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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

Cardiovascular and hormonal responses to food ingestion in humans with spinal cord transection.

In sympathetic denervation due to primary autonomic failure, ingestion of food causes a fall in blood pressure (BP) and exacerbates postural hypotension. It is not known whether these responses occur in tetraplegics with physiologically complete cervical spinal cord transection, who also have sympathetic dysfunction because of disruption of descending spinal sympathetic pathways. We, therefore, studied the effect of a liquid meal on BP, heart rate (HR) and neurohormonal levels in tetraplegics. Paraplegics with low lesions and without sympathetic dysfunction served as controls. After food ingestion, there was no fall in BP in tetraplegics or in controls. HR did not change in either group. After fund, plasma noradrenaline was unchanged in tetraplegics, but rose in controls, while plasma renin activity (PRA) rose in tetraplegics but not in controls. The fall in BP and rise in HR on head-up tilt after the meal in tetraplegics was similar to that before the meal. There was no change in PRA following pre-prandial tilt in either group; post-prandial tilt raised levels in the tetraplegics, unlike in controls. Thus there is considerable variance in the responses to food between tetraplegics and paraplegic controls, and even greater differences when compared with published data in other autonomic disorders with sympathetic dysfunction; this may relate to the site and the nature of the sympathetic lesion and the ability to activate compensatory mechanisms.

Adult

Neurological issues.

The case histories of two patients who had had a spinal cord injury (SCI) were selected by the senior author and sent to four experts in the field of SCI. Based on the 1992 American Spinal Injury Association (ASIA) and International Medical Society of Paraplegia (IMSOP) standards, the four participants plus the senior author recorded the motor and sensory scores, the ASIA impairment scale (AIS), the neurological level (NL) and the zone of partial preservation (ZPP). Several minor scoring errors occurred among the participants, especially with motor scores when key muscles could not be tested due to pain, or external immobilization devices. Difficulties with interpretation occurred with the motor levels and the ZPP for the patient with a complete injury. This exercise points to the need for all examiners of SCI patients to thoroughly familiarize themselves with the standards and to use the motor and sensory scores to arrive at a NL and ZPP. They also indicate a need to revise the standards to clarify the determination of sensory levels and how to score muscles whose strength is inhibited by pain.

Adult

Agitation.

Agitation is a frequent clinical problem that adds significant morbidity to the hospital course. Agitation is usually part of an ambiguous constellation of cognitive and psychiatric symptoms, with a fluctuating clinical course. Observation of vastly different symptoms occurring at different times leads to misdiagnosis or underrecognition of serious underlying disorders. The most common causes of agitation include delirium, dementia, and acute psychosis. Risk factors attributable to hospitalization include pain, anxiety, and stressors endemic to intensive care. Agitated states may have multiple causes, and each potential contributor must be pursued and treated independently. Definitive diagnosis is dependent on a comprehensive history, patient observation, physical examination, and selective diagnostic studies.

Adult

Hypothermia.

Hypothermia in the hospitalized adult may be a primary process, as in exposure, or a result of a multitude of disease processes or iatrogenic factors. The condition affects virtually every metabolic process in the body. A thorough understanding of the pathophysiology of hypothermia enables the clinician to differentiate between the hypothermic syndrome and underlying illness and can assist in the detection and management of clinical sequelae. A reliable patient history is the most helpful diagnostic tool, but careful physical examination and laboratory studies are also important for detection of primary or secondary illness.

Adult

Diaspirin cross-linked hemoglobin is efficacious in gut resuscitation as measured by a GI tract optode.

The objective of this study was to compare the efficacy of diaspirin cross-linked hemoglobin (DCLHb) with that of standard resuscitative fluids in restoring intestinal mucosal oxygenation and villous architecture after hemorrhage. Male rats were bled to a base deficit of 5 +/- 2 nmol/l under propofol anesthesia and monitored for 90 minutes postresuscitation with DCLHb, blood, lactated Ringer's solution, albumin, or nothing (DNR) for mucosal oxygen tension (Pmo2) and physiologic and laboratory parameters. Small intestinal histologic specimens were obtained and scored independently by two investigators blinded to therapy on a scale of 0 (normal) to 4 (worst). All treatments restored Pmo2; only DCLHb did so without exceeding baseline values. For untreated rats (DNR), Pmo2 was not restored. Normal mucosal architecture was maintained only in DCLHb-treated rats. As Pmo2 increased, mucosal score improved. In a rat model of controlled hemorrhage, Pmo2 changes measured by an optode correlated with gut histological abnormalities. By these criteria, DCLHb is superior to crystalloid, colloid, and blood in gut resuscitation.

Animals

A prospective study of surgeon-performed ultrasound as the primary adjuvant modality for injured patient assessment.

