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Biomedical subjects

B J Schmidt

Publications and source records attributed to B J Schmidt.

At least 19 recordsLinked to original sources
PubMed2006

Subacute delayed ascending myelopathy after low spine injury: case report and evidence of a vascular mechanism.

STUDY DESIGN: Case report of a patient with subacute delayed myelopathy after an acute low thoracic spine injury. OBJECTIVES: To draw awareness to a rarely described complication with potential to add devastating neurological insult to the original spinal cord injury, and to discuss evidence supporting a vascular mechanism. SETTING: Health Science Centre, Winnipeg, Manitoba, Canada. CASE REPORT: A 35-year-old woman developed clinical and MRI evidence of ascending myelopathy, extending up to C5, 16 days after a T11/12 fracture dislocation. The distribution of MRI signal abnormality, MRI evidence of prominent venous markings, and association with upright mobilization and the wearing of a thoraco-lumbo-sacral orthosis, suggest that elevated spinal venous pressure in conjunction with low arterial pressure may have induced impaired spinal cord vascular perfusion. CONCLUSION: After recent spinal cord injury, factors exacerbating spinal venous hypertension and/or arterial hypotension may in some patients lead to impaired spinal cord perfusion. These factors should be considered and corrected if symptoms or signs of progressive myelopathy emerge in the first few days or weeks after injury.

Adult↗
PubMed2001

Voltage-sensitivity of motoneuron NMDA receptor channels is modulated by serotonin in the neonatal rat spinal cord.

Both N-methyl-D-aspartate (NMDA) and serotonin (5-HT) receptors contribute to the generation of rhythmic motor patterns in the rat spinal cord. Co-application of these chemicals is more effective at producing locomotor-like activity than either neurochemical alone. In addition, NMDA application to rat spinal motoneurons, synaptically isolated in tetrodotoxin, induces nonlinear membrane behavior that results in voltage oscillations which can be blocked by 5-HT antagonists. However, the mechanisms underlying NMDA and 5-HT receptor interactions pertinent to motor rhythm production remain to be determined. In the present study, an in vitro neonatal rat spinal cord preparation was used to examine whether NMDA receptor-mediated nonlinear membrane voltage is modulated by 5-HT. Whole-cell recordings of spinal motoneurons demonstrated that 5-HT shifts the region of NMDA receptor-dependent negative slope conductance (RNSC) of the current-voltage relationship to more hyperpolarized potentials and enhances whole-cell inward current. The influence of 5-HT on the RNSC was similar to the effect on the RNSC of decreasing the extracellular Mg(2+)concentration. The results suggest that 5-HT may modulate this form of membrane voltage nonlinearity by regulating Mg(2+) blockade of the NMDA ionophore.

Animals↗
PubMed2000

The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord.

Over the past 40 years, much has been learned about the role of serotonin in spinal cord reflex modulation and locomotor pattern generation. This review presents an historical overview and current perspective of this literature. The primary focus is on the mammalian nervous system. However, where relevant, major insights provided by lower vertebrate models are presented. Recent studies suggest that serotonin-sensitive locomotor network components are distributed throughout the spinal cord and the supralumbar regions are of particular importance. In addition, different serotonin receptor subtypes appear to have different rostrocaudal distributions within the locomotor network. It is speculated that serotonin may influence pattern generation at the cellular level through modulation of plateau properties, an interplay with N-methyl-D-aspartate receptor actions, and afterhyperpolarization regulation. This review also summarizes the origin and maturation of bulbospinal serotonergic projections, serotonin receptor distribution in the spinal cord, the complex actions of serotonin on segmental neurons and reflex pathways, the potential role of serotonergic systems in promoting spinal cord maturation, and evidence suggesting serotonin may influence functional recovery after spinal cord injury.

Animals↗
PubMed1999

Nutritional evaluation of children with phenylketonuria.

