Biomedical subjects
Publications and source records attributed to L Ott.
The known metabolic abnormalities and nutritional requirements of the brain injury, spinal cord injury, and acute stroke patient have been presented. Further investigations are required in all these conditions to identify specific nutritional requirements and metabolic abnormalities. The specific role of nutritional support on outcome, immune function, and body structure requires further study.
Patients with severe head injury are hypermetabolic and hypercatabolic, and manifest several components of the acute phase response. Interleukin-1 (IL-1) is a cytokine that mediates many aspects of the acute phase response, and rats with experimental head injury produce IL-1 of brain origin. IL-1 administered intracerebroventricularly to experimental animals has disproportionately greater systemic biologic effects compared with IL-1 injected intravenously. In this study, patients with severe head injury were evaluated to determine whether IL-1 activity in the ventricular fluid was increased and whether IL-1 levels correlated with some of the altered metabolic responses. Twelve hospitalized patients with head injury (24-hour peak admission Glasgow Coma Scale scores of 4 to 10) were evaluated on admission and longitudinally for 21 days after injury. IL-1 activity in ventricular fluid from patients with head injury was significantly elevated whereas IL-1 activity in cerebrospinal fluid from age- and sex-matched patients undergoing lumbar puncture for myelograms was not detectable (P less than 0.005). The patients with head injury had clinical and biochemical indicators of IL-1 activity such as fever, hypozincemia, and increased C-reactive protein levels that improved during the period of hospitalization. It is speculated that the elevated IL-1 activity may play a role in the altered metabolic response of patients with severe head injury.
Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 +/- 0.5 times predicted energy expenditure. Caloric balance [calories received = calories expended] was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 +/- 0.2 on admission to 1.98 +/- 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 +/- 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids.
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Few attempts have been made to examine the statistical problems that the user of compartmental models must face. Some properties of the estimators of parameters for one and two compartmental models based on nonlinear estimation were studied through simulation. Of particular interest were the effect of the experimental design and the effect of different error structures on the empirical sampling distribution for the estimators. For the one compartment model it was found that nonlinear estimation yielded essentially unbiased estimators that were normally distributed unless the random error for the model was large. In the two compartment model simulations, bias appeared in the estimators to the extent that bimodal sampling distributions of the estimators were observed as the random error for the model was increased.
The method for analyzing data leading to the estimation of a pA2 depends on the experimental design. Three different experimental designs are discussed. For each design, we provide a brief description of experimental situations that give rise to the design, a means for verifying relevant assumptions, and sample data with summary calculations.
Z-1-(4-Bromophenyl)-1-(3-pyridyl)-3-dimethylaminopropene dihydrochloride hydrate (zimelidine; H 102/09), a newly developed bicyclic substance, was tested in a pilot study for its clinical effect in 10 female patients with a depressive syndrome. Zimelidine inhibits the 5-hydroxytryptamine (5-HT) reuptake more potently than does chlorimipramine. The action on the norepinephrine reuptake is weaker compared with imipramine, also the cardiotoxic and anticholinergic effects are lower. Zimelidine was administered for 20 days in a daily dose of 150 mg. A significant (p less than 0.05) improvement from the beginning of the treatment to the 15th day was demonstrated in Hamilton rating scale and a self-rating scale (von Zerssen). Nevertheless, the zimelidine treatment had to be discontinued between the 15th and 18th days in 3 patients, because of agitation symptoms. The antidepressant action in some patients justifies the performance of controlled studies.
