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Biomedical subjects

H L Frankel

Publications and source records attributed to H L Frankel.

At least 19 recordsLinked to original sources
PubMed1992

Mortality, morbidity, and psychosocial outcomes of persons spinal cord injured more than 20 years ago.

Mortality, morbidity, health, functional, and psychosocial outcomes were examined in 834 individuals with long term spinal cord injuries. All were treated at one of two British spinal injury centres: the National Spinal Injuries Centre at Stoke Mandeville Hospital or the Regional Spinal Injuries Centre in Southport; all were 20 or more years post injury. Using life table techniques, median survival time was determined for the overall sample (32 years), and for various subgroups based on level and completeness of injury and age at injury. With the number of renal deaths decreasing over time, the cause of death patterns in the study group as it aged began to approximate those of the general population. Morbidity patterns were found to be associated with age, years post injury, or a combination of these factors, depending upon the particular medical complication examined. A current medical examination of 282 of the survivors revealed significant declines in functional abilities associated with the aging process. Declines with age also were found in measures of handicap and life satisfaction, but three quarters of those interviewed reported generally good health and rated their current quality of life as either good or excellent.

Adaptation, Psychological↗
PubMed1991

Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action.

BACKGROUND: Clonidine, a partial presynaptic and postsynaptic alpha-adrenoceptor agonist, has been shown to lower blood pressure in normal subjects but not in tetraplegics; however, the mechanisms of this action have not been elucidated. METHODS AND RESULTS: The hemodynamic and hormonal basis of the hypotensive action of clonidine was investigated in tetraplegics with complete cervical spinal cord transection and preganglionic sympathetic denervation, in patients with unilateral brachial plexus injury and postganglionic sympathetic denervation, and in normal subjects. In normal subjects, the fall in blood pressure after clonidine infusion was accompanied by a reduction in cardiac output that was predominantly due to a fall in stroke volume and in heart rate. The lack of fall in blood pressure, cardiac output, and stroke volume in tetraplegics indicates that these effects are exerted at a supraspinal level and require intact descending sympathetic pathways. After clonidine infusion, digital skin vasodilatation occurred in normal subjects, in the innervated but not the denervated limb of patients with unilateral brachial plexus injury, and in tetraplegics, indicating that this response is due to the central sympatholytic effect of clonidine. Plasma norepinephrine was much lower in tetraplegics compared with normal subjects, and after clonidine infusion, it fell substantially in normal subjects alone. Plasma renin activity did not change. Bladder stimulation in tetraplegics resulted in a rise in blood pressure and vasoconstriction in digital skin vessels. The inability of clonidine to significantly reduce or abolish the pressor and digital vasoconstrictor responses after bladder stimulation in tetraplegics indicates that clonidine does not exert a major effect on spinal preganglionic neurons or peripheral presynaptic alpha 2-adrenoceptors. CONCLUSIONS: Therefore, clonidine is a suitable drug for use in analyzing the central supraspinal levels of control in varying circulatory disorders, such as hypertension and postural hypotension.

Adolescent↗
PubMed1990

Wound healing and T-lymphocytes.

T-cell depletion leads to impaired wound healing. We studied the effect of combined T-helper and T-suppressor lymphocyte depletion on wound healing and compared it with the effect of all T-cell depletion. Groups of 10 male balb/c mice, 8 weeks old, underwent a 2.5-cm skin incision and subcutaneous implantation of polyvinyl alcohol sponges. Twenty-four hours prior to wounding one group was treated with 3OH12, a rat anti-mouse monoclonal antibody against the Thy-1.2 antigen present on all T-cells (1 mg); another group received 1 mg each of GK1.5 (anti-L3T4, CD4; anti-helper/effector subset) and 2.43 (anti-Lyt 2.1, CD8; anti-suppressor/cytotoxic subset). All monoclonal antibodies are cytotoxic in vivo. Controls received 1 mg of nonspecific rat IgG. Treatments were repeated weekly. Animals were sacrificed at 2 and 4 weeks postwounding. Equal depletion of all T- and Th- and Ts-subsets in peripheral blood and spleens was noted in the two experimental groups at sacrifice. Depleting Thy-1.2 cells (all T-cells) impaired wound healing as assessed by wound breaking strength and collagen synthesis. Combined anti-T-helper/effector and T-suppressor/cytotoxic depletion resulted in improved wound-healing parameters. This suggests that there is a Thy-1.2+, L3T4-, Lyt2- subpopulation of T lymphocytes which normally stimulates wound healing.

