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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 19 recordsLinked to original sources

[Patients returning after transplantation].

Numerous reports have dealt with patient survival and prognostic factors after renal replacement therapy. However, few data exist for patients after a failed renal transplant and who start dialysis again. With this purpose, we retrospectively studied 36 patients who returned to dialysis after a mean transplantation time of 42.8 +/- 7.8 months. Actuarial patient survival on dialysis after the failed renal transplant (D2) was 78%, 74%, 69% and 41% at 1, 2, 3 and 5 years after restarting dialysis respectively. In comparison, survival of patients who started dialysis without a previous history of a renal transplant showed rates of 91%, 85%, 79% and 64% at 1, 2, 3 and 5 years respectively. The difference was statistically significant only at one year after beginning dialysis therapy (78% vs. 91%, p < 0.025). There were no differences in plasma urea concentration by the time of starting both first (D1) and second (D2) dialysis treatments (37.4 +/- 1.9 and 38.8 +/- 2.9 mmol/L respectively). Instead, a statistically significant difference was found between corresponding serum creatinine values (1100.1 +/- 47.1 and 856.9 +/- 50.0 mumol/L respectively, p < 0.05). When actuarial survival and serum creatinine values at the start of D2 were analyzed, there was a statistically better survival at 1 year for patients with serum creatinine values under 900 mumol/L, as compared with those above 900 mumol/L (85% vs. 52%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Methionine5-enkephalin and opiate binding sites in the neurohypophysis of the bird, Gallus domesticus.

Uncertainties with respect to the cellular localization, binding characteristics and function of Met-enkephalin in the neurohypophysis of mammalian species prompted us to examine the neurohypophysis of a non-mammalian species for opioid material and opioid binding sites. In extracts of the neurohypophysis of the domestic fowl we found immunoassayable Met-enkephalin, but could not detect dynorphin(1-8)-like material. Met-enkephalin immunoreactivity was co-localized with mesotocin in the same nerve endings. Stereospecific opiate binding was specifically located in neurosecretosomes (isolated neurosecretory terminals) of the mesotocin type, as shown by autoradiography. Enkephalins therefore may modulate mesotocin release in an autocrine manner. The neurohypophysis of this common bird appears to be a favorable model for studies of enkephalin function in the absence of dynorphin.

Animals

Diversity in fine specificity and T cell receptor usage of the human CD4+ cytotoxic T cell response specific for the immunodominant myelin basic protein peptide 87-106.

Multiple sclerosis (MS), a human demyelinating disease, is thought to be caused by an autoimmunologic process, and myelin basic protein (MBP) is considered a likely autoantigen. Studies of T cell lines (TCL) responding to different parts of the MBP molecule have indicated that amino acids 87 through 106 contain an immunodominant epitope of MBP. We have demonstrated previously that amino acids 89 through 99 represent the core of this 87-106 peptide epitope. Importantly, this epitope is not only encephalitogenic in SJL/J mice and Lewis rats but also has been shown to be recognized by human cytotoxic TCL in the context of four HLA-DR molecules that are associated with MS in different geographic areas. If the immune response to MBP peptide 87-106 was homogeneous with respect to epitope specificity and TCR usage, specific immunotherapies targeting the interaction of peptide, MHC, and TCR might be possible. In this study, the fine specificity of 29 CD4+ cytotoxic, long term, and limiting dilution TCL that had been generated against whole MBP and were derived from four MS patients and two healthy relatives was dissected using truncated and alanine-substituted peptides for the 87-106 peptide. In addition, the TCR alpha and beta chain usage of 15 CD4+ TCL was determined. Using truncated peptides, the presence of several nested immunogenic epitopes within amino acids 87 to 106 was demonstrated. TCL with identical restriction elements and similar responses to truncated peptides could be differentiated further using alanine-substituted peptides. Finally, heterogeneity of TCR usage was shown not only for those lines that differed in their peptide specificity but also for some that showed identical responses and were restricted by the same HLA-DR antigen. In conclusion, the CD4+ cytotoxic T cell response to the immunodominant MBP peptide 87-106 demonstrates a high degree of heterogeneity at the level of fine specificity and TCR usage. These findings indicate that specific immunotherapies aimed at TCR in MS will probably be more complicated than previously anticipated.

