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Biomedical subjects

W R Kennedy

Publications and source records attributed to W R Kennedy.

At least 73 records · Page 4Linked to original sources

Long-term follow-up of polyneuropathy in diabetic kidney transplant recipients.

Nerve conduction and electromyography (EMG) of insulin-dependent (type 1) diabetic patients with end-stage nephropathy was studied before and up to 10 yr after kidney transplantation (KTx). A series of nondiabetic KTx patients served as a comparison group. Motor nerve conduction velocity (NCV) was measured in the ulnar, median, peroneal, and tibial nerves; sensory NCV was measured in the median nerve. EMG was performed in the first dorsal interosseus, flexor carpi radialis, anterior tibialis, and gastrocnemius muscles. In 68 pre-KTx diabetic patients, the mean NCV was below normal in all nerves, and the mean amplitudes of the evoked muscle action potential (MAP) were low normal in the upper extremity and below normal in the lower extremity. The values of the comparison group were within the normal range. At 1 (n = 57), 5 (n = 23), and 10 (n = 10) yr after KTx, the mean NCV of the diabetic patients remained essentially unchanged, but MAP amplitudes of all muscles had declined. EMG revealed progression of the denervation process, especially in muscles of the lower extremities. We conclude that diabetic neuropathy continues to progress by a progressive axonal loss after correction of uremia by KTx.

Action Potentials↗

Pancreas transplantation in nonuremic, type I diabetic recipients.

Between July 1978 and January 1988, 111 of 210 pancreas transplants were in nonuremic, nonkidney (NUNK) recipients in whom complications of diabetes were judged more serious than the potential side effects of antirejection therapy. In all NUNK cases, the 1-year patient survival rate (PSR) and graft survival rate (GSR) were 90% and 39%. Since November 1984, 1-year PSR and GSR for 62 NUNK recipients of pancreas transplants alone (PTA) were 93% and 48%, compared to 89% and 37% for 28 pancreas transplants after (PAK) and 89% and 73% for 20 simultaneous (SPK) with a kidney transplant. The 1-year GSR for 1984-88 technically successful (TS) PTA cases (n = 47) was 63%, versus 75% for PAK (n = 13) and 86% for SPK (n = 17) cases. The 1-year GSRs, by technique and source for 1984-88 PTA cases, were 58% for bladder-drained cadaver (n = 30), 51% for enteric-drained related (n = 32), and 29% for enteric-drained cadaver (n = 17) donor transplants, and 75% (n = 24), 77% (n = 16), and 38% (n = 13) for the corresponding TS cases. Of NUNK recipients, 35 have had grafts function for more than 1 year and all but 3 were treated with cyclosporine (CsA). In the CsA-treated recipients, serum creatinine increased and creatinine clearances decreased by a magnitude of 40% during the first 6 months but thereafter remained stable in all but 2 patients. In the patients with functioning grafts studied at 1 year, retinopathy remained stable in 59% and progressed in 41% of the eyes (n = 39). Motor nerve conduction velocities were significantly increased and muscle action potentials remained stable in 24 patients with functioning grafts studied at 1 year, while in 14 patients in whom transplants failed there was a significant decrease in evoked muscle action potentials. A sustained euglycemic, insulin-independent state can be established in nonuremic, nonkidney diabetic recipients of pancreas transplants alone, with a beneficial effect on neuropathy, lack of an immediate benefit on advanced retinopathy, and an effect on nephropathy compounded by the influence of CsA on renal function.

Cyclosporins↗

Unicompartmental arthroplasty of the knee. Postoperative alignment and its influence on overall results.

One hundred consecutive medial compartment knee arthroplasties for osteoarthritis were reviewed for overall clinical result and postoperative alignment. Follow-up evaluation ranged from 24 to 123 months with 51 months being the median. The Marmor knee rating system was used. The alignment of the knee relative to the mechanical axis of the leg (center of the femoral head to the midpoint of the ankle mortise) was determined by a standing three-foot roentgenogram. Of the arthroplasties, 90% were excellent or good results. Superior results were obtained when the mechanical axis fell in the center of the knee (Zone C) or slightly medial to the center (Zone 2). Causes of failure included fractures, femoral component loosening, and excessive lateral compartment or patellofemoral wear. Cartier and Villers' preoperative templating system was modified for intraoperative alignment with the mechanical axis falling into Zone C or Zone 2.

Aged↗

Comparison of right colon, left colon, and rectal carcinoma.

Three hundred fifteen cases of adenocarcinoma were analyzed for differences between lesions in the right colon, left colon, and rectum for the period 1978 to 1983. The right colon cancers accounted for 1/3 of the cases and were associated with a higher incidence of anemia. The incidence of obstruction was the same between the right and left colon but lower for the rectal lesions. Left colon and rectal cancers had a higher incidence of gross bleeding than right colon cancers, but all had a high rate of occult blood in the stool. The Duke stage of the lesions, which was similar throughout the colon and rectum, is a reliable prognostic indicator.

