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Biomedical subjects

W R Kennedy

Publications and source records attributed to W R Kennedy.

At least 19 recordsLinked to original sources
PubMed1992

Longitudinal neurophysiologic studies in a patient with metachromatic leukodystrophy following bone marrow transplantation.

We describe a girl with late infantile metachromatic leukodystrophy. The patient has been followed up with serial neurologic and neurophysiologic examinations for 8 years following bone marrow transplantation, which she underwent when she was 4 3/4 years old. Her older sister died from metachromatic leukodystrophy at the age of 8 years, whereas our patient has retained significant cognitive and motor skills. Serial neurophysiologic studies initially demonstrated continued deterioration after the bone marrow transplantation, but since then, most results have remained stable or improved. Although, to our knowledge, there have been no previous serial studies of metachromatic leukodystrophy, individual case studies suggest that these findings in our patient are very unusual. With the advent of possible treatment for this condition, there is a need for further serial neurophysiologic studies to characterize the natural progression and the possible detection of progression or reversal with treatment.

Action Potentials↗
PubMed1992

Influence of posture on cardiorespiratory reflexes in normal subjects and patients with diabetes mellitus.

This study was designed to assess the effect of patient posture, either sitting or supine, on the results and diagnostic yield of tests of cardiorespiratory reflexes on 25 normal subject controls and 128 patients with diabetes mellitus. The heart rate changes during slow breathing at 6 per minute (delta R6) and during a Valsalva manoeuvre (highest heart rate during manoeuvre divided by lowest heart rate within 30 s after manoeuvre; Valsalva ratio) were measured from the electrocardiographic signal and tachometry. In control subjects, heart rate changes during slow breathing averaged 25.0 when sitting and 21.3 when supine (p < 0.01); Valsalva ratio averaged 1.90 and 1.83 (p > 0.2) respectively. In diabetic patients, mean values for heart rate changes during slow breathing were 6.1 and 5.1, and mean values for Valsalva ratio were 1.23 and 1.28 in sitting and supine postures respectively. According to our normal limits, heart rate changes during slow breathing was below normal in 109 patients tested when sitting and in 113 tested when supine, and Valsalva ratio was abnormal in 103 and 95 respectively. These results indicate that subject posture is an important variable of cardio-respiratory reflex testing, and should be standardized to allow comparisons of individual results.

Adult↗
PubMed1991

The effects of autologous nerve transplants on motor and sudomotor reinnervation by regenerative axons.

The functional reinnervation rate of sweat glands (SGs) and muscle in the mouse paw were compared following resection of a 4 mm segment of sciatic nerve. Repair was by graft of the same segment with epineural sutures or by suturing the proximal and distal stumps to a teflon tube that contained saline alone or saline plus the unattached nerve segment. Pilocarpine activated SGs first reappeared at 23 days postoperation in mice with a direct graft, at 29 days in mice with a nerve transplant in the tube, and at 32 days in mice with an empty tube. The number of reinnervated SGs increased progressively in number to a maximum of about 65% of the control counts by 60, 60 and 67 days, respectively. Compound muscle action potentials evoked by sciatic nerve stimulation were first recorded from the interossei muscles at 24, 27 and 31 days postoperation in the same groups of mice. The action potential amplitude increased to average values of about 2 mV by 58, 62 and 69 days. These results indicate that a direct nerve graft allows faster and higher functional recovery than tubulation repair, and that a nerve transplant slightly accelerates the reinnervation rate, probably due to the presence of nerve trophic products inside the tube. Unmyelinated and myelinated axons regenerated at equal rates.

Action Potentials↗
PubMed1991

Quantitation of the alternate movement rate in normal and diabetic subjects.

Functional abnormalities of alternate movement rate (AMR) of finger and foot tapping were quantitated in 162 patients with diabetic neuropathy and 30 control subjects using a simple electronic device. The quantitative AMR (QAMR) averaged 29.5 +/- 3.0 for finger tapping and 20.4 +/- 3.7 for foot tapping in controls, and 27.5 +/- 4.8 (P less than 0.05) and 17.0 +/- 5.6 (P less than 0.005) for finger and foot, respectively, in diabetic patients. Fifty-one patients had abnormal QAMR in the finger and 79 in the foot. The QAMR values correlated with the results of nerve conduction studies of patients. Testing for abnormalities of AMR is a useful addition to the testing of dysfunction secondary to diabetic neuropathy. It provides quantitation of a common, subject-initiated, functional task more accurately than possible by clinical observation.

Adult↗
PubMed1991

Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation.

