[Functional and esthetic aspects of therapy for lip cancer].
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Biomedical subjects
Publications and source records attributed to G Grimm.
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A marked release of glutaraldehyde from commercially available pericardial bioprosthetic heart valve (BHV) material in washing solutions was found by high performance liquid chromatography (up to 1.8 ppm of glutaraldehyde per gram of dry tissue). In vitro endothelial cell proliferation rate was impaired dose-dependently in the presence of increasing glutaraldehyde concentrations of the cultivation medium (r = 0.9; p less than 0.05). Cultivation of endothelial cells was impossible on the surface of commercially available BHV material, but successful and uninhibited when toxic glutaraldehyde ligands of the BHV material were antagonized by treatment with L-glutamic acid.
In 27 (78%) of 36 patients with massive hemolysis (defined as a fall in hematocrit of more than 12% within 12 h due to intravascular red cell destruction), hypertriglyceridemia (plasma triglycerides greater than 175 mg/dl) was present or appeared within two days after the hemolytic crisis. Eighteen subjects with triglycerides exceeding 300 mg/dl (peak 516 +/- 39 mg/dl) were further analyzed. The development of hyperlipidemia was independent of the etiology of hemolysis (microangiopathic hemolytic disease 7, toxicemia 3, parainfectious complications 3, autoimmune hemolysis 2, glucose-6-phosphate dehydrogenase deficiency 2). Factors known to increase plasma triglycerides, such as shock, infections, or pancreatitis, were present in only a few cases. Hemolysis-associated complications were activation of intravascular coagulation (16), coma (13), acute renal failure (13), and respiratory insufficiency (5), organ dysfunctions indicating diffuse microvascular injury. Plasma triglycerides fell within a few days if the cause of red cell destruction was eliminated. In 5 of the 8 patients presenting with triglycerides below 175 mg/dl, severe hepatic dysfunction was present. We conclude that hemolysis causes transient hyperlipidemia, either directly by red cell destruction or indirectly by inducing intravascular coagulation, and possibly due to both increased triglyceride synthesis and decreased catabolism.
Forty-five patients with Wilson's disease (WD) were prospectively studied: 27 had neurological deficits, 12 hepatic signs, and 6 were asymptomatic. Kayser-Fleischer rings occurred in 23 of the neurological patients and in only 4 of the hepatic patients. Neurological features were extremely variable with respect to frequency and severity. Most frequent were dysdiadochokinesis (25 patients), dysarthria (23), bradykinesia (17), and posture tremor (14). Fifteen, mainly long-term treated patients, presented with rather discrete neurological abnormalities which predominantly consisted of dysarthria and various forms of tremor. Eight patients had a parkinsonian type of neurological WD associated with signs of an organic mood syndrome. Three patients were predominantly hyperkinetic, presenting with dystonic and choreatic movements. In 1 patient, ataxia was the predominant neurological feature. There was a clear-cut correlation between the severity of neurological impairment and the restriction in functional capacity. Nine patients were not able to engage in salaried employment or were retired. Psychiatric symptoms and behavioural disorders were common, varying from mild personality and psychological disturbances to severe psychiatric illness resembling psychotic disorders and major depressive syndromes. Significant mental deterioration was not found in the patients. Disturbances of mood were observed in 12 patients, all of whom had neurological abnormalities. There was a history of an attempted suicide in 7 patients, and a history of an organic delusional syndrome in 3.
Diagnostic and prognostic value of evoked potentials (EP) were studied in 5 patients with severe herpes simplex encephalitis (HSE). Latency of the third negative cortical N70 peak, elicited by median nerve stimulation, was prolonged in 3 survivors with Glasgow coma score of less than or equal to 6 (115 vs 71 ms in controls, p less than 0.05), but normal after improvement of the acute disease. N70 right to left interhemisphere difference was increased initially in the 4 survivors (26 vs 3 ms in controls, p less than 0.05) indicating focal brain involvement, a crucial finding in HSE. The first cortical N20 peak was preserved in all survivors even during deep coma where evaluation of brain function is difficult. Auditory brainstem EP were normal in all patients and useful to exclude brainstem death. In severe HSE, somatosensory long-latency EP are an effective monitor of the level of impaired consciousness and can detect brain focal signs. Short-latency N20 components may be predictive of the outcome.