CONTEXT: Dietary phenylalanine (PA) restriction is the most effective form for reducing its excess in the blood and is the only efficient method for treating phenylketonuria. The diet is complex and should be adapted to combine the patients' eating habits, growth and development. It depends basically on the use of industrialized products as substitutes free of PA for proteins that are not fully supplied. OBJECTIVE: To evaluate the nutritional status of children with phenylketonuria (PKU) by anthropometric measurements and food intake. DESIGN: Cross-sectional study. SETTING: Children with PKU attending the Association of Parents and Friends of Handicapped Children (Associação de Pais e Amigos dos Excepcionais - APAE) and normal children attending at municipal day care centers in São Paulo. PARTICIPANTS: 42 children with PKU and 31 normal children aged 1 to 12 of both sexes were assessed in two groups, under and over 7 years of age. MAIN MEASUREMENTS: Weight and height measurements. RESULTS: Children with PKU ingested calories, calcium, iron, zinc, and copper below the recommended values, whereas the protein intake was within the normal range. Food intake in the group of normal children was within normality rates. The height/weight Z-score means for children with PKU were 0.47 for those under 7 years and 1.86 for 7 year-olds and over; in normal children the means were 0.97 <7 years and 1.54 >/=7 years, with no statistically significant difference. The height/age Z-score means were significantly lower in the PKU children <7 years (-1.23) than in the normal controls (0.91). CONCLUSIONS: The data presented demonstrate the importance of nutritional surveillance in patients with PKU so as to support adequacy of nutrient intake and to guarantee growth within the relevant standards.

Calcium, Dietary↗
PubMed1999

Plasma zinc, copper, and erythrocyte superoxide dismutase in children with phenylketonuria.

Children with phenylketonuria (PKU) are treated with semisynthetic diets restricted in phenylalanine (PHE). The formulae must supply those trace elements and vitamins that are usually supplied by whole protein foods. We studied the effects of phenylalaline restricted diets in 42 children with PKU (P) and 31 normal (N) children, aged 1-12 y, divided into two groups (below and above 7 y). Plasma zinc and copper were analyzed by means of atomic spectrophotometry, and superoxide dismutase (CuZnSOD) activity was measured in erythrocytes, through NBT inhibition and its profile, as determined by isoelectric focalization. Plasma zinc of PKU children > or = 7 years old was significantly lower than that in the control group (17 mumol/L versus 20 mumol/L) but still within the normal range; in children < 7 years no substantial differences were found between the two groups. Plasma copper was not statistically different between PKU and normal children. Qualitative activity of CuZnSOD presented the same electrophoretic profile in both normal and PKU. Quantitative activity was not different in both P (1210 U/g Hb < 7 versus 1328 U/g hemoglobin (Hb) > or = 7) and N (1675 U/g Hb < 7 versus 1367 U/g Hb > or = 7). We concluded that children with PKU presented normal mean levels of zinc and copper, with preserved function, measured by enzyme activity.

Child↗
PubMed1998

NMDA receptor-mediated oscillatory properties: potential role in rhythm generation in the mammalian spinal cord.

Previous studies have demonstrated that (1) NMDA receptor activation occurs during locomotor network operation in lower and higher vertebrates and (2) NMDA induces active membrane properties that can be expressed as intrinsic voltage fluctuations in cells located in the spinal cord of lower vertebrates, as well as in neurons located in supraspinal regions of the mammalian nervous system. This paper reviews recent data showing that NMDA can induce similar inherent membrane potential behavior in synaptically isolated motoneurons and interneurons in the mammalian (in vitro neonatal rat) spinal cord. These TTX-resistant voltage fluctuations include rhythmic oscillations and plateau potentials, as well as low-frequency long-lasting voltage shifts (LLVSs). 5-HT facilitates the transformation of LLVSs into oscillatory events, and 5-HT receptor antagonists have the reverse effect. In the absence of TTX, locomotor-related rhythmic drive potentials in spinal cord neurons can display nonlinear voltage behavior compatible with NMDA receptor activation, although other voltage-activated conductances are not excluded. Suppression of the nonlinear voltage response associated with NMDA receptor activation, via removal of Mg2+, disrupts locomotor patterns of network activity. The potential role of NMDA receptor activation in the operation of mammalian locomotor networks is discussed in the context of these recent observations.

