Immune complexes in the sputum of patients with cystic fibrosis suffering from chronic Pseudomonas aeruginosa lung infection.

12 cystic fibrosis (CF) patients chronically infected with mucoid P. aeruginosa and presenting multiple precipitins in serum against this bacterium and 12 patients without P. aeruginosa infection were examined for occurrence of soluble immune complexes in their sputum sol phase by a complement consumption assay and a solid phase rheumatoid factor binding assay. The correlation between the results obtained in the two assays was significant (r = 0.625, p less than 0.01). The patients chronically infected with P. aeruginosa showed a significantly (p less than 0.01) higher frequency of immune complex activity in their sputum sol phase, as compared to the patients without P. aeruginosa lung infection. These findings point to the possibility that chronic lung infection with mucoid P. aeruginosa in CF may be an immune complex disease.


Effect of thyroxine treatment on carnitine levels in mice.

The effect in mice of 8 subcutaneous injections of 20 microgram of L-thyroxine at 12 hr-intervals on the carnitine concentration in the heart and skeletal muscle tissue was studied. In skeletal muscle tissue, the thyroxine treatment resulted in a depressed carnitine concentration. The mean values were 1.59 +/- 0.034 (S.E.M.) and 2.03 +/- 0.045 mumol/g noncollagen protein and 1.11 +/- 0.035 and 1.45 +/- 0.037 mumol/g dry weight for the thyroxine treated and the control animals, respectively. Thyroxine produced myocardial hypertrophy. The thyroxine treated animals had lower cardiac values when dry weight was used as reference base 4.17 +/- 0.10 mumol/g dry weight than the control group, 4.69 +/- 0.18 mumol/g dry weight. No statistically significant difference was found between the two groups when the cardiac carnitine concentration was expressed per g noncollagen protein or as carnitine in the entire hearts. Thus, thyroxine has been showed to influence the metabolism of carnitine in mice.


Degree of sedation obtained with various doses of diazepam and nitrazepam.

Using critical flicker fusion (CFF) determination and estimation of drowsiness in eight healthy volunteers the sedative-hypnotic effects of diazepam and mitrazepam were studied. Three dose levels of each drug were used, so that dose-effect curves could be produced. The most reliable results were obtained with the CFF method, and significant dose-effect relations could be demonstrated. The CFF deviation after diazepam initially related well to the concentration in blood serum, but after 4--6 hours the CFF depression vanished rapidly, while the drug concentration remained high. After nitrazepam the signs of drowsiness occurred similarly, while the drug concentration in serum showed on an average a slower rise. The effects began to disappear before the nitrazepam concentration had reached a peak. A rapid tachyphylaxis at the receptor sites seems to be responsible for this incongruity. Nitrazepam exerted significantly stronger sedative effects than diazepam, particularly when the respective serum concentrations were taken into account. This confirms that nitrazepam should be a more efficient sleeping drug, although diazepam also has considerable sedative-hypnotic action.


Reduced myocardial blood flow in acute and chronic digitalization.

The myocardial blood flow was measured by the 133Xenon disappearance curve from the left ventricular wall following an injection of 133Xenon in the left coronary artery in 8 dogs without digoxin pretreatment and in 8 chronically digitalized dogs. The myocardial blood flow was significantly less (30%) in the digitalized dogs than in the dogs without pretreatment. In the digitalized dogs as well as in those without pretreatment an intravenous injection of digoxin resulted in a further significant decrease of the myocardial blood flow of about 20% and a significant increase of the coronary vascular resistance. The reduced myocardial blood flow both during acute and chronic digitalization is beleived to be of clinical importance.


The influence of protein binding on the pharmacokinetics of sulphadimethoxine in rabbits.

The pharmacokinetics of sulphadimethoxine was investigated in rabbits at five dose levels. A significant nonlinearity of dose dependent pharmacokinetics was demonstrated. A large dose dependent change in per cent of sulphadimethoxine bound to plasma proteins was shown. It is concluded that the nonlinearity of the pharmacokinetics of sulphadimethoxine is mainly caused by the dose dependent changes in per cent of drug bound to plasma proteins.


Lithium chloride toxicity and pharmacodynamics in inbred mice.

Inbred strains of male mice (C3H, DBA, BALB, C57) were used to determine whether genetic factors play a role in lithium toxicity. Significant differences in the LD50 for LiCl were observed between the mouse strains after a subcutaneous injection of 37 degrees isotonic LiCl. The LD50 values in the C3H, DBA, BALB and C57 strains were 17.4, 17.6, 18.2, and 19.4 mmol/kg, respectively. Significant differences were also observed between the mouse strains in the concentrations of lithium in plasma, heart, liver, kidney and brain 2 hrs. after a subcutaneous injection of 15.1 or 18.2 mmol/kg LiCl, but the lithium concentrations were not related in an obvious manner to LiCl toxicity. The results show that genetic factors can influence the toxicity and pharmacodynamics of lithium.


The effect of lithium on the iodide concentrating mechanism in mouse salivary gland.

The iodide concentrating mechanism, measured as the gland to plasma (G/P) 125I- concentration ratio, was measured in male mouse submandibular glands after the animals had been fed with varying amounts of lithium chloride for intervals ranging from 0 to 8 weeks. After acute exposure (by injection) to lithium the G/P 125I- fell compared to control values and was further depressed at high serum lithium values. Chronic exposure to lithium was characterised by an increase in the G/P 125I- ratios at therapeutic serum lithium concentrations. It is suggested that lithium has a direct effect on the iodide concentrating mechanism that may be independent of any action of thyroid stimulating hormone during this process. The effect may be important in the formation of lithium induced goitre.


Levels of dopamine, norepinephrine and 5-hydroxytryptamine in different regions of the rat brain in thallium toxicosis.

The levels of dopamine, noradrenaline and 5-hydroxytryptamine were estimated in the hypothalamus and limbic areas, corpus striatum, cerebellum and the brain-stem of rats administered thallous acetate (5 mg/kg i.p.) daily for 7 days. Significant decreases in the concentration of dopamine occurred in the hypothalamus, limbic areas and corpus striatum. Noradrenaline did not reveal significant alteration in any of the regions of the brain examined. The concentration of 5-hydroxytryptamine was significantly lowered in the corpus striatum, cerebellum and the brain-stem.


Dextran induced hypoalbuminaemia as a model for the study of influences of protein binding on the pharmacokinetics of drugs.

A model for examination of the effect of hypoalbuminaemia on drug pharmacokinetics in laboratory animal is described. The model has been used to investigate the effect of protein binding on the kinetics of sulphadimethoxine in rabbits. A greater volume of distribution of sulphadimethoxine is shown in the dextran induced hypoalbuminaemic rabbits in comparison with control animals. It is concluded that the suggested model is convenient for investigation of the influences of protein binding on drug pharmacokinetics.


Pharmacokinetics of clomethiazole in healthy adults.

The systemic availability of clomethiazole was assessed by comparing blood levels after intravenous and oral administration. Clomethiazole was rapidly absorbed after oral administration to volunteers, particularly when administered as syrup. The fraction of the given dose that reached the systemic circulation after 1 capsule of clomethiazole (192 mg clomethiazole) was 0.25 +/- 0.18, after 2 capsules (384 mg clomethiazole) 0.38 +/- 0.18, and after 15 ml syrup (480 mg clomethiazole)  0.42 +/- 0.20. The time-blood concentration profiles were consistent with a two-compartment open model and the mean elimination half-lives of 3.6--5.0 hrs. were found for the different formulations and administration routes. Elimination half-lives showed little variation and a mean systemic clearance of 49 ml/min./kg was found for clomethiazole after intravenous administration. Clomethiazole is bound to human plasma proteins (63.4 +/- 1.6%, 37 degrees), a binding which is not affected by Vacutainer sample tubes. The blood/plasma distribution of clomethiazole was 0.76 +/- 0.02 at 37 degrees. A sensitive mass fragmentographic assay for the determination of clomethiazole in blood/plasma down to levels of 1 ng/ml (6.2 nmol/l) is described.


Actions of a new vasopressin analogue (1-deamino-6-carba-[8-arginine]-vasopressin) on regional blood flow in pregnant guinea pigs.

Regional blood flow responses to 1-deamino-6-carba-(8-arginine)-vasopressin (dCAVP) were investigated in pregnant guinea pigs by the radioactive microsphere technique. Intravenous injection of 0.1 microgram/kg body weight caused a moderate rise in mean arterial blood pressure from 6.8 to 7.9 kPa, a significant reduction in tissue perfusion of the stomach, mammary gland, urinary bladder and vagina, and a significant increase in renal and cerebral blood flow. In a small number of animals given 1.0 microgram/kg of dCAVP, which evoked a strong pressor response, it was also possible to demonstrate a reduction in cutaneous and pancreatic blood flow and an augmentation of adrenal blood flow. Uterine and maternal placental blood flow did not alter significantly following administration of this vasopressin analogue.


The degree of methylation and organ distribution of mercury in some birds of prey in Norway.

The concentrations of total mercury and methyl mercury were determined in organs from several species of birds of prey. The organ distributions were calculated for each species. For total and non-methyl mercury, significant differences were found between the species. For methyl mercury no such differences were found. The liver: kidney ratios in White-tailed Eagle were 1 : 2.4 and 1 : 0.9 for total and methyl mercury, respectively. The corresponding figures for the Eagle Owl were 1 : 0.7 and 1 : 0.8. The distribution pattern and the degree of methylation were mainly dependent on the mercury levels, and there seemed to be an inverse relationship between the total mercury levels and the percentages of methyl mercury in the organs, especially in the kidney. There were good correlations between the methyl mercury concentrations in the liver, kidney, and muscle. The demethylation of methyl mercury seems to be a significant detoxication route for methyl mercury in birds of prey.


Excretion of intravenously injected copper-64 in sheep.

Copper-64 was injected intravenously into three sheep. The total excretion of copper in sheep was low since only 1.4--1.7% of the dose injected was excreted during a period of 60 hrs. following the injection. It was found that the biliary system was not a main excretory pathway for copper; other routes of excretion into the gastrointestinal tract seemed to be more important. The urinary and the biliary excretion were of comparable magnitude. The activity in the bile was found to be lower than in the plasma throughout the sampling period. It is assumed that a low excretion capacity of copper in the bile of sheep may be a possible factor of importance for the high susceptibility of this species to excess of copper.


