Steady state hormonal secretion in traumatic quadriplegia.

Physiologically complete cervical spinal cord transection results in motor and sensory quadriplegia and interruption of the sympathetic neural pathways; this condition leads to metabolic deficiencies suggestive of abnormal endocrine function. An investigation of the non-stimulated secretion of some of the hormones influencing metabolism was undertaken by evaluating thyroxine, iodothyronine binding index, testosterone, growth hormone, calcitonin, and parathyroid hormone in venous blood of fasting healthy subjects and quadriplegic patients. The effect of the duration of the paralysis was examined by repeating the evaluations at different periods after onset. The results show that 1) thyroxine was low for 2 months after onset in 21 patients and normal thereafter in 53 patients, 2) testosterone was low throughout the study in 62 patients; the decrease is greatest during the first 2 months, 3) growth hormone was often increased in 46 patients for 8 months after onset, and nearly normal afterward in 25 patients, 4) calcitonin was normal in 22 patients throughout the study, and 5) parathyroid hormone was normal in relation to normal serum calcium as early as 6 days after onset in 79 out of 83 patients. These data do not preclude a parathyroid hormone increase at onset or alterations in the patterns of circadian secretion and in the responses to specific stimulation for the hormones evaluated. Therefore, it may be concluded only that the steady state secretion of these hormones is not altered by traumatic quadriplegia per se, but is temporarily modified by the original insult to the nervous system, and by changes in life pattern and the heavy sedation that follows. The results suggest that the minor endocrin changes occurring in quadriplegic patients during the early period of paralysis will be rapidly overcome by rehabilitation to an active life pattern.

The urinary excretion of collagen degradation products by quadriplegic patients and during weightlessness.

Urinary total hydroxyproline, peptide-bound hydroxyproline, hydroxylysine glycosides, and calcium were measured in three healthy individuals subjected to weightlessness for eighty-four days and in three young quadriplegic patients. The former group had significant calciuria but no evidence of collagen degradation. The latter group, however, had conspicuous calciuria and also excreted large amounts of collagen breakdown products. This documented degradation of matrix may be related to the continuous calciuria, osteoporosis, and cutaneous dystrophic changes occurring in quadriplegics.

A study of osteoporosis as it relates to metabolic manifestations in edentulous women.

Among some patients, regardless of age, the jaw loses bone mass, leading to loosening and falling out of otherwise healthy teeth. This study seeks to establish whether this bone loss is associated with the metabolic manifestations of other forms of localized decalcifications, such as in Paget's disease, or with generalized osteoporosis. Sixteen women being fitted with dental implants to compensate for bone losses provided 24-hour urine samples for the quantitative determination of calcium and galactosyl hydroxylysine, a bone collagen metabolite. These patients provided demographic information, relevant medical, dental, and dietary history, a profile of their current medications, and the status of their smoking and exercise habits. Urinary excretion of galactosyl hydroxylysine, which is increased in the presence of progressive increased bone resorption, remained within normal values in the patients of this study. These results suggest that the thinning of the jaw bones and subsequent tooth loss of these subjects were osteoporotic processes too limited and too localized to produce measurable increases in urinary bone metabolites.

Urinary in vitro sedimentation: effects of nondialyzable components and heparin.

To determine whether nondialyzable urinary solids which are rich in hydroxyproline polypeptides, could act as nuclei in the formation of crystal aggregates, urine from patients with spinal cord injury (SCI) was pooled for 7 days and its nondialyzable fraction was separated and lyophilized. The ability of this extract to influence the formation of crystals was tested in vitro in a synthetic urine system. The concentrations of calcium, hydroxyproline, and uric acid, as well as the pH, were varied to simulate a range of possible situations in vitro. In the presence of the extracts, when the pH of the synthetic urine was increased from 5.5 to 6.5, the weight of the sediment decreased; in contrast, when the pH was increased from 7.0 to 8.5, the weight of the sediment increased. A similar synthetic urine system was used to test the effect of heparin, a medication often given SCI patients, on crystallization. In this instance, the pH was not altered. Heparin lowered the weight of sediments formed in solutions with uric acid concentrations of less than 50 mg/dl, but had varying effects in solutions with higher uric acid concentrations.

Increased urine calcium during hyperalimentation in quadriplegia: report of 2 cases.