Animals↗
PubMed1989

Pharmacodynamics and pharmacokinetics of the oral antispastic agent tizanidine in patients with spinal cord injury.

The efficiency and duration of action of a single oral dose (8 mg) of tizanidine in patients with spinal cord injuries were determined by studying its antispastic, cardiovascular and sedative effects along with its pharmacokinetic profile in five tetraplegic and five paraplegic patients. After the administration of tizanidine, there was a reduction in spasticity in both groups within half an hour, with the effects lasting for 3 to 4 hours. There was no rebound increase in blood pressure. There was a greater increase in sedation in the tetraplegics than in the paraplegics. Plasma tizanidine levels rose within half an hour after dosing and peaked at one hour. The levels had fallen to 15 percent by 6 hours. The plasma half-life was 2.7 +/- 0.06 hours. We conclude that oral tizanidine has antispastic effects in patients with spinal cord injuries without affecting the power of non-involved muscle groups. It has minimal effects on blood pressure and it lowers heart rate. Side effects include sedation and dryness of mouth.

Administration, Oral↗
PubMed1989

Inhibition of wound repair by thymic hormones.

To further define the role of the thymus in wound healing, we studied the effects of two thymic hormones on fibroplasia in normal euthymic and in nude athymic mice. Groups of 10 mice underwent a 2.5 cm dorsal skin incision with subcutaneous placement of polyvinyl alcohol sponges. Starting on the day of wounding, the following daily injections were given: (1) thymopentin (TP5), an active synthetic pentapeptide of thymopoietin, a naturally occurring thymic hormone (1 microgram/day/IM); (2) thymulin or facteur thymique serique (FTS), a naturally occurring circulating thymic hormone (0.2 microgram/day/IM); (3) control saline solution (0.1 ml/day/IM). All mice were killed 4 weeks after wounding, and wound breaking strength and hydroxyproline content of the sponge granulomas were measured. The results show that both thymic hormones impaired wound breaking strength and reparative collagen synthesis in normal and athymic mice. The magnitude of the wound healing impairment induced by the two hormones was equal in the thymus-bearing and in the nude mice. The data support previous findings, which suggested that the thymus has an inhibitory effect on wound healing.

Animals↗
PubMed1988

Haemodynamic actions of clonidine in tetraplegia--effects at rest and during urinary bladder stimulation.

We studied the haemodynamic effects of clonidine (2 micrograms/kg/iv) in 7 tetraplegics and 7 normal subjects. Measurements of blood pressure, stroke volume, cardiac output and digital (finger) skin blood flow were made before and after clonidine for 60 minutes. Blood pressure, stroke volume and cardiac output did not fall in tetraplegics, unlike normals. Resting digital skin blood flow was higher in tetraplegics and fell after clonidine. In normal subjects however, an increase in digital skin blood flow occurred after clonidine. The pressor and digital vasoconstrictor responses to bladder stimulation were attenuated after clonidine. The inability of clonidine to induce a fall in blood pressure, stroke volume, cardiac output and cause peripheral vasodilation in tetraplegics is consistent with its central sympatholytic effects. Attenuation of the responses to bladder stimulation suggest an effect on spinal sympathetic neurones.

Adolescent↗
PubMed1988

Haemodynamic, hormonal and urinary responses to postural change in tetraplegic and paraplegic man.

We have studied the haemodynamic, hormonal and urinary effects of postural change in 6 tetraplegic patients, 6 paraplegic patients and 6 normal subjects. Measurements of blood pressure and heart rate, plasma renin activity, plasma aldosterone, urine volume and electrolyte excretion were made for 60 minutes while sitting and 60 minutes while recumbent. In tetraplegics the blood pressure was lower when sitting and rose during recumbency, unlike paraplegics and normal subjects. Plasma renin activity and aldosterone were higher in tetraplegics when sitting compared to normal subjects and did not fall during recumbency. Urine output increased significantly after recumbency in tetraplegics, but not in paraplegics or normal subjects. Both urinary sodium and potassium excretion were lower in tetraplegics and higher in paraplegics compared to normal subjects when sitting. In paraplegics the fall in both sodium and potassium excretion did not appear to be related to change in posture. Our observations indicate that recumbency induces a diuresis in tetraplegics but not in paraplegics or in normal subjects. The diuresis in tetraplegics may be related to the accompanying haemodynamic and hormonal changes induced by recumbency.