A comparative study on the effects of disulfiram, cyanamide and 1-aminocyclopropanol on the acetaldehyde metabolism in rats.

1-aminocyclopropanol (ACP) is a potent inhibitor of aldehyde dehydrogenase (ALDH) in vivo and in vitro. Like cyanamide it has a rapid onset of action in vivo with the highest inhibition occurring after 2--24 hrs. and a long duration of action like disulfiram with measurable inhibition after 144 hrs. All the three inhibitors decreased the activity of the mitochondrial low-Km ALDH strongly in vivo, however, in markedly different doses. Cyanamide inhibited the high-Km ALDH only in vivo, whereas in vitro, the hihgh-Km ALDH was unaffected by cyanamide but significantly inhibited by disulfiram and ACP. The inhibition produced by the inhibitors appeared to be irreversible. Acetaldehyde protected the low-Km enzyme at different extents depending on the inhibitor used. The inhibition of ALDH in intoxicated and control rats and its relation to acetaldehyde oxidation and the disulfiram-ethanol reaction are discussed.


Enhancement of urine prostaglandin excretion by chlorazanil in dogs.

In conscious dogs chlorazanil (2.5 mg/kg intravenously) markedly enhanced (5--10 fold) urinary excretion of prostaglandin E2 and F2alpha. The effect came to a peak at 15--30 min. following the administration. Chlorazanil did not modify renal blood flow or inulin clearance in non-pretreated or indomethacin pretreated dogs and the plasma renin activity remained unchanged. A marginal natriuretic and antikaliuretic activity by chlorazanil was similarly observed in non-pretreated dogs and dogs pretreated with indomethacin. The possible effects of the prostaglandins released by chlorazanil remained obscure. In vitro chlorazanil (10(-4) M) exhibited a moderate inhibition of 15-OH-prostaglandin dehydrogenase but an enhanced excretion of 15-keto-13, 14-dihydro PGE2alpha in vivo suggested that chlorazanil increased renal prostaglandin activity by increased prostaglandin synthesis, probably due to increased precursor availability. This was presumably mediated by some as yet unknown factor since chlorazanil ( 4 x 10(-5)M) failed to affect the release of precursor and prostaglandins from isolated Krebs-Henseleit perfused rabbit kidneys.


Fluoride, fluoride resistance and glycolysis in cultured cells.

Long-term (several years) exposure to fluoride induced decreased production of lactate in cultured, fluoride resistant LS cells. In intact, sensitive cells, 6 mM NaF had no effect on glycolysis, whereas in homogenates, from both resistant and sensitive cells, lactate production was blocked by 6 mM NaF, indicating the cell membrane to be a barrier to fluoride. A lower intracellular rather than extracellular fluoride concentration was found in the sensitive cell with a ratio of 0.4, whereas fluoride resistant cells excluded fluoride from their intracellular milieu.


Effect of fluoride on the activity of ornithine decarboxylase in normal and fluoride resistant LS cells.

Renewal of growth medium caused an induction of ornithine decarboxylase (ODC) activity in LS cells grown in suspension culture. Addition of low concentrations of fluoride ions to the growth medium (up to 1.3 mM) resulted in a further increase in this induction of ODC-activity, whereas addition of 6 mM fluoride caused an inhibition of the induction and resulted in reduced ODC-activity as compared to controls. Since sodium fluoride had no stimulatory or inhibitory effect on the ODC-activity assay, it is likely that the effect is exerted on the regulation of ODC-activity in the cells. The effect of fluoride ions on the induction of ODC-activity upon renewal of the growth medium was markedly less pronounced in fluoride resistant LS cells.


Central effects of endogenous and exogenous GABA.

Exogenous GABA administered into the lateral ventricle of the brain in Wistar rats in doses of 75, 200 and 600 microgram per rat, and endogenous GABA whose cerebral level was raised by intraperitoneal administration of hydroxylamine (Hx) in doses of 30, 50 and 75 mg/kg had a significant inhibitory effect on the central nervous system. This effect was abolished by bicuculine (Bc). The central effect of exogenous and endogenous GABA was manifested by reduced spontaneous and exploratory locomotor activity, decreased body temperature, potentiation of hexobarbital and chloral hydrate general anaesthesia and increase of haloperidol-induced catalepsy. On the other hand, no effect of GABA was observed on motor hyperactivity induced with amphetamine and on stereotypy induced with amphetamine and apomorphine.


The adrenergic influences on the hypothalamic and neurohypophysial oxytocic activity in long-term dehydrated male white rats.

Rats dehydrated up to 12 days were given intraperitoneally phenoxybenzamine hydrochloride or amphetamine sulfate in daily doses of 0.2 mg/100 g or 0.5 mg/100 g, respectively. In not dehydrated animals, both drugs decreased significantly the hypothalamic and neurohypophysial oxytocin content. In dehydrated rats the oxytocin activity in the hypothalamo-neurohypophysial system diminished progressively; under such conditions, inhibition of alpha-adrenergic receptors (brought about by using phenoxybenzamine as pharmacological tool) as well as the stimulation of the alpha- and beta-adrenergic receptors (caused by amphetamine administration) potentiated the effects of osmoreceptor stimulation.


Effect of septal forebrain lesions on soluble fibrin monomer complexes in blood.

Soluble fibrin monomer complexes (FM) in blood were measured in septal forebrain lesioned rats on the 4th, 12th, 17th and 21st postoperative days by using the protamine sulfate-induced precipitation method. It was found that septal lesions resulted in a statistically significant increase of FM as compared to the control sham lesioned animals. This increase was positively correlated with heightened emotional reactivity induced by septal lesions. The results obtained suggest that damage to the septal forebrain area may activate the process of intravascular coagulation.


Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) after submaximal exercise in human subjects.

In 79 swimmers aged 13--15 years the concentration of 2,3-DPG was determined in the erythrocytes at rest and 1 minute after the end of 7 minutes of submaximal exercise on an arm ergometer. In the examined subjects no significant changes were found in 2,3-DPG concentration in the erythrocytes. A non-significant tendency was demonstrated for a decrease in 2,3-DPG content of erythrocytes related to the post-exercise rise of blood lactate concentration.


Tissue catecholamine and arterial blood pressure changes in non-anaesthetised rats following administration of a new derivative of furanocarboxylic acid with pressor effect.

The effect of a new derivative of furanocarboxylic acid MePAF-4 on the arterial blood pressure, heart rate and the concentration of catecholamines in the brain, heart and adrenals was assessed in non-anaesthetised rats. MePAF-4 was given orally in a single dose of 60 mg/kg (1/30 of LD50)administered during 9 days (at the same daily dose), of injected intravenously in a dose of 10 mg/kg. After intravenous injection MePAF-4 had a significant pressor effect associated with bradycardia but without changes in the tissue concentration of catecholamines. After a single oral dose a slight, transient (60 min) rise of the arterial blood pressure was observed, while the heart rate showed no statistically significant changes. Repeated oral administration of MePAF-4 raised the brain dopamine level and adrenal adrenaline level with simultaneous increase in the weight of these organs. No detectable effects of the long term MePAF-4 administration on the arterial blood pressure and heart rate were observed.


Effect of fibrinogen degradation products (FDP) on heart rate and some metabolic parameters in the rat.

Investigations were carried out in vitro and in vivo on the effects of FDP on the rat heart. It was found that FDP have a positive chronotropic and inotropic effect. In in vivo investigations it was shown that the peptides raise the activity of phosphorylase a in the heart and increase slightly blood FFA and lactate levels decreasing glycogen content in the myocardium. The effects of the examined peptides are blocked partly by propranolol and reserpine, while phentolamine failed to change the FDP action. These data suggest that FDP exert chronotropic and inotropic effects through their action on the beta-adrenergic receptors in the myocardium.


Transducer for arterial and venous blood pressure recording.

The construction of a pressure transducer for acute experiments is described. The transducer is intended for direct recording of arterial and venous blood pressure in animals. The characteristics of arterial and venous blood pressure records obtained with a mercury manometer by the classic method and with the transducer are compared.


Ultrastructure of different types of skeletal muscle fibers of hypokinetic rats.

It has been found in the rat that prolonged hypokinesia results in degeneration or atrophy of most of the intermediate fibers, many of the red fibers and only some of the white fibers.


Effect of secretin on antipyrine elimination during extracorporeal perfusion of the isolated guinea pig liver.

The aim of these investigations was to elucidate in which part of the bile system (canaliculi or ductules) antipyrine is secreted actively into bile during extracorporeal perfusion of isolated guinea pig liver. Twelve perfusions were performed including 6 control and 6 with secretin. After 1, 2 and 3 hours from the onset of perfusion the perfusion fluid and bile samples were taken for determination of antipyrine concentration. It was demonstrated that secretin increases the volume of secreted bile, the concentration of antipyrine was decreased and the total amount of antipyrine eliminated with bile remained unchanged. The obtained results refute the hypothesis that antipyrine is secreted into bile in the ductular phase and suggest that this process takes place at the level of biliary canaliculi.


The constant value of the total concentration of potassium and sodium in tissue water in animals.

With age, the Musculus longissimus dorsi in pigs showed an increase in the potassium content and a decrease in the sodium content. The total concentration of potassium and sodium in milimoles in one litre of tissue water, here referred to as the "Sum k", is a constant value. The same mean Sum k had been obtained earlier by Blaxter and Rook for various kinds of tissue in cattle of different age. Approximate mean Sums k were calculated from the water, potassium and sodium contents in the muscles of man and pig at different stages of development, as reported in another publication. The constant character of Sum k was shown to be due to the equal concentration of potassium and sodium ions. This allows to calculate the quantity of water in the tissue from the potassium and sodium ions it contains and the percentage of extracellular or cellular water in total water. A consideration of the relationship between Sum k and osmotic pressure in the tissues proved an absence of concentration symmetry between the cellular and extracellular fluids which Sum k had seemed to suggest. Consequently, the total potassium content was multiplied by the asymmetry coefficient, fK, and then the Sum kc = mM (FKK + Na) per litre of water. From Blaxter and Rook's equation it was calculated that fK = 0.856 and Sum kc 148.8 mM.


Prognosis of post partum mental disturbance. A prospective study of primiparous women and their 4 1/2-year-old children.

