Biomedical subjects

S W Carmichael

Publications and source records attributed to S W Carmichael.

At least 37 records · Page 2Linked to original sources

PubMed1991

Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients.

Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.

Adult↗

PubMed1991

Ischemic injury to the spinal cord or lumbosacral plexus after aorto-iliac reconstruction.

Between January 1, 1980, and June 30, 1989, 9 patients (6 males and 3 females) developed ischemic injury to the spinal cord or lumbosacral plexus following 3,320 operations on the abdominal aorta (0.3%). The incidence of this complication was 0.1% (2 of 1,901) after elective and 1.4% (3 of 210) after emergency abdominal aortic aneurysm repair, and 0.3% (4 of 1,209) after repair for occlusive disease. Three of the latter had prior clinical evidence of distal embolization. Eight grafts were bifurcated (aorto-iliac:four, aorto-femoral: three, aorto-ilio-femoral:one). One patient underwent extra-anatomic revascularization. Only two patients had supraceliac aortic cross-clamping and one patient underwent exclusion of both internal iliac arteries. Four patients had hypotension. Early mortality was 22% (two of nine). Severe perioperative complications, mostly due to associated visceral and somatic ischemia and sepsis, were present in seven of the nine patients. The extent and type of the neurologic injury correlated with long-term outcome. Patients with ischemic injury of the lumbosacral roots or plexus had better recovery. Attention to the pelvic circulation and the collateral blood supply is important. Use of gentle technique to prevent embolization, avoidance of hypotension and prolonged supraceliac cross-clamping, revascularization of at least one internal iliac artery, and the use of heparin may decrease but not eliminate paraplegia. Once this unexpected complication occurs, careful neurologic evaluation should be done to localize the lesion and aid prognosis.

Aged↗

PubMed1991

Decreased levels of [Met]enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide in parkinsonian adrenal medulla.

Adrenal medullary tissue was collected from parkinsonian patients at autopsy and at the time of autologous transplantation of the adrenal medulla to the caudate nucleus, and from nonparkinsonian patients at autopsy and during nephrectomy. Levels of the following neuropeptides were measured by radioimmunoassay in samples of the medullary tissue: neuropeptide Y (NPY), substance P (SP), [Met]enkephalin ([Met]ENK), vasoactive intestinal peptide (VIP), peptide YY, and bombesin-like immunoreactivity. Regression analysis was used to establish a relationship between patient age, time to organ harvest, and peptide levels in nonparkinsonian tissue. Levels of [Met]ENK, VIP, NPY, and SP were significantly lower in parkinsonian adrenal medullae than that predicted from the control group. These results suggest that the adrenal medulla of a parkinsonian patient is severely compromised, either by the disease process itself or by the antiparkinsonian medications used to treat the symptoms of the disease.

Adrenal Medulla↗

PubMed1991

Infraclavicular ulnar nerve entrapment due to a chondroepitrochlearis muscle.

The chondroepitrochlearis muscle is an extremely rare muscle, arising from the pectoralis major, crossing over the neurovascular bundle in the axilla and inserting into the brachial fascia and medial epicondyle of the humerus. This paper presents the first known neurological complication due to the chondroepitrochlearis muscle.

Adult↗

PubMed1991

Partial median nerve entrapment in the distal arm because of an accessory bicipital aponeurosis.

We present a newly described entrapment of the median nerve caused by compression in the distal arm because of an accessory bicipital aponeurosis. It is characterized by the paresis or paralysis of muscles innervated by the anterior interosseous branch of the median nerve--the flexor pollicis longus, the flexor digitorum profundus, and the pronator quadratus--as well as other more proximal median nerve innervated muscles, namely, the pronator teres and flexor carpi radialis. Sensibility is intact. The site of the Tinel's sign in the distal arm and the clinical appearance of an accessory bicipital aponeurosis help to localize the lesion. Electrodiagnostic studies are also important in establishing the site of the entrapment. The clinical and surgical findings are correlated with the internal topography of the median nerve at its site of compression. It is important to differentiate this syndrome from the classic anterior interosseous syndrome and other nerve entrapments at the elbow and arm. Surgical exploration is indicated if there is no clinical or electromyographic improvement in three to four months after the onset of symptoms.

