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Biomedical subjects

J L Ochoa

Publications and source records attributed to J L Ochoa.

At least 19 recordsLinked to original sources

Temperature-dependent double spikes in C-nociceptors of neuropathic pain patients.

Five patients with small-fibre neuropathy characterized by temperature-dependent spontaneous pain, hyperalgesia/allodynia and signs of neurogenic inflammation were studied clinically and thermographically, and by microneurography. Thermography revealed hyperthermia confined to painful and hyperalgesic skin of distal extremities, in absence of sympathetic vasomotor denervation. Quantitative sensory testing documented either reduced thresholds or increased suprathreshold magnitude for heat pain. Microneurography identified 13 primary cutaneous C-nociceptors generating abnormal impulses in response to electrical stimuli and, in one patient, nociceptors firing spontaneously. All five patients showed examples of double spikes, in which a single brief electrical stimulus occasionally or regularly evoked two impulses. In one case, a second impulse occurred at one of three different delays. In all five patients, warming of the skin increased the probability of a second impulse occurring. Impulse doubling has previously been reported as occurring rarely in normal subjects and is attributable to unfiltering of multiple orthodromic impulses due to unidirectional conduction failure at branch points. A higher incidence of double firing in neuropathic pain patients is probably due to a reduced safety factor for conduction in the terminal arborizations of their C-nociceptors. These observations show that unidirectional conduction block provides a peripheral mechanism of temperature-dependent nociceptor hyperactivity in small-fibre neuropathy that may contribute to hyperalgesia.

Adolescent↗

Peripheral projections of sensory fascicles in the human superficial radial nerve.

The sensory territories of different cutaneous fascicles of the superficial radial nerve were delineated by microneurography at the level of the distal forearm in humans. Three fascicular patterns were found at this level: one supplying the dorsum of the radial aspect of the dorsum of the hand over the first dorsal interosseous space; another supplying the lateral aspect of the first metacarpal extending to the lateral aspect of the thumb; and a third innervating the second interosseous space and the proximal phalanx of the index and middle fingers. The compound fascicular territory is comparable to the classical territory described for the superficial radial nerve. Intraneural microstimulation of individual fascicles did not evoke paraesthesiae or pain beyond their fascicular territory, regardless of the stimulus intensity. We conclude that the superficial radial nerve at the forearm in man is composed of only three fascicles, as shown by the present study and from previous anatomical work. Referred pain seems related to nerve activity in afferent fibres from fascicles supplying deep tissues and muscles, not from cutaneous afferents.

Electric Stimulation↗

Partial reversal of conduction slowing during repetitive stimulation of single sympathetic efferents in human skin.

AIMS: To describe and identify the function of a class of human C fibre with an unusual response to repetitive electrical stimulation. Other C fibres slow progressively at 2 Hz (type 1), reach a latency plateau (type 2) or hardly slow at all (type 3). METHODS: C fibres innervating hairy skin were recorded by microneurography in the superficial peroneal nerves of 19 healthy volunteers. Baseline electrical stimulation of the skin was at 0.25 Hz, and activity-dependent slowing recorded during stimulation at 2 Hz for 3 min and after a 3-min pause in stimulation. RESULTS: In 41 units, there was a partial recovery of latency during repetitive stimulation. These were classified as 'type-4' units, and identified as sympathetic efferents, since they exhibited spontaneously activity, which was enhanced by manoeuvres that increase sympathetic outflow (15 of 16 cases) and/or suppressed by a proximal anaesthetic block (eight of eight cases). The peak slowing during 2 Hz trains averaged 6.47 +/- 2.06% (mean +/- SD, n=41), but after 3 min the slowing had reduced to 4.90 +/- 2.20%, which was less than in all type 1 (nociceptor) fibres but similar to that in type 2 (cold) fibres. Compared with cold fibres, type-4 sympathetic fibres slowed more after the first 10 impulses at 2 Hz (2.57 +/- 0.45%) and also after a pause in stimulation (1.66 +/- 0.51%). CONCLUSIONS: The distinctive activity-dependent slowing profiles of these type-4 sympathetic C units may help identification in vitro, and suggest that hyperpolarization-activated channels have a particularly prominent role in the axonal membrane.

Adolescent↗

Spectrum of cutaneous hyperalgesias/allodynias in neuropathic pain patients.