Sixty-nine women who had been studied in connection with their first para-natal period were followed up 4 1/2 years later. Information was collected both from the mother (semi-structured interview) and her child (play session). Those 16 mothers who had been severely mentally handicapped during their first post partum period were compared with the others. About half of the women in the handicapped group reported repeated and/or prolonged periods of impaired mental health even during the following years. Further, the women in the handicapped group reported a poor relationship to the partner more often than the others. The same women more often than the others experienced difficulties in adapting to the parental role; e.g. their general attitude towards the child, as estimated by the interviewer, was more often a rejecting one. They were also described more negatively by their children than women that had not been severely handicapped. It is concluded that women mentally disturbed post partum run a high risk of poor mental health even in the future and that in these cases the mother-child relationship may often develop in an unfavourable way.


Diagnosis of schizophrenic borderline states.

The aim of this paper is to contribute to the clinical description of the group of schizophrenic borderline patients. In the first place important clinical features pointed out in older, basic papers will be restated. Secondly, additional observations, not used in clinical practice before, at least not explicitly, are described, data which are believed to be useful for the diagnosis of the states in question as well as for the differential diagnosis from other conditions, neuroses in particular. In the latter regard the following points are considered to be of outstanding importance: the presence or absence of a primary gain; the presence or absence of strivings to obtain an emotional secondary gain; the nature of the interpersonal relationship; the composition of the single symptoms. Pseudonormal, pseudoneurotic and pseudopsychopathic states are characterized. Micro-psychotic and overt psychotic states are described. Clinical differences from schizophrenic psychosis as observed in patients in the nuclear group of the schizophrenias are pointed out.


EEG immediately after unilateral ECT.

EEG was continuously recorded in 15 patients for a period extending from just before to 1/2 hour after unilateral ECT. Fourier analysis was performed on the EEG following 15 right-sided treatments and five left-sided treatments. During the induced seizure, epileptic slow-wave activity had significantly greater power on the treated side. Immediately after the seizure, there was significantly more delta activity and less alpha and beta activity on the treated side. This asymmetry, though becoming less marked, was usually still present at the end of the recording period. Analysis of other variables associated with the treatment showed that there was a significant correlation between the time to eye-opening after ECT and both the duration of the seizure and the amount of anaesthetic administered. The similarity between these induced unilateral seizures and unilateral seizures occurring spontaneously in some epileptics is discussed.


The switch process in manic-depressive illness. Circadian variation in time of switch and sleep and manic ratings before and after switch.

Research data collected on 75 Bipolar I patients, hospitalized at the NIMH between 1963 and 1975, were reviewed to identify "switches" into and out of mania. There were 27 "slow" switches (i.e. occurring over a period of 2--6 days) in 14 patients and 89 "rapid" switches (i.e. occurring in 24 hours or less) in 35 patients. No patient showed both "rapid" and "slow" switches during his hospitalization. Among the 89 rapid switches, 52 switches were into mania and 37 were out of mania. Rapid switches into and out of mania occurred significantly more often in the morning (7 a.m. to 3 p.m.) than at night (11 p.m. to 7 a.m.) or in the evening (3 p.m. to 11 p.m.). Estimated average sleep time on the night prior to switch into mania showed a significant drop as compared to sleep time on the second, third and fourth nights prior to switch. Patients who switched into mania at night were rated as significantly more manic during the 4 days following the switch than patients who switched in the morning or evening. Patients who switched into mania at night and evening were rated as sleeping significantly less during the 4 days following the switch than patients who switched in the morning.


Lumbo-omental shunt for drainage of cerebrospinal fluid--an experimental study in dogs. I. The transport of cerebrospinal fluid from the lumbar subarachnoid space, studied by 169Yb-DTPA and a gamma camera.

Studies using an experimental cerebrospinal fluid (CSF) shunting procedure are presented. By transposing a pedicle graft of the greater omentum to the lumbar subarachnoid space, the CSF absorption of the omentum can be utilized. Monitoring the absorption of intrathecally administration of 169Yb-DTPA by gamma camera sequential pictures 1 to 17 months after the shunt procedure, a rapid transport of radionuclide from the lumbo-omental shunt to the systemic venous blood was demonstrated.


Dural arteriovenous malformation with false aneurysm and exophthalmos. A successfully treated case.

A case of dural arteriovenous malformation with giant non-traumatic false aneurysm in the left middle fossa is reported. A 10-year-old female patient was admitted to our hospital with pulsating exophthalmos of the left eye, which was successfully treated  by ligation of the main feeder and finally by the radical excision of the dural AVM and false aneurysm. False aneurysm of non-traumatic origin is so rare that only two cases were detected in the literature (Reina et al., Sakaki et al.), and no previous case of false aneurysm complicated by dural AVM seems to have been reported.


Pitfalls in the diagnosis of arrested hydrocephalus.

Arrested hydrocephalus probably results from improvement of CSF circulation during growth. Although a generally accepted condition, its mode of onset, its presence in a given patient, and time required to establish the absence of progressive hydrocephalus have not been defined. Five patients are presented with ostensibly arrested hydrocephalus due to: aqueductal stenosis, communicating hydrocephalus, and Dandy-Walker malformation. In a period ranging from 4 to 13 years, they presented clinical signs of decompensation with intracranial hypertension. One had never had a shunt procedure. Another two were performing well in school until they suddenly deteriorated. The diagnosis of arrested hydrocephalus requires close follow-up well into adolescence, with periodical neurological and psychomotor evaluations.  Sequential observation of the ventricular size with computed tomography (CT) is recommended.


Disturbances of the coagulatory system in patients with severe cerebral trauma. I.

This is an investigation into thromboplastin time, partial thromboplastin time, plasma thrombin time, fibrinogen, and platelets in 30 patients with severe brain injury over 7--14 days. Platelets showed a very marked initial decrease and a slow return to normal around the seventh day. Fibrinogen was initially lowered in most of the cases, and raised from the second day onward. Changes in the other laboratory values were less definite. Latent signs of consumption coagulopathy were not accompanied by bleeding disorders, or by disseminated intravascular  coagulation at autopsy. The severity of laboratory value changes clearly correlated with the extent of brain damage, and was significantly higher when the patient did not survive the first week after injury.


Duration of the respiratory periods of uniform respiratory rhythms in 35 patients with neurosurgical diseases.

Analysis of uniform respiratory rhythms in 35 neurosurgical patients showed that the mean duration of respiratory periods was between 8.60 and 71.51 seconds. The scatter around the mean value increases with the increase of the duration of the respiratory period. For an individual patient there is a one-peak distribution of the duration of respiratory periods. The duration of respiratory periods increases with age. There is a group of patients in whom the respiratory periods last over 40 seconds. This group is difficult to classify. There are no correlations between the acid-base values, blood gas values, and the duration of respiratory periods. Analysis of 10 autopsy cases showed lesions in the brain stem without any particular prevalence.


Histological and ultrastructural study of intracranial saccular aneurysmal wall.

The material studied consists of 10 cases of intracranial saccular aneurysms. Four came from autopsies, and in each of the other six aneurysmal wall was obtained at surgery after clipping of the aneurysm. The most significant findings from this pathological study are the almost complete disappearance of the internal elastic lamina at the level of the aneurysmal neck, sclerosis of the muscle coat, and in satellite vessels and vasa vasorum disruption of the internal elastic lamina and partial luminal occlusion. The importance of ischaemic changes in the aneurysmal wall is discussed. Rupture of the aneurysm at the distal extremity of the sac depends probably on the progressive brittleness of its wall which becomes sclerotic and less resistant to the blood pressure within. Splitting or rupture of the aneurysm appears to be dependent on degenerative ischaemic alterations in its wall.


The management and prognosis of gliomas of the optic pathways in children.

A follow-up study was made of 24 children with gliomas of the optic pathways. In gliomas restricted to one optic nerve, total excision should be performed. The prognosis is excellent. Radiotherapy is not indicated. In gliomas of the anterior chiasma a biopsy should be taken; occasionally partial removal is indicated. The prognosis is good. Radiotherapy is indicated only if the follow-up shows a progression in the visual signs. In most cases the growth of the tumour seems to be arrested. The vision remains stable, and most patients have a useful degree of vision in at least one eye. In gliomas of the posterior chiasma with hypothalamic signs the prognosis is poor. A biopsy and radiotherapy are indicated. Occasionally, long remissions are seen.


An evaluation of gliomas of the anterior visual pathways. A 10-year survey.

Thirteen cases of the childhood type of optic glioma from a 10-year period were studied. Particular attention was paid to the pre-operative neuro-ophthalmological and radiological findings. The patients all underwent explorative craniotomy when biopsy specimens were removed for histopathological study. Post-operative radiotherapy was given in 12 cases. In the follow-up period five patients showed deterioration of visual function, three patients showed unchanged visual function, and one patient showed improved visual function. In the remaining four patients, visual function could not be adequately determined. Three patients died in the course of the follow-up period. Retrospectively it was possible, on a histopathological basis, to divide the patients into three groups. It is suggested that the future management of these patients should consist of explorative craniotomy with diagnostic biopsy. Radiotherapy should be confined to selected cases, as only a minority of optic gliomas are radiosensitive.


Supratentorial recurrences of gliomas. Results of reoperations on astrocytomas and oligodendrogliomas.

On the basis of our previous investigation regarding histological transformation of recurrent astrocytomas and oligodendrogliomas we report the clinical results of reoperations. The present observations deal with 121 cases: grade 1 astrocytomas (45), oligodendrogliomas (12), grade 2 astrocytomas (47), and oligodendrogliomas (17), respectively. In all these a second reoperation was performed in 14 cases. Operative mortality was relatively high, but without significant difference in the two groups of maligancy: 24.5% and 29.6%. Survival times in both groups showed striking individual differences. We achieved post-reoperation survivals exceeding one year in 18 and 14 cases, respectively. The results of second reoperations were generally poor. We find no remarkable differences in survival time following reoperations in primary grade 1 and grade 2 tumours. Similarly, malignant change proved to be not decisive for survival times. On the contrary, most of our patients with unchanged grade 1 astrocytomas, reoperated on after a longer interval, achieved a short second survival only. Prolongation of life expectancy by radiotherapy is doubtful. Irradiation seems to be necessary with malignantly transformed tumours if the patient did not have any treatment before reoperation.


The mode of mitochondrial degeneration in gliomas.

