Protein binding properties of prazosin.

Protein binding properties of prazosin. The serum protein binding proerties of prazosin were determined by the equilibrium dialysis technique, using radiolabeled drug of high specific activity. At concentrations typically found in human therapy, prazosin is bound to serum proteins to the extent of approximately 92 percent. This value is not altered in the presence of several other drugs frequently diminished in conjunction with prazosin.


Physiological disposition and subcellular localization of 14C-fenclorac in the rat. The physiologic disposition and subcellular tissue localization of 14C-fenclorac was studied in rats receiving single and multiple oral doses of the drug. The drug was primarily excreted via renal and fecal routes. The 24-hour urinary and fecal elimination rates were 41 and 17% respectively, of the administered dose. The daily elimination rates of drug/drug metabolites were not altered when the treatment period was extended to seven days, suggesting that the processes for the renal and fecal clearance of drug were not affected by this treatment schedule. Studies on the distribution of 14C-fenclorac in slected tissues revealed that hepatic, renal and splenic tissue to plasma ratio of the label twenty-four hours after a single dose was 1.53, 3.88 and 0.11, respectively. Similar results were observed in rats receiving multiple doses of 14C-fenclorac. The 14C-label was distributed throughout the subcellular organelles with the highest concentration in the cytosol and lower levels in the mitochondria and microsomes. Furthermore, these experiments demonstrated that both metabolic (hepatic) and excretory (kidney) organs do not accumulate fenclorac in animals receiving the drug up to seven days.


Acetaminophen-induced glutathione depletion in diabetic rats. The time course of acetaminophen-induced hepatic glutathione depletion and recovery in control and streptozotocin-diabetic female rats was investigated. Initial hepatic glutathione levels were significantly higher in control animals. After a 1 g/kg intraperitoneal dose of acetaminophen, maximum depletion of reduced glutathione (GSH) occurred within 2 h in diabetics and began to increase thereafter, while maximum GSH depletion occurred at approx. 4 h in controls and did not begin to return to normal until after 12 h. The time course for changes in hepatic oxidized glutathione (GSSG) after acetaminophen administration followed that for GSH in both control and diabetic rats. Diurnal variations in hepatic glutathione levels do occur, but these variations can not explain the changes which occur following acetaminophen administration or the differences observed between control and diabetic rats. Diabetic rats are more susceptible to the glutathione depleting effects of high-dose acetaminophen, suggesting that the diabetic may be less able to detoxify drugs and foreign chemicals.


The effects of ticrynafen in the rat.

The effects of ticrynafen in the rat. The effects of ticrynafen, a uricosuric diuretic, were examined utilizing free-flow micropuncture and clearance techniques in the rat. The intravenous infusion of ticrynafen (50 mg/kg body wt/hr) had no effect on glomerular filtration rate, but resulted in significant increases in urine flow from 4.4 +/- 0.7 microliter/min/g kidney wt to 19.2 +/- 2.6 (p less than 0.001); in urinary sodium excretion from 0.14 +/- 0.07 micronEq/min/g kidney wt to 2.35 +/- 0.52 (p less than 0.01); and in urinary urate excretion from 2.8 +/- 0.2 microgram/min/g kidney wt to 4.0 +/- 0.2 (p less than 0.005). There was no change in urinary phosphate excretion. The end-proximal TF/Pinulin ratio was 2.66 +/- 0.18 in control and 2.67 +/- 0.16 in experimental periods (p=NS). In awake animals, ticrynafen administration resulted in a decrease in CH2O from 6.47 +/- 0.12% to 3.50 +/- 0.69 (p less than 0.05), but no change in TCH2O. These studies demonstrate that ticrynafen is a uricosuric and diuretic agent in the rat. The natriuresis appears to derive from an inhibitory action of this agent in the cortical diluting segment of the nephron. In comparison to a related uricosuric diuretic, MK-196, ticrynafen is a less potent agent with respect to both its uricosuric and diuretic properties in the rat.


The estrogenicity of delta-9-tetrahydrocannabinol (THC): THC neither blocks nor induces ovum implantation, nor does it effect uterine growth. The estrogenicity of THC was assessed in three estrogen-sensitive systems. The drug did not block implantation when injected (s.c.) on Day 0 of pregnancy: on Day 6, 95% (3 mg/kg) and 86% (12 mg/kg) of the mice had embryos as did 96% (P greater than 0.1) of the controls; implantation occurred in only 9% (P less than 0.005) of mice treated similarly with estradiol (E2; 0.15 mg/kg). Nor did THC induce implantation: pregnant mice were ovariectomized on Day 1, treated daily with progesterone (2 mg, s.c.) and injected (i.p.) with THC on Day 3: at mg THC/kg 39% had embryos, as did 41% of those at 6 mg/kg; these rates do not differ (P greater than 0.99) from that of the controls (38%); in contrast, ova implanted in 75% (P less than 0.025) of E2-treated mice (4.0 microgram/kg). The average number of implanting ova was the same in all groups in both experiments. THC did not cause uterine hypertrophy: ovariectomized mice were injected (s.c.) for 14 days with THC (3 or 6 mg/kg) or E2(2 microgram/kg): the uterine weight, total uterine protein and total uterine glycogen of the ovariectomized controls was 24 +/- 2 mg, 3 +/- 0.3 mg and 11 +/- 3 mg respectively and the values for the THC-treated mice were not different (P greater than 0.05); in contrast, E2 increased (P less than 0.01) uterine weight to 139 +/- 9 mg, uterine protein to 5 +/- 0.6 mg and uterine glycogen to 62 +/- 8 mg. It is concluded that THC is not estrogenic.


Re-evaluation of the uptake of desoxyfructo-serotonin by human platelets, and of its effect on the uptake of serotonin. Employing C14-glucose and C14-serotonin (5HT) as precursors, we have synthesized desoxyfructo-5HT [1-desoxy-1-(5-hydroxytryptamine)-D-fructose] labelled either in the sugar or 5HT moieties, and examined the uptake of the labelled substrate by washed human platelets. Desoxyfructo-5HT appears to interact with the 5HT uptake site, effectively inhibiting the uptake of H3-5HT. However, our data indicate that contrary to published reports, the entry of desoxyfructo-5HT into platelet vesicles or cytoplasm is negligible.


Relative sensitivities and specificities of tests for small airways obstruction. This study compared several physiologic maneuvers for detecting small airways obstruction (SAO). Volume of isoflow best separated young smokers (average age--27.6; average cigarette consumption--9.3 pack years) from nonsmokers; this was true for comparisons of both population means and incidence of individual abnormality. However, assessment of individual abnormality by any test was greatly influenced by the criteria used to define abnormality. The best combination of test sensitivity and specificity was achieved by using the 95% confidence limits derived from a control population from the same laboratory. Even so, test results did not correlate significantly with pack years of cigarette smoking. Then, although tests for SAO are very sensitive, their prognostic value in young smokers is uncertain since abnormality presumably should correlate with extent of smoking.


Accuracy of screening for pulmonary embolism in the emergency room. Pertinent historical, clinical, and laboratory findings were recorded for 37 consecutive patients who presented to the emergency room complaining of shortness of breath and chest pain but without evidence of coronary insufficiency, pneumonia, or musculoskeletal injury. 13 had pulmonary embolism suggested by lung scan with or without pulmonary angiogram, or, in 2 cases, by right heart catheterization. As a group, these patients in whom embolism was judged probable approached fairly closely the profiles of previous studies of patients with documented pulmonary emboli. Nonetheless, they differed very little, and in no clinically useful way short of lung scans and invasive studies, from the remaining 24 patients in whom embolism was judged unlikely. In the population served by this emergency room, which has a high morbidity from chest diseases and putative predisposing conditions to pulmonary embolism, screening patients for high and low probability groups for this diagnosis cannot be done on clinical grounds alone. Six-projection ventilation-perfusion lung scanning may be the only acceptable screening examination, and should be available directly from the emergency room in hospitals with an active emergency service.


