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Biomedical subjects

R S Goldstein

Publications and source records attributed to R S Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1991

Different effects of the biogenic amines dopamine, serotonin and octopamine on the thoracic and abdominal portions of the escape circuit in the cockroach.

1. The escape behavior of the cockroach, Periplaneta americana, is known to be modulated under various behavioral conditions (Camhi and Volman 1978; Camhi and Nolen 1981; Camhi 1988). Some of these modulatory effects occur in the last abdominal ganglion (Daley and Delcomyn 1981a, b; Libersat et al. 1989) and others in the thoracic ganglia (Camhi 1988). Neuromodulator substances are known to underlie behavioral modulation in various animals. Therefore, we have sought to determine whether topical application of putative neuromodulators of the escape circuit enhance or depress this circuit, and whether these effects differ in the last abdominal vs. the thoracic ganglia. 2. Topical application of the biogenic amines serotonin and dopamine to the metathoracic ganglion modulates the escape circuitry within this ganglion; serotonin decreases and dopamine enhances the response of leg motoneurons to activation of interneurons in the abdominal nerve cord by electrical or wind stimulation. 3. The neuropil of the thoracic ganglia contains many catecholamine-histofluorescent processes bearing varicosities, providing a possible anatomical substrate for dopamine release sites. 4. Topical application of octopamine to the terminal abdominal ganglion enhances the response of abdominal interneurons to wind stimulation of the cerci. In contrast, serotonin and dopamine have no effect at this site. 5. It is proposed that release of these biogenic amines may contribute to the known modulation of the cockroach escape response.

Animals↗
PubMed1991

Normal segmentation and size of the primary sympathetic ganglia depend upon the alternation of rostrocaudal properties of the somites.

Metameric organization of the dorsal root ganglia (DRG) and ventral roots depends on the alternation of rostrocaudal properties within the somites. In addition, the size of DRG is likely to be regulated by the adjacent mesoderm, because unilateral creation of a paraxial mesoderm with only rostral somitic (RS) halves, leads to the development of non-segmented DRG that are larger and contain more cells than the sum of the contralateral, control DRG. We have now extended our studies of the role of the paraxial mesoderm in the morphogenesis of the peripheral nervous system (PNS) to another metameric PNS component, the sympathetic ganglia (SG). The development of the primary sympathetic chain was studied in chick-quail chimeras with multiple half-somite grafts using quantitative morphometric analysis. In the presence of an exclusively rostral or caudal somitic mesoderm, segmentation of the initially homogeneous primary sympathetic chain into ganglia is prevented. Therefore, the SG, like the DRG and ventral roots, require the normal rostrocaudal alternation of the somitic mesoderm for segmental morphogenesis. On embryonic day 4 (E4), there is a 38% average decrease in the volume of the primary sympathetic chain opposite a RS mesoderm, compared with the primary chain on the unoperated side. This is in contrast to the average increase of 27% in the volume of the DRG opposite the grafted mesoderm in the same embryos. Our results, and classical observations, have led us to propose a model in which the mesoderm controls DRG and SG size by modulating the partition of migrating NC precursors between the anlage of these two ganglion types. According to this model, the reduction in SG volume and concomitant increase in DRG volume observed opposite RS grafts, results from the arrest in the DRG anlage of neural crest cells that normally migrate to the SG.

Animals↗
PubMed1991

Influence of noninvasive positive pressure ventilation on inspiratory muscles.