Adult

Persistent worsening of stroke sequelae after delayed seizures.

Though the role of cerebral ischemia as an etiologic factor for epilepsy is accepted, the effect of seizures on stroke sequelae has received little attention. We describe 10 patients with poststroke partial epileptic seizures that were followed by persistent worsening of the previous neurologic deficit. Of 38 other patients with poststroke seizures who were examined during the same period, eight suffered transient neurologic worsening (Todd's phenomenon). Persistent worsening was associated with longer seizures and longer partial seizures before generalization. Risk factors, age, sex, other seizure features, and characteristics of previous stroke were irrelevant to developing persistent worsening of stroke sequelae. None of the patients with persistent worsening showed a new lesion or an extension of the previous ischemic area on computed tomography or magnetic resonance imaging, except one who had a first hemorrhage that spared the cortex and who suffered a second hemorrhage, which was lobar. Persistent worsening of a neurologic deficit following a seizure in patients with previous stroke may not be uncommon and may be due to a direct effect of the seizure itself on the infarcted area.

Adult

HTLV-I-specific cytotoxic T lymphocytes in the cerebrospinal fluid of patients with HTLV-I-associated neurological disease.

Recently, it has been shown that in patients with human T-cell lymphotropic virus type I (HTLV-I)-associated neurological disease, high levels of HTLV-I-specific cytotoxic T lymphocytes (CTLs) could be detected in the peripheral blood. These CTLs predominantly recognized products of the pX region of HTLV-I, had a CD8+ phenotype, and were human leukocyte class I restricted. Moreover, these responses were not detected in asymptomatic, HTLV-I-seropositive individuals. This implied a role for these CTLs in the pathogenesis of the neurological disorder associated with HTLV-I. We have extended these observations by demonstrating HTLV-I-specific CTLs directly from lymphocytes obtained from the cerebrospinal fluid of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Uncultured cerebrospinal fluid lymphocytes were used directly as effectors on a variety of targets expressing HTLV-I. These cells were lysed in a virus-specific and HLA class I-restricted manner. Moreover, the cerebrospinal fluid lymphocytes were sorted into purified CD8+ populations, cloned by limiting dilution, and assayed for CTL activity. An exceedingly high proportion of these resultant lines were shown to be cytolytic and precursor frequency analysis indicated that as many as 1 in 500 cells were HTLV-I-specific CTLs. The majority of these CTL lines recognized HTLV-I gene products encoded within the pX region of HTLV-I. The significance of these HTLV-I-specific CTLs in the central nervous system of patients with HTLV-I-associated neurological disease is discussed with regard to the potential role of CTLs in the pathogenesis of this disease.

Adult

Using gadolinium-enhanced magnetic resonance imaging lesions to monitor disease activity in multiple sclerosis.

The highly variable clinical course and the lack of a direct measurement of disease activity have made evaluation of experimental therapies in multiple sclerosis (MS) difficult. Recent studies indicate that clinically silent lesions can be demonstrated by magnetic resonance imaging (MRI) in patients with mild relapsing-remitting MS. Thus, MRI may provide a means for monitoring therapeutic trials in the early phase of MS. We studied 12 patients longitudinally for 12 to 21 months with monthly gadolinium (Gd)-enhanced MRIs. The data have been used to identify the most effective design of a clinical trial using Gd-enhanced lesions as the outcome measure. Frequent ( > 1/mo) Gd-enhancing lesions were observed in 9 of the 12 patients, indicating that the disease is active even during the early phase of the illness. The frequency of the lesions was not constant; there was marked fluctuation in lesion number from month to month. However, the magnitude of the peak number of lesions and the frequency of the peaks varied among patients. Because of this variability, the most effective use of Gd-enhancing lesions as an outcome measure in a clinical trial was a crossover design with study arms of sufficient duration to allow accurate estimation of lesion frequency. Monitoring Gd-enhancing lesions may be an effective tool to assist in the assessment of experimental therapies in early MS.

Adult

The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study.