Aldosterone↗
PubMed1988

Vascular effects of clonidine in patients with tetraplegia and unilateral brachial plexus injury.

Evidence from studies in both animals and in tetraplegics with complete cervical spinal cord transection and preganglionic lesion, indicates that clonidine lowers blood pressure predominantly by a centrally mediated action. We have investigated the haemodynamic basis of this action and performed additional studies in patients with unilateral brachial plexus injury and postganglionic lesions, to further determine the site and mechanism of its action. Blood pressure fell after clonidine in normal subjects but not in tetraplegics. In normal subjects, the fall in blood pressure was associated with a fall in cardiac output, due to a fall in both heart rate and stroke volume. Digital skin vasodilatation occurred after clonidine in normal subjects and only in the innervated limb in patients with unilateral brachial plexus injury. In tetraplegics and in the denervated limb in unilateral brachial plexus injury, there was no vasodilatation; instead a vasoconstrictor response occurred, due to the peripheral adrenoceptor action of clonidine. We conclude that the fall in blood pressure and cardiac output in normal subjects after clonidine were due to its central sympatholytic action. Digital skin vasodilatation after clonidine in normal subjects and the innervated limb in unilateral brachial plexus injury was due to the withdrawal of vasoconstrictor tone and requires intact descending sympathetic pathways.

Adult↗
PubMed1987

Neuroendocrine control of vasopressin secretion and its effect on blood pressure in subjects with spinal cord transection.

The osmotic and cardiovascular control of arginine vasopressin (AVP) secretion, and the effect of this hormone on cardiovascular regulation were assessed both in normal controls and in subjects with tetraplegia. Infusion of hypertonic saline caused a marked rise in blood pressure in the tetraplegics but not in the normal controls. Head-up tilt resulted in a greater AVP response in the tetraplegics than in the controls because of the additional hypotensive response in the tetraplegics. Infusion of AVP itself at physiological concentrations had little effect on blood pressure in the normal subjects but resulted in a marked rise in blood pressure in the tetraplegics. Tetraplegics therefore show appropriate release of AVP to both osmotic and cardiovascular stimuli but increased sensitivity to the pressor effects of this hormone.

Adult↗
PubMed1986

Renal vascular responses to saralasin in conscious chemically denervated rabbits and patients with tetraplegia.

To determine the relative contributions of direct angiotensin-II-like myotropism and sympathetic nerve stimulation to the partial agonist effect of saralasin, the renal vascular responses to i.v. saralasin (5, 10, 20 micrograms/kg/min) were assessed in normal conscious rabbits before and after sympatholytic treatment with guanethidine (24 mg/kg/day for 9 days) and in 6 chronic tetraplegic patients (0.5, 1, 5 micrograms/kg/min) before and after alpha-adrenoreceptor blockade with i.v. thymoxamine (1 mg/kg/h). In rabbits saralasin reduced effective renal plasma flow (ERPF) and glomerular filtration rate (GFR), and increased renal vascular resistance (RVR) without affecting mean arterial blood pressure (BP). Responses were similar in both groups, but recovery following saralasin was more prolonged after treatment with guanethidine. When 0.1 microgram/kg/min (one fiftieth of the smallest i.v. dose) was infused just proximal to the renal arteries in 4 conscious rabbits (chronically cannulated), renal perfusion fell and RVR increased. In tetraplegics saralasin produced a transient rise in BP and variable increase in RVR; neither response being altered by thymoxamine. These results suggest that saralasin-induced renal vasoconstriction is independent of central and peripheral sympathetic activation, and is probably due to an intrinsic angiotensin-II-like myotropic action.

Adult↗
PubMed1985

Physical ability in relation to anthropometric measurements in persons with complete spinal cord lesion below the sixth cervical segment.