Influence on the depth of inhalation on the effect of the beta 2-receptor-stimulating drug fenoterol hydrobromide (berotec). Study of the influence of different modes of administration of 200 microgram of fenoterol showed that in a selected group of patients, two thirds of the maximal obtainable decrease in airway resistance could be achieved within 3 min of local application of 200 microgram fenoterol onto the nasal mucosa, without inhalation into the lower airways. Aspects of the potential pathways by which inhaled substances reach their receptor or target sites are discussed.


[Effect of chronic hypercapnia on the gastric acid secretion in rats: a comparative study in vitro (author's transl)]. Rats are made hypercapnic by breathing 8% CO2 for a week. Their stomachs, removed under anaesthesia in a hypercarbic atmosphere, are placed in a special chamber and the acidic secretion (free + titratable) is measured in vitro in relation to different parameters of the controlled atmosphere. The secretion depends on the gas composition. Under the same conditions (mucosa CO2 = 8%, serosa CO2 = 10%) the in vitro secretion of the hypercapnic subjects (n = 32) is lower than that in the normal rats (n = 27), the latter secretion decreasing more rapidly with the duration of the in vitro measurement. The differences between the hypercapnic and the control subjects are in the order of +/- 10% in titratable acidity (mEq/l/h/cm2) and +/- 20% in free acidity (muEq/l/h/cm2).


Pulmonary sarcoidosis: roentgenographic, functional, and pathologic correlations. Discrepancies were observed between functional (PFT), chest roentgenographic, and open lung biopsy findings (granulomata, interstitial pneumonitis, angiitis, and fibrosis) in 81 patients with clinical diagnosis of sarcoidosis. A combination of normal PFT and Type 1 roentgenographic findings (hilar lymphadenopathy) was associated with minimal lung lesions without fibrosis. Type 1 findings alone did not preclude extensive lesions or fibrosis. Advanced roentgenographic and PFT abnormalities correlated with the presence of extensive lung lesions. The pulmonary diffusing capacity correlated best with specific and overall lung pathology, and roentgenographic types. Only this test differentiated the extent of granulomata and the roentgenographic types. Moderate degrees of other pathologic changes were not distinguished by any other PFT. Degrees of overall lung pathology correlated with an individual PFT and most significantly with overall PFT (p less than 0.001). Serial studies of PFT are a practical and valuable means for assessment of the disease process in sarcoidosis.


Giant fibrous pleural mesothelioma associated with myocardial restriction and hypoglycemia. A giant pleural fibrous mesothelioma was the cause of severe nonobstructive ventilatory incapacity, myocardial restriction with congestive failure and hypoglycemic episodes in a 58-year-old man. Surgical resection resulted in complete recovery of respiratory function and disappearance of hypoglycemic episodes.


On the boundary conditions used in calculations of gas mixing in alveolar lungs. The lung boundaries exhibit a tight barrier for any insoluble gas; hence boundary conditions for lung gas mixing have to account for the absence of both diffusive and convective fluxes across the lung walls. Scrimshire et al. (1978) have, in contrast, used the less rigid boundary condition that only the net flux be zero. As we believe this boundary condition to be inappropriate for the study of insoluble gases, the results derived appear to have no physiological significance.


Pulmonary receptor chemosensitivity and the ventilatory response to inhaled CO2 in the turtle. Ventilatory responses of unanesthetized turtles to changes in the intrapulmonary CO2 content of a vascularly isolated and an intact lung were measured during spontaneous breathing. The hyperpnea associated with inhalation of CO2 by the vascularly isolated lung was 19% of that associated with inhalation of CO2 by the intact lung. Transection of the vagus nerve supplying the isolated lung abolished this response. We conclude that both inhibition of pulmonary stretch receptor discharge with increasing levels of FICO2 and a functional increase in central inspiratory volume threshold during hypercapnia contribute to tidal volume increases following CO2 inhalation in normal animals. The major component of the ventilatory response of intact turtles to increasing levels of FICO2, however, was an increase in respiratory frequency. When CO2 was inspired only by the vascularly isolated lung the increase in respiratory frequency was only 21% of that recorded when the same levels of CO2 were inspired by the intact lung. Thus the ventilatory response of turtles to increasing levels of FICO2 is primarily dependent upon concomitant hypercapnia.


Respiration and heart rate in exercising land crabs. Land Crabs, Cardisoma guanhumi, were fitted with respiratory masks and E.C.G. electrodes and run for 10 or 20 min on a treadmill at speeds of 150 and 300 cm/min. Aerobic metabolism increased linearly with the speed of locomotion. The recovery period was characterized by a large oxygen debt. The primary respiratory adjustment to exercise was an increased ventilation volume; only a minor increase in oxygen extraction occurred. The respiratory exchange ratio increased during exercise and during recovery, presumably correlated with a metabolic acidosis. These results are similar to data collected for exercising vertebrates and the net cost of locomotion of crabs appears similar to quadrupeds. However, the heart rate in exercising crabs changed in an unexpected way: during moderate exercise no change was noted, but during heavy exercise a bradycardia developed. The reduction in rate resulted from an increase in interbeat interval and frequent pauses in the heart beat.


The accuracy and spatial resolution of the measurement of tissue oxygen removal rate. An analysis is presented of factors determining the accuracy and spatial resolution of a method for the estimation of oxygen removal rate in tissues using a multi-cathode electrode placed on the tissue surface. The effect of oxygen consumption by the cathodes is shown to be small for 25-micrometer diameter cathodes, but covering the tissue surface with a thin oxygen oxygen-permeable plastic film can introduce a systematic error into the estimate of removal rate, the size of which depends upon the oxygen diffusion coefficient and solubility in the plastic compared with those in the tissue. Spatial resolution is shown to be adequate for distinguishing changes in removal rate over distances of a few hundred microns, and the averaging of removal rate in the direction normal to the tissue surface is weighted heavily towards the superficial tissue layer.


Pulmonary O2 diffusing capacity estimates from assumed log-normal VA/Q distributions. Steady-state pulmonary gas exchange has been measured in hypoxia in 33 mongrel dogs with the aim of comparing DLO2 estimates obtained with three procedures differing by the models assumed for functional inhomogeneity. In the first procedure the lung was assumed to be homogeneous and the corresponding DLO2 estimate was 15 mumol . min-1. Torr-1 . kg-1. In the second procedure, which is the one commonly used in respiratory physiology, alveolar dead space was considered as the unique form of functional inhomogeneity and the corresponding DLO2 estimate was 31 mumol . min-1. Torr-1 . kg-1. In the third procedure, which has been specially worked out for this study, functional inhomogeneity was represented by a log-normal distribution of the VA/Q ratios and the corresponding DLO2 estimate was 50 mumol . min-1 . Torr-1 . kg-1. The relation between the DLO2 estimates by the second and by the third procedures was found to depend upon the blood pH. This could be explained on the basis of the effects of acidosis on the blood capacitances for O2 and for CO2. Analysis suggests that in hypoxia where normally the O2 capacitance is about half the CO2 one, the third procedure yields DLO2 estimates about twice as large as those obtained by the second one.