Two acute quadriplegic adolescent boys with hypercalcemia had large increases in urine calcium during calcium-free, or nearly free, intravenous hyperalimentation. The calcium which spilled in the urine proved to be of endogenous origin since it was accompanied by proportional amounts of hydroxyproline. To limit the endogenous bone losses during hyperalimentation, it is recommended that calcium in an amount equal to that loss be added to the perfusate so that only exogenous calcium is spilled in the urine.

Free amino acid excretion in tetraplegic patients.

Free amino acid chromatographic fingerprints obtained in automated analysers in 24-hour urines may help to quantitate muscle and collagen changes occurring after cerival spinal cord injury. The technique was used to compare the urine of six healthy and ten tetraplegic men, 18 to 25 years old, three of whom became paralysed in diving, one in a mountain fall, one one in the fall of a pipe, four in car accidents, and one in a football game. Nine weeks to 14 years after injury, the tetraplegics excreted less total free amino acids, lysine, and 3-methylhistidine than the controls, whereas hydroxyproline and hydroxylysine were similar in both groups. Values of urine 3-methylhistidine, measured 9, 13, 19 and 20 weeks post onset in one patient, and 9, 12, 16, 18, 23, and 26 weeks post onset in another, were related to the duration of paralysis. These results indicate that collagen and muscle metabolism may not be quantitated by measuring urine free amino acids.

Metabolic and endocrine changes in spinal cord injury: I. The nervous system before and after transection of the spinal cord.

This is the first article of a 4-part series which provides a comprehensive, concise review and analysis of the pertinent literature published over the last 25 years on the metabolic and endocrine consequences of spinal cord injury. This article begins with a brief overview of the physiology of the nervous system, and then reviews the metabolic changes associated with the motor paralysis which follows cervical spinal cord injury. Studies reviewed on SCI patients include investigations of body composition (lean mass, fat, creatinine, water, electrolytes), urine composition (creatinine, uric acid, fluid balance, electrolytes), and the blood flow and histochemistry of paralyzed muscles. Studies reviewed from animal models include investigations of the properties of muscle cells, membranes, somatic receptors, and the kinetics of electrolytes in paralyzed limbs, and how succinylcholine modified these properties and kinetics. Information from articles reviewed here is organized under the following headings: problems studied, methods of investigation and results, conclusions, summary of results, discrepancies, areas of needed research, and practical clinical implications. Highlights of pertinent data contained in the original articles are organized in tables to facilitate direct comparisons between similar studies and between data on healthy and spinal cord injured subjects.

Metabolic and endocrine changes in spinal cord injury: IV. Compounded neurologic dysfunctions.

This is the last of a 4-part series which provides a comprehensive review and analysis of the pertinent literature published over the last 25 years on the metabolic and endocrine consequences of spinal cord injury (SCI). The studies on SCI patients reviewed in this article include reports and investigations concerning calcium kinetics, bone minerals in blood and urine, collagen metabolites in urine, bone-related vitamins, hormones and enzymes, osteoporosis, urinary stones, ectopic calcifications, and bone histology and chemistry. Information from articles reviewed here is organized under the following headings: Problems studied, Methods of investigation and results, Conclusions, Summary of results, Discrepancies, Areas of research needed, and Practical clinical implications. Highlights of pertinent data contained in the original articles are organized in tables to facilitate direct comparisons between similar studies and between data on healthy and spinal cord injured subjects.

Spinal cord injury and serum erythropoietin.

The origin of the temporary reduction in hematocrit and hemoglobin occurring after spinal cord injury (SCI) may be related to the neurologic dysfunction and to a change in erythropoietin (Ep) synthesis and/or secretion. Serum Ep, vital capacities, and numerous hematologic profiles were obtained in 12 cervical SCI patients during the first 12 weeks and 13th to 27th post-injury weeks, and in 8 thoracic SCI patients during the first 8 weeks and 9th to 28th weeks. Serum iron, iron binding, and saturation were obtained in 4 cervical SIC patients and blood gases in 10 patients with cervical SCI and in 6 with thoracic SCI. The results in all patients showed increased Ep values, returning to normal after 8 weeks in the thoracic SCI patients only. The few results on iron kinetics showed a tendency to low values, suggesting the necessity for further investigation. In an attempt to explain the Ep increase in SCI patients, the relative influence of the renal pelvic nerves and of the sympathetic nerves on its secretion, are examined.

Measurement of hydroxylysine glycosides in urine and its application to spinal cord injury.