Adult↗

PubMed1991

The cubital tunnel and ulnar neuropathy.

The anatomy of the cubital tunnel and its relationship to ulnar nerve compression is not well documented. In 27 cadaver elbows the proximal edge of the roof of the cubital tunnel was formed by a fibrous band that we call the cubital tunnel retinaculum (CTR). The band is about 4 mm wide, extending from the medial epicondyle to the olecranon, and perpendicular to the flexor carpi ulnaris aponeurosis. Variations in the CTR were classified into four types. In type 0 (n = 1) the CTR was absent. In type Ia (n = 17), the retinaculum was lax in extension and taut in full flexion. In type Ib (n = 6) it was tight in positions short of full flexion (90 degrees to 120 degrees). In type II (n = 3) it was replaced by a muscle, the anconeus epitrochlearis. The CTR appears to be a remnant of the anconeus epitrochlearis muscle and its function is to hold the ulnar nerve in position. Variations in the anatomy of the CTR may explain certain types of ulnar neuropathy. Its absence (type 0 CTR) permits ulnar nerve displacement. Type Ia is normal and does not cause ulnar neuropathy. Type Ib can cause dynamic nerve compression with elbow flexion. Type II may be associated with static compression due to the bulk of the anconeus epitrochlearis muscle.

Biomechanical Phenomena↗

PubMed1991

Microscopic anatomy of the baboon (Papio hamadryas) adrenal medulla.

Adrenal medullas of 2 baboons perfused with formaldehyde/glutaraldehyde and tannic acid were studied by light and electron microscopy. Tissues were postfixed in OsO4. This procedure allows identification of noradrenaline cells on the basis of a selective reaction of glutaraldehyde with noradrenaline vesicles. As positive control for noradrenaline cells, similarly treated mouse adrenal medullas were also examined. Light microscopic examination of thick sections of baboon medullas did not show noradrenaline cells. In contrast, mouse adrenal medullas showed noradrenaline cells scattered in small groups among the much lighter adrenaline cells. By electron microscopy no noradrenaline cells were seen in the baboon medulla while mouse adrenal medullas showed noradrenaline cells with vesicles possessing exceedingly dense cores and light spaces within their limiting membranes. Otherwise, the majority of the baboon chromaffin cells showed chromaffin vesicles which were round or elongated, 150-520 nm in diameter, and heterogenous in electron density. Cytoplasmic densities were occasionally seen attached to the inner aspect of the plasmalemma, particularly along areas close to blood capillaries. These densities could be chromaffin vesicles in the process of exocytosis. This is the first report of exocytotic profiles in a primate medulla. Occasional small vesicle-containing cells also were present. The vast majority of their vesicles were electron dense. Several possible alternatives for the varied catecholamine vesicular osmiophilia, were discussed. It was suggested that this could be attributed to varied concentration of noradrenaline and adrenaline neurohormones among the vesicle population.

Adrenal Medulla↗

PubMed1990

The secretion of catecholamines, chromogranin A and neuropeptide Y from the adrenal medulla of the cat via the adrenolumbar vein and thoracic duct: different anatomic routes based on size.