Ultrasound diagnostic imaging, having been used in Germany in the trauma setting for more than 15 years, has unique qualities that give it distinct advantages over other tests (DPL, CT), and is gradually gaining acceptance by surgeons in the United States. In this prospective study, experienced surgeon sonographers successfully used ultrasound as the primary adjuvant modality to detect hemoperitoneum and pericardial effusion in injured patients. The ultrasound evaluations of 371 patients demonstrated that in 65 patients with significant injuries, ultrasound detected 53, that is, had an 81.5% sensitivity and 99.7% specificity. They conclude that ultrasound should be the primary adjuvant instrument for the evaluation of injured patients because it is rapid, accurate, and is potentially cost-effective.

Adolescent

Increased hypoxic ventilatory sensitivity during exercise in man: are neural afferents necessary?

1. The acute ventilatory response to 3 min periods of hypoxia (AHR) was examined in nine patients with clinically complete spinal cord transection (T4-T7) during (a) rest and (b) electrically induced leg exercise (EEL). 2. EEL was produced by surface electrode stimulation of the quadriceps muscles so as to cause the legs to extend at the knee against gravity. End-tidal PCO2 was held constant 1-2 mmHg above resting values throughout both protocols. 3. On exercise, the average increase in metabolic CO2 production (VCO2 +/- S.E.M.) was 41 +/- 5 ml min-1. Venous lactate levels did not rise with exercise. 4. Baseline euoxic ventilation did not increase significantly with EEL, but there was a consistent and highly significant increase in the ventilatory response to hypoxia during EEL (mean delta AHR +/- S.E.M. of 1.6 +/- 0.21 min-1). 5. We conclude that an increase in hypoxic sensitivity during exercise can occur in the absence of volitional control of exercise and in the absence of afferent neural input from the limbs.

Adult

Indications for obtaining surveillance thoracic and lumbar spine radiographs.

The purpose of this study was to identify risk factors for thoracic/lumbar spine fractures in patients with blunt injuries and subsequently establish indications for obtaining surveillance thoracolumbar radiographs. Retrospective review of all patients with blunt injuries (n = 1485) admitted in 1992 to a level I trauma center with a discharge diagnosis of thoracolumbar spine fracture established entrance criteria for a 4-month prospective study. Relative risk of fracture (RR) was calculated. Retrospective. Seventy-six percent (176 of 233) had radiographs; 21% had fractures; one diagnosed late. Prospective. One hundred percent (167 of 167) had radiographs; 9% (15 of 167) had fractures; none diagnosed late or missed. Forty percent (26 of 65) of patients with fractures had no pain or tenderness; 35% (9) required surgical spinal fixation. Our data define these indications for obtaining thoracolumbar radiographs in patients with blunt injuries: back pain (RR1), fall > or = 10 feet, ejection from motorcycle/motor vehicle crash > or = 50 mph, GCS score < or = 8, (all RR2), and neurologic deficit (RR10). The sensitivity of our surveillance radiography protocol has increased to 100%. The absence of back pain does not exclude significant thoracolumbar trauma.

Adult

Minimizing admission laboratory testing in trauma patients: use of a microanalyzer.

OBJECTIVE: Routine admission laboratory test protocols in injured patients are costly and involve excessive phlebotomy and turnaround time. The purpose of this prospective study was to evaluate the utility of (1) a microanalyzer, NOVA-SP5 (which provides rapid results on minimal blood volume), and (2) each component of our standard laboratory test battery. METHODS: Laboratory test results for 200 consecutive injured patients admitted to a level I trauma center were evaluated by paired sample analysis. Our standard battery [60 mL: ($348): type and screen, complete blood count, PT/PTT, electrolytes, BUN, creatinine, glucose, calcium, amylase, ethanol level, and arterial blood gas] run "stat" in the central laboratory was compared to the microanalyzer profile [< 1 mL: ($182): hemoglobin, hematocrit, electrolytes, glucose, Ca2+, and arterial blood gas] run by the trauma team in the resuscitation area. Patient data and laboratory turnaround time (from time of admission to time results obtained) were recorded. Data were analyzed by linear regression. RESULTS: Components of the paired samples correlated well (r2 0.78 to 0.99). Turnaround times were 64 (+/- 3) and 6 (+/- 1) minutes for standard analysis and microanalysis, respectively. Only two of the 26 patients requiring emergent surgical procedures had standard results available preoperatively. These patients had twice as many laboratory abnormalities as the remainder. Minimal diagnosis or intervention resulted from those values exclusive to standard analysis (white blood count, amylase, ethanol level, BUN, creatinine, platelet count, PT, and PTT). Six of ten abnormal BUN or creatinine results normalized, including two values in patients who received contrast for portable intravenous pyelography, and in all patients without a history of hypertension or diabetes. Platelet count and PT/PTT were normal in 85% of non-head-injured patients, compared with 58% of those with GCS score < or = 8. CONCLUSIONS: Microanalysis is accurate, expedient, conserves blood, and is sufficient for evaluation of most trauma patients. Those with hypertension, diabetes, or severe head trauma may require additional testing. Routine use of this technique could reduce cost substantially ($16,000/100 patients). The role of microanalysis in follow-up laboratory evaluation of injured patients remains to be elucidated.

Adult

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

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

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

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

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

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

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

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