera from food served on an international aircraft.

In February 1992, an outbreak of cholera occurred among persons who had flown on a commercial airline flight from South America to Los Angeles. This study was conducted to determine the magnitude and the cause of the outbreak. Passengers were interviewed and laboratory specimens were collected to determine the magnitude of the outbreak. A case-control study was performed to determine the vehicle of infection. Seventy-five of the 336 passengers in the United States had cholera; 10 were hospitalized and one died. Cold seafood salad, served between Lima, Peru and Los Angeles, California was the vehicle of infection (odds ratio, 11.6; 95% confidence interval, 3.3-44.5). This was the largest airline-associated outbreak of cholera ever reported and demonstrates the potential for airline-associated spread of cholera from epidemic areas to other parts of the world. Physicians should obtain a travel history and consider cholera in patients with diarrhoea who have travelled from cholera-affected countries. This outbreak also highlights the risks associated with eating cold foods prepared in cholera-affected countries.

Adolescent↗
PubMed1996

Activation of the JAK-STAT signal transduction pathway by oncostatin-M cultured human and mouse osteoblastic cells.

Oncastatin M (OSM) is one member of the leukemia inhibitory factor/interleukin-6 family of cytokines that has been shown to be a growth regulatory molecule. In osteoblastic cultures, OSM causes marked phenotypic changes and the enhanced secretion of interleukin-6. In this study, we have shown that stimulation of murine and human osteoblastic cultures and a human osteosarcoma cell line with OSM resulted in the tyrosine phosphorylation of a number of cellular proteins including members of both the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) family of signaling proteins. The JAKs, a family of intracellular kinases, and the STATs, a family of transcription factors, have both previously been shown to be tyrosine phosphorylated and activated in response to various cytokines, interferons, and growth factors in cells of non-skeletal origin. Using three different sources of cells of the osteoblast lineage, we demonstrate that OSM induces a rapid but transient tyrosine phosphorylation of the three JAK family members tested, JAK1, JAK2 and Tyk2. In addition, two members of the STAT family, Stat1alpha and Stat3, are tyrosine phosphorylated in osteoblastic cells in culture in response to OSM. OSM activation of this pathway in cells of the osteoblast lineage will result in the transcription of specific genes that ultimately may be associated with osteoblast function.

Animals↗
PubMed1995

Characterization of the osteoclast vacuolar H(+)-ATPase B-subunit.

During bone resorption, osteoclasts acidify the extracellular bone resorbing compartment via a vacuolar H(+)-ATPase (V-ATPase), which resides in the ruffled-border membrane. In an effort to characterize the composition of the osteoclast V-ATPase catalytic domain, we have isolated a cDNA clone that encodes the V-ATPase B-subunit from a cDNA library constructed from highly purified chicken osteoclasts. Comparison of the predicted amino-acid sequence with the published sequences of isoforms of V-ATPase B-subunits from other sources revealed that the chicken osteoclast B-subunit is brain type and not kidney type. Furthermore, only clones encoding the brain type isoform of subunit B could be generated by PCR from a cDNA library prepared from human osteoclastoma osteoclast-like cells. Northern blot analysis revealed that two B-subunit mRNAs, approx. 1.7 and 3.5 kb in length, are expressed in chicken bone marrow mono-nuclear cells, brain and kidney, although the relative amounts of these two transcripts were different in each tissue. In brain, the 3.5-kb mRNA was predominantly expressed. In bone marrow cells, the levels of the 1.7-kb mRNA were higher than in other tissues and expression of this message was increased by 1,25-dihydroxyvitamin D-3, suggesting that this mRNA is specifically upregulated during osteoclast differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Sympathetic and afferent neurones projecting into forelimb and trunk nerves and the anatomical organization of the thoracic sympathetic outflow of the rat.