Secretion of the adrenal medulla was stimulated in nine cats by insulin-induced hypoglycemia. Levels of catecholamines (mol. wt 153-183), neuropeptide Y (mol. wt 4254) and chromogranin A (mol. wt 48,000) were measured in concurrently collected samples of adrenolumbar venous blood and thoracic duct lymph for up to 4 h following insulin administration. Insulin-induced hypoglycemia elicited an increase in the secretion of catecholamines, which reached peak levels in the adrenolumbar venous plasma at 1.5-2 h and in the lymph at 2.5 h. Although catecholamines were the most numerous measured molecules in the lymph, levels of norepinephrine and epinephrine were 75-250-fold less than those found in the adrenolumbar venous plasma. Neuropeptide Y in the adrenolumbar venous plasma reached peak levels between 1 and 1.5 h; at this time approximately 20% of the peak venous amount was detected in the lymph. Chromogranin A was found in approximately equal amounts in both plasma and lymph; the peak level in the plasma occurred at 1.5-2 h, while that in the lymph was reached at 2-3 h. We suggest that the size of a molecule influences the route it takes following exocytosis from the chromaffin vesicle. Smaller molecules such as catecholamines may pass directly into the circulation, while larger molecules such as chromogranin A may be temporarily sequestered in the interstitial space before passing into the lymph, and hence into the circulation.

Adrenal Medulla↗

PubMed1990

Adrenal medullary transplantation into the brain for treatment of Parkinson's disease: clinical outcome and neurochemical studies.

Transplantation of adrenal medulla into the caudate nucleus as treatment for Parkinson's disease was performed in eight patients. Although our previous 6-month follow-up revealed early modest improvement, an extension of that follow-up to 1 year disclosed no additional gains in any patient. At the end of 1 year, only one patient could be categorized as moderately improved; three patients were mildly improved, and four patients were unimproved. The rationale for transplanting adrenal medulla was to reestablish a physiologic source of dopamine to the striatum. We measured cerebrospinal fluid (CSF) and plasma catecholamines and metabolites before and after transplantation. Conjugated dopamine (the predominant form of dopamine found in the CSF) and homovanillic acid (the major dopamine metabolite) were modestly and inconsistently increased in the CSF. Conjugated and free epinephrine and norepinephrine, as well as 3-methoxy-4-hydroxyphenylglycol concentrations were not increased in CSF after graft placement, an indication that the adrenal chromaffin cells were no longer producing high levels of these nondopamine catecholamines and metabolites. CSF cortisol concentrations were not increased after transplantation, compared with values from controls, consistent with low numbers of functioning adrenal cortical cells contaminating the graft (or poor survival). Posttransplantation CSF did not induce a neurotrophic effect in cell cultures of 15-day embryonic rat dorsal root ganglion or PC12 (rat pheochromocytoma) cell lines. Survival of samples of patients' adrenal medullary tissue for 2 weeks in tissue culture attested to the viability of the graft at the time of transplantation. The relative concentrations of dopamine to epinephrine or norepinephrine increased in these cultured adrenal medullary cells, presumably because of loss of the glucocorticoid influence on catecholamine synthesis. A wide variety of factors could have contributed to our failure to replicate the earlier impressive results of adrenal-to-brain transplantation reported by others. Continued transplantation studies in animal models of parkinsonism are necessary for better elucidation of these factors.

Activities of Daily Living↗

PubMed1990

Mechanisms of toxicity and cellular resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium in adrenomedullary chromaffin cell cultures.

