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Biomedical subjects

W R Kennedy

Publications and source records attributed to W R Kennedy.

At least 37 records · Page 2Linked to original sources
PubMed1996

Clinical and histologic evaluation of psoriatic plaques treated with a flashlamp pulsed dye laser.

BACKGROUND: Psoriatic plaques can be cleared by destruction of the dermal papillae. Dilated vessels, the major component of psoriatic dermal papillae, can be selectively destroyed with yellow light lasers. Previous investigators have demonstrated partial clearing of psoriatic plaques after treatment with a pulsed dye laser (PDL) (585 nm). OBJECTIVE: This study was designed to examine the clinical and histologic events of psoriasis treated with the PDL. METHODS: Psoriatic plaques were treated with a short (450 microseconds) and long (1500 microseconds) pulse-width PDL. Photographs of the plaques were used for clinical assessment. Biopsy specimens were examined microscopically. RESULTS: Significant clinical improvement was seen, and no significant difference between the long and short pulse-width lasers was found. Patients responding to treatment with the PDL remained in remission for up to 13 months. Histologic normalization occurred after treatment. Two pretreatment vascular patterns were seen: vertically oriented vessels with few horizontal vessels and numerous tortuous vessels. Tortuous vessels were associated with poor clinical results. CONCLUSION: The PDL can induce prolonged remission in chronic plaque psoriasis. The vascular pattern may help to distinguish those patients likely to respond to this treatment.

Adult↗
PubMed1996

Quantitation of epidermal nerves in diabetic neuropathy.

We describe methods to quantify epidermal nerve fibers (ENFs) in skin biopsy specimens from diabetic candidates for pancreas transplantation and control subjects. ENFs and the dermal-epidermal basement membrane were stained by immunohistochemical methods, imaged with a confocal microscope, and quantified using a neuron tracing system. The number of ENFs per surface of epidermis was diminished in diabetic subjects. ENF number and summed length of all ENFs per volume of epidermis examined were also decreased. Length and number of branch points of single surviving ENFs were similar in skin of control and diabetic subjects. The methods and results constitute a basis for continued study of the effects of the euglycemia that attends successful pancreas transplantation and the effects of therapy in patients with various types of polyneuropathy.

Cell Count↗
PubMed1995

Innervation of cutaneous structures in the mouse hind paw: a confocal microscopy immunohistochemical study.

The normal innervation of structures in mouse foot pads was investigated with immunohistochemistry and confocal microscopy. Nerves were visualized by incubating Zamboni fixed, thick, frozen sections with antibodies to protein gene product 9.5 (PGP 9.5), vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, and protein zero. The antibodies were localized using cyanine 3.18 labeled anti-rabbit gamma globulin. PGP 9.5 immunolocalization showed dense nerve bundles at the base of the foot pad with branches to larger blood vessels, sweat glands and epidermis. Sweat gland tubules were surrounded by numerous sudomotor axons; single fibers accompanied the sweat duct toward the skin's surface. Nerve bundles containing myelinated and unmyelinated axons ran through and around the centrally located sweat gland cluster to end in free nerve endings and Meissner's-like corpuscles at the apex of the foot pad. Other bundles running parallel to the epidermis gave arcuate branches that supplied epidermis on the sides of the pads with a rich nerve network, principally with free nerve endings that often reached the most superficial cell layers of epidermis. Calcitonin gene-related peptide-immunoreactive (-ir) nerves were distributed to dermis and epidermis in lower density than PGP 9.5-ir fibers. Substance P-ir fibers were less numerous; most terminated as free endings in deeper layers of epidermis. Vasoactive intestinal peptide-ir nerves almost exclusively innervated sweat glands, ducts and blood vessels, but not epidermis. The mouse hind paw has potential to serve as a model system for investigations of functional and morphological changes that affect peripheral and autonomic nerves under diverse experimental conditions.

Animals↗
PubMed1995

Keratinocyte muscarinic acetylcholine receptors: immunolocalization and partial characterization.