Cardiorespiratory reflexes were studied during slow breathing and a Valsalva maneuver in 232 Type 1 (insulin-dependent) diabetic subjects. At 1 to 7 years follow-up, death occurred in 23.4% of 175 patients with abnormal reflexes and in 3.5% of 57 patients with normal reflexes. The mortality rates of diabetic subjects with abnormal reflexes were 17% at 2.5 years, 33% at 5 years and 40% at 7 years, significantly higher than for patients with normal reflexes (4.6%, 4.6% and 13.8%). Among patients with abnormal reflexes, patients with a functioning pancreas transplantation had better survival rates than patients with a failed transplantation, and in long-term follow-up better than patients without transplantation. A functioning transplantation prevented the progressive decline of cardiorespiratory reflex function that occurred over time in control patients.

Adult↗
PubMed1991

Cardiovascular responses to tilting in healthy and diabetic subjects.

Cardiovascular responses to tilting from supine to upright and back to supine were investigated by measuring heart rate (HR) and blood pressure (BP) continuously by non-invasive methods. Subjects were 20 healthy controls, 17 diabetic patients (DN) with normal test results for parasympathetic cardiac function and 21 diabetics (DA) with abnormal results. In control subjects, tilting up and tilting back maneuvers induced opposite changes in HR, systolic (SBP) and diastolic BP (DBP). The most obvious responses appeared during the first 30 sec after either maneuver. The best measurements to detect sympathetic vasoconstrictor abnormalities during tilting up were derived from the recovery curve that followed the immediate fall in SBP, abnormal in 6 DN and 14 DA patients, and from the increase in DBP after the maneuver, abnormal in 7 and 16, respectively. Tilting back induced comparatively larger cardiovascular responses. The SBP remained stable after 10 sec in the controls, but increased above normal limits in 7 DN and 20 DA patients. The DBP fell during the first 10 sec in controls, but not in 4 DN and 17 DA patients. Continuous monitoring of BP during tilting is a more sensitive test of autonomic function than classical BP measurements made at a few selected intervals. The results challenge the view that parasympathetic dysfunction precedes and occurs more frequently than sympathetic dysfunction.

Adult↗
PubMed1991

Effects of laminin on functional reinnervation of target organs by regenerating axons.

Reinnervation of sweat glands, skeletal muscle and skin was studied in the mouse paw after section of the sciatic nerve and repair by entubulation with collagen conduits, with and without a coating of laminin. After operation, sweat glands activated by pilocarpine reappeared at 32 days and increased in number to 67% of control counts. Muscle action potentials (during sciatic nerve stimulation) were recorded from the interosseus muscle at 39 days. The potential amplitudes increased to 30% of controls. The first withdrawal response from pin prick to the paw was observed at about 34 days, the response score increasing to 66% of control. There were no significant differences at any test interval between the control group and the group with laminin added.

Animals↗
PubMed1991

Evaluation of thermal and pain sensitivity in type I diabetic patients.

Thermal sensitivity was studied in 280 type I diabetic patients and in 75 control subjects. Warm and cool thresholds, temperature sensitivity limen (difference between warm and cold thresholds, TSL), and hot and cold pain thresholds were quantitated on the skin of the index finger, hand, foot and medial calf. The diabetic group had mean values that were significantly different from controls in all variables except the pain thresholds in the upper extremity. TSL was the most sensitive parameter, being abnormal in 57, 63, 79 and 78% of patients in the four skin sites tested. Hot pain sensitivity was abnormal in 37, 21, 39 and 26% of patients in the same sites. Thermal sensitivity abnormalities were more frequently observed than abnormalities in motor and sensory nerve conduction studies. Thermal tests correlated with the duration of the diabetes, although there were abnormalities at all stages of the disease. The results show that diabetic neuropathy has a variable presentation in different types of nerve fibres.

Adolescent↗
PubMed1991

Baroreflexes in patients with diabetes mellitus.

We evaluated baroreflexes in 58 diabetic and 15 control subjects by determining the latency of response between the end of a Valsalva maneuver (VM) and points on the resultant blood pressure and heart rate (HR) response curves. Prolonged latencies indicative of sympathetic dysfunction were demonstrated in 44% to 88% of diabetic subjects. The results challenge the view that sympathetic dysfunction cannot be detected before parasympathetic abnormalities are manifest. Baroreflex latencies reflected sympathetic dysfunction early in the course of diabetes, sometimes in patients with normal HR responses to deep breathing and to a VM.

Adult↗
PubMed1990

Effects of pancreatic transplantation on diabetic neuropathy.