Bovine adrenomedullary chromaffin (BAMC) cells, cultured in a defined medium, were used to study the mechanisms of toxicity and cellular resistance to the catecholamine neuron toxicants 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+). The viability of the cells was assessed biochemically [cellular catecholamine content and the catalytic activities of tyrosine hydroxylase (TH) and lactate dehydrogenase (LDH)] and anatomically (by electron microscopy). When cultures of BAMC cells were exposed to MPTP or MPP+ for 3 days, a marked loss of cellular catecholamines and TH activity was observed. The addition of an inhibitor of monoamine oxidase (MAO) B (Ro 19-6327), but not MAO A (clorgyline), prevented the toxicity of MPTP but not that of MPP+. In addition, the cellular toxicity of MPP+, but not MPTP, was antagonized by desmethylimipramine, an inhibitor of cellular catecholamine uptake. The toxicity of MPP+ was time dependent, with losses of TH and the release of cellular LDH occurring after 48 h in culture. Catecholamine depletion occurred somewhat sooner, being evident after 24 h of exposure to MPP+. The cellular toxicity of MPP+ was concentration dependent and significantly enhanced by inhibitors of catecholamine vesicular uptake (reserpine, tetrabenazine, or Ro 4-1284). Electron microscopic examination of cells treated with either MPP+, tetrabenazine, or their combination revealed that MPP+ damaged BAMC cells and that this damage was markedly potentiated by the inhibition of vesicular uptake by tetrabenazine. The concentration of glucose in the culture media of untreated cells slowly decreased as a function of time. The rate of glucose consumption was markedly accelerated by MPP+ treatment and the losses in cell TH and the release of LDH into the media were preceded by a 99% depletion of glucose from the media. In cultures not treated with MPP+, lactate accumulated in the media as a function of time. Addition of MPP+ to the media increased the formation of lactate, in a concentration-dependent manner. Reserpine pretreatment further enhanced the production of lactate in response to MPP+. Culturing cells in glucose-free medium greatly potentiated the effects of MPP+ on cellular TH and catecholamines. The toxicity observed after 3 days' exposure of BAMC cells to MPP+ could be prevented when the medium was replaced with fresh medium every 24 h. The effects of glucose deprivation and reserpine were observed to be additive. The ability of MPP+ to affect mitochondrial function is determined by the capacity of the storage vesicle to sequester the pyridinium, acting as a cytosolic "buffer."(ABSTRACT TRUNCATED AT 400 WORDS)

1-Methyl-4-phenylpyridinium↗

PubMed1990

Measurement of lumbar CSF levels of met-enkephalin, encrypted met-enkephalin, and neuropeptide Y in normal patients and in patients with Parkinson's disease before and after autologous transplantation of adrenal medulla into the caudate nucleus.

The levels in lumbar cerebrospinal fluid (CSF) of neuropeptide Y (NPY), methionine enkephalin (Enk), and Enk contained in amino- and carboxy-terminus extended forms (X-Enk) were examined in nine control patients undergoing elective surgical procedures and in eight patients with advanced Parkinson's disease, before and after the autologous transplantation of adrenal medullary fragments into the right caudate nucleus. The levels of CSF Enk and X-Enk before surgery in patients with Parkinson's disease were significantly less than those observed in control patients (Enk, 166 +/- 38 vs 264 +/- 44 pg/ml; X-Enk, 794 +/- 416 vs 1497 +/- 153 pg/ml). NPY levels did not differ (221 +/- 25 vs 193 +/- 23 pg/ml). After surgery, lumbar CSF samples were taken at 6 weeks, 12 weeks, 6 months, and 9 months. Placement of adrenal medullary fragments into the striatum had no effect on the levels of NPY or Enk at any time point. The levels of X-Enk were significantly enhanced only at 12 weeks (1138 +/- 140 pg/ml) but were at presurgical levels again by 6 months. These data suggest that the transplant was not functionally contributing to the CSF levels of these peptides.

Adrenal Medulla↗

PubMed1989

Ultrastructural demonstration of exocytosis in the intact rat adrenal medulla.

Evidence is presented for morphological proof of exocytosis in the rat adrenal medulla in situ. Techniques were modified to allow perfusion of the intact adrenal gland with secretagogues (or electrical stimulation) followed by tannic acid. Unstimulated specimens demonstrated exocytotic (omega-shaped) profiles filled with flocculent material. This flocculation was also seen in the intercellular space. Stimulation of the adrenal medulla also resulted in the appearance of exocytotic profiles and an accumulation of the flocculent mass. This was often most evident in the subendothelial space. This is the first demonstration of exocytosis in the rat adrenal medulla by electron microscopy. The techniques used in this study will be useful for studying the pathway of secretory products of the adrenal chromaffin cell before they enter the vascular system.

Adrenal Medulla↗

PubMed1989

Decreased catecholamine content in parkinsonian adrenal medullae.