We have reported previously that human keratinocytes synthesize and secrete acetylcholine and that muscarinic cholinergic drugs have effects on keratinocyte proliferation, adhesion, and migration. This study defines the location of muscarinic acetylcholine receptors in human epidermis and describes some pharmacologic and molecular properties of these receptors. Confocal microscopy employing the anti-muscarinic receptor monoclonal antibody M35 visualized the receptors in the intercellular areas of normal human epidermis. Using immunoelectron microscopy, the receptors appeared to be attached to the keratinocyte plasma membranes. Functional, high-density (Bmax = 8.3 nmol/2 x 10(6) cells) and high-affinity (Kd = 21.5 nM) muscarinic receptors were demonstrated by saturable binding of the reversible radioligand [3H]quinuclidinyl benzilate to the surfaces of freshly isolated epidermal cells at 0 degrees C. Receptor proteins were separated by gel electrophoresis. An apparent isoelectric point of pH 4.3 was determined in immunoblots of sodium-cholate-solubilized receptors separated on isoelectric-focusing gels. Three protein bands, two at approximately 60 kDa and one at 95 kDa, were visualized in immunoblots of membrane-bound or solubilized receptors separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The covalent, irreversible ligand [3H]propylbenzilylcholine mustard confirmed these results. Thus, human keratinocytes express a heterogeneous population of muscarinic cholinergic receptors. Because human keratinocytes also express nicotinic cholinergic receptors, endogenously secreted acetylcholine may control different biologic processes in these cells by activating different types of their cholinergic receptors.

Antibodies, Monoclonal↗
PubMed1995

Neuropathy profile of diabetic patients in a pancreas transplantation program.

We describe the results of extensive neurologic evaluation of 290 patients with insulin-dependent diabetes mellitus who came to our institution as potential recipients of a pancreas transplant. Large nerve fibers were evaluated by motor and sensory nerve conduction, small sensory fibers by thermal sensation thresholds, vagal and vasomotor functions by cardiovascular reflexes, and sympathetic sudomotor fibers by silicone imprints and evaporimetry. A scored anamnesis revealed symptoms of neuropathy in 86% of patients; 94% had an abnormal neurologic examination. The most frequently abnormal measurements of motor conduction were the amplitude of the extensor digitorum brevis muscle action potential to peroneal nerve stimulation and the conduction velocity of peroneal and tibial nerves in more than 80% of patients. Sensory nerve action potentials were abnormal in 76% and the distal latency of the sural nerve in 91%. Heart rate variability with deep breathing and during a Valsalva's maneuver was abnormal in 90% and 88%. Sudomotor function was reduced in 59% on the foot. Thermal sensitivity limen was above normal limits in 95% in the foot and 77% in the hand. Composite indexes of the degree of abnormality found for each type of function tested were correlated one with another, but were not predictive of results for any other test. The neuropathy of most patients was symmetric, involving to a similar degree motor, sensory, and autonomic nerves. Thus, diabetic neuropathy is very common and severe among patients who decide to be candidates for pancreas transplantation.

Adult↗
PubMed1994

Innervation and vasculature of human sweat glands: an immunohistochemistry-laser scanning confocal fluorescence microscopy study.

Secreting tubules, nerves fibers, and blood vessels in human sweat glands (SGs) were fluorescently stained by immunohistochemical and lectin methods for examination with a laser scanning confocal microscope (LSCM). Using these techniques, the three-dimensional distribution of up to three substances within a single specimen was investigated by collecting a series of optical sections for each of three fluorophores. Each SG received several nerve fibers. These branched into delicate bands of one or more axons that ran longitudinal to the sweat tubule then encircled the tubule. A heavy complement of capillaries was interwoven among the sweat tubules. Sweat ducts were accompanied from the SG toward the skin surface by one or two longitudinally oriented nerve fibers and capillaries. Immunoreactive staining of nerves was heaviest with protein gene product 9.5 antibody, but triple labeling showed that immunoreactivity to calcitonin gene-related peptide, vasoactive intestinal polypeptide, and synaptophysin was also present in the same axons. Substance P-immunoreactive axons were sparse in SGs but were present in other areas of the skin. The techniques used have considerable potential in examination of human skin biopsies for diagnosis of disorders affecting the somatic and autonomic nervous systems.

Adolescent↗
PubMed1993

The innervation of human epidermis.

Using immunohistochemical procedures numerous nerve fibers have been found in all cell layers of human epidermis. These nerves originate from nerve trunks in the dermis, enter the epidermis, then divide distally to eventually end in small enlargements, near the surface of the skin and in deeper areas. Some endings may be external to stratum granulosum cells. Epidermal nerves appear to have a three-dimensional territorial distribution in relationship to the skin's surface. The presence of epidermal nerve fibers was confirmed by electron microscope studies. The nerves are presumed to be sensory in nature. The existence of epidermal nerve fibers will necessitate changes in present theory of structure and function of peripheral sensation.

Epidermis↗
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↗