A new technique to evaluate the degradation of skin or bone collagen by measuring glucosylgalactosyl hydroxylysine and galactosyl hydroxylysine is presented. The method utilizes an automated amino acid analyzer. Eluents used are lithium buffers, and the color reagent is ninhydrin. Both glycosides elute in 3.5 h. Samples require minimum preparation. Urinary concentrations of both glycosides in ten patients with cervical spinal cord injuries of less than six months duration were higher than in five healthy controls. Proportional increases were different for each of the two glycosides. Variations in the proportional increase of each glycoside indicate different rates of degradation of skin and bone collagen. Repeated evaluations of the two urinary glycosides may help to predict whether patients are likely to develop skin- or bone-related clinical complications.

Biochemical changes in skin composition in spinal cord injury: a possible contribution to decubitus ulcers.

Patients with spinal cord injury (SCI) have an increased susceptibility to ulcers of the skin due to pressure. Immediately after the injury, SCI patients have a greatly increased degradation of collagen from both bone and skin. Loss of collagen from the skin could account for a reduction of the skin's ability to resist mechanical insults. This paper describes the results of an investigation into the role of collagen metabolism in the etiology of pressure ulcers. Skin biopsies have been obtained from healthy non-paralysed volunteers, and from insensitive and sensitive skin in SCI patients. The amino acid content of the insensitive skin was considerably lower than in sensitive skin. The activity of the enzyme lysyl hydroxylase was also lower in the insensitive skin. Lysyl hydroxylase activity in the sensitive skin was similar to enzyme activity in control skin biopsies of the same body area.

Metabolic and endocrine changes in spinal cord injury: III. Less quanta of sensory input plus bedrest and illness.

This is the fourth article (Part III) of a 4-part series which provides a comprehensive review and analysis of the pertinent literature published over the last 25 years on the metabolic and endocrine consequences of spinal cord injury (SCI). The studies on SCI patients reviewed in this article include reports and investigations concerning plasma ACTH, plasma and urine corticosteroids and their diurnal variations at rest and during stress, of fasting values of TSH and growth hormone, thyroxine, testosterone, and of urinary skin collagen metabolites and urinary tryptamine. Information from articles reviewed here is organized under the following headings: Problems studied, Methods of investigation and results, Conclusions, Summary of results, Discrepancies, Areas of research needed, and Practical clinical implications. Highlights of pertinent data contained in the original articles are organized in tables to facilitate direct comparisons between similar studies and between data on healthy and subjects with spinal cord injuries.

Metabolic and endocrine changes in spinal cord injury: II (section 2). Partial decentralization of the autonomic nervous system.

This is the 3rd article (part II, section 2) of a 4-part series which provides a comprehensive review and analysis of the pertinent literature published over the last 25 years on the metabolic and endocrine consequences of spinal cord injury (SCI). The present article describes the consequences of totally removing the sympathetic and partially removing the parasympathetic nervous system from brain integration. The studies reviewed in this section include reports and investigations concerning fluid and electrolyte balance, renin, and aldosterone. Information from studies reviewed in this article is organized under the following headings: Problems Studied, Methods of Investigation and Results, Conclusions, Summary of Results, Discrepancies, Areas of Needed Research, and Practical Clinical Implications. Highlights of pertinent data contained in the original articles are organized in tables to facilitate direct comparisons between similar studies and between data on healthy subjects and SCI patients.

Metabolic and endocrine changes in spinal cord injury: II (section 1). Consequences of partial decentralization of the autonomic nervous system.

The article is section 1 of the second part of a 4-part series which provides a comprehensive, concise review of pertinent literature published in the last 25 years on the metabolic and endocrine consequences of spinal cord injury (SCI). This article describes the consequences of total removal of the sympathetic and partial removal of the parasympathetic nervous system from brain integration. Subjects reviewed include bradycardia, altered coagulation, blood pressure instability, relation of hypotension to level of injury, blood and urine neurohormones, hemodynamic responses to stress and fluid infusions, neural components of glucose regulation, evaluation of catecholamines and their metabolites at different time periods, and evaluation of catecholamies, blood dopamine hydroxylase, and prostaglandins during hypotension and hypertension. Other studies reviewed include investigations of metabolic and circulatory responses to exogenous norepinephrine and physiologic and biochemical responses to intense cold and to sodium depletion. Data are organized under the following heads: a. Problems Studied, b. Methods of Investigation and Results, and c. Conclusions. Pertinent highlights from the original articles are organized in tables, to facilitate direct comparisons between similar studies and between data on healthy subjects and SCI patients. Additional studies dealing wth partial decentralization of the autonomic nervous system will be reviewed in section 2 of Part II of this series.