OBJECTIVES: The aim of this study was to discern the pathophysio-logical bases for neuropathic hyperalgesias. METHODS: In this study, neurological and neurophysiological evaluation of 132 consecutive hyperalgesia patients using rigorous clinical and laboratory protocols were carried out. RESULTS: Two discrete semeiologic entities emerged: classic neurological vs atypical, fulfilling taxonomically complex regional pain syndrome (CRPS) II and I, respectively. The classic group (34.9%) exhibited sensorimotor patterns restricted to nerve distribution and documented nerve fiber dysfunction. Among them four (3.03%) had sensitization of C-nociceptors, seven (5.3%) had central release of nociceptive input, and 35 (26.52%) probable ectopic nerve impulse generation. The atypical group (65.1%) displayed weakness with interrupted effort; non-anatomical hypoesthesia and hyperalgesia; hypoesthesia or paresis reversed by placebo, or atypical abnormal movements, and physiological normality of motor and sensory pathways. CONCLUSIONS: Spatiotemporal features of neuropathic hyperalgesia constitute key criteria for differential diagnosis between CRPS II and I and, together with other behavioral sensorimotor features, signal psychogenic pseudoneurological dysfunction vs structural neuropathology. 'Neuropathic' hyperalgesias may reflect neuropathological or psychopathological disorders.

Adolescent↗

Quantitative sensory testing: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). METHODS: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. RESULTS: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. CONCLUSIONS: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST.

Diabetic Neuropathies↗

Isolation of Prorocentrum lima (Syn. Exuviaella lima) and diarrhetic shellfish poisoning (DSP) risk assessment in the Gulf of California, Mexico.

A benthic toxic dinoflagellate identified as Prorocentrum lima (Syn. Exuviaella lima), and designated as strain PRL-1, was isolated from the coast of El Pardito (Coyote) Island in Baja California Sur, Mexico, after a fisherman poisoning incident involving consumption of liver from Lutjanus colorado, and Mycteroperca prionura fish. Purification and culturing was done in ES-Si medium, under 12:12 light/dark cycle (4 x 20 W cool-white fluorescent lamps), at 22 degrees C and constant stirring during 28 days. Whole cells were toxic to Artemia franciscana and its methanolic extract to mouse and to the marine yeast Debaryomyces hansenii. Chromatographic analysis (TLC and HPLC-MS) of such extract indicated an unusual proportion (1:2) okadaic acid (OA) and dinophysistoxin-1 (DTX-1). Estimated total toxin content by mouse bioassay (based on OA toxicity) was 19 pg/cell, a value significantly higher than that found by HPLC-MS (about 5.2 pg/cell, taking into account OA and DTX-1 only), suggesting that additional toxic components of unidentified nature are detected with the bioassay. This is the first report of a successful isolation and culturing of a toxic dinoflagellate from the Gulf of California, Mexico.

Animals↗

Slowly conducting afferents activated by innocuous low temperature in human skin.

1. Microneurography was used to search for primary afferents responsive to innocuous low temperature in human nerves supplying the hairy skin of the hand or foot. Eighteen units were identified as cold-specific units: they displayed a steady-state discharge at skin temperatures in the range 28-30 degrees C, they were sensitive to small changes in temperature, and they responded vigorously when a cool metal probe touched their receptive fields (RFs). They were insensitive to mechanical stimuli and sympathetic activation. Their RFs comprised one, or at most two, spots less than 5 mm in diameter. 2. Nine units were characterised in detail by a series of 10 s cooling and warming pulses from a holding temperature of 35 degrees C. The threshold temperature for activation by cooling was 29.4 +/- 2.0 degrees C (mean +/- S.D.). Adaptation of the responses to supra-threshold cooling pulses was partial: mean peak and plateau firing rates were maximal on steps to 15 degrees C (35.9 and 19.9 impulses x s(-1), respectively). Three of these units also displayed a paradoxical response to warming, with a mean threshold of 42.3 degrees C. 3. Sixteen of the eighteen cold-specific units were also studied by electrical stimulation of their RFs. They conducted in the velocity range 0.8-3.0 m x s(-1). When stimulated at 2 Hz, their latency increased according to a characteristic time course, reaching a plateau within 3 min (mean slowing (+/- S.D.) 5.2 +/- 1.1 %) and recovering quickly (50 % recovery in 17.8 +/- 4.5 s). 4. To reconcile these findings with previous studies of reaction times and the effects of nerve compression on sensation, it is concluded that either human cold-specific afferent fibres are incompletely myelinated 'BC' fibres, or else there are C as well as A(delta) cold fibres, with the C fibre group contributing little to sensation.

Cold Temperature↗

Isolation and characterisation of putative adhesins from Helicobacter pylori with affinity for heparan sulphate proteoglycan.