Intermittent positive pressure ventilation reduces inspiratory muscle electromyographic activity among patients with restrictive ventilatory failure. It has therefore been suggested that the reduction of energy expenditure at night could result in improved inspiratory muscle function during the day. Reported successes with nocturnal ventilation have not included measurements of inspiratory muscle endurance. We therefore electively ventilated six (five female, one male) patients (mean +/- SD) aged 36 +/- 13 years in whom respiratory failure (room air PaCO2, 60 +/- 13 mm Hg; PaO2, 44 +/- 11 mm Hg; SaO2, 75 +/- 12 percent) was consequent on restrictive ventilatory disease (vital capacity, 25 +/- 7 percent predicted; FEV1/FVC, 81 +/- 12 percent; total lung capacity, 40 +/- 5 percent predicted; MIPRV -42 +/- 10 cm H2O; MEP, 81 +/- 28 cm H2O). Positive pressure ventilation was administered with a customized closely fitting nasal mask attached to a volume-cycled pressure-limited ventilator. Full respiratory polysomnographic measurements as well as arterial blood gases, pulmonary function, distance walked in six minutes, and inspiratory muscle endurance were measured at baseline and after 3 and 14 months of ventilation. Ventilation improved saturation (baseline on O2; SWS 87 +/- 10, REM 79 +/- 14, ventilator on R/A; SWS 90 +/- 6, REM 89 +/- 5 percent) and transcutaneous Pco2 (baseline on O2; SWS 85 +/- 26, REM 94 +/- 39, ventilator on R/A; SWS 53 +/- 9, REM 58 +/- 9 mm Hg). During ventilation, the quantity and distribution of sleep was similar to that observed prior to ventilation. Daytime gas exchange improved as did the six-minute walking test (initial test = 429 +/- 120 m, three months after ventilation = 567 +/- 121 m), both of these improvements being sustained at 14 months. Inspiratory muscle endurance measured using a pressure threshold load (mean mouth pressure = 45 percent MIPRV) improved from 7.1 +/- 3.4 minutes at baseline to 14.8 +/- 7.6 minutes at 3 months, an improvement sustained at 14 months. There was no change in measured lung volumes or respiratory muscle strength. We conclude that the improvement in nocturnal gas exchange, daytime functioning, and arterial blood gases resulting from nocturnal positive pressure ventilation is associated with an increase in inspiratory muscle endurance sustained at 14 months.

Adult↗
PubMed1991

Hepatic and renal conjugation (Phase II) enzyme activities in young adult, middle-aged, and senescent male Sprague-Dawley rats.

Acetaminophen (APAP)-induced nephrotoxicity is age dependent in male Sprague-Dawley rats: nephrotoxicity occurs at lower dosages of APAP in 12- to 14-month olds compared with 2- to 3-month olds. The mechanisms responsible for enhanced nephrotoxicity in 12-month-old Sprague-Dawley rats are not entirely clear, but may be related to age-dependent differences in APAP metabolism in liver and/or kidney. Major pathways of hepatic APAP metabolism include sulfation and glucuronidation; glutathione conjugation represents a pathway for detoxification of reactive oxidative APAP metabolites. The present studies were designed to quantify in vitro activity of three Phase II enzyme activities: glutathione S-transferase using 1-chloro-2,4-dinitrobenzene as substrate, UDP-glucuronyl transferase using APAP as substrate, and sulfotransferase using APAP as substrate, in subcellular fractions of liver and kidney of 3-, 12-, 18-, and 30-month-old naive male Sprague-Dawley rats. In liver, glutathione S-transferase, UDP glucuronyl transferase, and sulfotransferase activities were not significantly different in rats from 3 through 30 months of age. Renal UDP glucuronyl transferase and sulfotransferase activities were similar in rats from 3 through 30 months of age. In contrast, renal glutathione S-transferase activity was characterized by a lower Km in 12- and 30-month olds when compared with 3-month olds. These data suggest that the reduced total systemic clearance of APAP in 12-month-old male Sprague-Dawley rats previously observed cannot be attributed to age-dependent differences in hepatic APAP metabolism. In addition, it is unlikely that differences in renal APAP metabolism contribute to age-dependent APAP nephrotoxicity.

Acetaminophen↗
PubMed1991

Characterization of the renal effects and renal elimination of sulotroban in the dog.

The renal effects and renal handling of the nonprostanoid thromboxane receptor antagonist, sulotroban (4-[2-(phenylsulfonylamino)ethyl]phenoxyacetic acid), were characterized in dogs. Sulotroban was infused i.v. at 0.06, 0.2, 0.6 and 1.0 mg kg-1 min-1 (plus prime) for 180 min. Arterial blood pressure was reduced significantly during infusion of the 1.0 mg kg-1 min-1 dosage only. Diuresis, characterized by increases in both fractional and absolute urinary excretion of sodium, potassium, chloride and calcium, and decreases in urine osmolality occurred at each of the sulotroban dosages tested. The renal clearance of sulotroban exceeded the glomerular filtration rate, suggesting renal secretion of sulotroban. The transport maximum for sulotroban secretion was approximately 160 micrograms kg-1 min-1. Renal cortical slices from naive dogs accumulated [14C]sulotroban against a concentration gradient. Sulotroban accumulation was blocked by metabolic inhibitors (dinitrophenol and sodium azide) and inhibitors of organic anion transport (probenecid and p-aminohippurate), but not by inhibitors of organic cation transport (cyanine and tetraethylammonium), suggesting that tubular secretion of sulotroban is mediated by an organic anion transport system. It was concluded that: 1) decreases in blood pressure occurred only after high dosages and were associated with high plasma sulotroban concentrations; 2) diuresis occurred at all dosages and may represent a separate pharmacological action unrelated to thromboxane receptor antagonism; and 3) renal excretion of sulotroban in the dog occurs by both filtration and tubular secretion with secretion occurring via an organic acid transporter.

