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Biomedical subjects

W F Collins

Publications and source records attributed to W F Collins.

At least 19 recordsLinked to original sources
PubMed1992

Differential effect of castration on the somal size of pudendal motoneurons in the adult male rat.

We have examined the organization of the androgen sensitivity of pudendal motoneurons in adult male rats. Comparisons of mean somal cross sectional area of pudendal motoneurons identified by retrograde labeling with horseradish peroxidase were made between three treatment groups: castrates with testosterone propionate supplementation, castrates with placebo, and sham castrates. Bulbospongiosus and ischiocavernosus motoneurons were sensitive to androgen treatment, whereas external anal sphincter and external urethral sphincter motoneurons were not.

Animals↗
PubMed1992

Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data. Results of the second National Acute Spinal Cord Injury Study.

The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.

Acute Disease↗
PubMed1991

Pudendal motor and premotor neurons in the male rat: a WGA transneuronal study.

Anatomical studies using retrograde neuronal tracers were carried out to identify pudendal motoneurons and putative lumbosacral interneurons involved in the generation of penile reflexes in the adult male rat (Sprague-Dawley). In agreement with previous studies, injection of the direct neuronal tracers, horseradish peroxidase or fluoro-gold, into the left M. bulbospongiosus (dorsal division) resulted in direct retrograde labeling of motoneurons only in the ipsilateral dorsomedial (DM) nucleus. In contrast, similar injections of the transneuronal tracer, wheat germ agglutinin (WGA), resulted in direct retrograde labeling of ipsilateral DM motoneurons as well as transneuronal labeling of contralateral DM motoneurons and of bilaterally located putative spinal interneurons. The WGA-labeling was determined to be transneuronal by a series of nerve cut experiments. The direct retrograde WGA-labeling of ipsilateral DM motoneurons and the transneuronal WGA-labeling of contralateral DM motoneurons and bilateral putative spinal interneurons occurred with different time courses. Direct retrograde labeling of ipsilateral DM motoneurons was seen at 20 hours survival and persisted up to 7 days survival. The shortest survival period for detecting transneuronal labeling of contralateral DM motoneurons and putative interneurons was 2 days. Transneuronal WGA-labeling of contralateral DM motoneurons was transient in that the intensity of label increased from 2 to 3 days survival but was markedly reduced at 7 days survival. At the same time, the number of WGA-labeled putative interneurons increased with longer survival times up to 7 days. WGA-labeled putative interneurons were located primarily in regions receiving dendritic projections from WGA-labeled DM motoneurons and, in particular, 1) the ventral gray matter between the DM and dorsolateral nuclei and 2) near the central canal and extending dorsally to the dorsal gray commissure. The rapid and extensive transneuronal transport between DM nuclei suggests that direct synaptic coupling may mediate coordinated, bilateral activation of DM motoneurons.

Animals↗
PubMed1991

Interaction of baseline synaptic noise and Ia EPSPs: evidence for appreciable negative correlation under physiological conditions.

1. In the anesthetized cat, simultaneous intracellular recordings from pairs of spinal motoneurons were undertaken to see whether the amplitude of single-fiber excitatory postsynaptic potentials (EPSPs) in both cells fluctuated in a coordinated manner that would indicate correlative mechanisms at either pre- or post-synaptic level. Although these recordings revealed correlated fluctuations in the baseline, the single-fiber Ia/EPSPs recorded with the spike-triggered averaging technique exhibited no correlated fluctuations and, unexpectedly, virtually no increase in baseline variance associated with the EPSP. However, the fact that these experiments were carried out under conditions of high baseline synaptic noise (i.e., with muscle stretch) may have influenced the outcome because of interaction between EPSP and synaptic noise, and this possibility was evaluated explicitly. 2. A given connection was studied under low noise by electrically stimulating a single Ia fiber in the absence of muscle stretch. The same connection was analyzed under conditions of high noise by activating the fiber and all other stretch receptor afferents with muscle stretch and by using spike-triggered averaging to extract the EPSP. The differences in mean EPSP amplitude at a given connection under conditions of low noise and high noise were minimal. 3. Fluctuations in EPSP amplitude were then determined to see whether these were influenced by presence of baseline synaptic noise and whether the interaction was nonlinear. Two methods were used to measure EPSP fluctuations: measurement of the variance associated with the EPSP, and determination by the use of deconvolution methods of the discrete amplitude components associated with the EPSP. 4. An increase in baseline variance was observed during the EPSP evoked under low noise conditions at all six connections studied in this way. This increase disappeared at two of these connections when examined under high noise. This may help to explain the results obtained in pairs of motoneurons. 5. The deconvolution results were used to calculate the variance of the noise-free EPSP. This was found to differ from the variance of the EPSP amplitude distribution measured directly from the change in baseline variance associated with the EPSP. Analytic techniques suggested that this difference could be explained in most cases by negative correlation between the EPSP and baseline synaptic noise. These considerations led to an analytic method to assess the reliability of the deconvolution result. 6. Simulation studies revealed that the baseline variance increase associated with the EPSP is also highly dependent on the correlation between signal and noise.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