A pool of heparan sulphate-binding proteins (HSBPs) from Helicobacter pylori culture supernates was obtained by sequential ammonium sulphate precipitation and affinity chromatography on heparin-Sepharose. The chromatographic procedure yielded one major fraction that contained proteins with heparan sulphate affinity as revealed by inhibition studies of heparan sulphate binding to H. pylori cells. Preparative iso-electric focusing, SDS-PAGE and blotting experiments, with peroxidase(POD)-labelled heparan sulphate as a probe, indicated the presence of two major extracellular proteins with POD-heparan sulphate affinity. One protein had a molecular mass of 66.2 kDa and a pI of 5.4, whilst the second protein had a molecular mass of 71.5 kDa and a pI of 5.0. The N-terminal amino acid sequence of the 71.5-kDa HSBP did not show homology to any other heparin-binding protein, nor to known proteins of H. pylori, whereas the 66.2-kDa HSBP showed a high homology to an Escherichia coli chaperon protein and equine haemoglobin. A third HSBP was isolated from an outer-membrane protein (OMP) fraction of H. pylori cells with a molecular mass of 47.2 kDa. The amino acid sequence of an internal peptide of the OMP-HSBP did not show homology to the extracellular HSBP of H. pylori, or to another microbial HSBP.

Adhesins, Bacterial↗

Debaryomyces hansenii growth in nonsterile seawater ClO2-peptone-containing medium.

We found that the marine yeast Debaryomyces hansenii strain C-11 (CIBNOR yeast collection, La Paz, Mexico) is highly tolerant to chlorine dioxide (ClO2), a powerful biocide agent. A direct application of this observation is the fermentation of the yeast in a nonsterile medium with an initial concentration of 0.3 mg/L of ClO2. The disinfectant helps to avoid the growth of unwanted microorganisms while allowing the development of the yeast. Because the concentration of ClO2 decreases during the fermentation, we ascribe to D. hansenii cells a "biocontrol" action that contributes to the collection of a contaminant-free yeast cell biomass.

Bacteria↗

Abnormal movements in complex regional pain syndrome: assessment of their nature.

Abnormal movements may be a clinical feature in complex regional pain syndrome (CRPS), but their basic nature is unclear. Between August 1989 and September 1998, patients fulfilling diagnostic criteria for CRPS (I or II) and displaying abnormal movements were entered into a prospective study. Fifty-eight patients, 39 women and 19 men, met entry criteria; 47 had sustained a minor physical injury at work. The patients exhibited various combinations of dystonic spasms, coarse postural or action tremor, irregular jerks, and, in one case, choreiform movements. Patients underwent rigorous clinical and laboratory evaluation aimed at characterizing their neurological disturbance. Surprisingly, no case of CRPS II but only cases of CRPS type I displayed abnormal movements. In addition to an absence of evidence of structural nerve, spinal cord, or intracranial damage, all CRPS I patients with abnormal movements typically exhibited pseudoneurological (nonorganic) signs. In some cases, malingering was documented by secret surveillance. This study highlights abnormal movements in CRPS as constituting a key clinical feature that differentiates CRPS I from CRPS II. They are consistently of somatoform or malingered origin, signaling an underlying psychoneurological disorder responsible for the entire CRPS profile.

Adolescent↗

Toxicities and distribution of tetrodotoxin in the tissues of puffer fish found in the coast of the Baja California Peninsula, Mexico.

Toxicities and tetrodotoxin distribution in tissues of five puffer fish species commonly found in the littoral of Baja California Peninsula, Mexico (Sphoeroides annulatus, S. lobatus, S. lispus, Arothron meleagris and Canthigaster punctatissima) were evaluated by bioassay and HPLC. The toxicities estimated as tetrodotoxin-equivalents of all species were more than 0.42 microg/g in at least one of the tissues tested, and the highest was found in S. lispus liver (130 microg/g).

Animals↗

Copper-zinc superoxide dismutase from the marine yeast Debaryomyces hansenii.

We have isolated the cytosolic form of Cu-Zn superoxide dismutase (SOD) from the marine yeast Debaryomyces hansenii. This enzyme has a subunit mass of 18 kDa. The preparation was found to be heterogeneous by IF electrophoresis with two pI ranges: 5.14-4.0 and 1.6-1.8. The enzyme preparation had a remarkably strong stability at pH 6.0-7.0, surviving boiling for 10 min without losing more than 60% of activity. On Western blots, this enzyme was recognized by antibodies raised in rabbits against D. hansenii extracts, while only a weak cross-reaction could be detected using antibodies generated against either Saccharomyces cerevisiae or bovine erythrocyte Cu-Zn SODs. In sequencing analysis, a peptide obtained by trypsin digestion was found to have 85% identity to the S. cerevisiae Cu-Zn SOD.

Amino Acid Sequence↗

Truths, errors, and lies around "reflex sympathetic dystrophy" and "complex regional pain syndrome".