Animals↗
PubMed1991

Segmentation of sensory and sympathetic ganglia: interactions between neural crest and somite cells.

The segmental pattern of peripheral ganglia in higher vertebrates is generated by interactions between neural crest and somite cells. Each mesodermal somite is subdivided into at least two distinct domains represented by its rostral and caudal halves. Most migratory pathways taken by neural crest cells in trunk regions of the axis, as well as the outgrowth of motoneuron fibers are restricted to the rostral domain of each somite. Experimental modification of the somites, achieved by constructing a mesoderm composed of multiple rostral half-somites, results in the formation of continuous and unsegmented nerves, dorsal root ganglia (DRG) and sympathetic ganglia (SG). In contrast, both neurites and crest cells are absent from a mesoderm composed of multiple-caudal half somites. However, the mechanisms responsible for gangliogenesis within the rostral half of the somite, appear to be different for DRG and SG. Vertebral development from the somites is also segmental. In implants of either multiple rostral or caudal somite-halves, the grafted mesoderm dissociates normally into sclerotome and dermomyotome. However, the morphogenetic capabilities of each somitic half differ. The lateral vertebral arch is continuous in the presence of caudal half-somite grafts and is virtually absent in rostral half-somite implants. Therefore, the rostrocaudal subdivision of the sclerotome determines the segmental pattern of neural development and is also important for the proper metameric development of the vertebrae.

Animals↗
PubMed1990

Intrinsic susceptibility of the kidney to acetaminophen toxicity in middle-aged rats.

Acetaminophen (APAP)-induced nephrotoxicity is age-dependent in male Sprague-Dawley (SD) rats: middle-aged (9-12 months old) rats exhibit nephrotoxicity at lower dosages of APAP than do young adults (2-3 months old). The present study was designed to test the hypothesis that the intrinsic susceptibility of renal tissue to APAP toxicity is increased in middle-aged rats. APAP toxicity was evaluated in renal slices from naive 3- and 12-month-old male SD rats incubated with 0-50 mM APAP for 2-8 h. Renal slice glutathione (GSH) and APAP concentrations were determined; renal function was assessed by organic anion (para-aminohippurate, PAH) and cation (tetraethylammonium, TEA) accumulation; and cell viability was assessed by lactate dehydrogenase (LDH) leakage. At each concentration of APAP tested, accumulation of APAP by renal slices was similar in 3- and 12-month-olds. APAP toxicity in renal slices from both 3- and 12-month-old rats was characterized by concentration-dependent increases in LDH leakage. In contrast to APAP nephrotoxicity in vivo, APAP toxicity in renal slices was accompanied by decreased accumulation of PAH and TEA. Additionally, APAP produced marked reductions in renal slice GSH content in a concentration-dependent manner: however, in contrast to APAP nephrotoxicity in vivo, APAP-induced GSH depletion in vitro did not precede cytotoxicity. No consistent age-dependent differences in the time- and concentration-response curves for APAP nephrotoxicity were observed. These data suggest that APAP cytotoxicity in vitro is not increased in 12-month-old rats. However, since the pattern (and mechanisms) of APAP cytotoxicity in vitro appears to be different from that observed in vivo, extrapolation of in vitro cytotoxicity to in vivo nephrotoxicity is limited. Therefore, age differences in intrinsic susceptibility of the intact kidney cannot be excluded as a mechanism contributing to enhanced APAP nephrotoxicity in middle-aged rats.

Acetaminophen↗
PubMed1990

The microenvironment created by grafting rostral half-somites is mitogenic for neural crest cells.