The Sterling Hall of Medicine, Yale University School of Medicine.

A brief history of the Sterling Hall of Medicine at Yale University is presented; this building was erected and dedicated in 1925. This event signified the beginning of a new era for the Yale University School of Medicine, making it possible to attract a caliber of faculty that has enabled the School to attain its present place in medical education.

Connecticut↗
PubMed1990

A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study.

Studies in animals indicate that methylprednisolone and naloxone are both potentially beneficial in acute spinal-cord injury, but whether any treatment is clinically effective remains uncertain. We evaluated the efficacy and safety of methylprednisolone and naloxone in a multicenter randomized, double-blind, placebo-controlled trial in patients with acute spinal-cord injury, 95 percent of whom were treated within 14 hours of injury. Methylprednisolone was given to 162 patients as a bolus of 30 mg per kilogram of body weight, followed by infusion at 5.4 mg per kilogram per hour for 23 hours. Naloxone was given to 154 patients as a bolus of 5.4 mg per kilogram, followed by infusion at 4.0 mg per kilogram per hour for 23 hours. Placebos were given to 171 patients by bolus and infusion. Motor and sensory functions were assessed by systematic neurological examination on admission and six weeks and six months after injury. After six months the patients who were treated with methylprednisolone within eight hours of their injury had significant improvement as compared with those given placebo in motor function (neurologic change scores of 16.0 and 11.2, respectively; P = 0.03) and sensation to pinprick (change scores of 11.4 and 6.6; P = 0.02) and touch (change scores, 8.9 and 4.3; P = 0.03). Benefit from methylprednisolone was seen in patients whose injuries were initially evaluated as neurologically complete, as well as in those believed to have incomplete lesions. The patients treated with naloxone, or with methylprednisolone more than eight hours after their injury, did not differ in their neurologic outcomes from those given placebo. Mortality and major morbidity were similar in all three groups. We conclude that in patients with acute spinal-cord injury, treatment with methylprednisolone in the dose used in this study improves neurologic recovery when the medication is given in the first eight hours. We also conclude that treatment with naloxone in the dose used in this study does not improve neurologic recovery after acute spinal-cord injury.

Acute Disease↗
PubMed1988

Modulation of EPSP amplitude during high frequency stimulation depends on the correlation between potentiation, depression and facilitation.

High frequency bursts were delivered every 2 s to single group Ia fibers in anesthetized cats. The modulation of EPSP amplitude in target motoneurons was determined. Changes in EPSP amplitude during the high frequency stimulation (facilitation or depression) were correlated with those occurring 2 s after the burst (potentiation). Connections displaying high levels of potentiation exhibited more depression resulting in a net negative modulation. Negative amplitude modulation was greatest at connections on low rheobase ('small') motoneurons that develop large EPSPs. Positive modulation occurred at a subset of connections on high rheobase ('large') motoneurons that exhibit small EPSPs. We suggest that these synaptic properties permit the appropriate amount of depolarization to be delivered to the heterogeneous elements of the motoneuron pool during high frequency Ia fiber activity characteristic of the step cycle.

Action Potentials↗
PubMed1986

The spinal cord injury problem--a review.

The incidence of spinal cord injury in the United States is between 50 and 55 million per year. The personal and societal costs have been an impetus for experimental studies that defined the posttraumatic pathological and biochemical changes from which the hypothesis has arisen that a portion of the resulting neurological deficit is caused by the response of the spinal cord to the injury. Alteration in this response has been a therapeutic goal. Clinical series over a number of years with varied treatment regimens have failed to show any significant difference in neurological outcome. A single randomized clinical trial of 'high dose' 'low dose' steroid treatment failed to support the secondary injury response hypothesis. The experimental studies and lack of therapeutic effectiveness of present treatment both support the concept of further experimental studies and further randomized clinical trials. It is important to test the hypothesis of secondary injury since, if it is a cause of a portion of the resultant loss of neurological function, the benefit of its control would extend beyond spinal cord injury to other central nervous system injuries.