Adult↗

Collateral reinnervation of sweat glands.

The collateral reinnervation of mouse sweat glands has been studied by a method that allows serial evaluation of the course of reinnervation in intact animals. The method is based on the finding that the activation of secretion from newly denervated sweat glands by pilocarpine or nerve stimulation is completely absent seven days after nerve section but returns with reinnervation. These characteristics allowed serial detection of footpad sweat glands newly reinnervated by collateral sprouting of the remaining intact saphenous nerve after section of the sciatic nerve. The number of saphenous innervated glands increased five- to sevenfold and the total saphenous sweat territory was greatly expanded across the volar surface of the hind paw. There was less enlargement when the sciatic nerve was allowed to regenerate and participate in reinnervation of sweat glands. None of the reinnervated glands were dually innervated by saphenous and sciatic nerves, as is the case in normal glands. When the saphenous nerve was sectioned after saphenous collateral sprouting was complete and after sciatic regeneration had innervated an apparent maximal number of glands, the sciatic nerve reacted by advancing farther into the formerly enlarged saphenous territory and re-reinnervated many of the glands. Collateral sprouting by sudomotor axons is more abundant and more widely dispersed than reported for larger nerve fibers to skeletal muscle and to low-threshold mechanoreceptors. It more closely resembles sprouting of nociceptive axons.

Animals↗

Quantitation of the sweating deficiency in diabetes mellitus.

This report introduces quantitative tests for the evaluation of sweating and the results obtained in 81 diabetic and 30 control subjects. The tests rely on the ability of pilocarpine, introduced into the skin by iontophoresis, to stimulate sweating from fully or partially innervated sweat glands but not from denervated glands. Many diabetic patients had a reduced number of excitable sweat glands and a low volume of sweat per square centimeter of skin. The results of the sweat tests correlated best with the clinically determined perception of pain from pinprick. The similar degree of involvement of sudomotor axons and pain-conveying axons may be related to the known similarity in size and reinnervation patterns. There was poor correlation of the sweating deficiency with alpha motor conduction velocity and with denervation of foot muscles as determined by the evoked muscle action potential. The number of excitable sweat glands was usually normal if the muscle action potential was above 0.5 mv, and often normal even when a muscle action potential was unobtainable. Every diabetic patient with abnormal sweating and several with normal sweating had reduced heart rate fluctuation during a standard Valsalva maneuver or during slow respiration.

Adult↗

Ultrastructure of the secretory epithelium, nerve fibers, and capillaries in the mouse sweat gland.

The ultrastructure of the mouse sweat gland was examined, in support of neurological studies of sweat glands and their relationships to the autonomic nervous system. It was found that the mouse sweat gland is similar to that of the rat and has only one type of secretory cell. Many nerve fibers are entwined with the secretory tubule and contain accumulations of round, clear vesicles, some microtubules, but apparently no neurofilaments. Cholinesterase is found in the clefts between nerve fibers and their ensheathing Schwann cells. The nerve fibers tend to run parallel with capillaries, but have no close association with either the capillaries or the secretory epithelium. Capillaries provide an abundant blood supply to the sweat gland and are fenestrated. The relationships between cellular elements of the sweat gland provide no direct evidence of the mechanisms involved in neurogenic sweating, although it seems likely that effector substances are diffusely distributed.

Animals↗

Rodent eccrine sweat glands: a case of multiple efferent innervation.

The sweat territories of peripheral nerves to the hind-paw of the mouse were defined by a silastic impression mold method that allowed identification of every secreting sweat gland. It was found that the tibial, sural, saphenous and peroneal nerves all contribute to the innervation of foot pad sweat glands, and there is extensive overlapping of the sweat territories of the different peripheral nerves. Most sweat glands could be activated by electrical stimulation of axons in two or three peripheral nerves or in separate fascicles of one nerve. This was interpreted to indicate that these sweat glands receive multiple innervation and that sweat glands in the overlap regions between autonomous zones of adjacent cutaneous nerves can receive axons from each nerve. Partial denervation of sweat glands by section of one source of innervation did not prevent the gland from sweating during stimulation of intact axons to the gland, or after pilocarpine treatment. Totally denervated glands did not exhibit denervation hypersensitivity; they became unresponsive to pilocarpine, acetylcholine and adrenaline. These characteristics allowed detection of the appearance and progression of reinnervation (and reactivation) of denervated sweat glands by collateral branching from sudomotor fibers. Not only do these results increase our basic understanding of the anatomical relations between peripheral nerves and the sweat glands they innervate, but they also demonstrate that the mouse sweat gland provides a useful model system for studying neuropathology of the sympathetic nervous system.