Forty cases of hemolysis (drop of hematocrit greater than 12%/12 h) were retrospectively analyzed for hyperamylasemia and pancreatic complications. In 15 subjects the serum amylase level was greater than 360 U/l, i.e., three times the normal range, in ten the amylase level exceeded 900 U/l. Excluding patients in circulatory shock and/or hepatic coma, acute pancreatitis as defined by an elevation of serum amylase and clinical signs (epigastric pain) was present in four, with additional ultrasound findings (pancreatic swelling) and/or laparatomy/postmortem findings in a further six subjects (total ten patients = 25%) with various causes of hemolysis: autoimmune hemolysis 2, microangiopathic hemolytic anemia 2, toxicemia, G-6-PDH deficiency, septic abortion, malaria, Wilson's disease, and hypophosphatemia, one case each. In all subjects acute renal failure and in seven an activation of intravascular coagulation was seen. Three patients died (33% vs 47% of all hyperamylasemic patients and 46% of the whole group), but none of the deaths was attributed to pancreatitis. Pancreatic postmortem findings were diffuse edema and patchy parenchymal necrosis in two cases and petechial bleeding in one case. We conclude that acute pancreatitis is a complication of massive hemolysis, occurring at a prevalence of above 20%. It may progress from diffuse edema and inflammation to focal necrosis, rarely if ever to gross hemorrhage, and does not contribute to the high mortality of massive hemolysis. Back pain in hemolysis might originate from the pancreas rather than from the kidneys.
In 11 patients with decompensated cirrhosis and deteriorating renal function, the effect of the vasoconstrictor substance 8-ornithin vasopressin (ornipressin; POR 8; Sandoz, Basel, Switzerland) on renal function, hemodynamic parameters, and humoral mediators was studied. Ornipressin was infused at a dose of 6 IU/h over a period of 4 hours. During ornipressin infusion an improvement of renal function was achieved as indicated by significant increases in inulin clearance (+65%), paraaminohippuric acid clearance (+49%), urine volume (+45%), sodium excretion (+259%), and fractional elimination of sodium (+130%). The hyperdynamic circulation was reversed to a nearly normal circulatory state. The increase in systemic vascular resistance (+60%) coincided with a decrease of a previously elevated renal vascular resistance (-27%) and increase in renal blood flow (+44%). The renal fraction of the cardiac output increased from 2.3% to 4.7% (P less than 0.05). A decline of the elevated plasma levels of noradrenaline (2.08-1.13 ng/mL; P less than 0.01) and renin activity (27.6-14.2 ng.mL-1.h-1; P less than 0.01) was achieved. The plasma concentration of the atrial natriuretic factor increased in most of the patients, but slightly decreased in 3 patients. The decrease of renal vascular resistance and the increase of renal blood flow and of the renal fraction of cardiac output play a key role in the beneficial effect of ornipressin on renal failure. These changes develop by an increase in mean arterial pressure, the reduction of the sympathetic activity, and probably of an extenuation of the splanchnic vasodilation. A significant contribution of atrial natriuretic factor is less likely. The present findings implicate that treatment with ornipressin represents an alternative approach to the management of functional renal failure in advanced liver cirrhosis.
OBJECTIVE: To evaluate the impact of respiratory alkalosis on the elimination of intravenously infused lactate. DESIGN: Prospective, randomized, crossover study. SETTING: Medical ICU of a university hospital. PATIENTS: Eight patients treated by ventilatory support for neurologic or neuromuscular diseases. INTERVENTIONS: Patients were investigated on two occasions: during normoventilation (pH 7.42 +/- 0.1, PCO2 41 +/- 2 torr [5.5 +/- 0.2 kPa]) and during respiratory alkalosis (pH 7.59 +/- 0.1, PCO2 27 +/- 2 torr [3.6 +/- 0.2 kPa]) induced by controlled hyperventilation. To evaluate lactate elimination kinetics, 1 mmol/kg body weight of L-lactic acid was infused over 5 mins. MEASUREMENTS AND MAIN RESULTS: Arterial lactate concentrations and blood gas values were determined before and repeatedly after the infusion. Lactate elimination variables were calculated from the plasma curve by using a two-compartment model. Respiratory alkalosis increased plasma lactate from 1.56 +/- 0.1 to 2.49 +/- 0.2 mmol/L (p less than .001). The lactate elimination half-life increased from 4.57 +/- 0.2 mins at pH 7.42, to 9.96 +/- 1.1 mins during pH 7.59 (p less than .01), and beta half-life increased from 12.2 +/- 1.9 to 44.1 +/- 1 mins (p less than .01). Whole-body clearance decreased 40% from 24.2 +/- 2.9 to 14.3 +/- 2.0 mL/kg body weight-min (p less than .01). CONCLUSIONS: Respiratory alkalosis increases the basal concentration of plasma lactate and decreases clearance of infused lactic acid. These findings provide further evidence of the adverse effects of alkalosis.