A two-compartment model of blood acid-base state at constant or variable temperature. Information available in the literature on the acid-base properties of oxygenated mammalian blood at a constant or variable temperature was put together into a synthetic model; this also aimed at reconciling the single compartment descriptions of acid-base vs temperature relationships in closed ('anaerobic') conditions with the standard dual compartment analysis of isothermal titrations. Experimental values for the concentrations of blood constituents, buffer dissociation constants, etc. were introduced into the set of physicochemical equations governing the steady-state distribution of CO2, electrolytes and water between plasma and red cells. Design of the model was such as to permit monitoring of all variables (e.g. concentrations) throughout any simulated acid-base transformation. A fairly good fit was obtained between model predictions and experimentally-determined relationships or quantities not introduced into the model from the start. Applications to variable temperature titration and to the effects of changes in blood composition or osmolality are presented. The latter underline the implicit assumptions made by neglecting such variables in current presentations of blood acid-base state.


Effects of dopamine, norepinephrine and 5-hydroxytryptamine on the carotid body of the dog. The effects of bolus intracarotid (IC) infusions of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) on activity in single or few-fiber carotid chemoreceptor afferent nerve preparations were studied in pentobarbital anesthetized dogs. In addition, the effects of intravenous (IV) infusions of DA were also assessed. IC injections of DA (10 microgram) and (5-HT) (1 microgram) consistently produced a burst of intense activity followed by a period of inhibition. A similar effect was seen with IC NE (20--40 microgram) injections, but the burst of excitation occurred in only 45% of the injections. Inhibition of activity was seen in 88% of the IC NE injections. Low IC doses of all 3 amines produced inhibition of chemoreceptor afferent activity. High doses of DA IV (approximately 60 microgram/kg/))produced excitation followed by depression, while lower doses (approximately 21 microgram/kg) produced only inhibition. The excitatory effects of all 3 amines were blocked by d-tubocurarine (50--435 microgram/kg IV). Inhibitory effects of all 3 amines were blocked by dihydroergotamine (140--270 microgram/kg). The inhibitory effect produced by DA was specifically blocked by haloperidol (50--400 microgram/kg IV). We conclude that DA, NE and 5-HT can modulate carotid body activity by increasing or decreasing responses to physiologic stimuli.


Ventilatory responses to carbon dioxide inhalation after vagotomy in chickens. Both vagus nerves in 7 anesthetized chickens were cut midcervically. Inspired PCO2 was increased from 0 to 28 torr by successive 3.5 or 7 torr increments and then increased directly to 70 torr. At each level of PICO2, steady-state measures of PaCO2, [H+]a, VT, f and VE were made. When PICO2 was raised to 7 torr, PaCO2 AND [H+]a were above their control levels (i.e. PICO2 = 0); at each successive level of PICO2, both PaCO2 and [H+]a increased. Minute volume increased at 28 torr PICO2 but changes in VT and f individually were not significant. At 70 torr PICO2, VE and VT increased but f was not changed from its control value. We have previously suggested that CO2-sensitive intrapulmonary chemoreceptors mediate the arterial isocapnic hyperpnea at low PICO2 in chickens. The observation that vagotomy abolishes regulation of PaCO2 at low PICO2 is consistent with this hypothesis, since the afferent pathway of avian intrapulmonary chemoreceptors is predominantly vagal.


Patterns of disability related to joint involvement in rheumatoid arthritis. The relationship between particular disabilities and specific impairments of which these disabilities could be the consequence has been explored. Assessments of performance of activities of daily living (ADL) have been simplified by factor analysis, and the resultant factors have been related to the sites of joint involvement in patients with rheumatoid arthritis. Our preliminary findings on the grouping together of various ADL activities are meaningful in terms of underlying impairments, and at the same time indicate an approach for simplification of ADL assessments so as to enhance their value for research and the evaluation of outcome. The results are entirely consistent with a comprehensive model of disablement.


Circumferential measurements in the assessment of synovitis of the knee. In a quest for a objective assessment of synovitis of the knee, the value of circumferential measurements of the knee at two levels has been tested. Measurement 1 cm above the patella was shown to be more precise and to correlate better with the quantity of synovial fluid aspirated than measurement at mid-patellar level. The size of change necessary for statistical significance frequently exceeded the change likely to be found in clinical practice. The precision of measurement is greater in normal than in rheumatoid knees, and can be increased by using the mean of duplicate measurements rather than a single measurement. In clinical trials, the use of one observer throughout will increase the reliance that can be placed on the changes in measurements.


A simple goniometer for measuring hip function. A goniometer was designed and developed in an attempt to find an objective method of measuring hip flexion and extension in walking as as indication of hip function. Existing goniometers were found to be inadequate for clinical and research use because either they did not provide sufficient information or the information they provided was more than necessary, requiring bulky and time-consuming power devices. The present goniometer is a compromise, providing a quick and easy-to-use clinical and research tool which measures total flexion and extension in walking.


Persistent local cutaneous atrophy following corticosteroid injection for tendinitis. A 21-year-old female, treated with triamcinolone for tendinitis in the oblique muscles of both forearms, developed a skin atrophy, localized around the injection points. The patient was followed over a period of more than five years during which a partial remission of the skin changes was observed. A synopsis covering local use of steroids for various diseases is given.


[Transitory ischemia of the mesencephalon caused by vertebral angiography]. Vertebral angiography, performed using catheterization according to Seldinger, is followed by a transitory Weber syndrome. The Authors maintain that the vessel spasm of the vertebro-basilar territory, visible during the angiography, is the main cause of the transitory ischemic attach at the base of the mesencephalon.


[Dantrolene in juvenile spasticity: 3 months of daily observation]. After a clarifying outline on the most recent anatomo-physiopathologic acquisitions about muscular tone and spasticity, the Author presents the results of a prolonged administration (three months) which was daily controlled, in an Institute for dyskinetic subjects. At the dose of 1 mg/kg/die during the first week, 2 mg/kg/die during the second week and 3 mg/kg/die during the third and the following ones (total posology pro die divided into 3 post-prandium administrations), Dantrolene was administered to 16 subjects of both sexes, whose average age was 13, who presented marked spasticity sometimes accompanied by dystonia. An evaluation was given on these parameters: 1) spasticity estimated in three degrees according to Morosini, 2) passive articular movement (wideness and easiness of maximum excursion), 3) capability of voluntary decontraction, 4) motoricity of relation (motorial difficulty) and 5) dystonic component if present. As a global results, out of 16 cases, nine improved (56%) and seven (44%) remained unaltered. Since the drug resulted to be inefficacious in all cases with dystonia, the global improvement recorded among "pure spastics" rised to 66% of cases. Neither intolerances nor negative secundary effects were noticed.


[Long-term anticonvulsant therapy and calcium and phosphorus metabolism]. The authors examined 114 epileptic patients who were taking anticonvulsant drugs from different periods of time. Serum and urinary calcium and phosphorus and serum alkaline phosphatase levels have been studied. Roentgenographic researches have been made in order to asses the bone mineral content. Urinary D-glucaric acid excretion as a quantitative index of hepatic enzyme induction has been determined in some subjects. The results show the presence of minor alterations both in calcium and phosphorus metabolism and in bone structure at a subclinical level. These findings suggest the importance of climatic and nutritional factors in the development of bone alterations pointed out by several authors in epileptic patients on long-term anticonvulsant therapy.