Animals↗
PubMed1998

Whole cell recordings of lumbar motoneurons during locomotor-like activity in the in vitro neonatal rat spinal cord.

Whole cell current- and voltage-clamp recordings were obtained from lumbar motoneurons in the isolated neonatal rat spinal cord to characterize the behavior of motoneurons during neurochemically induced locomotor-like activity. Bath application of serotonin (10-100 muM) in combination with N-methyl-D-aspartate (1-12 muM) initially produced tonic membrane depolarization (mean = 26 mV), increased input resistance, decreased rheobase, and increased spike inactivation in response to depolarizing current pulse injections. After the initial tonic depolarization, rhythmic fluctuations of the motoneuron membrane potential (locomotor drive potentials; LDPs) developed that were modulated phasically in association with ventral root discharge. The peak and trough voltage levels of the LDP fluctuated above and below the membrane potential recorded immediately before the onset of rhythmic activity. Similarly, firing frequency was modulated above and below prelocomotion firing rates (in those motoneurons that displayed neurochemically induced tonic firing immediately before the onset of rhythmic activity). These observations are consistent with an alternation between phasic excitatory and inhibitory synaptic drives. The amplitude of LDPs and rhythmic excitatory drive current increased with membrane depolarization from -80 to -40 mV and then decreased with further depolarization, thus displaying nonlinear voltage-dependence. Faster frequency, small amplitude voltage fluctuations were observed superimposed on the depolarized phase of LDPs. In some motoneurons, the trajectory of these superimposed fluctuations was consistent with a synaptic origin, whereas in other cells, the regular sinusoidal appearance of the fluctuations and the occurrence of superimposed plateau potentials were more compatible with the activation of an intrinsic membrane property. One motoneuron displayed exclusively excitatory phasic drive, and another motoneuron was characterized by inhibitory phasic drive alone, during rhythmic activity. These findings are compatible with the concept of a central pattern generator that is capable of delivering both excitatory and inhibitory drive to motoneurons during locomotion. The data also suggest that the rhythmic excitatory and inhibitory outputs of the hypothetical half-center model can be dissociated and operate in isolation.

Action Potentials↗
PubMed1998

NMDA receptor-mediated oscillatory activity in the neonatal rat spinal cord is serotonin dependent.

The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and on N-methyl--aspartate (NMDA) receptor-induced membrane voltage oscillations was examined using an in vitro neonatal rat spinal cord preparation. Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and extensor electroneurograms or ventral root recordings, was abolished by 5-HT receptor antagonists. Intrinsic motoneuronal voltage oscillations, induced by NMDA in the presence of tetrodotoxin (TTX), either were abolished completely or transformed to long-lasting voltage shifts by 5-HT receptor antagonists. Conversely, 5-HT application facilitated the expression of NMDA-receptor-mediated rhythmic voltage oscillations. The results suggest that an interplay between 5-HT and NMDA receptor actions may be critical for the production of rhythmic motor behavior in the mammalian spinal cord, both at the network and single cell level.

Acetylcholine↗
PubMed1997

IFN-gamma inducibility of class II transactivator is specifically lacking in human tumour lines: relevance to retinoblastoma protein rescue of IFN-gamma inducibility of the HLA class II genes.