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We assessed the functional and structural brain disturbances in Wilson's disease (WD) by evoked potentials (EPs) and magnetic resonance imaging (MRI). All the 25 neurologically symptomatic and 44% of the 16 asymptomatic patients, assessed by both EPs (n = 48) and imaging (n = 41), had at least 1 abnormality of either prolonged EP conduction times, imaging-outlined presence of cerebral lesions, or brain atrophy. Our findings indicate that EPs and MRI are sensitive techniques for the evaluation of brain involvement in WD.
Lung transplantation has been available as a therapeutic option for patients with end-stage lung disease for only a short period of time. Since this procedure is now being successfully performed with increasing frequency in various transplantation centers, we must now begin to consider transplantation as a therapeutic options in patients with lung diseases unresponsive to medical therapy. Physicians are required to know principles involved for determination of suitable candidates and operative procedures of choice. We report here our experiences of preoperative assessment of patients undergoing lung transplantation. Patient selection, indications, contraindications, choice of operation, appropriate timing for transplantation and preoperative rehabilitation methods are discussed. It is concluded that appropriate recipient selection remains an important determinant for the success of this treatment modality.
Mixed disulfides of methanethiol represent a relative estimate for an exposure to methanethiol. The concentrations of methanethiol-mixed disulfides, methionine, 4-methylthio-2-oxobutyrate and ammonia were measured in patients with different stages of hepatic encephalopathy, in patients with chronic kidney failure and in healthy subjects. In patients with hepatic encephalopathy, the mean serum concentrations of all these compounds were elevated. However, the elevations of methanethiol-mixed disulfides were small and partly caused by decreased renal function. In addition, the levels of methanethiol-mixed disulfides did not differ significantly between the different grades of hepatic encephalopathy. The concentrations of methanethiol-mixed disulfides were substantially lower than those previously observed in healthy subjects after an oral methionine load or in a patient with a deficiency in methionine adenosyltransferase, the latter without causing encephalopathy. We concluded that the role of methanethiol in the pathogenesis of hepatic encephalopathy is probably minor, if not insignificant. In the patients with hepatic encephalopathy, a significant correlation was found between the concentrations of methionine and 4-methylthio-2-oxobutyrate and between 4-methylthio-2-oxobutyrate and methanethiol-mixed disulfides, supporting the theory that methanethiol is formed by way of the methionine transamination pathway. Evidence is provided that, besides the methionine transsulfuration pathway, the transamination pathway is also impaired in patients with hepatic encephalopathy.
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Treatment of 9 patients with Wilson's disease was prospectively studied with evoked potentials and magnetic resonance imaging (MRI). Oral penicillamine therapy led to a decrease in auditory brainstem (ABP) and somatosensory (SEP) conduction times in 6 and 4 neurologically symptomatic patients, respectively. ABP and SEP were normal in 3 other symptom-free patients. MRI showed cerebral lesions in 4 of 7 patients. Quantified indices of brain atrophy were unaffected by treatment. ABP and SEP may reveal a reversible component of the disease that cannot be detected by MRI, and may be a more sensitive measure of treatment efficacy.
The present study was designed to investigate hemodynamics and gas exchange during weaning from mechanical ventilation (assist/control mode) to spontaneous breathing with continuous high flow (chf)-CPAP, and to study the predictive value of these parameters in respect of longterm success or failure of weaning. Hemodynamic and gas exchange parameters were obtained in 10 patients without severe pulmonary and cerebral dysfunction at -240, -60, -30, and -15 min before, and at +15, +30, +45, +60, +120, +180, +240 min after chf-CPAP. During chf-CPAP significant increases in heart rate/min (92 +/- 17 to 103 +/- 20), cardiac index (3.9 +/- 0.7 to 4.4 +/- 1.0 1/min.m2), respiratory rate/min (15 +/- 1 to 28 +/- 7), PaCO2 (36.7 +/- 3.0 to 41.2 +/- 5.9 torr) and oxygen delivery (12.2 +/- 2.7 to 13.9 +/- 2.3 ml/min.kg) were found. Arterial and pulmonary artery pressures rose only briefly within the first hour. All other parameters changed non-significantly. In the 4 patients who required mechanical ventilation 12 to 34 hours after the end of the study we found a significantly more pronounced increase in heart rate than in those who where weaned successfully (114 +/- 19 vs 89 +/- 9). Increases in heart rate, respiratory rate, cardiac index, PaCO2 and oxygen delivery can therefore be expected during weaning from mechanical ventilation to spontaneous breathing with CPAP. A pronounced increase in heart rate may suggest a weaning failure.