[Use of substances modifying serotonin metabolism in the treatment of narco-cataplexy (considerations on 5 cases)]. The AA., after a critical analysis of the new proposed treatments for the narco-cataplexy, report their experience about the therapeutic possibilities of this syndrome with particular manipulations of cerebral serotonin (5-HT). In 5 patients they tried to act on the two sides of the sleeping-waking cycle by using a diurnal administration of Methysergide (5-HT inhibitor) and an evening loading of L-Tryptophan combined with Benserazide (dopa-decarboxilase inhibitor). The immediate and long term results on the nercoleptic as well as cataplectic symptoms can be considered good. Conversely treatments with Clomipramine alone exerted poor beneficial effects in these patients. The AA. discuss the physiopathogenetic mechanisms which are thought to be involved in this disease.


[Subarachnoid hemorrhage as the 1st clinical manifestation of neurinoma of the acoustic nerve]. The association of sub-arachnoidal hemorrhage and benignant tumors of the pontocerebellar angle represent a rare event. The authors describe a case of neurinoma of the acoustic nerve which revealed itself with a sub-arachnoidal hemorrhage. After recalling the other only observation reported in literature, the authors discuss both its clinic and etiopathogenesis.


[The general intelligence factor: psychometric study. Approach to the problem of mental deterioration]. The authors have measured the correlation coefficient between W.B. and P.M. scores in 80 normal subjects, comparable for age and school. A mutual relationship between the two tests, connected by the hypothetical general intelligence factor "g", was really demonstrated. Correlation coefficient was positive and significative between W.B. total scores, excepted verbal scores, and P.M., the highest one between subtests 8, 9 and P.M. The intra-tests correlation between W.B. total scores and each subtest score was also evaluated: between sub-tests 8, 9 and W.B. total scores the highest one again. A new qualitative interpretation of mental deterioration in clinical neurology and psychiatry is suggested on the base of these results.


[Primary spinal tumors of multiple localization]. The authors report the case of a patient submitted to an operation of spinal tumors with multiple localization which, beside enriching the rare observations existing in literature, presents and hypertensive hypertension hydrocephalus with non common pathogenesis and points out considerable difficulties of interpretation of the histologic picture. After examining literature and describing the case in detail, the authors discuss the etiopathogenesis of hydrocephalus and examine the histologic aspect of extirpated tumors.


[Clinical and angiographic aspects of a unilateral chronic convexity subdural hematoma]. The Authors reviewed 52 cases of unilateral chronic subdural hematoma (c.s.h.) of the convexity from the clinical and angiographic point of view. They stated that it is possible to subdivide the c.s.h. into three main clinico-angiographic types: type 1: with focal symptoms and with almost always "biconvex" shape; type 2: with signs of intracranial hypertension and with "transitional or "biconvex" shape; type 3: with prevalent consciousness alterations and with "transitional" or "crescentic" shape. The shifting of the medial structure in relationship with the size of the hematoma is also discussed.


[Clonazepam in painful syndromes of the head]. A study of 46 patients has shown that Clonazepam is an effective drug in preventing attacks of pain in essential trigeminal and glossopharyngeal neuralgia and in Sluder's syndrome. The therapeutic action of the drug is less evident in different types of migraine, among which only the combined headache presents good results to the treatment. The effective dose of this drug is generally not greater than 3 mg/die and does not give rise to side effects in long-term prescription.


[Pathology and classification of colorectal polyps]. This survey deals with the principles of classifying colorectal polyps and with the fundamentals of anatomic pathology of these growths. In this connection, the epithelial neoplastic types, which are now known as adenomas, are of particular importance in so far as they are the potential precursors of carcinomas of the colon and rectum (""adenoma cancer sequence''). The polypectomy specimen alone enables definite histo-pathological diagnosis.


[Radiological diagnosis of colorectal polypi and carcinomas which have not progressed]. Provided examination conditions are optimal, we are now able to detect changes of the wall of the colon from about 5 mm diameter upwards and thus to further clarify the diagnosis and to initiate appropriate treatment. Hence, the demand for early or timely diagnosis can be met by means of x-ray diagnosis in respect of processes of the colon.


[Fracture of skull-comparative study of conventional and computer-assisted roentgenological examination (author's transl)]. Using a skull like phantome imaging characteristics of conventional x-ray technique and computerized tomography are compared. The contrast transfer function of x-ray films proofs to be superior, whichis due to overrange artefacts found in computerized tomography. Only 8 out of 50 skull fractures diagnosed by plain film technique were identified on computer-tomograms. Even though CT technique is excellent for the detection of intracranial lesions, fractures are more easily seen on conventional films. This is especially important for analysing size and site of impression fractures.


[Reactive osseous changes in intracranial types of meningioma (author's transl)]. Reactive osseous changes are so characteristic of meningiomas that diagnosis of meningioma is not infrequently possible by merely x-raying the cranium. The x-ray film shows flat or bed-like growing intracranial types (meningioma en plaque) which occupy little space or none at all, where the skeletal changes are most prominent. This type of meningioma escapes contrast medium diagnosis and is positive only in the conventional x-ray of the cranium or - in the state of beginning spread - in the tomogram.


[Radiation-risk in roentgendiagnostic of the gastro-intestinal tract (author's transl)]. The probability to induce leukemia or malignoma by roentgenexamination of the gastrointestinal tract is quite small. Basing on riskestimations of the ICRP and own measurements, the probability is about 1:25,000 in angiography. For x-ray examination of the stomach-duodenum, the small bowl, and the colon the radiation risk is approximatively 1:300,000 to 1:800,000. The probability to provoque radiation induced mutations, manifesting themselves in future children or grandchildren, is quite similair for male patients. On the other hand the risk for future children and grandchildren of female patients is a bit higher. An exception is the roentgenexamination of the colon, because direct exposure of the testes is in general inevitable.


[Microdocumentation of x-ray film via the "linear system" (author's transl)]. The new Federal German Roentgen Law in operation for the last two years governs not only the proprietary rights in respect of x-ray documentation but also the obligation regarding its accountability. Similar regulations are in preparation in other European countries. Since the discussions on individual problems of maintaining and cataloguing x-ray films and on approaches towards solving the production of duplicates, are common knowledge, there is no need to go into them once again, not lease because of their complex nature. Nevertheless, these problems are touched upon in the present article in the manner of key words in order to illustrate to what extent the Linear System meets the requisite demands.


Serum copper compared to erythrocyte sedimentation rate as indicator of disease activity in Hodgkin's disease. Serum copper and erythrocyte sedimentation rate were recorded in 54 patients with active Hodgkin's disease and at 186 occasions in 78 patients during stable complete remission. Relatively high and age-dependent normal limits for erythrocyte sedimentation rate were used. Each of the tests was elevated in 70% of patients with active disease. During remission serum copper was elevated in 14% and erythrocyte sedimentation rate in 16.5% of the determinations. Thus the two tests are considered not far from equal in their ability to discriminate between presence and absence of specific disease activity in Hodgkin's disease. Simultaneous elevation during remission occurred in less than 5% of the recordings as compared to 61% during active disease. It is therefore concluded that serum copper level may be of some value as a supplement to erythrocyte sedimentation rate.


Erythrocyte volume and count: a linear relation descriptive of population differences. In a sample of 215 adult males the mean red cell volume decreases linearly with increasing red cell concentration. The mean corpuscular volume and the red cell count are found uncorrelated with age of subject. Of these subjects 69 are identified as smokers and 114 as nonsmokers. Linear regression analysis shows negative linear relation for the smoking-defined groups, with slopes judged to be no different. When the regression lines are constrained to be parallel the line for smokers is displaced upward by 2.7 fl. No difference is found in mean corpuscular haemoglobin concentration or reticulocyte count. Haematocrit, haemoglobin, mean corpuscular haemoglobin are also reported. Viscosity of blood is greater in smokers. Optical determination of cell volume and area confirms the linear relation of volume and count.