Adrenal Cortex Hormones↗
PubMed1986

On the specificity of sensory reinnervation of cat skeletal muscle.

Experiments were addressed to the following questions: when a muscle nerve is sectioned and regenerates to what extent are muscle receptors (spindles and tendon organs) reinnervated? is the reinnervation specific? that is, do group Ia and spindle group II fibres preferentially reinnervate spindles and do group Ib fibres preferentially reinnervate tendon organs? what are the consequences to the afferent of failure to re-establish appropriate receptor innervation? In normal cats, and in cats 3, 6 or 9 months after section and resuture of the medial gastrocnemius muscle nerve, medial gastrocnemius afferent fibres in continuity were impaled in dorsal rootlets for recording and stimulation. Receptor innervation was determined electrophysiologically by manipulation of the medial gastrocnemius muscle. Afferent fibre type was determined by the presence (group Ia or spindle group II) or absence (group Ib) of field potentials in the homonymous motoneurone pool in response to activation of the afferent fibre. In normal cats, two-thirds of recorded afferents innervated spindles; 89% of these generated field potentials detected in the motoneurone pool. One-third of recorded afferents innervated tendon organs; none of these generated such field potentials. In operated cats, about half of the recorded afferents innervated spindles, about one-third responded abnormally or not at all to muscle manipulation, and fewer than one-tenth innervated tendon organs. Numbers of afferents which innervated spindles increased with time. The proportion of afferents generating field potentials was smaller in operated than in normal animals (40% vs. 60%) and declined progressively with time. Field potentials were generated by fibres in all categories of receptor reinnervation. This ability was lost at long post-operative intervals by fibres failing to reach the muscle. Conduction velocity of fibres fell in operated animals. Fibres reinnervating their original type of receptor (e.g. group Ia fibre----spindle) exhibited greater conduction velocity than fibres innervating an inappropriate receptor or no receptor. From these findings and other considerations (see Discussion) we conclude that following section and resuture of the medial gastrocnemius muscle nerve: about 75% of afferents regenerate into the medial gastrocnemius muscle, many more spindles than tendon organs become reinnervated, random populations of groups Ia and Ib (and probably spindle group II) fibres reinnervate spindles, fibres which fail to re-establish appropriate receptor innervation also fail to recover normal conduction velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Amplitude modulation of EPSPs in motoneurons in response to a frequency-modulated train in single la afferent fibers.

In anesthetized cats, single group Ia fibers were activated with a train of 52 stimuli whose interspike intervals were obtained from the discharge of a group Ia fiber in a walking cat (courtesy of Dr. G. E. Loeb, NIH). The EPSPs recorded in motoneurons to which the afferents projected were averaged in register (EPSP1, EPSP2, ..., EPSP52) in response to multiple presentations of the train at a rate (0.77 Hz) similar to the stepping rate of the cat. Amplitudes of these averaged EPSPs were found to be highly variable, depending both on afferent discharge rate and history of activation. The initial EPSP was generally potentiated, and EPSPs in the high-frequency (greater than 200 Hz) middle portion of the train were generally reduced in amplitude. Connections at which the first EPSP was most potentiated tended to be those which showed the most depression of EPSP amplitude during the high-frequency portion of the train. Thus, at some connections, modulation of EPSP amplitude during the frequency-modulated train was much greater than at other connections. In general, the extent of modulation was greater on low-rheobase motoneurons than on high-rheobase motoneurons. We suggest that these differences in transmission permit type S (i.e., low-rheobase) motoneurons, which on average generate the largest EPSPs, to reach threshold at low levels of input (size principle) but prevent excessive depolarization due to temporal summation during high-frequency stimulation.

Afferent Pathways↗
PubMed1985

Crossing dendrites may be a substrate for synchronized activation of penile motoneurons.

The morphology of perineal and extensor hindlimb motoneurons in adult male rats was examined using retrograde labelling with wheat germ agglutinin and horseradish peroxidase. Bulbocavernosus and levator ani motoneurons, located in the spinal nucleus of the bulbocavernosus, were organized as distinct clusters of motoneurons in the medial ventral area of the lumbar (L6-L5) spinal cord and possessed prominent contralaterally projecting dendritic arborizations. In similar experiments, laterally located soleus and extensor digitorum longus motoneurons did not exhibit a similar organization. These findings are discussed with respect to their possible role in the synchronized bilateral activation of penile muscles.