Chicken embryo neural crest cells that migrate into a paraxial mesoderm constructed of multiple rostral half-somites from quail embryos form unsegmented "polyganglia," instead of distinct dorsal root ganglia (DRG). We report here that the environment that is created by grafting rostral somitic (RS) moieties not only is permissive for neural crest cell migration and consequent DRG formation but also is mitogenic for the DRG precursor cells. On embryonic day 3.5 (E3.5), 1 day after surgery, there is a 42% average increase in volume of the polyganglia compared with the corresponding DRG on the unoperated side. The volume increase is accounted for by an increased number of DRG cells--an average of 46% more cells are found in the polyganglia. The increases in volume and cell number are still present a day later at E4.5 (38% and 52%, respectively) and are observed in both limb-forming and non-limb-forming regions of the embryonic axis. The mechanism for this increase in cell number and volume in the polyganglia is enhanced proliferative activity. On E3.5 the proportion of cells incorporating thymidine of the total DRG cell number is 45% higher in the polyganglia than the control side, when embryos are given a short pulse before sacrifice. This indicates that rostral sclerotomal environment stimulates the crest cells to proliferate. The difference in volume between the polyganglia and the normal DRG continues to grow until at least E8, when the polyganglia are twice as large as the control DRG. The continued increase in volume can also be accounted for by the mitogenic effect of the RS grafts, since on E4.5 the percentage of thymidine-labeled cells compared with the total cell number in DRG is 28% higher in the polyganglia than in control ganglia. This study demonstrates that the somitic microenvironment regulates the proliferation of neural crest cells in the nascent DRG.

Animals↗
PubMed1990

Effect of caffeine on ventilatory responses to hypercapnia, hypoxia, and exercise in humans.

The effect of oral caffeine on resting ventilation (VE), ventilatory responsiveness to progressive hyperoxic hypercapnia (HCVR), isocapnic hypoxia (HVR), and moderate exercise (EVR) below the anaerobic threshold (AT) was examined in seven healthy adults. Ventilatory responses were measured under three conditions: control (C) and after ingestion of either 650 mg caffeine (CF) or placebo (P) in a double-blind randomized manner. None of the physiological variables of interest differed significantly for C and P conditions (P greater than 0.05). Caffeine levels during HCVR, HVR, and EVR were 69.5 +/- 11.8, 67.8 +/- 10.8, and 67.8 +/- 10.9 (SD) mumol/l, respectively (P greater than 0.05). Metabolic rate at rest and during exercise was significantly elevated during CF compared with P. An increase in VE from 7.4 +/- 2.5 (P) to 10.5 +/- 2.1 l/min (CF) (P less than 0.05) was associated with a decrease in end-tidal PCO2 from 39.1 +/- 2.7 (P) to 35.1 +/- 1.3 Torr (CF) (P less than 0.05). Caffeine increased the HCVR, HVR, and EVR slopes (mean increase: 28 +/- 8, 135 +/- 28, 14 +/- 5%, respectively) compared with P; P less than 0.05 for each response. Increases in resting ventilation, HCVR, and HVR slopes were associated with increases in tidal volume (VT), whereas the increase in EVR slope was accompanied by increases in both VT and respiratory frequency. Our results indicate that caffeine increases VE and chemosensitivity to CO2 inhalation, hypoxia, and CO2 production during exercise below the AT.

Administration, Oral↗
PubMed1990

Daytime hypercapnia in the development of nocturnal hypoxemia in COPD.

Arterial oxyhemoglobin saturation (SaO2) falls to a variable extent during sleep in patients with COPD. These nocturnal falls in SaO2 may contribute to the development of pulmonary hypertension, nocturnal cardiac arrhythmias, and death during sleep. In order to determine which physiologic factors measured during wakefulness might contribute to the development of nocturnal hypoxemia, we performed multiple stepwise linear regression analyses in 48 patients with stable COPD with mean and lowest nocturnal SaO2 as dependent variables. It was concluded that the two chief variables, measured while awake, which are associated with alterations in nocturnal oxygenation in patients with COPD are baseline awake SaO2 and PaCO2. Hypercapnia appears to be a risk factor for the development of nocturnal hypoxemia in patients who are normoxic while awake.

Humans↗
PubMed1989

Strain differences in acetaminophen nephrotoxicity in rats: role of pharmacokinetics.

Strain differences in susceptibility of rats to acetaminophen (APAP)-induced nephrotoxicity have been previously reported. Young adult male Fischer-344 (F-344) rats are susceptible whereas weight-matched Sprague-Dawley (SD) rats are not susceptible to APAP nephrotoxicity. The present study was designed to evaluate the role of pharmacokinetics in strain-dependent APAP nephrotoxicity. Age-matched (2-month-old) male F-344 and SD rats received 250-750 mg APAP/kg, i.v., or 0-1000 mg APAP/kg, i.p. Pharmacokinetic variables were evaluated following i.v. APAP and 24 h urinary excretion of APAP and major metabolites was determined following both i.v. and i.p. administration of APAP. Following i.p. administration, nephrotoxicity was observed only in F-344 rats following 1000 mg APAP/kg; SD rats were not susceptible to APAP-induced nephrotoxicity. In contrast, nephrotoxicity did not occur in either F-344 or SD rats administered APAP i.v. Pharmacokinetic variables (volume of distribution, apparent systemic clearance, and apparent terminal half-life) of APAP were similar in F-344 and SD rats. No striking differences in the pattern of specific urinary metabolites were observed between F-344 and SD rats treated with i.p. or i.v. APAP. Thus, strain differences in APAP-induced nephrotoxicity do not appear to be due to differences in pharmacokinetics or major pathways of APAP metabolism.