Evidence against collagen activation of platelet-associated factor XI as a mechanism for initiating intrinsic clotting. Collagen activation of platelet-associated Factor XI has been proposed as a mechanism for initiating intrinsic clotting independent of Factor XII. Since this could explain the lack of bleeding in patients with hereditary Factor XII deficiency, prekallikrein deficiency and high molecular weight kininogen deficiency, we subjected the hypothesis to rigorous testing. Incubation of isolated platelets with collagen and calcium ions failed to generate activity shortening the clotting time of an activated Factor XI (XIa) assay that had been modified to eliminate effects due to platelet-associated activated Factor V. Nor could generation of traces of Factor XIa in such mixtures be detected by incubation with purified Factor IX and testing for the generation of activated Factor IX (IXa) in clotting and amidolytic assays. Moreover, when blood or platelet-rich plasma containing added 125I-Factor IX was incubated with calcium ions and collagen and then subjected to reduced sodium dodecyl sulfate polyacrylamide gel electrophoresis, the radioactivity profiles revealed only native 125I-Factor IX without evidence of the polypeptide chains of Factor IXa. The negative results of this study mitigate against the hypothesis that collagen activation of platelet-associated Factor XI represents a physiologically significant mechanism for initiating clotting independent of Factor XII.


Hexokinase deficiency in erythrocytes: a new variant in 5 members of a Finnish family. 15 cases of congenital haemolytic anaemia have thus far been attributed to hexokinase (HK) deficiency in erythrocytes. We report some clinical, biochemical and genetic findings from 5 members of a Finnish family with this deficiency. The proband, a 1-year-old girl, was the only patient with anaemia. All subjects had either mild or marked reticulocytosis. Red cell ATP levels were at the lower range of normal in all subjects and 2,3-DPG was abnormally low in one. The activities of red cell enzymes, other than HK, were within or above the normal range, respectively. The Km-values for glucose and fructose were elevated (ATP normal) in the subjects with HK deficiency. We speculate that the family represents heterozygosity of a mutant allele and that there is phenotypic variation associated with the HK mutant. The locus might be subject to mutations which lead to a variety of HK variants and to a spectrum of diseases. This point of view is in accordance with the overwhelming variation of reaction kinetics and metabolic effects of this and other reported cases.


Retention in glass bead columns as a measure of leucocyte adhesiveness. II. Influence of platelets and erythrocytes. The influence of platelets and erythrocytes on the retention of leucocytes in glass bead columns was studied. Leucocyte retention increased when platelet retention was stimulated by the presence of erythrocytes. In the presence of only a few erythrocytes, platelet retention was low, and platelets did not influence leucocyte retention. When only a small number of platelets was present, erythrocytes inhibited leucocyte retention. The platelet-dependent leucocyte retention increased as the volume passed through the columns was increased. However, the platelet-independent leucocyte retention did not change when the sample size was increased. In blood from patient with thrombocytopenia or defect in platelet function and in normal blood treated with inhibitor of platelet adhesion, neutrophil retention was reduced. However, erythrocyte-free leucocyte suspensions from these cases showed normal leucocyte retention. Thus, experiments with whole blood may serve as a model for the study of platelet-leucocyte interaction. However, for the study of leucocyte adhesiveness per se, isolated leucocytes seem more suitable than whole blood.


Fatal iron intoxication with multiple coagulation defects and degradation of factor VIII and factor XIII. A severe iron intoxication in a 15-year-old girl resulted in profound damage to vital organs and multiple clotting defects, but no haemorrhagic diathesis. Investigation revealed not only impaired synthesis of coagulation factors but also abnormal proteolysis by plasmin as well as by other proteolytic enzymes liberated from leucocytes and damaged tissue cells affecting especially factor VIII and factor XIII.


Serum erythrocyte folate levels in thalassaemic patients in Thailand. The mean serum and adjusted red cell folate levels, as measured by microassay using Lactobacillus casei, respectively were 8.87 +/- SD 3.28 microgram/l and 436 +/- SD 107 microgram/l in 76 normal subjects, 4.22 +/- SD 2.70 microgram/l and 182 +/- SD 114 microgram/l in 55 patients with beta-thalassaemia/Hb E disease and 6.36 +/- SD 2.95 microgram/l and 320 +/- 158 microgram/l in 37 patients with Hb H disease. The mean serum and adjusted red cell folate values of the patients with beta-thalassaemia/Hb E disease and the mean serum folate value of the patients with Hb H disease were significantly lower than those of the normal subjects (P less than 0.001). 33% of the beta-thalassaemia/Hb E patients and 8% of the Hb H patients showed low serum folate levels (less than 3 microgram/l) whereas 84% of the former and 45% of the latter showed low adjusted red cell folate levels (less than 270 microgram/l). The group of beta-thalassaemia/Hb E disease with low serum folate levels had lower mean haemoglobin concentration and lower mean adjusted red cell folate level than the group with normal serum folate levels. Since the Thai diets have high folate content, the observed low serum and erythrocyte folate levels in thalassaemic patients most likely occur from massively increased erythropoiesis. Folate, 5 mg/d, is now routinely prescribed to such patients especially to those with severe anaemia.


The proliferative states of circulating granulopoietic stem cells in man. The fraction of granulocyte-macrophage colony-forming cells (CFC) in DNA synthetic phase in blood from 25 normal adults and those in blood and bone marrow from 8 haematologically normal subjects were evaluated by in vitro culture of cells with and without prior exposure to 3H-thymidine (12.5 muCi) for 1 h at 37 degrees C. The exposure of blood cells from normal adults to 3H-thymidine resulted in 26 +/- 10% reduction in colony formation and in 14 +/- 10% reduction in cluster formation. There was no difference in the magnitude of reduction in colony formation following exposure to 3H-thymidine by cells in blood and those in bone marrow in 6 of the 8 haematologically normal subjects. These findings indicated that about one fourth of the circulating CFC in normal adults are in proliferative state and that significant difference in proliferative states between CFC in blood and those in bone marrow probably does not exist in the majority of haematologically normal subjects.


Red cell inclusion bodies in a case of preleukaemia. A 26-year-old female patient is reported in whom red cell inclusion bodies (Hb-H) and thrombocytopenia appeared more than 5 years before the emergence of atypical chr. myeloid leukaemia. Attention is drawn to the fact that the recently uncovered mechanism of acquisition of Hb-H (absence of transcription of specific genes) has previously been implicated in other biochemical changes typical of leukaemia.


A platelet defect in a patient with eosinophilic leukaemia: absent ristocetin-induced platelet aggregation associated with a reduced platelet sialic acid content. Platelets from a patient with eosinophilic leukaemia were not aggregated by ristocetin. The defect was not corrected by normal human plasma and was due to a platelet abnormality. The patient's platelets also showed a diminished sensitivity to aggregation by bovine factor VIIIVWF. The defect was not associated with a prolonged bleeding time. No abnormalities were detected in ADP, collagen or thrombin-induced platelet aggregation. Biochemical studies showed that the platelets were deficient in sialic acid. This deficiency was associated with a reduced staining for glycoprotein I following SDS-polyacrylamide gel electrophoresis. The results suggest an acquired platelet surface abnormality.