Morphologically abnormal mitochondria from human glial tumours are described. For each tumour both the appearances of the mitochondria, and the subsequent mode of degeneration and formation of osmiophilic pigment is characteristic. The significance of these observations is discussed, and it is suggested that the mode of degeneration observed reflects directly a fundamental abnormality in composition compared to normal mitochondria.


Lumbo-omental shunt for drainage of cerebrospinal fluid--an experimental radionuclide study in dogs. II. Evaluation of transport routes from lumbar subarachnoid space to venous blood.

In a series of dogs, the transport routes of intrathecally administered 99Tcm-DTPA from an omental graft to the venous blood were studied by scintillation probes placed over the portal and external jugular veins and by blood samples from the inferior vena cava. It was found early in the course of investigation that a rich revascularization frequently occurred between the transplanted omentum and the surrounding muscles. In all dogs, the omental graft was divided, in its muscle tunnel about 5 cm outside the dural sac, 13--19 months after the implantation. Even after this a rapid transport to the venous system of radionuclide could be demonstrated. The revascularization of the graft was also studied morphologically in two dogs means of microangiography.


Variability of the respiratory phase, respiratory pause, and numbers and durations of respirations during periodic breathing.

The analysis of cycles of periodic breathing (Cheyne-Stokes rhythms) in 35 patients showed wide variability of mean values of respiratory phases. The respiratory pauses are usually shorter and the scatter of the mean values is smaller. Only in four cases were respiratory pauses longer than respiratory phases. The duration of the respiratory phase becomes extended through the increase of number of single respirations. The latter also shows a very small scatter. The respiratory rate in 32 out of 35 patients was higher than normal and is to be considered as tachypnoea.


Propranolol in neurosurgical patients with sinus tachycardia. Cardiovascular effects and mode of use.

Cardiac rate (CR) and systolic arterial blood pressure (ABP) response to the intravenous injection of one, two, or three mg propranolol were recorded in 77 patients with traumatic, neoplastic, or haemorrhagic intracranial lesions and sinus tachycardia. In most patients tachycardia occurred with no cause except the intracranial lesion; in the other patients induction of general anaesthesia or surgical procedures on the brain appeared to have an initiating role. A central imbalance, with increased sympathetic cardiotropic influences is suggested and discussed. (I) First administrations of propranolol always reduced CR but had different effects on ABP from case to case; in all the patients 2.05 +/- 0.84 mg of drug lowered CR by 28 +/- 14/min (P less than 0.01), and ABP by 4.7 +/- 11 torr. CR decrease and ABP changes were without relation to the injected dose. Previous digitalization (desacetyllanatoside C) did not modify CR response to propranolol but reduced (P less than 0.05) its arterial hypotensive action. Positive correlations were found between basal CR and CR decrease (P less than 0.01), basal CR and ABP changes (P less than 0.01), CR decrease and ABP changes (P less than 0.05). Halothane appeared to potentiate CR response (P less than 0.01). (II) CR effect was less when the same dose of propranolol was repeated within 90 min (P less than or equal to 0.05). Usefulness and the mode of use of propranolol were critically evaluated.


The action of sodium nitroprusside on the pial vessels.

This study in cats investigates the action of sodium nitroprusside on the pial vessels by systemic and local administration, with an intravital microscopic window technique and a photometric technique for graphic documentation of vessel diameter changes. Intravenous infusion caused vasodilatation parallel with decreasing blood pressure. Pial arterioles dilated more than venules, smaller vessels more than larger ones. Local administration caused maximal dilatation within 5--10 seconds. With blood pressure returning to normal after i.v. therapy, pial vessels remained wider than they were before hypotension at the same pressure level. From these data it is concluded that the substance acts longer on the brain vessels than on vessels elsewhere in the body, and that cerebrovascular autoregulation to blood pressure changes is disturbed during this period.


The Girard ultrasonic fragmentor.

Ultrasonic fragmentation can be used to fragment various tissues such as the lens, the vitreous, the iris and ciliary body, so that they may be aspirated through a 23-gauge cannula. Since the technique was first described in 1973, it has been used in 148 eyes in a variety of conditions with encouraging results.


Microsurgery and lacrimal system.

Where epiphora results from canalicular obstruction, it is usually possible to cure the patient by reconstructing the canaliculi themselves. Resort to artificial bypass tubes is thus not often necessary. This paper discusses the role of the operating microscope in facilitating reconstruction of the lacrimal canaliculi so that longer segment of obstructed canaliculus can be reopened and more accurate reconstitution of the anatomy achieved. The place of fibre optics is outlined. Easier techniques for repairing lacerated canaliculi are described.


[The influence of birth-weight to further development of body-weight during childhood and adolescence (author's transl)].

Infants with higher birth-weight produce in further life more frequently an obesity. This also proves right for boys and girls. Sex differences appear not in early childhood but after beginning attendance at school.


[About the sexual hygiene of mental retarded boys, an exercise of the sexual pedagogic (author's transl)].

The sexual hygiene of mental retarded boys is examinated. In comparison with normal school boys is pointed out the necessity of sexual pedagogic education. The striking more numerous quote of balanitis in mental retarded boys is discussed with a critical review of Literature about the cleanness of the hands while miction of man, about the cleanness of the inferior abdomen, the cleanness of the pants and the hygiene of the toilet. The conclusion is drawn, that the cleaning of the foreskin has also to be observed by the mental retarded men, boys once a week and youths day by day.


[On the phenomenology of juvenile sexual delinquency and on the phenomenology of juvenile sexual deliquents--child-neuropsychiatric aspects of prevention of deviating sexual behavior. Phenomenology of adolescent sexual delinquency from a social and medical point of view. Prevention of deviant sexual behaviour (author's transl)].

Among manifold causes and conditions there are two essential roots: unfavourable social background and cerebroorganic disturbances. Crime prevention must increasingly concentrate on infancy and youth. Emphasis is laid upon crime preventive possibilities of sex education and the importance of child neuropsychiatry within the framework of complex public measures to combat criminality.


[On connection between music therapy and music pedagogics during childhood (author's transl)].

In this article is explained, that, in spite of existing communities between music therapy and cooperating remedial education on the one hand and music education on the other, we can separate with regard to the method music therapy as one form of psychotherapy from educational influence. But in practice at therapy of children with psychical disturbances we always must take into considerations the education object in view.


Factors associated with mortality in older people.

A random sample of older people from Edinburgh (215 men and 272 women aged 62--90 years) was examined clinically and by a questionnaire. Various measurements were made. Five years later, mean values of measurements were compared in those who had died and in survivors. Where significant differences occurred, regression techniques were used to separate age and mortality effects. Variables in which death was the predominant independent variable in the regressions were body weight, bi-iliac diameter, FEV1.0, transverse chest diameter, index of kyphosis, leucocyte ascorbic acid and some nutrient intakes in men plus transverse cardiac diameter and leucocyte ascorbic acid in women. Apart from index of kyphosis in men and cardiac diameter in women, mean values were significantly larger in survivors. Dichotomous variables from questionnaire and examination significantly related to mortality were 'possible' ischaemic heart disease in women, diastolic hypertension in men, persistent cough in men and dyspnoea worse than grade 2 in men and women. Cigarette smoking had no mortality effects in this study.


High-dose steroid therapy of intracranial tumour in the elderly.

Twenty elderly patients with intracranial tumour were treated with high-dose steroids (beta- or dexamethasone 12--16 mg per day). Six of eight patients with primary intracranial malignancies and four of six with metastatic tumours showed a definite response of conscious level and/or neurological deficit. One of two patients with lymphoma responded but neither of two with meningioma. Six patients were able to return home. Two patients suffered serious, and three minor, side-effects attributable to steroid therapy, but this treatment has a definite place in the management of intracranial tumour in old age.


Are potassium supplements for the elderly necessary?

Plasma and total-body potassium (TBK) were measured in 19 elderly patients receiving diuretics and potassium supplements for cardiac failure and in 13 elderly controls. The mean value for the ratio of TBK to fat-free mass (TBK:FFM) was significantly reduced in the patient group. TBK:FFM showed a negative correlation with age but no correlation with plasma potassium or dose of supplements. When controls and patients were matched for sex and age decade, the mean TBK:FFM was decreased significantly in the diuretic group, giving a mean potassium deficit of 13.3%. These results suggest that ageing influences potassium status, and that diuretics and cardiac failure have a greater effect on TBK in old age than in youth or middle age.


Psychosocial factors in elderly patients admitted to a psychiatric hospital.

Over a three-year period, 204 consecutive patients admitted to a psychiatric unit for the elderly were studied and their progress was followed for a further two years. For three-quarters, it was their first ever admission to such a unit. More than half were suffering from a functional psychiatric disorder. In 35.8% a life stress was of aetiological importance. 27.9% were discharged to their own homes, 31.9% into care and 35.3% died. 17.6% were admitted on at least one further occasion. Male sex, age over 75 and the presence of organic psychiatric disorders were associated with an unfavourable outcome. Age under 75, married civil status and functional psychiatric disorder were associated with a favourable outcome. Re-admission was common amongst females who were admitted with a diagnosis of psychotic depression, and discharged to their own homes. A life stress including a loss of physical health in the year preceding admission did not adversely affect outcome. At a time of life when many losses are experienced and physical powers are reduced, the elderly seem remarkably resilient and able to work through the crisis which has brought about their admission.


The avocational pursuits of rehabilitants with traumatic quadriplegia.

The pre- and post-disability avocational pursuits of 35 persons with traumatic quadriplegia were surveyed in terms of frequency of participation and enjoyment of activities. The patterns delineated suggested the need for improved avocational training programs, particularly in the cognitive and social spheres.


Sequential advancing flexion retention attachment: a locking device for the wrist-driven flexor hinge splint.

The Sequential Advancing Flexion Retention Attachment (SAFRA) was developed for cervical spinal cord-injured patients with a muscle grade of poor to fair in the wrist extensors. It is used on a standard wrist-driven flexor hinge hand splint with adjustable tenodesis bar. Through the development of the SAFRA, maintained prehension can be obtained without externally powered devices such as CO2 or electrically powered orthoses. The patient's increased functional abilities are discussed and advantages summarized.


The returning therapist: a group approach.