Reestablishment of the euglycemic state by successful transplantation of the pancreas might halt or reverse diabetic neuropathy. To test this possibility we evaluated neurologic function by clinical examination, nerve conduction studies, and autonomic-function tests in patients with insulin-dependent (Type I) diabetes mellitus before and after successful pancreatic transplantation. Sixty-one patients were studied before and 12 months after transplantation, 27 again after 24 months, and 11 again after 42 months. A control group of patients with Type I diabetes treated with insulin underwent the same studies at similar intervals--48 patients before and after 12 months had elapsed, 21 again after 24 months, and 12 again after 42 months. In the control group, neuropathy tended to worsen during the follow-up period. The scores on the clinical examination indicated increased impairment after 12 months. Composite indexes of the degree of abnormality found on neurophysiologic testing of the function of peripheral motor, sensory, and autonomic nerves indicated decreased autonomic function after 12 months. The examination score and the three index values worsened slightly but not significantly in the patients followed for 24 and 42 months. In contrast, in the patients who had received pancreatic transplants, the neuropathy tended to improve. There was significant improvement in the motor and sensory indexes 12 months after transplantation and in the sensory index 24 months after transplantation. The other measures improved slightly but not significantly at these times, as did all four measures in the patients studied 42 months after transplantation. We conclude that the progression of diabetic polyneuropathy may be halted through the restoration of a euglycemic state by successful pancreatic transplantation.

Adult↗
PubMed1990

The effect of a conditioning lesion on sudomotor axon regeneration.

The effects of a conditioning lesion on the rate of sudomotor axon regeneration were judged by the recovery of sweat gland (SG) secretion after cholinergic stimulation. Three groups of mice were given a conditioning lesion by crushing the sciatic nerve at mid-thigh 4, 7, and 14 days before a test lesion. A 4th group received a conditioning crush of the tibial nerve at the ankle 7 days before the test lesion. Control mice had a single test lesion. SG reinnervation in control mice began 19 days after the test lesion, and was functionally complete by 41 days. In groups with the conditioning lesion 4, 7, and 14 days before the test operation, the first reactive SGs reappeared at 16, 15, and 16 days respectively after the test lesion, and maximal recovery occurred by 33, 32, and 39 days. In mice with the distal conditioning lesion, reinnervation began at 19 days and was maximal by 36 days. In summary, a nerve conditioning lesion placed from 4 to 14 days prior to and at the same site as a test lesion significantly accelerated the growth rate of the fastest regenerating unmyelinated sudomotor axons and reduced the time until most SGs were reinnervated. A more distally placed test lesion reduced the interval for recovery.

Adaptation, Physiological↗
PubMed1990

Changes in sudomotor nerve territories with aging in the mouse.

This study evaluates sudomotor function in the hindpaw of young and aged mice. Sweating was stimulated by pilocarpine injection and by electrical stimulation of the sciatic, tibial, peroneal, sural and saphenous nerves. The number of responsive sweat glands of the paw was determined by the silicon mold technique. The results obtained provide evidence that the number of functioning sweat glands of the hindpaw tended to decrease in aged mice. The peripheral sudomotor territories and the complement of sweat glands for individual nerves declined slightly with age. Moreover, the number of sweat glands responsive to cholinergic stimulation was decreased when compared with the number responsive to electrical stimulation of the sciatic nerve in aged mice. These and previous observations suggest that the number of sudomotor axons in the peripheral nerve, as well as their capabilities for compensatory reinnervation of sweat glands by regeneration and by sprouting, is reduced with aging.

Aging↗
PubMed1990

Influence of pancreas transplantation on cardiorespiratory reflexes, nerve conduction, and mortality in diabetes mellitus.

Cardiorespiratory reflexes (CRR) were studied by measuring heart-rate variation during 6 breaths/min respiration and a Valsalva maneuver in 232 insulin-dependent diabetic subjects. Abnormalities were found in 175 patients. During a 7-yr follow-up, 41 (23.4%) patients with abnormal and 2 (3.5%) with normal CRR tests died. The mortality rates of diabetic patients with abnormal autonomic function tests were 17% at 2.5 yr, 33% at 5 yr, and 40% at 7 yr, significantly higher (P less than 0.002) than in patients with normal tests (rates of 4.6, 4.6, and 13.8% at the respective intervals). Nerve conduction studies (NCS) were indicative of somatic neuropathy in 148 of 205 patients. Mortality rates were higher in patients with abnormal NCS than in those with normal results (P less than 0.025). Among patients with abnormal autonomic function, patients with a functioning pancreas transplantation (PTx) had better survival rates than patients with a failed PTx (P less than 0.005) and, on long-term follow-up, better rates than patients without PTx. Similar results were found comparing the same group of patients who had abnormal NCS.

Adult↗
PubMed1989

Sympathetic sudomotor function in diabetic neuropathy.