Acute renal insufficiency occurring during intravenous desferrioxamine therapy. A patient of 14 years suffering from secondary haemosiderosis and thalassaemia major was treated with i.v. desferrioxamine in doses up to 3 g/d. Urine iron loss ranged from 46-158 mg/d. Despite improvement in cardiac and hepatic status the patient developed acute renal insufficiency of the pre renal type. The possible role of desferrioxamine in this complication is discussed. Desferrioxamine given s.c. or i.v. effects a marked urinary iron loss but its use may not be without significant complications.


Analysis of reasons and locations of burns on hands. During the period 1971-76, 1055 patients with fresh burns were treated at our hospital. Of these, 461 (88 females, 373 males) had sustained burns on altogether 783 hands. This amounts to 45% of the total number of fresh burns. In 322 cases both hands were involved, amounting to 31% of all cases of fresh burns, or 70% of all patients with burned hands. Whereas 82% of patients with hand burns had injuries to both hands, only 10% had sustained an injury to the right hand alone and 8% to the left hand alone. Cases of burns limited to the hands alone accounted for only 4.7% of all burn injuries. The main cause of burn injuries was thermal accident--most often steam explosions and the spraying of scalding liquids. The total number of hands injured by thermal agents totalled 707, i.e. 90% of all burned hands. Most of these were deep skin burns. Chemical agents were mainly responsible for this type of burn, whereas electrical burns were chiefly full thickness skin injuries. Analysis of the location of burns showed that 643 (82%) hands of the altogether 783 injuries sustained involved the wrist, 620 (79%) the metacarpus, 684 (87%) of the fingers. Some 321 hand burns (41%) were of a circumferential nature. A majority of burned hands were injured on the dorsal surface. The burn injuries of hands in 246 (53%) persons were connected with their professional work.


Tattooing, a new hope for secondary leukoderma. A 10-year material of 1,000 post-burn patients have been reviewed. Dyschromia was found to be one of the commonest post-burn sequelae in both partial thickness and superficial burn. Patches of leukoderma surrounded by a zone of hyperpigmentation was the main feature in partial thickness burn, while hyperpigmentation follows superficial burn. Tattooing was tried on 30 patients as a permanent camouflage for leukodermic patches in exposed areas. Histological studies on 7 volunteers were carried out, showing the histological pattern of dyschromia and tattooing. The trial proved to be a success, though it still needs further refinement and improvement.


Induced ischemia: means of prediction of demarcation line of necrosis after electrical injury. An experimental study on rabbit ear. Necrosis due to an electrical injury extends by progressive obstruction of blood vessels. Means of inhibiting expansion of necrosis and predicting early the demarcation line after an electric injury were studied in the local electric injury of a rabbit ear produced by application of an electric current of 50 Hz, 1800 V for 1 sec between the right ear and the right posterior leg. Although no effective method of inhibiting expansion of necrosis was obtained, a method of predicting a demarcation line of necrosis was obtained by inducing ischemia of the ear early after the application of an electric current. From three hours to three days after the application of the electric current, ischemia of the ear was induced by compressing it between a pair of blood pressure cuffs at a pressure of 300 mmHg. As a result, the area proximal to the expected demarcation line of necrosis became white by ischemia, while the peripheral part remained dark red because of thrombi, and the expected demarcation line was clearly observed. Two to three weeks after the application of the electric current, the ear almost invariably fell off at this expected line. Therefore, in the electric injury of the hand, it can be distinguished clinically whether or not the area will become necrotic by inducing ischemia from the tips of the fingers to the upper arm early after the electric injury.


Use of the low air loss bed system in treatment of burns patients. When a person is confined to bed, whatever the reason, small areas of soft tissues are compressed between the skeleton and the supporting surfaces. Transient circulatory disturbances resulting in epidermis to dermis damage or finally deep penetrating necrosis involving subcutaneous tissues, fascia muscle and bone may result. In the case of the severely burned patient who has already sustained gross trauma, any further destruction of tissues is to be avoided at all costs. The Low Air Loss Bed System offers many advantages in the care and management of the burns patient. There is a definite saving of nursing time by rendering unnecessary constant attention to the patient for preventative skin care, positioning, bed pan etc. The nurse is then able to devote her time positively to the more involved needs of the patient and family. It will also provide for periods of rest that are so often lacking, especially in the initial stages of treatment. The patient does not have to be kept on a rigid regime of Q2H turning. He is turned only for wound care, physio- and general body cleansing. His position may be contoured without having to touch him circumferentially. Any lifting and positioning necessary is easier for staff members due to the design of the unit, and more comfortable for the patient. Over a period of two years, eighteen patients with varying extent and degree of burn injuries were treated on the bed. This paper will describe the mechanical operation of the bed and experiences with nursing management and monitoring of the system.


A strong hospital-school liaison: a necessity for good rehabilitation planning for disfigured children. Next to the family, the school exerts the most influence on a child's normal development and social adjustment. Discharge planning for a child who has been burned must properly involve school teachers and guidance counselors as well as parents. Ideally, the hospital social worker initiates contact with school personnel in much the same way she does the patient's family. She identifies many of the same emotions (grief, fear, anger, and denial) which can affect the ability of the teacher to cope with the new responsibilities and demands imposed on him in receiving a burn scarred child in the classroom. The new federal law in the United States provides guidelines for providing services to handicapped children, but the school staff must be emotionally and psychologically prepared in order for the goals of the law to be achieved. The burn unit social worker is best prepared to carry out this very sensitive and important aspect of planning for a successful reentry, and whenever possible works closely with the hospital school teacher who is cognizant of special education services and the school system's ability to provide them. Case studies are presented showing the impact of both short and long term intervention with the school.


Group meetings benefit families of burned children. Recognition must be given to the continuing burden carried by parents of children who have been discharged from a burns hospital. Weekly parents' meetings under the direction of social workers are offered during clinic hours in an effort to maintain support and offer guidance. Unlike other therapeutic groups, these parents are not screened by interests, background or age. Their only common denominator is that of having a severely burned child. Also, unlike other groups, the participants change each week, depending on the clinic schedule. However, despite the lack of continuity in participation, the parents have come to know that by returning to the group at any time, they can find help and understanding and often receive renewed strength for coping. It is interesting to note that the same problems recur in the meetings' content: 1) Adjustment of the home schedule immediately following discharge in order to deal with the demands of the children and the time required for skin care, 2) parents' tendency to project their guilt by over-protecting the children, 3) adolescent problems stemming from burn scars affecting body image and self-esteem, 4) changes in marital relationships. Often, parents of children who are still in the acute stage attend these meetings and take their first cautious steps toward facing the future supported by "those who have been there". All learn that this is an hour when they may freely question, share feelings, and leave knowing they are supported and not alone.


Rehabilitating families with burned children. A critical factor in the successful or unsuccessful life adjustment of the badly burned patient is his family's reaction to this chronic problem, its ability to support him, and to help him pursue the long course of treatment and its many associated problems, and to also help him navigate the social world into which he must go. The high incidence of emotional disturbance in families sustaining burn injuries makes it vital to deal effectively and in a sustained manner to assess the types of emotional disturbances which exist in these families and to see how they influence the responses to the injuries and to the long and arduous treatments that follow. Different patterns of adaptation occur, some much related to economic class and special types of psychiatric disorder in the family. Some reactions of chronic grief and intermittent helplessness and hopelessness may transcent all groups, but the ability to follow through in later care varies enormously, and is correlated with the overt depression of the mother. Several types of reaction are epitomized in the cases presented, along with directives for their management, and the interplay of social, somatic, and psychological factors which lead to these patterns will be delineated.