The ultrastructure and immunostaining with antibodies against actin, desmin, and vimentin were studied in the peritubular myofibroblasts of testes from normal men and men with Klinefelter' syndrome (KS). The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In control testes, only types a and b tubules were present, whereas the testes from men with KS showed types b, c, d, and e tubules. The ultrastructural study revealed abundant microfilament bundles with electron-dense bodies in the cell periphery of the myofibroblasts in a and b tubules. In c tubules, the microfilament bundles of the myofibroblasts were lacking in electron-dense bodies. Myofibroblasts in tubules d and e showed scanty microfilament bundles. Immunostaining of peritubular myofibroblasts with anti-actin antibodies was intense in tubule types a-c and scanty in types d and e. Immunostaining of myofibroblasts with anti-desmin antibodies was intense in tubule types a and b, and negative in types c-e. Immunostaining with anti-vimentin antibodies was weak in tubule types a-c and intense in types d and e. Quantitative study revealed that with the progression of sclerosis, the number and volume per cross-sectioned tubule of actin-containing cells and, mainly, desmin-containing cells decrease while the number and volume of vimentin-containing cells increase.

Actins

Cardiovascular reflexes in patients with malignant disease.

Although some authors have reported clinical features of autonomic dysfunction in patients with malignant disease only a few systematic studies have been carried out. We have investigated the autonomic function of 48 patients with carcinoma or lymphoma by testing their cardiovascular reflexes, and compared their results with those of 62 healthy volunteers. Our patients showed a smaller increase in heart rate and a greater fall in blood pressure on standing up, as well as a smaller rise in blood pressure in response to contralateral handgrip. The study group showed a higher percentage of established sympathetic lesion (54.2% vs 27.4%, p: 0.008) and of atypical pattern of global autonomic function impairment (50% vs 24.2%, p: 0.03) than the control group. Our data suggest that patients with malignant disease suffer from a definite autonomic dysfunction.

Aged

EMLA partially relieves the pain of EMG needling.

The aim of this study was to evaluate the efficacy of the topical analgesic cream EMLA in alleviating the pains caused by needling in electromyography (EMG). During the course of regular neurophysiology clinics, 34 Caucasian patients of both sexes, aged 21 to 69 yr (mean 38.5 +/- 11.4 SD), scheduled for electromyography, were studied. The EMLA was spread thickly on two EMG sites on each arm: E site, on the lateral dorsal aspect of the forearm and A site, on the thenar eminence. Randomization was pre-established. Whenever EMLA was applied blindly on one of the sites of the arm, the placebo was applied on the homologous site of the other arm. After at least 45 min of application (range 45-145 min, mean = 72.3 +/- 22.2), the needle was inserted into the skin and into the muscle. Then the electromyographist asked the patient to score his degree of pain on a visual analogue scale (VAS 1-10 cm) for each level of insertion. The results showed that on the skin of E site, the pain was less after EMLA than placebo (VAS = 0.75 +/- 1.36 vs 3.10 +/- 1.75, P = 0.0001). The untreated E site (placebo) was less sensitive than the untreated A site (VAS = 3.10 +/- 1.75 vs 6.09 +/- 1.96, P = 0.0001). Muscle insertion on E site was less painful on the EMLA sites than placebo (VAS = 2.83 +/- 2.45 vs 5.73 +/- 2.30, P = 0.0001). The VAS scores for skin and muscle insertion on A site were identical whether EMLA or placebo had been applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous

Axillary plexus block using a peripheral nerve stimulator: single or multiple injections.

This prospective, randomized, double-blind study was undertaken to evaluate the success rates of axillary brachial plexus block performed with the help of a peripheral nerve stimulator when either one, two or four of the major nerves of the brachial plexus were located. Seventy-five patients undergoing upper limb surgery were randomly allocated to one of the following five groups according to the nerve and number of nerves to be located; G-1: musculo-cutaneous, radial, median and ulnar nerves; G-2: musculo-cutaneous plus one of the other three nerves; G-3: radial nerve; G-4: median nerve; G-5: ulnar nerve. The sensory block was evaluated before surgery and cutaneous anaesthesia was considered to be present when the needles of a Wartenberg Pinwheel were no longer felt in all the dermatomes of the nerves implicated in the surgical site. Otherwise, the block was considered to need completion before surgery. Only one out of the 15 patients in G-1 and G-2 needed completion of their block before surgery whereas seven out of 15 for G-3 and eight out of 15 for G-4 and G-5 needed completion of their block (P less than 0.01). We conclude that when performing an axillary block with the help of a peripheral nerve stimulator, stimulation of the musculo-cutaneous nerve and one other nerve or stimulation of all four major nerves of the brachial plexus gives a higher success rate than stimulation of only one nerve, whether the stimulated nerve is the median, radial or ulnar.