Career patterns of married female occupational therapists create a need for reactivation mechanisms to help nonpracticing therapists reenter the work force. As a channel for reactivation activities, a group was designed for such therapists and it met regularly for three years focusing on: 1. refresher education to regain clinical skills and confidence, and 2. peer support for the decisions involved in combining employment with family responsibilities. Some group members participated in organizing continuing education opportunities and many became involved in such experiences prior to resuming careers as occupational therapists.


Injuries in short track asphalt racing.

Stock car racing is a popular activity. Although spectators are seldom injured, drivers at short asphalt tracks often sustain minor injuries. The neck and the knee are the most commonly injured areas. Rigid safety requirements are essential and help to prevent serious injuries. Severe injuries occur on an average of once a year, but no fatalities have been recorded at one short track that has been studied for a six-year period.


The routine sexual history.

A routine, practiced and comfortable sexual history can elicit problems of personal adjustment. This format fits smoothly and logically into the rest of the medical history. It includes a numerical rating of personal satisfaction and the perceived satisfaction of the partner. On another occasion, similar questions are answered by the partner and the responses are assessed. Information and simple counseling are then provided and can be of significant help in the relationship.


Ventricular septal defect due to myocardial infarction.

This dramatic and ominous complication usually occurs between the third and 14th day after acute myocardial infarction. The size of the defect varies from a pinhole to 4 cm. The sudden appearance of a loud systolic murmur, with or without a thrill, is often accompanied by rapid hemodynamic deterioration. This event must be differentiated from rupture of a papillary muscle with mitral regurgitation. If intensive medical treatment is ineffective, an attempt at surgical repair is indicated.


The benefits of surgery for asymptomatic gallstones.

The risk of a patient developing complications of asymptomatic cholelithiasis is high enough to justify the mortality associated with prophylactic cholecystectomy. The operation effectively stops the progression of calculous biliary tract disease. If performed when the patient is young enough and healthy enough to tolerate the operation, and before the occurrence of complications which increase the mortality risk, the overall mortality and morbidity of calculous biliary tract disease could be significantly reduced.


The kidney and pregnancy.

Many clinical parameters and biochemical values normally change as a result of the profound effect of pregnancy on the kidney. These changes include hydronephrosis, decreased BUN and uric acid, proteinuria and glycosuria (70 percent one time), frequency, nocturia, edema (80 percent) and reductions in blood pressure. "Normal is abnormal." A BUN of 20 mg. percent is the equivalent of 40 mg. percent in a nonpregnant woman, and a blood pressure of 120/80 in the 24th week of preganancy may be hypertensive.


Correlation of electrocardiographic and pathologic findings in healed myocardial infarction.

A correlative study in 50 cases of healed myocardial infarction compared the 12 lead electrocardiogram with pathologic observations. The electrocardiogram was interpreted according to established Minnesota codes with some modifications. The following conclusions were reached: (1) The electrocardiogram underestimates the extent of myocardial infarction. (2) When a healed myocardial infarct at a specific location is recognized with electrocardiographic criteria, it is likely that there are unrecognized infarcts involving other areas of the left ventricle. (3) Infarctions involving the lateral and inferobasal areas are frequently unrecognized. (4) The electrocardiogram is more likely to miss myocardial infarcts in patients with multiple, than in those with single, electrocardiographically diagnosed infarcts. (5) Apical myocardial infarction does not appear to have specific electrocardiographic findings, other than those related to general infarct localization by electrocardiogram, particularly in patients with anteroseptal or anterolateral infarction. (6) Abnormal Q waves, generally thought to indicate transmural myocardial infarction, are frequently found in subendocardial infarction. (7) The simplified electrocardiographic classification of myocardial infarct site (anteroseptal, inferior, anterolateral) used in this study is preferable to more detailed classifications previously suggested by others.


Effect of catheter position on the initiation of atrial echoes with atrial pacing and premature stimulation in patients with accessory pathways.

Eleven patients with an accessory pathway and reciprocating tachycardia were studied using both fixed rate atrial pacing and the atrial extrastimulus technique. Six of the patients had an accessory pathway that conducted in both the anterograde and retrograde direction; but the effective refractory period of their accessory pathway in the anterograde direction was relatively long and was greater than the longest coupling intervals that initiated atrial echoes. Five patients had an accessory pathway that conducted only in the retrograde direction. The extrastimulus technique could be used with stimulation sites near to and remote from the accessory pathway in 10 of the 11 patients. Atrial echoes were initiated by a single atrial extrastimulus at both sites in 7 of the 10 patients, and in each patient the upper limit of the echo zone was longer with stimulation at the site near the accessory pathway. In the other three patients atrial echoes were initiated only during stimulation at the site near the accessory pathway because either atrial refractoriness or atrioventricular nodal refractoriness was encountered before the echo zone was entered during stimulation at the site remote from the accessory pathway. Differences in the longest cycle length that initiated an atrial echo during fixed rate atrial pacing were similarly demonstrated in three patients. In these three patients, pacing at the site near the accessory pathway initiated echoes at a longer cycle length than pacing at the site remote from the accessory pathway. In three other patients the electrophysiologic characteristics of atrioventricular conduction prevented a demonstration of these differences. Catheter position is an important variable in the initiation of atrial echoes in patients with accessory pathways.


Stress myocardial imaging in mitral leaflet prolapse syndrome.

Mitral leaflet prolapse syndrome has been associated with anginal chest pain, atypical chest pain, electrocardiographic abnormalities and positive stress electrocardiograms. These features overlap those of ischemic heart disease. Furthermore, coronary artery disease is frequently associated with mitral leaflet prolapse. This study evaluated the usefulness of stress myocardial scintigraphy in distinguishing these two disorders. Thirty-two patients with an angiographic diagnosis of mitral leaflet prolapse were studied. Of the 22 patients (8 men and 14 women, mean age 48 years) with a normal coronary arteriogram, 5 had "typical" angina pectoris, 6 had resting electrocardiographic abnormalities and 6 had a positive stress electrocardiogram; all 22 patients had a normal stress myocardial scintigram. Of the 10 patients (7 men and 3 women, mean age 55 years) with at least 70 percent stenosis of one coronary artery, 6 had "typical" angina pectoris, 1 had resting electrocardiographic abnormalities and 7 had a positive stress electrocardiogram. Nine of these 10 patients had one or more demonstrable perfusion defects on stress myocardial scintigrams. It is concluded that mitral leaflet prolapse syndrome is not associated with regional myocardial ischemia as demonstrated with stress scintigraphy, and that stress scintigraphy, a noninvasive technique, is useful in distinguishing the mitral prolapse syndrome from mitral prolapse associated with coronary artery disease.


Assessment of coronary stenoses with myocardial perfusion imaging during pharmacologic coronary vasodilatation. IV. Limits of detection of stenosis with idealized experimental cross-sectional myocardial imaging.

Because atherosclerosis may be reversible, a routine noninvasive screening test for the reliable diagnosis of mild coronary arterial lesions would allow potential prevention of coronary events in specific patients through intensive dietary management, drug therapy and physical training. To determine the minimal coronary stenosis detectable with myocardial perfusion imaging techniques, standardized stenoses ranging from 31.4 to 72.5 percent diameter narrowing were applied to the left circumflex coronary artery of 12 open chest dogs. Indium-113m-labeled human albumin microspheres were injected into the left atrium under control conditions and technetium-99m human albumin microspheres during maximal coronary vasodilatation induced with intravenous dipyridamole. Hearts were removed, sliced into 1 cm thick cross sections and imaged under a gamma camera. The results demonstrate that 40 percent diameter coronary stenoses can be identified by imaging relative subendocardial underperfusion during pharmacologic coronary vasodilatation. An imaging technique sensitive enough to identify mild coronary lesions for diagnostic screening purposes requires (1) a potent stimulus for coronary vasodilatation, such as intravenous dipyridamole; (2) an imaging agent taken up by the myocardium in proportion to coronary flow at flow rates up to four or more times resting coronary flow so that differences in regional maximal flows caused by mild stenoses can be identified; and (3) cross-sectional tomographic myocardial imaging to visualize relative endocardial-epicardial perfusion, the most sensitive indicator of the hemodynamic effects  of coronary stenoses, and to exclude from the imaging field the interfering activity of lung, background and overlying heart structures.


Origin of so-called right and left ventricular arrhythmias in acute myocardial ischemia.

The anatomic origin of ventricular arrhythmias occurring immediately after coronary arterial ligation was studied in 32 dogs. The electrocardiogram and seven single or composite bipolar electrograms were recorded from various sites within and surrounding the ischemic area in the left and right ventricles. Delay and fragmentation in the activation of the epicardial ischemic zone of the left ventricle, bridging diastole, preceded the appearance of ventricular arrhythmias and were continuous during the rhythm disorders. So-called left and right ventricular arrhythmias were associated with similar delay and fragmentation in left ventricular ischemic epicardial activity. Multiple and simultaneous activation of both the right and left ventricles produced ventricular fusion premature complexes. Multiple exit points increased before ventricular fibrillation occurred. The ultimate origin of premature ectopic impulse formation in the ventricles is not necessarily related to one or more exit points in either ventricle. Ischemic damage to the heart produces ventricular arrhythmias that appear to originate from both ventricles. The site of origin of ventricular arrhythmias should not be the sole factor in assessing the benign or malignant properties of the arrhythmia.


Truncal or aortic valve stenosis in functionally single arterial trunk. A clinical, hemodynamic and pathologic study of six cases.

Stenosis of the semilunar valve in the presence of a functionally single arterial trunk is uncommon. Three patients with truncus arteriosus, two with tetralogy of Fallot and pulmonary atresia and one with pulmonary atresia and intact septum were diagnosed as having stenosis of the truncal or aortic valve on the basis of clinical, echocardiographic, hemodynamic and angiocardiographic findings. Echocardiograms consistently showed multiple diastolic closure lines and abnormal semilunar valves in addition to the aortic override in five patients and hypoplastic right ventricle in the patient with pulmonary atresia and intact septum. Peak systolic gradients between the left ventricle and truncus (or aorta) at cardiac catheterization ranged from 20 to 47 mm Hg. Retrograde aortography confirmed a domed and stenotic semilunar valve. Cyanosis was progressive in the three patients with pulmonary atresia. Two patients had arterial anastomosis, and one had a right ventricle-pulmonary arterial graft in addition to aortic valvotomy. One of the three patients with truncus arteriosus underwent complete repair in addition to truncal valvotomy but he died in the post-operative period. The other two patients with truncus arteriosus died of intractable congestive cardiac failure before surgical intervention. It is suggested that the presence of semilunar valve stenosis in these patients adversely affects the prognosis. The myocardium is already jeopardized as a result of hypoxia in pulmonary atresia and left ventricular diastolic overload in patients with truncus arteriosus. The added burden of semilunar valve stenosis may further compromise the functional status of the myocardium.