We have previously reported that HLA class II induction by IFN-gamma is rescuable by reconstitution of functional retinoblastoma protein (RB) in two RB-defective tumour lines: the breast carcinoma line, MDA-468-S4 (S4) and the non-small cell lung carcinoma line, H2009. To determine the range of tumours and tumour types in which RB rescues HLA class II inducibility, we examined another RB-defective tumour line, the retinoblastoma line, WERI-Rb1. As in the case of S4 and H2009, HLA-DRA and -DRB were non-inducible by IFN-gamma in WERI-Rb1. However, neither inducibility of DRA nor DRB mRNA was resulted in an RB-positive stable transformant of WERI-Rb1, WLRB-8. While guanylate-binding protein (GBP) inducibility indicated that the basic IFN-gamma signal transduction pathway remained intact in WERI-Rb1, mRNA for class II transactivator (CIITA), a mediator of the IFN-gamma activation of the HLA class II genes and several other genes related to immune function, was not detectable in IFN-gamma-treated WERI-Rb1, indicating that the lack of CIITA expression was responsible, at least in part, for the inability of RB to rescue HLA class II-inducibility. The HLA class II-associated invariant chain (Ii), the expression of which is also up-regulated by CIITA, was non-inducible in WERI-Rb1, consistent with non-inducible CIITA. Also, IFN-gamma failed to activate the DRA, DRB and Ii promoters in WERI-Rb1. However, exogenous CIITA expression in WERI-Rb1 activated the DRA, DRB and Ii promoter-chloramphinocol acetyltransferase constructs, confirming that CIITA was not induced in WERI-Rb1 and indicating that other proteins required for activation of the class II and Ii promoters were functional in this cell line. Examination of additional cell lines for GBP and CIITA induction revealed that a specific lack of the CIITA IFN-gamma response is common in human tumour lines. The possible role of CIITA defects in tumorigenesis is discussed.

Chloramphenicol O-Acetyltransferase↗
PubMed1997

NMDA receptor activation triggers voltage oscillations, plateau potentials and bursting in neonatal rat lumbar motoneurons in vitro.

Whole-cell recordings of lumbar motoneurons in the intact neonatal rat spinal cord in vitro were undertaken to examine the effects of N-methyl-D-aspartate (NMDA) receptor activation on membrane behaviour. Bath application of NMDA induced rhythmic voltage oscillations of 5.9+/-2.1 mV (SD) at a frequency of 4.4+/-1.5 Hz. Amplitude, but not frequency, of the voltage oscillations was membrane potential-dependent. Voltage oscillations could recruit action potentials and/or plateau potentials with or without superimposed bursting. Blockade of synaptic transmission with tetrodotoxin (TTX) sometimes resulted in a loss of oscillatory activity which could then be restored by increasing the NMDA concentration. After application of TTX, the trajectory of NMDA-induced oscillations was similar to the trajectory induced in the presence of intact synaptic networks, although the mean oscillation duration was longer and the oscillation frequency was slower (1.8+/-1.1 Hz). Current ramps delivered after bath application of NMDA demonstrated bistable membrane properties which may underlie the plateau potentials. Injection of intracellular current pulses could initiate, entrain and terminate individual plateau potentials. The results suggest that membrane depolarization produced by oscillations may activate other intrinsic conductances which generate plateau potentials, thereby providing the neuron with enhanced voltage sensitivity, compared to that produced by NMDA receptor activation alone. These oscillatory events may have a role in the regulation of motor output in a variety of rhythmic behaviours including locomotion.

Action Potentials↗
PubMed1997

Regional distribution of the locomotor pattern-generating network in the neonatal rat spinal cord.