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In an attempt to improve early enteral nitrogen replacement, nitrogen status was compared in two groups of head injured patients receiving enteral regimens of 38 to 51 kcal/kg/day with different protein concentrations. Eleven control patients received 1.5 g protein/kg/day and 10 study patients received 2.2 g protein/kg/day. Daily nitrogen excretion, corrected nitrogen balance, blood urea nitrogen changes, and enteral formula tolerance were compared between groups over a 10-day period. Those receiving 2.2 g protein/kg/day had significantly higher daily and cumulative nitrogen balances despite their higher nitrogen excretion levels. Over 10 days, the study group retained 9.2 g nitrogen. By comparison, the control group sustained a cumulative loss of 31.2 g nitrogen over 10 days, despite a mean intake of 109 g protein/day. In both groups, full strength, full rate feedings were not possible until day 10 postinjury. These data indicate that once enteral formulas are tolerated high nitrogen regimens are required to achieve positive nitrogen balance in acute severe head injury patients.
Every year several million people sustain brain injury. The development of an optimal metabolic and nutritional support program for brain-injured patients relies on an understanding of the metabolic response and nutritional complications that occur with brain injury. Severely brain injured patients have increased serum and urine levels of norepinephrine, epinephrine, and cortisol. These patients also have increased oxygen consumption and urinary nitrogen excretion. This group has observed hypozincemia, hyperzincuria, increased serum C-reactive protein and copper concentrations, and hypoalbuminemia in nonsteroid-treated severely brain-injured patients. Experimental head injury produces interleukin-1 (IL-1) of brain origin. This cytokine mediates many of the aspects of the acute phase response, including all of the metabolic abnormalities reported by our group. IL-1, when administered intracerebroventricularly to experimental animals, appears to have enhanced biological activity compared to that administered systemically. Interleukin-1 activity has been found in significant amounts in the intraventricular fluid of head-injured patients. We suggest that IL-1 acts in concert with traditional stress hormones such as epinephrine, norepinephrine, and cortisol to produce the profound metabolic disturbances observed in the head-injured patient.
Patients with alcoholic hepatitis are typically malnourished. A hypermetabolic state would explain, at least in part, the muscle wasting observed in these patients. However, data on hypermetabolism in liver disease are limited and conflicting. In this study, we evaluated measured energy expenditure (MEE) vs predicted energy expenditure (PEE), and MEE in relation to urinary creatinine excretion in 20 patients with moderate and severe alcoholic hepatitis, and 20 controls. Patients with alcoholic hepatitis had depressed creatinine height index (moderate 66%, severe 78%) demonstrating muscle depletion. Patients with alcoholic hepatitis also had depressed mean serum albumin concentrations, the moderate group 2.6 g/dl and the severe group 2.0 g/dl. The mean values for measured energy expenditure in moderate alcoholic hepatitis patients, severe alcoholic hepatitis patients, and the control group were: 1556 kcal, 1878 kcal, and 1943 kcal, respectively. The mean measured energy expenditures per g of creatinine for the same groups were: 1520 kcal, 1813 kcal, and 1043 kcal, respectively. The mean measured energy expenditure/predicted energy expenditure ratio was not increased in alcoholic hepatitis patients compared to controls. However, when related to urinary creatinine excretion, the alcoholic hepatitis patients had a mean measured energy expenditure that was 55% higher than controls. In conclusion, whereas the measured energy expenditure to predicted energy expenditure ratio was not elevated in alcoholic hepatitis patients compared to controls, the measured energy expenditure per gram of creatinine was significantly increased in alcoholic hepatitis patients, supporting the concept of alcoholic hepatitis as a hypermetabolic state.
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Patients with severe brain injuries have increased energy expenditures and urinary nitrogen excretion. Hypozincemia, hypoferremia, increased levels of acute phase proteins, depressed levels of negative acute phase proteins, and weight loss are common in these patients. The specific mediators of these responses are not known. Nutritional support may beneficially affect outcome in these patients, but enteral feedings are often not tolerated in the acute phase of injury. Animal investigations suggest that total parenteral nutrition and hyperglycemia may increase neuronal injury and worsen outcome. We review the current literature on nutritional support of brain-injured patients and examine the premises on which nutrition supplementation are based. More work is needed to define the metabolic responses and nutritional requirements of patients who sustain central nervous system injury.