The anatomy of the cervicothoracic sympathetic nerves was studied in the rat. Details of the arrangements of white and grey rami communicantes and superior cervical, middle cervical and stellate ganglia are given. Dorsal root and sympathetic ganglion neurones projecting to skin and muscle of the forelimb and trunk were labelled retrogradely with horseradish peroxidase (HRP) in order to study their number, segmental distribution and location. HRP was applied to forelimb nerves supplying skeletal muscles (Ramus profundus of radial nerve, RP) or hairy skin (N. cutaneus brachii lateralis superior of axillary nerve, CB), to mixed nerves (median nerve, ME; ulnar nerve, UL; radial nerve, RA) and to segmental thoracic nerves supplying hairy skin of the back (dorsal cutaneous nerve, CD) and to mixed internal intercostal nerves (IC). All sensory and sympathetic neurones were located ipsilaterally. In the forelimb nerves sensory somata were commonly restricted to two or three adjacent dorsal root ganglia (usually C6-7 for CB; C7-8 for ME; C7-Th1 for RA and RP; C8-Th1 for UL). Nearly all of the sympathetic somata were located in the middle cervical and stellate ganglia (fusion of C6-Th3). Some 0-0.4% lay in Th4 and Th5, none in the superior cervical ganglia. In the trunk nerves sensory somata were strictly segmentally organized. Sympathetic somata were distributed more widely over 4-5 segments with 50-55% in the segmental ganglion and up to 41% in the next caudal segment. From the data, it is estimated that 400 sympathetic (28%) and 1050 afferent neurones project into CB, 1660 (29%) and 4050 into RA, 540 (42%) and 760 into RP, 1010 (22%) and 3670 into ME, 880 (22%) and 3040 into UL, 350 (25%) and 1040 into IC and 500 (27%) and 1370 into CD.

Animals↗
PubMed1995

Alternative splicing generates a second isoform of the catalytic A subunit of the vacuolar H(+)-ATPase.

We have identified a second isoform of the catalytic A subunit of the vacuolar H+ pump in chicken osteoclasts. In this isoform (A2) a 72-bp cassette replaces a 90-bp cassette present in the classical A1 isoform. The A1-specific cassette encodes a region of the protein that contains one of the three ATP-binding consensus sequences (the P-loop) identified in this polypeptide, as well as the pharmacologically relevant Cys254. In contrast, the A2-specific cassette does not contain any of these features. These two isoforms, which appear to be ubiquitously expressed, are encoded by a single gene and are generated by alternative splicing of two mutually exclusive exons. The alternative RNA processing involves the recognition of a single site, the boundary between the A2- and A1-specific exons, as either acceptor (in A1) or donor (in A2) splice site.

Adenosine Triphosphate↗
PubMed1995

Tyrosine phosphorylation and translocation of the c-cbl protein after activation of tyrosine kinase signaling pathways.

The c-cbl protooncogene product (c-Cbl) is a 120-kDa protein that has been shown to bind to the Src homology 3 domains of various proteins, suggesting its involvement in signal transduction pathways. We identified one of the most prominent tyrosine-phosphorylated proteins in Fc gamma receptor (Fc gamma R)-stimulated macrophages to be c-Cbl. Tyrosine phosphorylation of c-Cbl occurred within 20 s after stimulation and reached maximum levels within 3-5 min. c-Cbl was also tyrosine-phosphorylated in epidermal growth factor (EGF) receptor-overexpressing cells upon EGF stimulation, in macrophages in response to CSF-1 treatment, and in v-src transformed cells. Furthermore, we found that c-Cbl associated with these kinases in vivo. In vitro, c-Cbl bound to the Src homology 3 domains of Src, Fyn, and Lyn in both unstimulated and Fc gamma R-stimulated macrophages. Examination of cells by immunofluorescence revealed that c-Cbl is diffusely distributed in the cytoplasm in both unstimulated macrophages and EGF receptor-overexpressing cells and translocated to a more specific compartment of the cell, consistent with the trans-Golgi region, following Fc gamma R clustering and EGF stimulation, respectively. These results suggest that c-Cbl is involved in the signaling pathways utilized by different types of tyrosine kinases.

Animals↗
PubMed1995

Mumps outbreak in a highly vaccinated school population. Evidence for large-scale vaccination failure.