Unreasonable expectations of reconstructive patients affecting rehabilitation. Common difficult and recurring problems develop which make the demands of certain cosmetic surgical patients appear reasonable or not reasonable to the people operating upon them. In spite of careful preparation and repeated instruction, a number of patients continue to entertain fixed and elusive ideas about themselves, their body images, and the results they desire from surgery. These wishes are often not logical, and derive from personal experiences of the patients, and are not related to the actual degree of deformity or the objective reactions that other people have to these defects. while it is generally true that more gross deformities force a more realistic perspective upon the patients and their families in contrast to many normal-looking persons who seek cosmetic surgery, this is not always the case. The authors attempt to examine and describe several specific cases of these problems, along with the psychological mechanisms which underlie them, and present possible ways in which such behavior can be managed by the aesthetic surgeon. An attempt is also intended to be as practical as possible about the use of the busy surgeon's time in these situations.


Public and professional reactions to the facially disfigured which interfere with rehabilitation. The rare appearance in public and the difficulty in obtaining follow-ups indicate the general tendency of facially disfigured people toward seclusion and restriction of their work lives and social functioning. Investigation of some of the reactions in the community, the underlying mental mechanisms, and the ways in which the nurses, doctors, and teachers they meet lead to the awareness of the ways in which professional and public attitudes may function synergistically against the rehabilitation and optimal functioning of these patients. The innate and biological mechanisms which cause observers of the disfigured to react with alarm, fear, rejection, and withdrawal are examined, as also are the ways in which professional attitudes differ, and how professional attitudes evolve. The variables of authoritarianism, friendliness, and the ways in which caretakers perceive and manage people in deviant roles in order to advance their rehabilitation will be  explored and illustrated with case examples. Techniques for educating doctors and nurses about handling disfigurement in the complex matrix of modern medical care will be outlined, with emphasis upon comprehensive care and the emerging concepts of a case manager system of care in the handling of these chronic and tragic problems.


Local and systemic changes of acid proteinases during advanced stages of burn injuries. Rats were subjected to burns extending to 15% of their body surface. Enzyme activities were measured by a slightly modified Barrett technique between the 12th and 18th day after the burn injury. A statistically significant activation of acid proteolytic enzymes, in relation to mg protein, was seen in liver, spleen, kidney and stomach. In relation to grams fresh weight, an activation was seen in the kidney. Necrotic skin subsequent to burn injury showed a marked rise in activation compared with the skin of the control group, as well as with the skin of the burned animals. Increased enzyme contents were also detected in the intact skin of burned animals, compared with the skin of the control group.


Acute renal failure in burns.

Acute renal failure in burns. We present the combined experience of a burns unit and a renal dialysis unit in treating acute renal failure in burn injury patients. A total of 28 cases have been treated of whom 4 regained normal renal function. We would like to emphasize the following points which may improve the usually very poor prognosis: early diagnosis, early daily haemodialysis, adequate feeding and the early amputation of non viable limbs. A search of the literature reveals that only 11 previously reported cases of burns injury patients being successfully dialysed for acute renal failure.


Comparison of methods of predicting burn mortality. Recent suggestions that patients "hopelessly burned" be permitted to die peacefully have refocused attention on the accuracy of different methods of predicting whether an individual burn patient will survive. The purpose of this presentation is to compare the accuracy of mortality predictions based upon four different statistical methods: (1) Baux's rule which adds the patient's age in years to the percentage of his body surface area burned--the original assertion was that values over 75 meant a very poor prognosis. (2) probit analysis, (3) discriminant analysis, and (4) logistic risk function analysis. Each of these methods was applied to data for over three thousand consecutive admissions to St. Mary's Hospital Burn Center in Milwaukee, Wisconsin. This data base and the four statistical models are described. Mortality predictions derived from the four models are compared, and some observations are made concerning the selection of an appropriate model for predicting burn mortality.


Toxin-specific ultrastructural alterations of the mouse liver after burn injuries and the possibility of a specific antitoxic therapy. Electron-microscopic studies in mice revealed similar and comparable mitochondrial alterations of the liver cells 5-7 days after either a sublethal controlled burn injury or an i.p. injection of an equivalent dose of a burn toxin. Electron microscopy 5 days after i.p. application of different amounts of the burn toxin in rats showed that the extent of the liver alterations correlates directly to the applied dose (occurrence of: cristolysis--intramitochondrial vacuolization--total vacuolar changes of mitochondria(. Controls with the non-toxic/"native" compound isolated from normal skin or excision of a skin piece identical in size to the sublethal burn showed no ultrastructural changes in the liver of mice or rats. In a 2nd series of experiments the therapeutic effect of an antitoxic IgG raised in sheep was tested. The first 3 days after a standard burn or an i.p. injection of 15 mg burn toxin mice obtained 10 mg of the antitoxic IgG (2x/day). Controls injected with the "native" compound or excised as described were treated in the same way. The results showed a specific complete immunological protection from mitochondrial alterations by either the toxin or the burn injury. These results suggest the possibility of an antitoxic IgG-therapy in severe burns.


Effect of cutaneous human or mouse burn toxin on the metabolic function of isolated liver cells. Studies on isolated perfused rat livers 5 days after either a sublethal burn or an i.p. injection of human/mouse burn toxin showed a significant inhibition of the glucose/urea synthesis and the ATP production concomitantly with ultrastructural mitochondrial damages. A direct specific effect of these burn toxins on enzymatically isolated liver parenchyma cells was found either after direct incubation of the isolated cells with the compound or 5 days after injection of the toxin to the animals followed by the isolation of the cells. Control experiments were performed with the "native" non-toxic precursor from normal skin. Liver cells of rats pretreated with the toxin showed an 100% increase of the amino-acid release while this increase was 70% after direct toxin incubation. Glycogen synthesis from lactate, alanin and fructose was significantly decreased in both toxin groups while the glucose synthesis was not altered. The degree of the inhibition of the glycogen synthesis was directly correlated to the number of ATP-dependent metabolic steps. A disturbance of the oxygen transfer system by structural damages of the mitochondria seems to be the basic mechanism for these specific metabolic alterations due to ultrastructural mitochondrial damages.


Transcapillary transport after thermal injury. The pathophysiology of the burn wound is characterized by an inflammatory reaction leading to rapid edema formation due to (1) dilatation of resistance vessels with increased effective transcapillary filtration pressure, (2) increased extravascular osmotic activity created in damaged tissue, and (3) increased microvascular permeability to macromolecules. In extensive burns increased microvascular permeability was found also in tissues remote from the thermal injury. These reactions are due to direct heat effect on the microvasculature and to chemical mediators of inflammation. Important is the increased biosynthesis of prostaglandins at the site of tissue injury which may partly explain vasodilatation, increased microvascular permeability and accumulation of polymorphonuclear leucocytes observed following thermal injury. The morphological interpretations of the changes in the functional ultrastructure of the blood-lymph barrier following thermal injury seem to be a remarkable and persistant increase in the numbers of vacuoles and many open endothelial intercellular junctions. Further less explored changes of the interstitial tissue after severe burn trauma seem to be of great importance.