The shifting paradigm of reflex sympathetic dystrophy-sympathetically maintained pains-complex regional pain syndrome is characterized by vestigial truths and understandable errors, but also unjustifiable lies. It is true that patients with organically based neuropathic pain harbor unquestionable and physiologically demonstrable evidence of nerve fiber dysfunction leading to a predictable clinical profile with stereotyped temporal evolution. In turn, patients with psychogenic pseudoneuropathy, sustained by conversion-somatization-malingering, not only lack physiological evidence of structural nerve fiber disease but display a characteristically atypical, half-subjective, psychophysical sensory-motor profile. The objective vasomotor signs may have any variety of neurogenic, vasogenic, and psychogenic origins. Neurological differential diagnosis of "neuropathic pain" versus pseudoneuropathy is straight forward provided that stringent requirements of neurological semeiology are not bypassed. Embarrassing conceptual errors explain the assumption that there exists a clinically relevant "sympathetically maintained pain" status. Errors include historical misinterpretation of vasomotor signs in symptomatic body parts, and misconstruing symptomatic relief after "diagnostic" sympathetic blocks, due to lack of consideration of the placebo effect which explains the outcome. It is a lie that sympatholysis may specifically cure patients with unqualified "reflex sympathetic dystrophy." This was already stated by the father of sympathectomy, René Leriche, more than half a century ago. As extrapolated from observations in animals with gross experimental nerve injury, adducing hypothetical, untestable, secondary central neuron sensitization to explain psychophysical sensory-motor complaints displayed by patients with blatantly absent nerve fiber injury, is not an error, but a lie. While conceptual errors are not only forgivable, but natural to inexact medical science, lies particularly when entrepreneurially inspired are condemnable and call for peer intervention.

Causalgia↗

Stability of some Cactaceae proteins based on fluorescence, circular dichroism, and differential scanning calorimetry measurements.

Characterization of three cactus proteins (native and denatured) from Machaerocereus gummosus (Pitahaya agria), Lophocereu schottii (Garambullo), and Cholla opuntia (Cholla), was based on electrophoretic, fluorescence, CD (circular dichroism), DSC (differential scanning calorimetry), and FT-IR (Fourier transform infrared) measurements. The obtained results of intrinsic fluorescence, DSC, and CD were dissimilar for the three species of cactus, providing evidence of differences in secondary and tertiary structures. Cactus proteins may be situated in the following order corresponding to their relative stability: Machaerocereus gummosus (Pitahaya agria) > Cholla opuntia (Cholla) > Lophocereu schottii (Garambullo). Thermodynamic properties of proteins and their changes upon denaturation (temperature of denaturation, enthalphy, and the number of ruptured hydrogen bonds) were correlated with the secondary structure of proteins and disappearance of alpha-helix.

Calorimetry, Differential Scanning↗

Cloning and sequencing of a cDNA encoding a copper-zinc superoxide dismutase enzyme from the marine yeast Debaryomyces hansenii.

Cu-Zn superoxide dismutase (SOD-1) is a ubiquitously occurring eukaryotic enzyme with a variety of important effects on respiring organisms. A gene (dhsod-1) encoding a Cu-Zn superoxide dismutase of the marine yeast Debaryomyces hansenii was cloned using mRNA by the RT-PCR technique. The deduced amino-acid sequence shows approximately 70% homology with that of cytosolic superoxide dismutase from Saccharomyces cerevisiae and Neurospora crassa, as well as lower homologies (between 55 and 65%) with the corresponding enzyme of other eukaryotic organisms, including human. The gene sequence encodes a protein of 153 amino acids with a calculated molecular mass of 15-92 kDa, in agreement with the observed characteristics of the purified protein from D. hansenii.

Amino Acid Sequence↗

Sciatic schwannoma of the thigh causing foot pain mimicking plantar neuropathy.

Two patients with plantar foot pain, one mistakenly thought to have tarsal tunnel syndrome, had complete resolution of pain after resection of a sciatic nerve schwannoma of the midthigh. The entire extent of the sciatic nerve should be evaluated in patients presenting with unilateral, neuropathic foot pain.

Diagnosis, Differential↗

Ectopic impulse generation and autoexcitation in single myelinated afferent fibers in patients with peripheral neuropathy and positive sensory symptoms.

Microneurographic studies were performed using cutaneous nerves of 8 patients with documented peripheral neuropathy who expressed positive sensory symptoms. Intraneural recordings in single myelinated fibers revealed: (i) ectopic generation of bursts of spontaneous action potentials; (ii) ectopic generation of ongoing repetitive discharges transiently interrupted by natural stimulation of the receptive field; and (iii) repetitive discharges triggered by a preceding action potential. These results provide direct evidence of a peripheral pathophysiological basis for spontaneous and stimulus-induced paresthesias and dysesthesias in patients with peripheral neuropathy.

Action Potentials↗