Adult

Copolymer-1-induced inhibition of antigen-specific T cell activation: interference with antigen presentation.

Copolymer-1 (Cop-1) has been shown to inhibit in vivo development of experimental allergic encephalomyelitis (EAE) in animals and has been reported to have some therapeutic benefit in relapsing/remitting multiple sclerosis (MS). The mechanism by which Cop-1 acts in vivo is not known. The present study demonstrates that Cop-1 inhibits the in vitro response of several antigen-specific murine T cell hybridomas restricted to I-A, and to a lesser extent, I-E. The ability of human myelin basic protein (MBP)-specific T cell lines (TCL) to lyse targets in the context of three HLA-DR types associated with MS was also impaired by Cop-1. The results suggest that the observed inhibition was due to competition between Cop-1 and nominal antigen for the class II major histocompatibility complex (MHC) peptide binding site.

Animals

The internal anatomy of the median nerve in the region of the elbow.

The internal anatomy of the median nerve in the region of the elbow has been studied by microdissection in 20 cadavers. Gross branching patterns were studied in an additional 14 cadavers. There are four major branches or branch groups: I to pronator teres, II to flexor carpi radialis, flexor digitorum superficialis, and palmaris longus; III to the anterior interosseous nerve; and IV to flexor digitorum superficialis. Three of these could be traced proximally within the main trunk of the median nerve, the average being I-10 cm; III-7.5 cm; IV-2 cm. This information should have clinical applications in repair and grafting of the median nerve near the elbow and in understanding clinical nerve compression sydromes.

Cadaver

Quantitative description of the dysarthria in women with amyotrophic lateral sclerosis.

Speech intelligibility and its phonetic and acoustic correlates were studied in a group of 10 women with amyotrophic lateral sclerosis (ALS). Intelligibility assessment with a word-identification test indicated that the most disrupted phonetic features pertained to velopharyngeal valving, lingual function for consonant contrasts of place and manner, and syllable shape. An acoustic signature analysis based on trajectories of the first and second formants in selected monosyllabic test words revealed that the mean slope of the second formant (F2) was reduced compared with that of a normal geriatric control group. This F2 slope reduction is interpreted to reflect loss of lingual motoneurons. Acoustic measures of phonatory function for sustained vowel prolongation demonstrated abnormalities in fundamental frequency, perturbations of frequency (jitter) and amplitude (shimmer), and signal-to-noise ratio. The data for women with ALS are compared with data for a normal geriatric control group of women and with data for a group of 25 men with ALS (Kent et al., 1990). Although the overall ranking of errors was similar for males and females with ALS, men were more likely to have impairments of voicing in syllable-initial position.

Adult

The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines.

The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells.

Animals

Trends in antimicrobial resistance of clinical isolates of Streptococcus pneumoniae in Bellvitge Hospital, Barcelona, Spain (1979-1990).

From January 1979 to December 1990 we studied the susceptibility of 1,492 pneumococcal strains isolated from adult patients in Bellvitge Hospital, Barcelona, Spain, to nine antimicrobial agents. Among clinically significant pneumococci, the incidence of penicillin-resistant strains increased from 4.3% in 1979 to 40% in 1990, and that of erythromycin-resistant strains also rose from 0% in 1979 to 9.4% in 1990. On the other hand, the incidence of strains resistant to tetracycline decreased from 76.1% to 37.6%, as did that of chloramphenicol-resistant strains, from 56.5% to 29.4%. The incidence of co-trimoxazole-resistant strains was about 40% throughout the study. Even more alarming was the finding that about 70% of penicillin-resistant strains showed multiple resistance to non-beta-lactam antibiotics. All pneumococci were susceptible to vancomycin, and all but six were susceptible to rifampin. We observed that isolates from cerebrospinal fluid and the respiratory tract were significantly more resistant to penicillin than were isolates from blood. The majority of strains (95%) belonged to serogroups or serotypes included in the 23-valent pneumococcal vaccine and 77.6% of penicillin-resistant strains belonged to groups 23, 6, 9, and 19.

Adult