Animals↗
PubMed1985

Potentiation of transmission at Ia-motoneuron connections induced by repeated short bursts of afferent activity.

Single medial gastrocnemius Ia-afferent fibers and motoneurons to which they projected were simultaneously impaled in anesthetized cats. Each Ia-afferent fiber was electrically stimulated once every 2 s with short high-frequency bursts (32 shocks at 167 Hz) followed by 1-11 test shocks. The resulting motoneuron excitatory postsynaptic potentials (EPSPs) were recorded and averaged in register. The interval between the end of one burst and the beginning of the next was 2 s; therefore, the amplitude of the first EPSP in the burst was considered to be a measure of efficacy of transmission 2 s after the burst. At most connections (23/29) the mean amplitude of the first EPSP in the burst was equal to or larger than the mean amplitude of control EPSPs produced by low-frequency (18-Hz) stimulation. Enhancement of transmission was maximum 50-100 ms after the burst, and the amplitude of the test EPSP delivered at this time was always greater than that of the control. The period of enhanced transmission appeared to decay more rapidly at connections with small EPSPs. The greatest amount of EPSP amplitude enhancement at 50 or 100 ms after the burst was observed at connections at which EPSP amplitude increased during the burst. The shape (rise time, half width) of potentiated EPSPs was the same as control EPSPs averaged during low-frequency (18-Hz) stimulation. Multiple shocks delivered at low frequency between bursts revealed that enhanced transmission following the high-frequency burst is very sensitive to the effects of low-frequency test stimulation. Furthermore, increasing the number of shocks during the interval between bursts reduced the enhancement of the first EPSP in the burst. We suggest that modulation of synaptic transmission after high-frequency bursts differs across Ia-motoneuron connections. These time-dependent changes associated with short bursts of firing (which are similar in frequency to those observed in Ia-fibers supplying hind-limb muscles during stepping) emphasize the necessity to consider the history of the discharge pattern of the group Ia fiber in assessing efficacy at individual Ia-motoneuron connections.

Animals↗
PubMed1985

A phase I trial of naloxone treatment in acute spinal cord injury.

Results of a Phase I trial of the opiate antagonist naloxone for treatment of patients with acute spinal cord injury are reported. Naloxone was administered in doses ranging from 5 to 200 mg/sq m (0.14 to 5.4 mg/kg) for up to 48 hours. The patients ranged in age from 16 to 79 years (mean 37 years). Twenty patients received naloxone as a loading dose of 5 to 50 mg/sq m (0.14 to 1.43 mg/kg), followed by a maintenance dose of 20% of the loading dose given as a continuous infusion hourly for 47 hours (Group 1). Nine patients received a loading dose of 100 to 200 mg/sq m (2.7 to 5.4 mg/kg) and a maintenance dose of 75% of the initial dose hourly for 23 hours (Group 2). These higher doses (2.7 to 5.4 mg/kg) have been found to be effective in experimental spinal cord injury. Neurological examinations were performed and somatosensory evoked potentials (SEP's) were obtained as soon after admission as possible and again 1, 2, 3, and 7 days, 3 weeks, and 6 weeks to 6 months after admission. The 20 Group 1 patients who received 1.43 mg/kg or less of naloxone showed no improvement in neurological status or SEP's. All but three (15%) of these patients had a complete neurological deficit at the time of admission. Treatment was begun an average of 12.9 hours after injury. Among the nine Group 2 patients treated with 2.7 mg/kg or more, there were five patients (56%) with incomplete deficits. This group received naloxone an average of 6.6 hours after admission. Two of the five Group 2 patients with incomplete lesions showed improvement in their neurological condition and/or SEP's within 36 hours of receiving the drug. One of the four Group 2 patients with a complete lesion at the time of admission was able to localize pressure sensation in his legs 36 hours after completion of the drug infusion. Four Group 2 patients (two with complete and two with incomplete lesions) have shown improvement in their SEP's, suggesting recovery of SEP's in a dose-related fashion. Four patients experienced increased pain after administration of the loading dose and during the maintenance infusion; in only one patient was this severe enough to require discontinuation of the drug. Of the 29 patients treated with naloxone, four died within 6 weeks of admission, for a mortality rate of 13.8%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study.