Animals↗

The sweating deficiency in diabetes mellitus: methods of quantitation and clinical correlation.

A method that measures the amount of sweat evaporating from the skin was used to quantitate the sweating deficiency that accompanies diabetic neuropathy. The decreased amount of sweat secreted after pilocarpine stimulation was proportional to the reduction in number of excitable sweat glands, and to the decrease in water measured by the summed volume of all sweat droplets secreted. The results also correlated favorably with the degree of sensory loss to painful stimuli, but not to the alpha motor nerve conduction velocity or motor axon loss evaluated by muscle action potentials evoked from foot muscles. Respiratory-cardiovascular reflexes, as measured by the Valsalva ratio, were always abnormal in patients with demonstrated sweating deficiency and often in patients with normal sweat function.

Adult↗

Hereditary proximal spinal and bulbar motor neuron disease of late onset. A report of six cases.

Six cases of a comparatively rare motor neuron disease are described. Essential features of this syndrome include (1) X-linked inheritance; (2) adult onset in the fourth to fifth decades; (3) slow progression; (4) predominant proximal and bulbar muscle involvement; and (5) absence of sensory or pyramidal tract signs. The previously reported finding of gynecomastia was absent, whereas longitudinal midline furrowing of the tongue was present in only one case. Electromyography in five patients revealed neurogenic changes. Muscle biopsies in two patients showed fiber type grouping with type I fiber predominance. The coexistence of this form of motor neuron disease and diabetes mellitus is prominent in family 2. It is important to recognize that these patients have a chronic, slowly progressive illness. The prognosis for longevity is good, although severe disability is inevitable. Management includes reassurance, supportive therapy, genetic counseling, and periodic testing for diabetes.

Chromosomes↗

Peripheral neurology of the diabetic Chinese hamster.

Genetically diabetic Chinese hamsters were examined anatomically and physiologically for evidence of peripheral neuropathy. Control animals were from non-diabetic strains. Conduction velocities in both motor and sensory components of the hind limb nerves were reduced 16-22% in diabetic compared with control hamsters. However, there was no reduction in nerve fibre diameters or other signs of abnormal morphology that could be correlated with these physiological effects. It is concluded that the diabetic hamster is useful as a model of human diabetic peripheral neuropathy, but the analogy is not precise. The neuropathy of moderately diabetic hamsters is generally less severe than human diabetic neuropathy in its clinical stages.

Animals↗

Individualized CME learning opportunities. A critical role for the community hospital.

This paper has attempted to define the critical role that community hospitals can play in continuing medical education, a type of education that historically has been oriented toward large group instruction, often at the expense of individualized learing. Professional societies and organizations, major medical faculties, and educational programs sponsored by various groups may well be the basic structures for providing high-quality new information. However, rarely do presentations by these groups involve reclarification, synthesis, and examination of present knowledge and behavior, nor do they typically allow physicians to share their experiences or learn by doing--all of which have great importance to the learning habits of practicing physicians. The local medical community, through use of an instructional format like the one outlined, may be able to fill this crucial gap.

Education, Medical, Continuing↗

Microvasculature of rabbit muscle spindles.

The microvasculature of the muscle spindle and its relationship to the microcirculation of teniussimus extrafusal muscle is described. Muscle spindles lie in close proximity and parallel to the central artery, vein, and nerve. The arterioles to spindle capillaries are third to fourth order branches of the central artery, whereas most arterioles to extrafusal capillaries are sixth to eighth order. Two or three capillaries enter each spindle. At least one entry consistently was encountered in the equatorial area near the sensory endings. Branches of intrafusal capillaries run longitudinally, anastomose with each other, and cradle the sensory zone in a longitudinal capillary loop. Capillaries in muscle spindles are larger than those in extrafusal muscle. These characteristic features are presumed to enhance the capability of these capillaries to provide sufficient circulation to the spindle, particularly to the region of the sensory endings.

Animals↗

Morphometric comparison of capillaries in muscle spindles, nerve, and muscle.

Morphometric study was performed on transverse sections of microdissected muscle spindles from rabbit tenuissimus muscles. It showed a statistically significant difference in size and structure between the intrafusal capillaries and those of extrafusal muscle. The former are larger in diameter, circumference, and area due to a proportionate increase in the number of endothelial cells. Vesicles within spindle endothelial cells are fewer, mitochondrial counts are greater, but in proportion to the increased number of endothelial cells, intercellular junctions are tight and pericyte coverage is greater. The basement membrane around endothelial cells and pericytes is thicker and more often multilayered. The endoneurial capillaries of tenuissimus intramuscular nerve are morphologically identical to intrafusal capillaries. The similarity of the capillaries of spindles to those in brain suggests that a blood-nervous system barrier extends from brain into the peripheral nerves and muscle spindles.

Animals↗