The regional distribution of spinal cord networks producing locomotor-like, as well as non-locomotor-like, activity was studied with the use of an in vitro neonatal rat preparation. Rhythmic activity was induced by bath application of either serotonin (5-HT), acetylcholine (ACh), N-methyl-D,L-aspartate (NMA), or combined 5-HT/NMA, and was monitored via hindlimb flexor (peroneal) and extensor (tibial) electroneurograms (ENGs) or ventral root recordings. In some experiments, synchronous patterns were produced by the addition of inhibitory amino acid (IAA) receptor antagonists. Selective application of 5-HT to cervical and thoracic cord regions induced rhythmic activity in these segments but failed to evoke hindlimb ENG discharge. Exposure of the isolated lumbar region to 5-HT produced tonic activity only. Application of 5-HT to the whole cord produced locomotor-like activity in hindlimb ENGs that persisted after midsagittal section of the spinal cord from the conus to the thoracolumbar junction. In other experiments, transverse hemisection of the rostral lumbar cord during whole cord exposure to 5-HT abolished rhythmic activity in ipsilateral hindlimb ENGs, suggesting that under these conditions rhythmic activity on one side of the lumbar cord was insufficient to maintain rhythmic activity on the contralateral side. Selective application of NMA or ACh to cervical and/or thoracic cord regions evoked rhythmic activity in these supralumbar segments, as well as rhythmic, but non-locomotor-like, activity in the lumbar region. In contrast to the effect of 5-HT, both NMA and ACh evoked rhythmic activity when applied solely to the lumbar region, and the side-to-side alternation produced by whole cord ACh application was uncoupled by midsagittal lesions of the lumbar region. In the presence of IAA antagonists, the side-to-side coupling of bilaterally synchronous rhythms was maintained despite extensive midsagittal lesions leaving all but one or two segments of either cervical, thoracic, or lumbar cord bilaterally intact, and rhythmic activity could be maintained even in single isolated hemisegments. The effects of 5-HT/NMA were similar to those observed with the use of 5-HT alone, although 5-HT/NMA induced rhythmic activity in hindlimb ENGs when applied selectively to supralumbar regions. The results suggest that 1) a 5-HT-sensitive oscillatory network, capable of producing a locomotor-like pattern of activity, is distributed throughout the supralumbar region of the spinal cord and mediates descending rhythmic drive to lumbar motor centers; 2) NMA- and ACh-sensitive rhythmogenic elements are distributed throughout the spinal cord, including the lumbar region; and 3) the spinal cord contains an extensive propriospinal network of reciprocal inhibitory and excitatory connections characterized by redundantly organized side-to-side projections.

Acetylcholine↗
PubMed1995

Pelvic and pudendal reflexes in the in vitro neonatal rat preparation.

Pudendal-to-pelvic and pudendal-to-pudendal reflexes are described in an in vitro brainstem-spinal cord neonatal rat preparation. Cystometrograms and peripheral pelvic nerve recordings were used to monitor excitatory micturition reflexes evoked by tactile perineal stimulation or by continuous electrical stimulation of the sensory pudendal nerve. Micturition was characterized by an increased bladder pressure and a period of tonic pelvic nerve activity during which time fluid was expelled from the urethra. Single stimuli delivered to the sensory pudendal nerve evoked a phasic response in the pelvic nerve (pudendal-to-pelvic reflex) or pudendal motor nerve (pudendal-to-pudendal reflexes). The pudendal-to-pelvic reflex consisted of a single response occurring after a mean latency of 98 +/- 24 ms. The pudendal-to-pudendal reflex was comprised of two responses, the first occurred at a mean latency of 105 +/- 11 ms and the second at 383 +/- 36 ms. Cervical or lower thoracic spinal transection did not alter the pudendal-to-pelvic reflex, however, the second component of the pudendal-to-pudendal reflex was abolished. The use of preganglionic pelvic and pudendal peripheral nerve recordings described in this study provide a direct measure of the reflex outflow from the CNS and can be used to examine developmental changes and neurochemical substrates within the CNS which contribute to micturition and coital reflexes in the rat.

Animals↗
PubMed1995

Effects of inhibitory amino acid antagonists on reciprocal inhibitory interactions during rhythmic motor activity in the in vitro neonatal rat spinal cord.