A multi-center double-blind randomized clinical trial was conducted by the National Acute Spinal Cord Injury Study Group to examine the efficacy of high-dose methylprednisolone (1000-mg bolus and 1000 mg daily thereafter for 10 days) compared with that of a standard dose (100-mg bolus and 100 mg daily for 10 days). No significant difference was observed in neurological recovery of motor function, pinprick response, or touch sensation 1 year after injury between the two treatment groups, after adjustment for other potentially confounding factors. Analyses that specifically took into account the patients' total steroid dose and relative weight confirmed the lack of a steroid treatment effect. The case fatality rate was 10.7% during the 1st year after injury, and this was not associated with the steroid treatment protocol or the patient's gender. Deaths did occur significantly more frequently among patients who were completely (15.3%) and partially (8.6%) plegic than among those who were paretic (2.5%, p = 0.0005), and among patients aged 50 years or older (38.6%, p = 0.0001).

Clinical Trials as Topic↗
PubMed1984

Efficacy of methylprednisolone in acute spinal cord injury.

A multicenter double-blind randomized trial was conducted to examine the efficacy of a high dose of methylprednisolone (1,000-mg bolus and daily thereafter for ten days) compared with a standard dose (100-mg bolus and daily thereafter for ten days) in 330 patients with acute spinal cord injury. No difference in neurological recovery of motor function or pinprick and light touch sensation was observed between the two treatment groups six weeks and six months after injury. The lack of a treatment effect was independent of the severity of the initial lesion or the time from injury to starting treatment. Although not statistically significant, early case fatality was greater in the high-dose protocol (relative risk of 3.1 and 1.9, less than or equal to 14 and 15 to 28 days after injury, respectively) but not from 29 to 210 days after injury. Wound infections of both trauma and operative sites were more prevalent in the high-dose regimen (relative risk of 3.6).

Acute Disease↗
PubMed1984

A review of treatment of spinal cord injury.

Spinal cord injury remains a devastating event to the person sustaining the injury. Not only the cost of acute and rehabilitation care, but also the loss of productivity of the victims who are often young men injured at a highly productive period of their lives are a costly illness for society as a whole. In the past 20-30 years, there has been continual improvement in the morbidity and mortality from spinal cord injury with the improvement in prevention of a second injury, prevention of secondary renal, pulmonary and cutaneous complications, better techniques for stabilization of the spinal column, and more effective utilization of remaining neurological function with improved rehabilitation therapy. It remains, however, difficult to demonstrate an effect from a wide range of 'acceptable' medical or surgical care on the resultant loss of spinal cord function. The lack of improvement in preventing or reversing the loss of spinal cord function in spite of marked variations in acute spinal cord injury care indicate that acceptable data are still lacking to determine the role of aggressive and conservative management. The need for a more organized approach to the problem is obvious.

Animals↗
PubMed1984

Heterogeneity of group Ia synapses on homonymous alpha-motoneurons as revealed by high-frequency stimulation of Ia afferent fibers.

Excitatory postsynaptic potentials (EPSPs) were recorded in medial gastrocnemius (MG) motoneurons following intraaxonal electrical stimulation of single spindle afferent fibers in anesthetized cats. High-frequency bursts of 32 shocks were delivered to the afferent axon and the EPSPs were averaged in the motoneuron. EPSP amplitude generally changed during the burst, in some cases increasing and in other cases decreasing, depending on the connection. Interpretation of these changes was complicated by potentiation of the initial EPSPs in the burst that occurred with the repeated bursts. The extent of the potentiation varied from connection to connection. The magnitude of facilitation or depression during a burst of standard frequency (167 Hz) was determined by comparison of EPSPs at the end of the burst with the mean EPSP obtained during low-frequency stimulation (18 Hz). Large amplitude EPSPs tended to depress, whereas the small amplitude EPSPs facilitated. Facilitation was more prevalent in motoneurons with large rheobases and depression was more often observed in small rheobase motoneurons. The use of partial correlations, which was necessary because of the inverse correlation between EPSP amplitude and motoneuron rheobase, revealed that facilitation-depression behavior during repetitive stimulation is correlated primarily with EPSP amplitude rather than with motoneuron rheobase. Acute transection of the spinal cord resulted in no change in motoneuron rheobase but considerable enlargement of mean EPSP amplitude at low frequencies of stimulation. A significant increase in the amount of depression during repetitive stimulation was noted under these conditions. These results indicate considerable heterogeneity in the response of individual connections to repetitive stimulation. We suggest that this heterogeneity results from differences in transmitter release at different connections. This heterogeneity must also have functional consequences related to susceptibility for firing of different motoneurons under various physiological conditions that can include afferent discharge frequencies equivalent to those used in this study.

Afferent Pathways↗