Collagen metabolite excretion as a predictor of bone- and skin-related complications in spinal cord injury.

Immediately after the trauma, spinal cord injury patients have an increased rate of collagen synthesis and an even greater increase of collagen degradation. Collagen lost from bone is implicated in the etiology of osteoporosis and heterotopic ossification, and collagen lost from skin might lead to a propensity to develop pressure ulcers. The urinary excretion of two collagen metabolites has been monitored and their fluctuation related to the onset of skin or bone complications in these patients. One metabolite, glucosyl-galactosyl hydroxylysine, is more abundant in skin collagen; the other, galactosyl hydroxylysine, is more abundant in bone collagen. The excretion of both metabolites increases after injury, reaching a peak between three and six months after injury, and declines gradually, reaching control values about a year after injury. If a skin pressure ulcer develops, the urinary excretion of the diglycoside remains elevated instead of gradually decreasing. Similarly, if osteoporosis or heterotopic ossification is diagnosed, the monoglycoside excretion does not return to control values until the bone turnover stabilizes. Monitoring of the urinary excretion of both glycosides might prove helpful in prompting early examination to establish the presence of emerging skin and bone complications. Thus, aggressive preventive therapy could be given sooner.

Immediate endocrine and metabolic consequences of traumatic quadriplegia in a young woman.

Onset of paralysis by cervical spinal cord injury led immediately to temporary adrenocortical activation and, within 2 days, to sustained skin and bone breakdown. Urine cAMP was increased, blood parathyroid hormone, renin activity, and electrolytes were normal, and fluid and electrolytes balance became negative during the initial 6 days of paralysis.

Drug absorption in spinal cord injury.

The absorption characteristics of drugs in spinal cord injury (SCI) were studied using an actively transported drug [riboflavin (RBF)] and a passively absorbed drug [acetaminophen (ACE)]. RBF absorption was studied following oral administration of 150mg RBF as 5'-phosphate flavin mononucleotide in ten clinically complete quadriplegic patients (C1 to C7, two to 15 months post-onset) and six control subjects matched for age, sex, and weight. Urinary excretion was measured under fasting (F) and nonfasting (NF) conditions for time to peak, peak excretion rate, and percent dose recovered. The results showed a significant difference (p less than 0.05) for all parameters between F and NF conditions for both the SCI and able-bodied groups. However, there was no significant difference for the same parameters between the two groups. ACE absorption was studied in five SCI clinically complete quadriplegic patients (C1 to C7, two to 15 months post-onset following the administration of a 650mg tablet. Serum samples were analyzed for ACE content and showed: time of peak, 1.35 +/- 0.6hr; maximum serum level, 6.8 +/- 2.68 micrograms/ml; half-life, 2.89 +/- 1.81hr; absorption lag time, 18.1 +/- 1.8min; area under the serum level-time curve, 21.8 +/- 6.7 micrograms/.hr/ml. When compared to able-bodied population data in the literature, there was a significant increase in the time to peak and lag time, and a decrease in the maximum ACE serum concentration obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic receptors in insensitive skin of spinal cord injured patients.

The factors responsible for the increased susceptibility to decubitus ulcers of the insensitive skin of spinal cord injury (SCI) patients are not known. Autonomic dysfunction leading to defective vascularity is a possibility. SCI removes cerebral control of the isolated nervous system which may mimic denervation hypersensitivity of autonomic neural synapses, where an increase in number and a scattering of the receptors on the postsynaptic membrane leads to abnormal responses. Since adrenergic receptors mediate vascular tone and regulate blood flow in the skin, it would be of great interest to determine whether the number and the concentration of receptors in the insensitive skin of SCI patients is modified as a function of time since injury. To achieve this aim, alpha and beta adrenergic receptors were measured in biopsies obtained from intact skin used to surgically repair decubitus ulcers in SCI patients admitted to The Institute for Rehabilitation and Research. Receptors were identified by competitive radioligand-binding assays in whole skin homogenates. Patients were divided into two groups: patients injured less than five years ("early") and patients injured more than five years ("late"). Alpha and beta adrenergic receptors in both cervical and thoracic SCI patients decreased in density in the "late" patients. The small sample size and the inherent large errors of the assay precluded achievement of statistically significant differences. Nevertheless, a definite trend is seen: Disconnection of the adrenergic neurons from brain integration may mimic denervation and lead to abnormal vascular responses in the insensitive skin.