Autopsy specimens of adrenal medullae from parkinsonian and nonparkinsonian patients were analyzed for free catecholamines by high-performance liquid chromatography with electrochemical detection. The total free catecholamine content (nanomoles free catecholamine per milligram protein) was significantly lower in the parkinsonian patients than in the control population when the values were corrected for age and time from death to organ harvest. It is not established whether this decreased catecholamine content in the adrenals of parkinsonian patients is a concomitant of the disease itself or whether it is secondary to drug therapies used to treat the symptoms of Parkinson's disease.

Adrenal Medulla↗

PubMed1989

Decreased adrenal medullary catecholamines in adrenal transplanted parkinsonian patients compared to nephrectomy patients.

Adrenal medullary catecholamines were measured in tissue samples from eight patients who underwent autologous transplantation of the adrenal medulla to the caudate nucleus as a treatment for Parkinson's disease. These adrenal catecholamine levels were compared to a group of patients of similar age who underwent unilateral nephrectomy for renal cell carcinoma. The levels of each catecholamine, expressed as nanomoles per milligram wet weight tissue, were significantly lower (P less than or equal to 0.005) in the parkinsonian patients than in the nephrectomy patients. These observations support data reported previously from autopsy specimens and suggest that the adrenal medullae of parkinsonian patients may be a compromised source of dopamine-producing tissue; this may limit its effectiveness in eliciting maximum clinical improvement following transplantation.

Adrenal Medulla↗

PubMed1989

Cerebrospinal fluid indices of blood-brain barrier permeability following adrenal-brain transplantation in patients with Parkinson's disease.

Cerebrospinal fluid (CSF) and serum or plasma concentrations of albumin, IgG and carbidopa were measured before and after adrenal-brain transplantation in patients with Parkinson's disease to indirectly assess blood-brain barrier (BBB) integrity. Previous studies in animals have suggested that the BBB is compromised by cerebral transplantation. CSF and plasma levodopa was also measured to permit comparison with the carbidopa values, recognizing that levodopa readily crosses the BBB via facilitated transport. Our patients underwent adrenal-brain transplantation in accordance with the method of Madrazo et al. (I. Madrazo, R. Drucker-Colin, V. Diaz, J. Martinez-Mata, C. Torres, and J. J. Becerril, 1987, N. Engl. J. Med. 316: 831-834) in which adrenal medullary pieces are implanted in the head of the caudate nucleus, in contact with the cerebrospinal fluid. All patients were maintained on oral carbidopa/levodopa therapy after surgery. CSF albumin/serum albumin and CSF IgG/serum IgG ratios were initially elevated above the preoperative baseline 6 weeks after the surgery; however, these values returned to the preoperative baseline by 6 months following the operation in six of seven patients. This suggested that the BBB was sufficiently intact to exclude these larger protein molecules from the CSF of these six patients. On the other hand, exogenously administered carbidopa, which normally is largely excluded from the cerebrospinal fluid by the BBB, was modestly increased in the CSF in four of the five patients in which it was measured. This suggests that the transplant BBB might be partially patent to small molecules for at least 6 months after the surgery. Whether increased passage of carbidopa into CSF and perhaps the transplant is of clinical significance has yet to be determined. Median CSF levodopa did not increase after surgery, probably because a limited defect in the BBB would be likely to be overshadowed by the effects of facilitated transport. CT scans performed following intravenous iothalamate meglumine contrast failed to reveal enhancement (dye leakage) near the transplantation site; however, artifact from the metal surgical clips used in the Madrazo procedure prevented good visualization of the area.

Adrenal Medulla↗

PubMed1989

Indomethacin attenuates the constriction of canine epicardial coronary arteries to acetylcholine in the absence of endothelium: contribution of platelets to vasoconstriction in vivo.