Estimation of pulmonary/systemic resistance ratios from echocardiographic systolic time intervals in young patients with congenital or acquired heard disease.

Previous work has shown the positive correlation of echocardiographic right ventricular preejection period/right ventricular ejection time ratio (RPEP/RVET) with pulmonary vascular resistance and pulmonary arterial diastolic pressure obtained at cardiac catheterization. However, the correlation was insufficient to predict pulmonary arterial diastolic pressure or vascular resistance from a given RPEP/RVET ratio. In this study the RPEP/RVET ratio was compared with left ventricular preejection period/ejection time ratio (LVEP/LVET) in 25 patients undergoing cardiac catheterization, and a strong correlation was found between the ratio (RPEP/RVET)/(LPEP/LVET) = R/L and the ratio of pulmonary arteriolar resistance/systemic arteriolar resistance (PAR/RS), especially when R/L was correlated with log10 PAR/RS (r = 0.902). A very high correlation (r = 0.960) was found between R/L  and log10 PAR/RS when the group was restricted to patients with a ventricular septal defect or a complete endocardial cushion defect. Regression equations for prediction of PAR/RS have been derived for the various groups.


Effect of afterload reduction on plasma volume during acute heart failure.

Previous investigations in our unit indicated that acute cardiogenic pulmonary edema is associated not only with an increase in left ventricular end-diastolic pressure and pulmonary arterial wedge pressure but also with a relative increase in colloid osmotic (oncotic) pressure and peripheral hemoglobin concentration. This combination of changes suggested that acute congestive heart failure with pulmonary edema, unlike chronic congestive heart failure, is associated with a contraction of intravascular blood volume. In this study, plasma volume changes were measured before and during the treatment of acute cardiogenic pulmonary edema in 14 patients with arteriosclerotic heart disease. The plasma volume measurement in all 14 patients before the initiation of treatment was either normal or decreased. After treatment with the alpha adrenergic blocking agent phentolamine, the plasma volume increased rather than decreased when measured 4 and 12 hours after the initiation of treatment. During this time colloid osmotic pressure and peripheral hemoglobin concentration progressively decreased. These findings suggest that acute cardiogenic pulmonary edema is associated with the extravasation of large quantities of plasma water from the intravascular compartment into the interstitial compartment and contraction of the intravascular plasma volume. The treatment of acute cardiogenic pulmonary edema is associated with the return of hypo-oncotic fluid from the interstitial compartment back into the intravascular compartment with expansion of plasma volume and reduction of colloid osmotic pressure and hemoglobin concentration.


Cross-sectional echocardiographic diagnosis of large left atrial tumor and extracardiac tumor compressing the left atrium. Limitation of M mode echocardiography in distinguishing the two lesions.

A case of a left atrial fibrosarcoma arising from the posterior left atrial wall and two cases of an extracardiac tumor compressing the left atrium were studied with M mode and cross-sectional echocardiography. In all three cases, M mode echocardiography revealed a mass of echoes just behind the aorta and did not distinguish a left atrial from an extracardiac tumor. By contrast, cross-sectional echocardiography allowed direct visualization of the location, size and movement of the tumor in all three cases and contributed to distinguishing the two lesions. This study indicates that cross-sectional echocardiography is more accurate than M mode echocardiography in the differential diagnosis of a large left atrial tumor and extracardiac tumor compressing the left atrium.


Hemodynamic pattern resembling pericardial constriction after acute inferior myocardial infarction with right ventricular infarction.

Two patients with acute inferior myocardial infarction complicated by cardiogenic shock are presented. Cardiac catheterization 2 and 7 days after infarction, respectively, revealed a hemodynamic pattern resembling constrictive pericarditis. Right coronary occlusion proximal to the right ventricular marginal branches was present in both patients. Resolution of the constrictive hemodynamic pattern was demonstrated in the one survivor at repeat catheterization 7 weeks after infarction. The mechanism for constrictive hemodynamics in these patients is unclear.


Fortuitous rupture of aortic aneurysm: a catastrophic event affording time for surgical cure.

The rupture of an aortic aneurysm is generally a fatal event, but occasionally the rupture will occur into an adjacent vascular structure, thereby preventing exsanguination and affording temporary survival. Three cases are presented illustrating the fortuitous nature of the rupture of an aortic aneurysm into a vascular structure. The first patient had an atherosclerotic abdominal aortic aneurysm that ruptured into the inferior vena cava and was successfully repaired. The second case demonstrates the formation of a fistula from the aorta to the left pulmonary artery in a patient with a syphilitic thoracic aortic aneurysm. In the third patient a dissecting aneurysm of the aortic root that communicated with the right ventricle after coronary bypass surgery was successfully repaired. Rarely, aortic aneurysms will rupture fortuitously into vascular capacitance structures. These three cases emphasize the need for early accurate diagnosis and the institution of appropriate surgical measures.


Effects of estrogen on human seminiferous tubules: light and electron microscopic analysis.

Morphological features of testes from four subjects after long-term treatment with ethinyl-estradiol (1--2 mg daily) and from five non-treated patients with prostatic carcinoma were studied by means of light and electron microscopy. The non-treated seminiferous tubules contained spermatagonia, spermatocytes, spermatids, spermatozoa, and Sertoli cells and showed no apparent morphologic abnormalities. On the other hand, the estrogen-treated testicular tissue contained only Sertoli cells and very few spermatogonia within the seminiferous tubules. The nuclei of Sertoli cells occasionally contained two nucleoli. The nucleolar complex was composed of a fine granular spherical body surrounded by a large granular, reticular network. The cytoplasm of the Sertoli cell contained osmiophilic lipid-like bodies. These lipid-like bodies appeared more pronounced in patients treated with higher doses of estrogen, suggesting a diminution of secretion of Sertoli cell hormone. Blebbing from the outer nuclear membrane appeared to have formed numerous vesicles in the cytoplasm. These vesicles usually contained several membrane-bound granular bodies. In the estrogen-treated testes, there was a marked increase in thickness and infolding of the basement membrane. Two unusual patterns of the basement membrane were observed: one appeared to be a reticular anastomosis, the other, an electron-dense trilayer. The morphological picture of seminiferous tubules from the estrogen-treated subjects appeared to correlate well with the suppressed plasma and testicular levels of testesterone, the undetectable circulating gonadotrophins, and the elevated plasma and testicular levels of estradiol-17 beta reported by Rodriguez-Rigau et al. ('77).


Induced ovulation, development of the corpus luteum, and tubal transport in the striped skunk (Mephitis mephitis).

Ovulatory pattern, development of the corpus luteum (CL), and early tubal transport are described for 6 unmated and 19 mated striped skunks (mephitis mephitis) killed after known copulation times. Ovulation is induced by copulation and occurs around 42 hours (range = 40--50 hours) after first insemination. Seventeen of 19 females killed between 36 hours and 19 days postcoitus had ovulated. Two females killed at 36 hours had not ovulated; however, their follicles showed preovulatory changes and were significantly larger (p less than 0.01) than those of unmated females. Six unmated females, killed during and three weeks after the normal breeding season, had not ovulated. Ovarian events, such as preovulatory changes, ovulation, and development of the corpus luteum (CL), are described for animals killed 36 hours to 19 days post-coitus. Maximum CL size occurred at 11 days post-coitus and coincided with the onset of embryonic migration and enlargement. Embryonic development reflected individual variation in ovulation times. The first polar body was extruded at ovulation and the second at fertilization. Pronuclear stages were predominant at 42 to 48 hours and 3 to 8-cell stages at 72 to 96 hours; morulae (containing up to 95 cells) entered the uterus at seven days. Blastocysts were observed first at 11 days when embryonic spacing and enlargement began. Implantation occurred by 19 days.


The basilar membrane of the bat, Pteronotus p. parnellii.

The basilar membrane of Pteronotus p. parnellii was studied by light and scanning electron microscopy in order to examine the relationship of membrane structure to the sharply tuned sense of hearing in this bat. The basilar membrane was found to differ from those of other mammals and other bats by showing virtually no change in width except at the extreme ends. Thickenings of the pars pectinata and pars tecta are well developed in Pteronotus; they show no sudden changes in their dimensions and in this way differ from the thickenings found in the European horseshoe bat whose sharply tuned sense of hearing seems at least partially dependent on sudden, marked changes in the structure of the basilar membrane. In Pteronotus the greater part of the basilar membrane, 7.5 mm or approximately 58%, lies within the enormous basal turn and within this turn there are steeply banked curves and one small 0.5-mm region where the membrane is straight. The straight portion is associated with a region of the cochlea where there is a marked change in the density of nerve fibers and where the stria vascularis, spiral ligament and fluid-filled spaces of the ear are enlarged.


Development of type I cells of the rabbit subclavian glomera (aortic bodies): a light, fluorescence and electron microscopic study.

The embryogenesis of the subclavian glomera (aortic bodies) is controversial. Past investigators have attributed the development of the Type I cells to mesodermal and/or neural elements. Based on the results of the present light microscopic, fluorescence histochemical and electron microscopic study of rabbit aortic bodies from 16 days of gestation (term:31 days) to four days postpartum, it appears that the Type I glomus cell are derived from cells of neural crest origin. The subclavian anlage is associated with cells of neural crest origin. The subclavian glomus anlage is associated with cells of vagal origin throughout its development. Evidence of Type I cell development from pre-existing mesodermal condensations is not observed. Type I cells exhibit formaldehyde-induced-fluorescence by the twentieth day of gestation. Dense-cored cytoplasmic vesicles are apparent by the sixteenth day of gestation. The number of cytoplasmic vesicles increases steadily, but the greatest increase of vesicles is observed between the twenty-eighth day of gestation and birth. Primitive Type I glomus cells exhibit abundant polysomes and rough endoplasmic reticulum indicative of synthetic activity. Nerve terminals are apparent adjacent to Type I cells by the twentieth day of gestation, but synaptogenesis does not occur until sometime between the twenty-fourth and twenty-eighth days of gestation. Abundant vascularity, characteristic of chemosensory glomera, is not achieved until the twenty-eighth day of gestation.