1. The role of inhibitory amino acid transmission in the coordination and generation of rhythmic motor activity was examined with the use of an in vitro neonatal rat spinal cord preparation. Before adding gamma-aminobutyric acid (GABA) or glycine receptor agonists and antagonists, rhythmic motor activity was induced by bath application of acetylcholine (ACh), N-methyl-D,L-aspartate (NMA), or serotonin (5-HT) while monitoring bilateral ankle flexor and extensor electroneurograms (ENGs). The timing of rhythmic flexor and extensor discharge was consistent with that seen during overground locomotion in 27% of 84 bath applications of these substances (n = 65 preparations). 2. Subsequent addition of the GABAA receptor agonist muscimol, the GABAB receptor agonist baclofen, or glycine, abolished rhythmic activity in 95% of the tested applications. 3. GABAB receptor blockade did not disrupt alternating patterns of ENG discharge. However, addition of the GABAA receptor antagonist bicuculline, or the glycine receptor antagonist strychnine, transformed alternating flexor-extensor and left-right activity into patterns characterized by bilaterally synchronous rhythmic activation of all hindlimb ENGs. The onset of individual ENG bursts was more abrupt following bicuculline or strychnine. Strychnine also synchronized high-frequency (4-8 Hz) packets of rhythmic discharge within ENG bursts. 4. Some preparations developed synchronous, but unstable, rhythmic activity in the presence of bicuculline or strychnine alone. However, NMA, 5-HT, or ACh was usually required in addition to these antagonists to promote sustained rhythmic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1995

An unusual sonographic appearance of a chronic renal peritransplant lymphocele.

Lymphoceles are the most common renal peritransplant collections. They typically develop and progress within 6 months of transplantation. Clinical presentation is varied and includes azotemia, lower extremity edema, fever, weight gain, tenderness over the allograft, palpable mass, and thromboembolic complications. Herein, we present a chronic peritransplant lymphocele with unusually thick and irregular internal septae which could easily be mistaken for other complex peritransplant or pelvic masses. In this case, color Doppler flow imaging helped to limit the differential diagnosis as well as to guide appropriate intervention. Additionally, we describe the pathophysiology of lymphocele formation and treatment options.

Adult↗
PubMed1994

Some limitations of ventral root recordings for monitoring locomotion in the in vitro neonatal rat spinal cord preparation.

Studies of the in vitro neonatal rat spinal cord have used ventral root recordings, among other methods, to monitor locomotion. However, whether ventral root activity reliably indicates the presence of hindlimb stepping has not been established. In the present study, we use an in vitro spinal cord-hindlimb preparation to analyse lumbar ventral root recordings obtained while simultaneously observing coordinated stepping movements or rhythmic alternation of ankle flexor and extensor nerve activity. During locomotion ventral root patterns included: tonic activity, rhythmic left-right alternation with in-phase activity of ipsilateral roots, and rhythmic activity that was in-phase both bilaterally and ipsilaterally at different segmental levels. Ventral root transection during rhythmic activity demonstrated that ankle flexor and extensor nerve activity depended on motor units coursing through common lumbar roots in 31/39 hindlimbs. These findings suggest that ventral root recordings alone are not a reliable means of monitoring phasic hindlimb flexor and extensor activity during locomotion in the in vitro rat preparation.

Acetylcholine↗
PubMed1994

A comparison of motor patterns induced by N-methyl-D-aspartate, acetylcholine and serotonin in the in vitro neonatal rat spinal cord.

Using an in vitro preparation from neonatal rat spinal cord, we compared the motor patterns induced by three putative locomotion-inducing substances. N-Methyl-D,L-aspartate (NMA) induced rhythmic hindlimb nerve activity in 17/20 preparations that was characterized by: (a) side-to-side alternation, but co-activated intralimb flexor-extensor pairs in 29%; (b) bilateral co-activation of all flexors and extensors in 24%; and c) rhythmic but poorly coordinated activity in 35%. Acetylcholine induced rhythmic activity in 34/35 preparations, which in 68% of animals was characterized by side-to-side alternation of co-activated intralimb flexor-extensor pairs. Only rarely did NMA (2/20 trials) and acetylcholine (1/35 trials) induce sustained ENG patterns compatible with hindlimb stepping. Serotonin, however, induced rhythmic activity in 22/24 preparations that was consistent with locomotion in intact rats in 13/22 (59%). These findings demonstrate that exogenously applied neurochemicals induce a variety of in vitro motor rhythms although some substances preferentially activate specific patterns. The results also highlight the importance of monitoring flexor and extensor activity from both hindlimbs in order to distinguish locomotor-like patterns from other types of neurochemically-induced rhythms.

Acetylcholine↗