This study was designed to evaluate the in vivo effect of acetylcholine on endothelial-damaged canine epicardial coronary arteries and the potential contribution of platelets to those acetylcholine-induced responses. Changes in left anterior descending artery cross-sectional area were determined by quantitative angiography in the closed chest anesthetized dog. Baseline cross-sectional area of the left anterior descending artery was not changed by removal of the endothelium by balloon-tipped catheter. Increased constrictor tone produced by prostaglandin F2 alpha was comparable in endothelium-intact and endothelium-removed vessels, supporting an endothelium-independent mechanism for prostaglandin F2 alpha in vivo. Acetylcholine produced anterior descending artery vasodilation with the endothelium intact; a comparable maximal dilator response was also obtained in the presence of increased constrictor tone (prostaglandin F2 alpha). In contrast, acetylcholine produced vasoconstriction of the anterior descending artery when the endothelium was removed. To evaluate the mechanism of acetylcholine-induced vasoconstriction in endothelium-removed vessels, the same protocol was completed in the presence of the platelet inhibitor indomethacin. Indomethacin did not alter baseline cross-sectional area or the dilator response to acetylcholine in endothelium-intact vessels. In contrast, the constrictor response in endothelium-removed vessels was antagonized, and a dilator response comparable with that in endothelium-intact vessels was produced by acetylcholine. The results of this study provide an experimental basis for the observations in human studies in which apparently atherosclerotic vessels constrict in response to acetylcholine. Removal of the endothelium in vivo abolishes the dilator response to acetylcholine and converts the acetylcholine response to vasoconstriction or vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1989

Adrenal medullary autograft transplantation into the striatum of patients with Parkinson's disease.

In eight patients with advanced Parkinson's disease, we performed autograft transplantation of adrenal medulla to the head of the caudate nucleus. Our technique was similar to that developed by Madrazo and co-workers in Mexico City. No major perioperative complications occurred except for somnolence in one patient for 8 days postoperatively. The follow-up period has been at least 6 months in seven of the patients, and only limited benefit has been apparent. The early morning Parkinson examination score in the "off" (unmedicated) state was significantly improved in one patient and slightly better in the other six. Diary card entries suggested a mild trend toward improvement (not statistically significant). Four of the seven patients were taking less levodopa 6 months after the operation than they had been preoperatively; three of five patients were no longer taking dopamine agonists postoperatively. We cannot exclude a placebo effect contributing to any of this improvement. A reduction in medication-induced dyskinesia was also noted, but this result may have been due to adjustments in doses or a slightly less potent effect of medication (or both factors). In summary, we have not yet been able to replicate the dramatic success reported for adrenal medullary transplantation by Madrazo's group, although our patients may have experienced mild to moderate improvement. We continue to maintain follow-up surveillance of these patients.

Adrenal Medulla↗

PubMed1989

Catecholamines in CSF, plasma, and tissue after autologous transplantation of adrenal medulla to the brain in patients with Parkinson's disease.

Catecholamine concentrations were measured in tissue samples of caudate and adrenal medulla in eight patients with Parkinson's disease who were taking L-dopa and were undergoing autologous transplantation of adrenal medulla to caudate nucleus. High-performance liquid chromatography with electrochemical detection was used for the measurement of analytes. Dopamine concentrations were quite similar in the caudate and the adrenal medulla; epinephrine and norepinephrine concentrations were some 600 times and 90 times higher, respectively, than that of dopamine in adrenal medulla but were barely detectable in caudate nucleus. Catecholamines and metabolites were also measured, before and after transplantation, in lumbar cerebrospinal fluid (CSF) and plasma 1 hour after the patients' first morning dose of L-dopa. The major fractions of the catecholamines in CSF were sulfoconjugated. The concentrations of sulfoconjugated but not free dopamine were modestly increased in CSF after the transplantation, although plasma concentrations were unchanged. CSF concentrations of free and conjugated norepinephrine and epinephrine, 3-methoxy-4-hydroxyphenylglycol, and homovanillic acid were unchanged after the transplantation. The data suggest that the grafted tissue does not retain its noradrenergic or adrenergic properties after transplantation, and that dopamine formation in the brain may be modestly increased. Plasma catecholamines were unaffected after the removal of one adrenal gland for the transplant.

Adrenal Medulla↗