Acetaminophen↗
PubMed1989

Catecholamine neurons in Aplysia: improved light-microscopic resolution and ultrastructural study using paraformaldehyde and glutaraldehyde (FaGlu) cytochemistry.

We have modified the formaldehyde-glutaraldehyde (FaGlu) histofluorescence method of Furness, Costa, and Blessing (1977a) and Furness, Costa, and Wilson (1977b) to examine wholemounts and sections of both juvenile and adult ganglia as well as peripheral tissues of Aplysia californica. FaGlu fluorescence is the result of a reaction between formaldehyde and tissue catecholamines to produce water-insoluble (fixed) fluorophores. In serially sectioned cerebral ganglia, 70-80 positive neurons were observed (many in clusters of 10-20 cells), many more than were found using the glyoxylic acid technique. Catecholamine-containing varicosities were densely packed in localized portions of the neuropil of all central ganglia. Exclusive localization in the neuropil of presumed dopamine release sites is similar to that previously found for the neuropeptide SCP but differs from the widespread ramification of varicose neurites containing 5-HT, FMRFamide, and ELH. The FaGlu technique also enabled us to study the ultrastructure of catecholamine-containing neurons. In contrast to the larger vesicles found in serotonergic and histaminergic neurons, these dopaminergic neurons contain 70 nm dense-cored vesicles.

Animals↗
PubMed1989

Acetaminophen and p-aminophenol nephrotoxicity in aging male Sprague-Dawley and Fischer 344 rats.

Strain differences in susceptibility of rats to acetaminophen (APAP)-induced nephrotoxicity have been reported previously. Young adult male Fischer 344 (F344) rats are susceptible, whereas weight-matched Sprague-Dawley (SD) rats are not susceptible to APAP nephrotoxicity. Susceptibility to APAP nephrotoxicity is also age dependent, at least in F344 rats. Middle-aged (12-15 months old) male F344 rats are more susceptible to APAP-induced nephrotoxicity than are young adult (2-4 months old) males. APAP nephrotoxicity in aging SD rats has not been evaluated. The present studies were designed to define strain differences in the nephrotoxicity of APAP and p-aminophenol (PAP), a nephrotoxic metabolite of APAP, using 2-, 3-, and 9- to 12-month-old F344 and SD rats. At 2 months of age, F344, but not SD, rats were susceptible to APAP-induced nephrotoxicity. However, at 3 months of age, strain differences were less marked, as susceptibility to APAP nephrotoxicity appeared to increase between 2 and 3 months of age only in SD rats. By 9-12 months of age, susceptibility to APAP nephrotoxicity was comparable in F344 and SD rats. No age- or strain-related differences were observed in the excretory pattern of urinary APAP and metabolites that might explain the increased susceptibility of aging rats to APAP nephrotoxicity. Strain differences in age-matched rats were not marked for PAP-induced nephrotoxicity. Susceptibility of both 3- and 12-month-old F344 and SD rats to PAP-induced nephrotoxicity was greater compared to strain-matched 2-month-old rats. In both F344 and SD rats, PAP nephrotoxicity increased only modestly between 3 and 12 months of age, indicating that increased susceptibility to PAP probably does not play a major role in the age-dependent increase in APAP nephrotoxicity. Thus, strain differences in APAP nephrotoxicity decrease with advancing age. The mechanisms mediating the increased susceptibility to APAP nephrotoxicity in middle-aged rats are not known but may relate, at least in part, to age-dependent differences in pharmacokinetics. The present study highlights the importance of considering the age of rats when evaluating drug toxicity. Even in young adult rats, subtle maturational changes in drug metabolism and/or disposition may occur, making toxicological evaluation in weight-matched rats of different strains and ages inappropriate.

Acetaminophen↗
PubMed1989

Correlates of arterial oxygenation during exercise in severe chronic obstructive pulmonary disease.