OBJECTIVES: To describe an outbreak and to identify risk factors for mumps occurring in a highly vaccinated high school population. (Note: Highly vaccinated means a population in which more than 95% have been vaccinated.) DESIGN AND PARTICIPANTS: Survey and cohort study of 307 (97%) of 318 students. OUTCOME MEASURES: Mumps was defined as an illness with 2 or more days of parotid swelling. Serologic confirmation of infection was obtained in eight cases, seven of which were evaluated for presence of IgM antibody using immunofluorescent antibodies. Vaccination records were verified for 297 (97%) students. RESULTS: Between October 3 and November 23, 1990, clinical mumps developed in 54 students (attack rate, 18%), 53 of whom had been vaccinated. Most cases (40 [77%] of 52) occurred 12 to 20 days after a school-wide pep rally. Immunofluorescent antibody testing of all seven specimens demonstrated IgM antibody to mumps. Risk factors for clinical mumps identified in multivariate analyses included female gender (odds ratio, 3.0; 95% confidence interval, 1.6 to 5.7) and source of vaccination other than the local public health clinic (students vaccinated by private providers [odds ratio, 3.0; 95% confidence interval, 1.3 to 5.2] or in other districts [odds ratio, 2.4; 95% confidence interval, 1.1 to 5.3]). CONCLUSIONS: The overall attack rate is the highest reported to date (and to our knowledge) for a population demonstrating virtually complete mumps vaccine coverage. Even verified documentation of vaccination may not be an accurate indicator of an individual's protection against mumps. Vaccination failure may play an important role in contemporary mumps outbreaks. We found no evidence to indicate that waning immunity (secondary vaccine failure) contributed significantly to this outbreak. A second dose of mumps vaccine, as recommended using measles-mumps-rubella vaccine, could potentially prevent similar outbreaks in secondary school populations in the future.

Adolescent↗
PubMed1995

Irritant dermatitis among workers cleaning up a pesticide spill: California 1991.

An outbreak of dermatitis occurred among county jail inmates who removed dead fish from the Sacramento River in California after a spill of metam sodium. The spilled chemical decomposes to methylisothiocyanate (MITC), a known skin irritant. A retrospective cohort study was conducted among the inmates and their crew leaders. Among 42 jail group members, 27 had dermatitis involving the feet and ankles; dermatitis was associated with lower extremity water contact (RR = 3.4, 95% CI 1.0-11.8); the attack rate increased with length of time spent in the water. For comparison, other state and federal employees who worked in the river at the same time were also interviewed. None reported dermatitis. Over three-quarters (24/31) of these other clean-up workers whose feet became wet changed to dry clothing immediately; none of the jail group changed immediately. The river concentration of MITC measured 20-40 ppb at the time of exposure. We speculate that prolonged wetness, occlusive boots, friction, and heat contributed to chemical irritation at this low concentration; the experience of the other clean-up workers suggests that this outbreak could have been prevented.

California↗
PubMed1995

Phantom limb pain: are cutaneous nociceptors and spinothalamic neurons involved in the signaling and maintenance of spontaneous and touch-evoked pain? A case report.

A patient suffered multiple fractures of the right leg and a left brain-stem infarction involving the anterolateral fasciculus of the central nociceptive system following multiple trauma. Later, the right leg was amputated, resulting in spontaneous and touch-evoked phantom pain and mechanical stump allodynia. However, quantitative sensory testing revealed considerable impairment of sensations normally mediated by cutaneous nociceptors and central spinothalamic systems on the right body side, including the stump but nearly intact touch and vibration senses. Quantitative assessment of peripheral nociceptive C-fiber function (axon reflex vasodilatation and flare) showed no abnormalities on both sides. Sympathetic blocks did not change spontaneous and evoked pain. Epidural and spinal anesthesia abolished evoked pain but had no effect on spontaneous phantom pain. Extirpation of a neuroma of the sciatic nerve did not alter spontaneous and evoked pain. TENS resulted in an increase in pain. We concluded the following. (i) Painful somatosensory memories that are responsible for phantom limb pain are located in the brain, most probably in the thalamus or cortex. (ii) Touch-evoked phantom pain and stump allodynia are not mediated by cutaneous nociceptive C and A delta fibers and spinal nociceptive pathways (spinothalamic tract). Activity in the lemniscal system (low-threshold mechanoreceptive A beta afferents, dorsal columns and medial lemnicus system) may be transferred to central pain signaling neurons in the thalamus or cortex resulting in touch-evoked pain sensations. (iii) Ongoing activity in cutaneous nociceptive C fibers and spinal nociceptive systems is not necessary to maintain central processes that account for spontaneous and touch-evoked pain sensations. Activity in nociceptors of deep somatic tissues might be more important.