Energy expenditure and substrate oxidation rate for fat, glucose and protein were evaluated by indirect calorimetry in 20 normal individuals, 35 patients with acute hepatitis and 22 patients with biopsy-proven alcoholic cirrhosis in the postabsorptive state. Measurements were done in the resting state after an overnight fast (10 to 12 hr). Oxygen consumption (ml/min/1.73 m2) in normal subjects, in patients with acute hepatitis and in patients with cirrhosis was 206.5 +/- 4.0 (mean +/- S.E.M.), 216.4 +/- 4.7 and 228.8 +/- 7.1 (p less than 0.05 vs. controls), respectively. When related to body surface area (kcal/min/1.73 m2), resting energy expenditure did not differ between normal subjects (0.98 +/- 0.02), patients with acute hepatitis (1.03 +/- 0.02) and cirrhotic patients (1.06 +/- 0.03). However, when related to 24-hr urinary creatinine excretion as an estimate of lean body mass, energy expenditure was increased in cirrhosis (p less than 0.0001). In cirrhosis an inverse association between the severity of liver disease according to Pugh and oxygen consumption and resting energy expenditure was found. In cirrhotic patients the percentages of total calories derived from fat (86% +/- 5%), carbohydrate (2% +/- 4%) and protein (12% +/- 1%) were different from those of normal controls who metabolized 45% +/- 4%, 38% +/- 4%, 17% +/- 1%, respectively. In acute hepatitis no alterations in metabolism could be found apart from a decreased protein oxidation rate. In conclusion no appreciable changes in energy metabolism exist in acute hepatitis. The pattern of fuel use in cirrhosis resembles that in starvation.(ABSTRACT TRUNCATED AT 250 WORDS)
Recently it was suggested that hepatic encephalopathy (HE) is mediated by an increased GABA-ergic tone. The logical consequence of such a hypothesis is the use of antagonists of the GABA -benzodiazepine receptor for treatment of HE. The experience with these drugs in human HE is limited. In order to get an estimate of the efficacy of this type of drug in humans 20 consecutive episodes of HE in 17 patients with acute or chronic liver failure were treated with flumazenil. All patients entered into the study were encephalopathic for up to 120 hours and failed to respond to conventional therapy. After an observation period of 8 hours, 15 mg of flumazenil were infused intravenously over 3 hours. Before and after treatment patients were examined neurologically and the Glasgow coma scale was calculated. In addition, somatosensory evoked potentials were recorded. In 5 out of 11 episodes in 10 patients with fulminant hepatic failure and in 7 out of 9 episodes in 7 patients with cirrhosis an unequivocal amelioration of HE was observed. The response to treatment occurred very rapidly. After stopping treatment in 8 out of these 12 episodes HE worsened again after 2 to 4 hours. The favourable clinical response was also documented by improvement of somatosensory evoked potentials. In 5 of the 8 episodes not reacting to flumazenil patients had signs of increased intracranial pressure. These findings indicate that flumazenil may be valuable in treatment of acute HE occurring in fulminant hepatic failure or in decompensated cirrhosis.
Thirty-eight patients with biochemically proven Wilson's disease underwent magnetic resonance-imaging (MRI) of the brain as well as neurological examinations. The patients were scanned using spin-echo (SE) sequences; the neurologist was looking for typical symptoms: dysarthria, tremor, ataxia, rigidity/bradykinesia and chorea/dystonia. Pathological MR findings believed secondary to this uncommon inherited disorder of copper metabolism were found in twenty-two subjects. Focal abnormalities were seen in the lenticular, thalamic and caudate nuclei as well as in brain stem and white matter; these lesions were best demonstrated on T2-weighted sequences as hyperintense areas. In eight patients we found diffuse brain atrophy with consecutive widening of the ventricular system. Five subjects showed mild, nineteen severe neurologic deficits. Generally there was no correlation between MR findings and clinical neurological symptoms; the impairment of cell-metabolism causing functional alterations of the brain precedes morphological changes. During treatment with the copper chelator D-penicillamine there seemed to be a phased course of disease. Shortening of T1-relaxation due to paramagnetic influence of copper was not seen; a possible explanation could be intracellular deposition--a proton-electron-dipolar-dipolar-interaction would therefore be impossible.