Occurrence of catecholamine-containing specific granules in the venous endothelia of carp.

The formaldehyde-induced fluorescence technique and the argentaffin reaction with ultra-thin sections were applied to the vessels of carp to demonstrate the presence of a catecholamine. After formaldehyde gas treatment for 30 minutes at 50 degrees C, the venous endothelia emitted a greenish-yellow fluorescence suggesting the presence of a primary catecholamine. In the endothelial cells of veins, the specific granules, consisting predominantly of spherical granules with a diameter of about 0.3 micrometer, showed heavily to moderately positive argentaffin reaction. Granules also occurred in the endothelial cells of arteries. However, these granules stained weakly or not at all with ammoniacal silver solution. It is concluded that the specific endothelial granules in veins of carp contain a primary catecholamine.


The neurohypophyseal capillary bed. II. Specializations within median eminence.

Vascular casts of the pituitary gland, median eminence and hypothalamus from several mammalian species were examined by scanning electron microscopy. These observations were correlated with light microscopic studies of injected, cleared median eminence-pituitary specimens and with light microscopic examination of serial sections of injected hypothalamic, median eminence, and pituitary specimens employing reflected lighting or epi-illumination. Transmission electron microscopy was employed to study long portal vessels on the ventral surface of the rat median eminence. In each of the species examined, the median eminence (infundibular) capillary  bed is subdivided into an external and an internal plexus. The external plexus (the neurohemal contact zone) receives an arterial supply from the superior hypophyseal arteries and is continuous with the capillary bed of the infundibular stem and process. Egress from the external plexus is possible via three vascular routes: (a) by fenestrated portal vessels and capillaries to the adenohypophysis, (b) by capillary connections to the medial basilar hypothalamus and, (c) by internal plexus capillaries to the ependyma of the median eminence. Median eminence vasculature is structurally organized to deliver (1) hypothalamic and neurohypophyseal peptides to the glandular pituitary via portal vessels, (2) hypothalamic and pituitary secretions to the medial basilar hypothalamus via capillaries, and (3) hypothalamic and pituitary secretions to distant brain sites through cerebrospinal fluid via ventricular and subarachnoid routes.


Investigations on the turnover of adrenocortical mitochondria. X. A correlated biochemical stereological study of the effects of chronic treatment with chloramphenicol on the mitochondria of the rat zona fasciculata.

The effects of chloramphenicol (CAP) on rat adrenocortical cells were investigated by biochemical and stereological methods. It was found that administering 50mg/kg of CAP every 12 hours provoked a persistent inhibition of the incorporation of 3H-leucine into mitochondrial proteins. Chronic treatment (up to 15 consecutive days) with this dose of CAP induced a significant decrease in the volume of the mitochondrial compartment, in the surface area of the outer and inner mitochondrial membranes and in the number of mitochondria per cell. These results confirm the hypothesis that the ACTH-induced maintenance of adrenocortical mitochondrial growth requires continuous mitochondrial DNA-dependent protein synthesis.


Spermatogonial intercellular bridges in whole-mounted seminiferous tubules from normal and irradiated rodent testes.

Whole-mounted seminiferous tubules from normal and irradiated rodent testes were examined by light microscopy. These studies reveal the presence of intercellular bridges in all classes of spermatogonia except for the new As stem cells. It was demonstrated that As stem cells divide to produce new As spermatogonia or paired daughter cells that are united by a cytoplasmic bridge. Evidence was given that all subsequent progeny of these paired A's up to and including the production of type B spermatogonia remain linked by cytoplasmic bridges in increasingly larger and more complex syncytial networks. It is proposed that the intercellular bridges mediate both differentiation and degeneration of spermatogonia. The maintenance of synchronous development within cohorts of spermatogonia is attributed to the bridges. Moreover, the fact that spermatogonia in both normal and irradiated testes degenerate in clusters is determined by the presence of intercellular bridges. Lastly, the integrity of the bridges appears essential for normal germ cell development.


Localization of vitamin A-storing cells in the mouse adrenal gland: an electron microscopic autoradiographic study.

Radioactive vitamin A acetate was stored in specific cells in the mouse adrenal gland. Radioactivity was detected in lipid droplets of fibroblast-like cells, whose distribution was from the capsule to the medulla. Their population was highest in the cortex. The morphology of these labeled cells was similar to that of vitamin A-storing cells in other organs of mouse (Yamada and Hirosawa, '76). Though functions of these cells are obscure, the fact that they are found in organs where metabolic activity of vitamin A is high suggests that they bear some role in the metabolism and storage of the vitamin.


Epidermal migration during the healing of suction blisters in rat skin: a scanning and transmission electron microscopic study.

Fluid-filled blisters, created on the skin of the inner surface of the pinna of heparinized rats by the application of suction, showed an intact basal lamina through which protruded hairs and remnants of hair follicles. The origin of epithelial cells and their spreading over the basal lamina were studied at intervals over 36 hours using scanning and transmission electron microscopy. The majority of epidermal cells arose from the outer root sheath of hair follicles and began to spread radially before 12 hours. By 36 hours the cells were confluent over most of the blister base. Inflammatory cells were few in number and rested mainly on the bare basal lamina rather than on the resurfacing cells. Some elongated epidermal cells showing tapering foot processes appeared to be migrating in from the epidermis at the edge of the blisters. The cells spreading from hair follicles were flat and polygonal. On these sheets of cells a few small folds and many filopodia were present at intercellular junctions and at the free margin of the leading cells. Large numbers of short microvilli covered the surface of some of the epidermal cells, especially at 24 and 36 hours; other epidermal cells were relatively smooth.


Ultrastructural identification of afferent fibers of cardiac origin in thoracic sympathetic nerves in the dog.

While cardiac afferent nerve activity has been recorded from the ventrolateral (VLCN) and ventromedial (VMCN) cardiac nerves, left dorsal and ventral ansae subclaviae, and left upper thoracic white rami communicantes, little anatomical evidence for the existence of afferent fibers in these nerves has been reported. This study was designed to characterize the normal ultrastructure of the above nerves and to identify afferent fibers in them through Wallerian degeneration produced by dorsal root ganglionectomy. Laminectomies followed by dorsal root ganglionectomies were performed on left thoracic roots T1-T4 in six mongrel dogs. The nerves to be examined were removed from two animals at 1, 2, and 3 weeks following ganglionectomy and prepared for electron microscopy. Control nerves were obtained from two normal dogs. Degenerating nonmyelinated fibers were characterized by watery axoplasm containing clumps of electron-dense material. Degenerating myelinated fibers were distinguished by the separation of their myelin lamellae, producing characteristic whorls. After three weeks, afferent nonmyelinated axons had degenerated in all nerves, leaving only layered processes of Schwann cells in these areas. Approximately 5-15% of the fibers in each nerve degenerated, indicating their afferent nature. Of these fibers, 85-90% were nonmyelinated C fibers and the remainder myelinated Adelta fibers. These results indicate participation of both Adelta fibers and a large population of C fibers in transmission of cardiac afferent activity.


Structure of the chicken's inner ear: SEM and TEM study.

The inner ears of 35 adult chickens were studied by TEM, SEM and light microscopy. Two well differentiated hair cell/nerve ending units were present: tall hair cells with small vesiculated nerve endings were located on the attached part of the basilar membrane; short hair cells with large vesiculated nerve endings were located on the free basilar membrane except for the distal tip. In this respect the chicken ear is similar to that of the pigeon. The chickens examined did have some unique features. Sensory cells of lenticular and hemispheric shape were also present at the proximal end. Bundles of long dense tubules were seen frequently within the sensory cell cytoplasm. Kinocilia were absent from the hair bundles of many of the sensory cells. The internal structure of the kinocilia which were present was atypical and consisted of a variable number of doublets. Eight peripheral plus one central doublet were found most frequently.


The fine structure of the ventricular surface of the area postrema of the cat, with particular reference to supraependymal structures.

The ependymal surface of the feline area postrema (AP) has been examined with the scanning and transmission electron microscopes. Particular attention was paid to the distribution and structure of supraependymal (SE) cells which have not been described before on this organ. A population of SE cells was found consistently on the cat AP; they were grouped most frequently toward the caudal aspect of the organ. Their structure bears a great resemblance to that of macrophages, containing: (1) many small apical vacuoles, (2) numerous lysosomes, and (3) phagosome-like bodies. Arrays of microvillous tufts and also singly-occurring microvilli are features of the unciliated ependymal surface of the organ. Tufts are often found in very close proximity to superficial blood vessels which are characteristically surrounded by large perivascular spaces.


Scanning electron microscopy of the kidney glomerular epithelium after treatment with polycations in situ and in vitro.

Changes in fine structure of glomerular epithelial cells (podocytes) were examined after treatment in situ and in vitro with polycations (i.e., protamine sulfate and poly-1-lysine). Scanning and transmission electron microscopic observations indicate that polycation-induced alterations of the glomerular epithelium are similar in many respects to those resulting from puromycin aminonucleoside nephrosis. These alterations include the formation of junctional complexes between adjacent podocyte processes, flattening and retraction of podocyte processes, extensive folding of the slit diaphragms, formation of interpedicular microbridges, and development of irregular knobby surface-microprojections. Prolonged treatment in vitro with high concentrations of polycations results in nearly complete loss of podocyte processes and the transformation of these once elaborate cells into simple polyhedral cells. The foregoing observations support the view that pedicel loss in puromycin aminonucleoside nephrosis may be due to a reduction in the glomerular epithelial polyanionic sialic acid surface coat.


The structure and innervation of cat knee menisci, and their relation to a "sensory hypothesis" of meniscal function.

Previous work on dog knee menisci demonstrated structural differences between the meniscal horns and the meniscal bodies (O'Connor, '76). Of particular interest was the observation that the meniscal horns possessed an abundant blood and nerve supply, while the meniscal bodies did not. The presence of nerves in the meniscal horns prompted the speculation that menisci might perform a sensory function. The present study was undertaken in order to establish whether or not similar regional differences existed in cat knee menisci, structures previously believed to lack a corpuscular mechanoreceptor system (Freeman and Wyke, '67). Differences between the meniscal horns and meniscal bodies similar to those reported in the dog were found to characterize cat knee menisci. In particular, the meniscal horns possessed a rich neurovascular supply, while the meniscal bodies did not. Most important, at least two morphologically different mechano-receptors were identified in the meniscal horns, but none were identified in the meniscal bodies.