Amputation Stumps↗
PubMed1995

Role of Na-H exchangers and vacuolar H+ pumps in intracellular pH regulation in neonatal rat osteoclasts.

Osteoclasts resorb bone by pumping of H+ into a compartment between the cell and the bone surface. Intracellular pH (pHi) homeostasis requires that this acid extrusion, mediated by a vacuolar-type H+ ATPase, be complemented by other acid-base transporters. We investigated acid-extrusion mechanisms of single, freshly isolated, neonatal rat osteoclasts. Cells adherent to glass coverslips were studied in the nominal absence of CO2/HCO3-, using the pH-sensitive dye BCECF and a digital imaging system. Initial pHi averaged 7.31 and was uniform throughout individual cells. Intrinsic buffering power (beta 1) decreased curvilinearly from approximately 25 mM at pHi = 6.4 to approximately 6.0 mM at pHi = 7.4. In all polygonally shaped osteoclasts, and approximately 60% of round osteoclasts (approximately 20% of total), pHi recovery from acid loads was mediated exclusively by Na-H exchange. In these pattern-1 cells, pHi recovery was 95% complete within 200 s, and was blocked by removing Na+, or by applying 1 mM amiloride, 50 microM ethylisopropylamiloride (EIPA), or 50 microM hexamethyleneamiloride (HMA). The apparent K1/2 for HMA ([Na+]o = 150 mM) was 49 nM, and the apparent K1/2 for Na+ was 45 mM. Na-H exchange, corrected for amiloride-insensitive fluxes, was half maximal at pHi 6.73, with an apparent Hill coefficient for intracellular H+ of 2.9. Maximal Na-H exchange averaged 741 microM/s. In the remaining approximately 40% of round osteoclasts (pattern-2 cells), pHi recovery from acid loads was brisk even in the absence of Na+ or presence of amiloride. This Na(+)-independent pHi recovery was blocked by 7-chloro-4-nitrobenz-2-oxa-1,3-diazol (NBD-Cl), a vacuolar-type H+ pump inhibitor. Corrected for NBD-Cl insensitive fluxes, H+ pump fluxes decreased approximately linearly from 96 at pHi 6.8 to 11 microM/s at pHi 7.45. In approximately 45% of pattern-2 cells, Na+ readdition elicited a further pHi recovery, suggesting that H+ pumps and Na-H exchangers can exist simultaneously. We conclude that, under the conditions of our study, most neonatal rat osteoclasts express Na-H exchangers that are probably of the ubiquitous basolateral subtype. Some cells express vacuolar-type H+ pumps in their plasma membrane, as do active osteoclasts in situ.

4-Chloro-7-nitrobenzofurazan↗
PubMed1995

Use and safety of acellular pertussis vaccine among adult hospital staff during an outbreak of pertussis.

During May and June 1993, 10 patients and 5 members of the clinical staff at a hospital in California were diagnosed with Bordetella pertussis infection. In addition to erythromycin prophylaxis, 630 (48%) of 1330 staff members received a half dose of acellular pertussis vaccine with tetanus and diphtheria toxoids (DTaP). To identify side effects of the vaccine, a questionnaire was completed by 344 (54%) of 630 vaccinated staff. Side effects were reported by 117 respondents (34%); 64 were classified as mild (local reaction at injection site) and 50 as moderate (systemic complaints or local reaction resulting in limitation of arm movement). Three vaccinees (< 1%) reported missing 1 or more days of work because of their symptoms. Local reactions at the injection site occurred in 100 (29%), systemic symptoms in 38 (11%), and limitation of arm movement in 18 (5%). This study indicates that use of half dose of DTaP in adults appears safe and should be considered as an adjunct to chemoprophylaxis during institutional outbreaks.

Adult↗
PubMed1995

Mechanical allodynia in postherpetic neuralgia: evidence for central mechanisms depending on nociceptive C-fiber degeneration.