Sympathetic nerve function was studied by the Silastic mold technique and by evaporimetry in the hand and the foot in 357 type I diabetic patients. The number of active sweat glands was below normal in 24% of patients in the hand and in 56% in the foot, while the sweat evaporation rate was low in 17% and 40% of patients, respectively. Computerized analysis of the molds, which allowed automatic sweat gland counts and estimations of the secretion volume of each sweat gland, detected abnormalities in 36% and 60% of patients. The Silastic imprint technique was found to be a sensitive test for detection of sympathetic nerve involvement, even in asymptomatic patients with normal clinical and nerve conduction examinations. Its sensitivity and accuracy has been enhanced by the computerized analysis of the molds.

Adolescent↗
PubMed1989

Small nerve fiber dysfunction in diabetic neuropathy.

Sensory and autonomic small nerve fiber function was studied in 142 type I diabetics and 45 control subjects. Thermal sensitivity (TS), hot pain sensitivity, and the activity of sweat glands (SGs) were quantitated on the dorsum of the hand and the foot. TS was abnormal in 86% of patients in the foot and 66% in the hand. TS was more sensitive than the hot pain threshold, the number of pilocarpine activated SGs, or the amount of sweat secreted, all of which were abnormal in about 50% of patients for the foot and less than 25% in the hand. Thermal and sweating tests correlated significantly with the scores of abnormal temperature and pinprick sensation obtained by physical examination but not with the duration of the diabetes. TS was also correlated with motor and sensory nerve conduction parameters, but SG number was not. The results indicate that diabetic neuropathy has a variable presentation in different types of nerve fibers.

Adolescent↗
PubMed1989

Sweat gland reinnervation by sudomotor regeneration after different types of lesions and graft repairs.

Clinical and experimental investigations have shown that recovery of motor and sensory functions after a nerve lesion varies with the type of lesion and the repair technique. We report a study on regeneration of sudomotor axons to sweat glands (SGs) in the mouse paw following different sciatic nerve injury procedures: freezing, crushing, and sectioning. After sectioning, repair was by primary suture or by grafting with the resected section or with conduits of plastic or collagen. Successful regeneration was marked by the reappearance of SG reactivity to pilocarpine. After a freezing or crushing lesion, SGs activated by pilocarpine reappeared by 17 days postoperation and then increased progressively in number until the preoperative number of SGs were again active at 41 days. Cutting the nerve followed by primary repair resulted in a short delay and a significant deficiency in reinnervation. Results obtained with a graft of a segment of resected nerve were similar to primary repair after nerve section and better than when grafts of plastic or collagen tubes were used. This suggests that substances provided by the grafted nerve segment and the type of conduit provided play important roles in the regeneration of unmyelinated axons.

Animals↗
PubMed1989

Long-term survival following kidney transplantation in 100 type I diabetic patients.

Between December 1966 and April 1978, 265 uremic patients with type I diabetes received primary renal allografts at the University of Minnesota. One hundred of the diabetic patients were alive with a functioning graft 10 years after transplantation. The actual 10-year patient and primary graft functional survival rates overall were 40% and 32%, respectively. For recipients of HLA-identical sibling (n = 45), mismatched living-related (n = 121), and cadaver donor grafts (n = 99), the actual 10-year patient survival rates were 64%, 33%, and 36%, respectively, and the actual 10-year graft functional survival rates were 62%, 28%, and 22%, respectively. The differences in patient and graft survival rates between HLA-identical graft recipients and recipients of mismatched related and cadaver grafts were significant (P less than 0.001). Of the 100 patients who survived into a second decade, at 15 years posttransplant 51% were alive, and 41% had functioning grafts. For recipients of HLA-identical sibling, mismatched living-related donor grafts, and cadaver donor grafts who survived 10 years, 47%, 57%, and 43%, respectively, were alive at 15 years, and 31%, 45%, and 43%, respectively, had functioning grafts. For recipients who made it to the second decade, patient and primary graft survival rates thereafter were not statistically different by donor source. Twenty-three patients died in the second decade after transplantation, 10 of cardiovascular disease. Twenty-five patients lost graft function in the second decade, 19 from death with a functioning graft. In regard to diabetic complications, recurrence of diabetic nephropathy was common, but only two patients lost graft function solely for this reason. In 21 patients (42 eyes) followed prospectively for 10 years, visual acuity deteriorated in 26%, was stable in 64%, and improved in 10% of eyes. Neurophysiological test results indicated that correction of uremia does not stop the progression of diabetic neuropathy in recipients of kidney transplants alone. Even without cyclosporine, nearly two-thirds of recipients of HLA-identical kidney grafts, more than one-quarter of recipients of mismatched living-related donor grafts, and more than one-fifth receiving cadaver grafts enjoyed an extension of life for more than 10 years.

Age Factors↗