A study was undertaken to determine the ability of patients with complete tetraplegia below cervical sixth segment to transfer in relation to their anthropometric characteristics. Thirty-six chronic patients were assessed and spasticity was measured. A discriminant function analysis was carried out to assess the extent to which a number of anthropometric and anatomical variables could predict the patients' final ability to effect a transfer. Using nine of the original 23 predictor variables it is possible to correctly classify a patient's eventual ability to transfer in 92% of cases.

Adolescent↗
PubMed1984

Rehabilitation after spinal cord injuries complicated by previous lesions.

Since Sir Ludwig Guttmann introduced the comprehensive modern clinical approach to the rehabilitation of spinal cord injured patients much experience has been accumulated. Modern spinal cord injuries centres have opened throughout the world, treating mainly acute spinal cord injuries in young patients. At Stoke Mandeville Hospital we have had the opportunity to treat several spinal patients who had suffered previous neurological or orthopaedic disorders. These complicated combinations affected the rehabilitation process and the presentations show clearly different aspects of the problem.

Achondroplasia↗
PubMed1984

The immediate pressor response to saralasin in man: evidence against sympathetic activation and for intrinsic angiotensin II-like myotropism.

The cardiovascular and hormonal effects of intravenous saralasin (0.5, 1 and 5 micrograms min-1 kg-1) were assessed in nine tetraplegic patients (with complete cervical spinal cord transaction above the sympathetic outflow) and in six normal subjects. In the tetraplegic patients, saralasin caused an immediate transient pressor response which was not dose-dependent and substantially greater than the pressor response in normal subjects. The pressor response in the tetraplegic patients was not accompanied by a rise in levels of plasma noradrenaline. In the tetraplegic patients, after alpha-adrenoceptor blockade with thymoxamine (1 mg kg-1 h-1), twice the dose of intravenous noradrenaline was needed to induce the same pressor response. The pressor response to saralasin (5 micrograms kg-1 min-1), however, was unaffected by thymoxamine. Saralasin caused minimal changes in levels of plasma renin activity and plasma aldosterone in both groups. There was no relationship between basal plasma renin activity and the pressor response in either group. We therefore conclude that the immediate transient pressor response to saralasin in man is not due to central sympathetic stimulation, is unlikely to be due to peripheral sympathetic activation and is probably the result of intrinsic angiotensin II-like myotropism.

Adult↗
PubMed1983

Autonomic neuropathy.

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Autonomic Nervous System Diseases↗
PubMed1979

Physiological responses to insulin hypoglycaemia in spinal man.

The physiologically responses to hypoglycaemia induced by fish insulin were studied in nine tetraplegic subjects with physiological complete cervical spinal cord transection between C4 and C8. During hypoglycaemia there was a reduction in both systolic and diastolic blood pressure unlike in normal subjects. This was accompanied by a rise in heart rate. The normal rise in plasma adrenaline levels did not occur. Plasma human insulin levels were suppressed. The usual neuroglycopenic symptoms accompanying hypoglycaemia did not occur in the tetraplegics.

Adult↗
PubMed1979

Antihypertensive effects of clonidine in tetraplegic subjects devoid of central sympathetic control.

1. The effects of 300 microgram of oral clonidine on blood pressure, heart rate, plasma noradrenaline and adrenaline concentrations were studied in seven tetraplegic subjects with physiologically complete cervical spinal cord transections. 2. Clonidine did not significantly change resting blood pressure during the 8 h of the study. Resting heart rate fell. Resting plasma noradrenaline and adrenaline concentrations, when measured 2 h after clonidine, were not significantly lower. 3. Urinary bladder stimulation resulted in a marked rise in blood pressure accompanied by an elevation in plasma noradrenaline but not adrenaline. The hypertensive response to bladder stimulation was substantially reduced by clonidine, the maximum suppression occurring 2-4 h after administration of the drug. The plasma noradrenaline response to bladder stimulation, when measured 2 h after clonidine, was significantly lower than the response before clonidine. In two tetraplegic subjects with indwelling catheters the rise in intravesical pressure caused by bladder stimulation was unchanged by clonidine. 4. The pressor response to intravenous noradrenaline in two tetraplegic subjects and to intravenous phenylephrine in a further two tetraplegic subjects was unchanged by clonidine. 5. Clonidine may have additional antihypertensive effects which occur independently of actions in the brain. These effects may be exerted by an action either on sympathetic neurones in the spinal cord or on presynaptic alpha-adrenoreceptors in the periphery.

Adult↗