In 12 zoster patients who had developed postherpetic neuralgia with dynamic mechanical allodynia and in six zoster patients who had recovered without pain, the functional role of nociceptive C-fibers in allodynia was assessed by quantifying axon reflex reactions induced by histamine iontophoresis within allodynic regions and in their contralateral sites. In patients with postherpetic neuralgia, histamine responses were reduced or abolished within allodynic areas, indicating degeneration of nociceptive C-fibers. In patients who recovered without pain, histamine responses were bilaterally identical, indicating complete regeneration of nociceptive C-fibers. These results demonstrate that sensitized nociceptive C-fibers are not involved in signaling and maintenance of allodynia. Alteration in CNS processing may reorganize synaptic ties between central pain-signaling pathways and mechanoreceptive A beta-fibers depending on afferent C-fiber degeneration rather than ongoing C-fiber input.

Herpes Zoster↗
PubMed1995

Muscle function after endoprosthetic replacement of the proximal tibia. Different techniques for extensor reconstruction in 17 tumor patients.

We analyzed in 17 patients the outcome of various surgical techniques for reconstruction of the extension apparatus after resection of the proximal tibia and tumor prosthesis implantation. The mean follow-up period was 5 (1.5-11) years. Knee extension and flexion strength were measured isokinetically by dynamometer and muscle activities of the vastus medialis, the vastus lateralis and the rectus femoris muscles determined by means of EMG. Muscle function of the operated leg was compared to that of the contralateral extremity by using various surgical techniques: fibula transposition, transposition of the gastrocnemius muscle, and combination technique. The results concerning the operated leg were compared within the 3 groups and the activity and strength of both legs were compared to those of a control group of healthy subjects matched for age and weight. The strength of extensor muscles of the healthy leg was greater than that of the control group in flexion position (60 degrees-90 degrees); the hamstring strength values were within the normal range. The strength of extensor muscles of the operated leg differed between groups II and III at 90 degrees in favor of group II (p < 0.01) and at 60 degrees to 20 degrees (p < 0.001) in favor of group III. Expressed in percentage ranges (nonoperated leg set at 100 percent) the flexor muscles averaged 30 percent, the extensor muscles represented on average 12 percent (9-17 percent) in group I, 9 percent (5-18 percent) in group II and 16 percent (6-26 percent) in group III, depending on the knee angle.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomechanical Phenomena↗
PubMed1995

Painful neuropathy: C-nociceptor activity may not be necessary to maintain central mechanisms accounting for dynamic mechanical allodynia.

OBJECTIVE: In neuropathic pain states, dynamic mechanical allodynia is mediated by large diameter A beta-fibers. We test whether ongoing peripheral C-nociceptor input is necessary to maintain central changes hypothetically responsible for A beta-mediated allodynia. CASE REPORT: A patient with long-standing diabetes mellitus demonstrated generalized signs of painless diabetic small fiber polyneuropathy. Following mechanical trauma, the patient additionally developed a typical neuropathic pain syndrome at the arm. Despite substantial impairment of cutaneous small fiber function, he complained of severe dynamic mechanical allodynia confined to a forearm skin area. METHODS AND RESULTS: Marstock test revealed a considerably increased cold perception threshold within the allodynic area and on the contralateral side. The patient could not perceive any warm sensation on either side. Histamine iontophoresis was not followed by any itch or pain sensations within the allodynic area or contralaterally. Nociceptive C-fiber axon reflex reactions were substantially impaired within the allodynic skin or contralaterally. Standard neurophysiological testing and quantitative vibrametry showed only mild impairment of large diameter sensory and motor fiber function at the arms. Cardiovascular reflex tests showed almost no heart rate variation indicating impairment of vagal small fiber function. CONCLUSIONS: (a) Cutaneous nociceptive C-fibers do not signal dynamic mechanical allodynia. This symptom may hypothetically be due to secondary changes in the central nervous system processing that might strengthen the synaptic ties between A beta-fibers and central nociceptive pathways, or due to peripheral multiplication of primary afferent low threshold mechanoreceptor input. (b) Ongoing nociceptive C-fiber input is not necessary to maintain either hypothetical mechanism. (c) Hypothetical secondary central hyperexcitability might work autonomously without any nociceptive C-fiber input for a long time or even indefinitely in some neuropathic patients.

Adult↗