In the present study, we have undertaken a detailed analysis of the respiratory physiologic correlates of SaO2 during mild constant-load exercise in 38 patients with severe but stable COPD. Several respiratory physiologic variables that would be expected to influence exercise SaO2 were entered into a stepwise multiple linear regression analysis with mean exercise SaO2 as the dependent variable. Two variables (Dco and resting SaO2) were found to correlate strongly with mean exercise SaO2 (multiple r = 0.80; p less than 0.00001) and accounted for 65 percent of the variability among patients. The PaCO2 influenced resting SaO2 but had no independent influence on exercise SaO2. Subsequently, the model of mean exercise SaO2 derived in the present analysis was found to accurately predict mean exercise SaO2 in a group of 19 similar patients (r = 0.85; p less than 0.0001). While these findings do not establish a cause-and-effect relationship, they may provide clinicians with further insight as to which patients are likely to desaturate during exercise.

Aged↗
PubMed1989

The role of a modulatory neuron in feeding and satiation in Aplysia: effects of lesioning of the serotonergic metacerebral cells.

Food-induced arousal in Aplysia is characterized by a progressive increase in the speed and strength of biting responses elicited by a seaweed stimulus. Data from semi-intact and dissected preparations suggest that the identified, serotonergic, metacerebral cells (MCCs) of the cerebral ganglion contribute to food-induced arousal by enhancing the strength of buccal muscle contractions, and by modulating the output of the central pattern generator for biting movements. In order to test this hypothesis in intact, free-moving animals and to determine if the MCCs play a role in satiation of feeding, the behavior of animals that had their MCCs destroyed by intracellular injection of proteases was compared with that of B Cell-Lesion and Dye injection control animals (Experiment 1) or surgical control animals (Experiment 2). Nonfeeding behaviors such as defensive withdrawal responses, locomotion, and righting reflexes were unaffected by MCC lesioning. Also unaffected by MCC lesioning were appetitive feeding behaviors and the amount of food needed to satiate animals. Significant behavioral deficits in consummatory feeding behaviors, which remained stable for periods exceeding 10 d, were observed in the MCC-lesioned animals but not in controls. Lesioned animals exhibited a slowing of rate of repetitive biting responses by 40% of controls and had reduced magnitudes of repetitive bites, particularly at the end of a testing run of 10 consecutive bites. The deficit in bite magnitude was minimally evident in food-deprived animals (Experiment 1) but became more pronounced as animals were fed to satiation (Experiment 2). MCC-lesioned animals still exhibited a residual build-up of the rate and magnitude of biting responses at the onset of feeding behavior. This suggests that, in addition to the MCCs, there are other sources of modulation that contribute to plasticity of consummatory responses during the food-induced arousal state.

Animals↗
PubMed1989

Approaches to rehabilitation of patients with ventilatory insufficiency.

Multi-disciplinary rehabilitation programmes are popular in Europe and North America in the management of patients with chronic respiratory disease. Patients experience an increase in exercise tolerance, a decrease in dyspnoea and spend fewer days in hospital after completing the programme. Criteria for admission often include a well motivated nonsmoking patient with severe but stable disease of the ventilatory system. Although most patients have chronic airflow limitation, we have received a number of referrals concerning patients with non-obstructive ventilatory insufficiency, particularly thoracic restrictive disease and neuromuscular disease. Such patients frequently have hypercapnic respiratory failure, easily aggravated by increased activity or respiratory tract infection. Therefore, they cannot engage in a supervised exercise training programme unless we can stabilize their clinical state. We consider elective mechanical ventilatory support a valuable tool in their rehabilitation. Such support is often required only at night. By preventing the sleep-related alterations in arterial blood gases the clinical course of the disease is stabilized, functional level is increased and patients are then protected from episodes of acute respiratory failure which may be life-threatening.

Aged↗
PubMed1988

Contrasting time course of catecholamine accumulation and of spontaneous discharge in experimental neuromas in the rat.

Catecholamine-containing sympathetic axons in rat sciatic nerve-end neuromas were visualized histochemically. Within a few hours of ligating and sectioning the nerve, axons began to accumulate catecholamine histofluorescence. Density of labelled fibers peaked 2-5 days postoperative, then declined rapidly so that little or no label was observed beyond 12 days. Sympathectomy eliminated staining; neonatal treatment with capsaicin had no effect. Accumulation and dissipation of histofluorescence preceded the rise and fall of electrical hyperexcitability in neuromas by several days respectively.

Animals↗