Sites of cerebrovascular injury induced by radiographic contrast media.

The object of this study was to determine the type of cerebral vessel affected by injection of radiopaque contrast agents used in cerebral angiography. Seventeen rabbits were prepared surgically for a left intracarotid injection of methylglucamine iothalamate (Conray 60) or methylglucamine diatrizoate (Reno-M-60). Extravasations of the tracers, Evans blue and horseradish peroxidase, occurred in the left half of the brain and occasionally in the right half. Within those areas of blood-brain barrier breakdown, the frequency of leakage was 60% for arterioles, 25% for venules, and 12% for capillaries. The leakage appeared to be primarily intercellular, rather than intracellular. This study provides evidence that greater blood-brain barrier alterations occur in arterioles and venules than in capillaries following cerebral angiography.


Programmable calculators in the field assessment of nutritional status.

Programmable electronic calculators can be used for many purposes in field studies in which anthropometric evidence of nutritional state is being collected. One of their most interesting uses is the rapid conversion of anthropometric measurements into percentages of the standard. Coefficients are given for such calculations for height, weight, and arm circumference.


A study of caffeine in tea. I. A new spectrophotometric micro-method. II. Concentration of caffeine in various strengths, brands, blends, and types of teas.

A new spectrophotometric micro-method for the determination of caffeine in tea is described. This method is then used to evaluate the caffeine content of a variety of brands and blends of bagged and loose hot tea prepared in different strengths and by different brewing methods. In addition, the caffeine content of instant tea, ice tea, and Mr. Coffee automatic tea is evaluated.


Metabolic studies with keto acids in uremia.

The utilization of a preparation containing the keto analogues of five essential amino acids was evaluated by nitrogen balance studies in five uremic patients receiving an 18 g protein diet. In all five patients the nitrogen balance improved when the diet was supplemented with ketoacids, becoming positive in three cases, and about zero in one case. In two cases the improvement in nitrogen utilization occurred without a prior period of adaptation with the protein-poor diet. The nitrogen balance was negative in two cases when reinvestigated after about 7 weeks, but one of these cases had a slight infection at the time of the study.


Comparison of the effects of keto acid analogues and essential amino acids on nitrogen homeostasis in uremic patients on moderately protein-restricted diets.

Comparisons of isonitrogenous supplements (1.2 g N) of essential amino acids and five keto acid analogues with four essential amino acids were made in seven patients with stable chronic renal failure (creatinine clearance, 4.6 to 16 ml/min) on moderately protein-restricted diets (4.60 to 7.8 g N per day). Full nitrogen balance data on the four patients who have already completed studies lasting 24 weeks are presented. No benefits of keto acid over amino acid supplements were observed. Two transient episodes of hypercalcemia occurred during keto acid treatment. There was no improvement of renal function with keto acids. Also, no carry-over effects were seen after keto acid treatment. It is concluded that any beneficial effects of keto acids in patients with chronic renal failure are only likely to occur in those taking a diet of less than 30 g protein daily.


Metabolic studies with keto acid diets.

Five patients with chronic renal failure taking a diet containing approximately 5 g N throughout were studied during two periods of 1 month each. Nitrogen balance, urea metabolism, and incorporation of 15N from urea into albumin on diet alone or with a keto acid/essential amino acid supplement were measured. Keto acids produced a reduction of plasma urea, urea synthesis, and urea excretion and an improvement in nitrogen balance. In patients who demonstrated the greatest change on ketoacids, 15N incorporation also increased, but their total incorporation of urea nitrogen was not nearly sufficient to account for the improvement in nitrogen balance. The role of keto acids in protein anabolism is not solely or even mainly explained by promotion of nonprotein nitrogen reutilization.


Evaluation of essential amino acids and keto acids in uremic patients on low-protein diet.

The effectiveness of a mixture of five analogues of essential amino acids and the remaining four essential amino acids as compared to a preceeding treatment period of the nine essential amino acids was evaluated in 16 chronic uremic patients fed a low-protein diet. During amino acid analogues supplementation, there was a tendency for blood urea nitrogen to fall whereas creatinine did not change. Serum phosphate decreased in most patients, whereas serum calcium rose in some subjects. Protein metabolism, as judged by serum transferrin, Clq, C3c, total complement activity, was improved. Furthermore, the concentrations of prealbumin and retinol-binding protein, which are elevated in uremia, showed a further increase that might favor a vitamin A intoxication.


Therapy with essential amino acids and their nitrogen-free analogues in severe renal failure.

The effects of therapy with essential amino acids and their nitrogen-free hydroxy and keto precursers on nitrogen and amino acid metabolism of patients with chronic renal failure were examined. Data obtained under treatment with essential amino acids and alpha-keto acid analogues showed higher levels of plasma amino acids, C3-complement, and transferrin than with a low-protein diet alone. Nitrogen balance became positive and plasma urea levels fell. With keto acid analogue therapy, these effects could be obtained with a reduced nitrogen intake. Supplementation of a low protein diet with alpha-hydroxy acid analogues was associated with more positive nitrogen balance and a rise in plasma histidine and methionine. However, plasma levels of three other essential amino acids fell.


Nitrogen balance in uremic patients on different amino acid and keto acid formulations--a proposed reference pattern.

Nitrogen balance was studied in 12 uremic patients given nitrogen intakes in varying formulations, either solely as amino acids or as keto acid and amino acid mixtures. It was shown that of the three formulas studied, the one that was most effective in promoting positive balance was the one having threonine as reference unit, with a relatively high tyrosine intake and lower methionine content, and histidine in the proportions found in human milk and in the egg pattern. Also, in all instances in which an amino acid formulation caused a deviation in nitrogen balance, the same effect was obtained with formulations containing keto acids. However, the effect with the keto acids was less pronounced.


Protein requirements in maintenance hemodialysis.

Protein requirements in maintenance hemodialysis patients are still unclear. Based on nitrogen balance studies and different analyses of protein and amino acid metabolism, the recommendations until recently were 1 g/kg of body weight, primarily of high biological value protein. According to the results of controlled long-term studies the 1 g recommendation now seems too low. The paper reports on the results of a controlled study undertaken to define protein requirements. The effect of supplementation with a special protein mixture is studied on the basis of 1 g of protein per kilogram of body weight intake and about 20 hr standard dialysis per week. The results suggest that 1.2 g of protein per kilogram of body weight primarily of high biological value protein and 35 kcal/kg of body weight should be prescribed for dialysis patients. In case of complications (bleeding, infection, and other stress situations) additional supplements are necessary.


Influence of essential amino acids and keto acids on protein metabolism and anemia of patients on intermittent hemodialysis.

Ten patients were treated with 10 g/day of essential amino acids orally; nine patients received 9.5 g/day of a mixture of essential amino acids (lysine, threonine, tryprophan, histidine, and tyrosine) and keto analogues of isoleucine, leucine, phenylalanine, valine, and methionine. A control group of 11 patients received no supplementation. All patients were on a liberal food intake amounting to 1 g of protein per kilogram of body weight and 31 kcal/kg of body weight daily. Before and 3 months after the beginning of the supplementation, the following parameters were measured: amino acids, albumin, transferrin, urea and creatinine concentrations in plasma, hemoglobin, and hematocrit in blood. None of these parameters was altered by either treatment. It is concluded that supplementation with essential amino acids or their keto analogues is ineffective in well-nourished dialysis patients.


Hormonal and metabolic responses to intravenous glucose in children on regular hemodialysis.

Blood glucose, plasma nonesterified fatty acids, amino acids, immunoreactive insulin, growth hormone, and immunoreactive glucagon responses to intravenous glucose were determined in 16 children on regular hemodialysis for chronic renal failure and nine healthy children. In the patients the fractional disappearance rate of glucose was significantly reduced, basal immunoreactive insulin was significantly raised, and while the early immunoreactive insulin response to glucose was similar in patients and controls, the late response was increased. Basal growth hormone was elevated in the patients and rose paradoxically following glucose. Fasting immunoreactive glucagon was significantly higher in the patients and was not suppressed by glucose. Plasma nonesterified fatty acid levels were lower in the patients and fell more markedly after glucose. Alanine levels, which were significantly raised in those with poor glucose tolerance, fell to normal after glucose and did not vary in those with more normal glucose tolerance. It is speculated that the metabolic and hormonal alterations may be interrelated and result from failure of normal glucose utilization.


The metabolic effects of hemodialysis with and without glucose in the dialysate.

The present study compares some of the metabolic effects of hemodialysis of fasting patients with and without glucose in the dialysate bath. Unlike glucose dialysis, glucose-free dialysis caused marked decreases in blood levels of glucose, insulin, lactate, and pyruvate along with profound increases in acetoacetate and beta-hydroxybutyrate. It is concluded that oxidation of fatty acids increases to meet energy demands and that the combined processes of glycogenolysis and gluconeogenesis serve to prevent critical hypoglycemia during glucose-free dialysis.


Insulin and growth hormone secretion in dialyzed children: influence of dietary manipulation.

The insulin and growth hormone responses to arginine and the growth hormone response to insulin were studied in 10 children undergoing chronic hemodialysis 1) under usual dietary prescription and 2) after 7 days of dietary manipulation (DM) decreasing mean carbohydrate intake from 48 to 36% and increasing lipid intake from 42 to 54% (percent of total energy) with the polyunsaturated/saturated fatty acids ratio being increased from 0.2 to 2. Mean fasting insulin and growth hormone were significantly decreased after DM: 10.3 +/- 3 muunits/ml and 19.9 +/- 3.5 ng/ml before and 4.3 +/- 0.8 muunits/ml and 9.3 +/- 2.4 ng/ml after DM. The mean arginine-induced insulin peak and the growth hormone peaks after arginine and insulin remained very high after DM. There was no decrease of mean plasma triglycerides: 214 +/- 30 mg/dl before and 237 +/- 26 mg/dl after DM. However, two children who had the greatest decrease in carbohydrate intake exhibited a decrease of triglycerides and of arginine-induced insulin secretion. The percent variation of insulin area after DM was significantly correlated with the percent variation of plasma triglycerides.