Acute effect of scalding injury on blood flow in muscle and subcutaneous tissue in the paw of the anaesthetized dog. Blood flow in muscle and subcutaneous tissue was studied before and after a scalding injury of the dog paw. The hydrogen clearance technique was used in anaesthetized dogs. As scalding of the paw resulted in an increased blood pressure and muscular movements, animals were given a muscle relaxant and ventilated artificially. Before scalding injury the blood flow was 29.8 and 19.7 ml per min per 100 g in muscular and subcutaneous tissue, respectively. After immersion of the paw for 10 sec in water of 100 degrees C the blood flow transiently increased and later decreased. No major changes were found in the contralateral paw. The decrease was most pronounced (50%) in subcutaneous tissue. In the acute situation the impeded circulation in the burn oedema may protect the organism from potentially harmful substances formed in the injured tissue.


Prostaglandins and thromboxanes in burn injury in man. The main urine metabolite of prostaglandin F2 alpha (5 alpha, 7 alpha-dihydroxy-11-ketotetranor-phostane-1, 16-dioic acid, PGF-metabolite) was determined by mass spectrometry (MS) and radioimmunoassay (RIA) in burned patients treated under routine conditions. The amount of the PGF-metabolite as determined by MS was 130 and 67 microgram/24 h (normal value 24 +/- 17 microgram/24 h) on days 3 and 5 respectively in one patient. In serial determinations using RIA the urine level of the PGF-metabolite was within normal values during the first days and rose to a broad peak 1-4 weeks after the injury. Thromboxane B2 (TXB2) was identified and quantitated in burn blister fluid. The amount of TXB2 was 1.7 ng/ml.


Evaporative water loss in partial skin loss in the first 24 hours. In experiments on laboratory pigs the healing of decorticated dermis and in deep dermal burns was studied. In both groups, the controls were left uncovered, while the experimental wounds were covered with an indifferent ointment for the first 24 hours only. After the first 24 hours all wounds were left exposed without further treatment. It was found, that wounds, covered by an indifferent ointment for the first twenty-four hours only penetrate to a lesser depth as compared to the uncovered controls; histological studies of the course of healing confirm this fact, as the wounds treated for the first 24 hours only heal one week earlier then the controls. The differences were more pronounced in burns than in mechanical decorticated wounds. The authors presume, that these facts underline the importance of evaporative water loss during the first 24 hours in deep dermal burns as well as the importance of local treatment at this initial stage.


Burn wound biopsy. Multiple uses in patient management. It is often exceedingly difficult to initially evaluate the depth of a burn wound and thus inaugurate appropriate definitive therapy. The clinical picture of the burn would may not always correlate with the true histologic depth of the injury. For this reason we have undertaken a program of obtaining punch biopsies of burn wounds in patients where the depth of the burn wound is equivocal. In such cases the biopsy has proven to be useful in guiding subsequent therapy. In addition to establishing the anatomic depth of injury, there are several other valuable uses of burn wound biopsies. The other uses are: diagnosis of invasive infection, quantitative bacterial culture, medical-legal values, psychological values and forensic utility.


Histology of healing of deep dermal burns in pigs. A standard deep second degree burn was worked out in pigs. The burn was inflicted with a hot iron, standardized by immediate retraction measurements. Biopsies were taken from the wounds on days 0, 1, 4, 7, 14, 21. Standard staining methods were used. Spontaneous healing was followed and results compared with mechanical partial skin loss healing.


Clinical forms of endotoxemia in burns.

Clinical forms of endotoxemia in burns. Two groups of patients in whom endotoxemia was suspected were studied with respect to the laboratory data, clinical picture and autopsy findings. The first group showed the signs of gram-negative septicemia (age range 3 to 54 years with burns of 25 to 80% TBSA) and the second group (age range 20 to 76 years with burns not greater than 20% TBSA) showed an unexpected deterioration of the patient's condition. In 15 patients we established the diagnosis of endotoxemia on positive Limulus test as well as on other laboratory examinations and on the clinical signs. Five different forms of endotoxemia were distinguished varying in the evoking circumstance, clinical manifestation and pathological findings at autopsy: (1) the so called laboratory form--all survived; (2) the pulmonary form displaying the most brief and fulminant course--all died; (3) the form of disseminated intravascular coagulopathy; (4) the form of endotoxic shock due to administration of antibiotics; (5) the form of endotoxic shock as terminal stage of protracted gram-negative septicemia--the fatal outcome was inevitable in all cases. The authors stress the importance of minding and preventing all circumstances that might provoke the endotoxic (septic) shock.


Gas gangrene as a complication of burns. Gas gangrene infection in burnt patients is a rare but often fatal complication. It may however, be successfully treated by the use of hyperbaric oxygen and later judicious amputation of dead tissues. Five cases of bacteriologically proven gas gangrene, three of whom survived, occurred out of a total of one thousand and sixty-four burns patients treated since 1964 in the McIndoe Burns Unit, and these we describe.


Endotoxemia and endotoxemia diagnostics. After the study of a group of severely burned patients with septicemia the authors reached the conclusion that the diagnosis of endotoxemia should be based on the following criteria: clinical condition, laboratory results and autopsy findings. Clinical findings can be subdivided into anamnestic data (such as age, liver function etc.) and direct clinical observation (taking into account states of stress and some specific surgical procedures). The most significant laboratory findings in the investigated group of patients were hypoxy, metabolic acidosis, lowered platelet count and positive Limulus test. Autopsy findings corresponded to findings in septicemia and shock. The authors also discuss the significance of activated lymphocyte accumulation in the liver following endotoxin administration in animals.


Systematic utilization of an antipseudomonas aeruginosa vaccine in a severe burn unit. The biological and clinical results of vaccination against pseudomonas aeruginosa infection have been analyzed for a group of 287 burned patients having over 25% surface burnt. The vaccine used was a cellular one inactivated by heat and containing 10 different strains. The effectiveness has been judged on the one hand by the increase in the antipseudomonas antibody count and on the other by comparing a group of vaccinated patients with a non-vaccinated group. After vaccination, the antipseudomonas aeruginosa antibodies increased from the 4th-5th day and reached an impressive increase after the 10th day. Clinically, protection is almost complete if one considers that pseudomonas aeruginosa positive blood cultures appear 15 days after vaccination, and above all the prognosis of these late infections. Both locally and generally, this vaccine has always been perfectly tolerated.


A ten-year retrospective study of sepsis in severely burned patients treated with or without silver sulfadiazinate. Three groups of extensive burn patients of the surgical intensive care unit (ICU) have been compared: Group I: twenty patients, who were treated locally without silver sulfadiazinate (1968-1970); Group II: the twenty first patients topically treated with silver sulfadiazinate (1970-1972); Group III: twenty similarly treated patients, with silver sulfadiazinate, six years later (1976-1977). The groups are statistically comparable. All bacteriological samples were computerized; the chi-square method was used for statistical analysis of the data. The main conclusions are: (A) Silver sulfadiazinate treatment reduced Pseudomonas aeruginosa and Proteus sepsis. No change in Coliform bacilli sepsis was observed. After six years, a rise in Klebsiella sepsis and Candida sepsis was noted. (B) A quantitative estimate of infections in each group was made by measuring the percentage of positive samples, taking into account the five above-mentioned strains. In the beginning, silver sulfadiazinate reduced quantitative sepsis, but this benefit decreased after six years; the same evolution was demonstrated for positive blood bacteriology; severe septicaemia showed a parallel pattern.


Metal sulfonamides as antibacterial agents in topical therapy. The apparent efficacy of zinc and cerium sulfadiazine and the metabolic role of other trace metals suggested that sulfonamide salts of these might be of therapeutic value. There is also a possibility that metal salts of other sulfonamides might be useful. Accordingly other sulfonamide salts of zinc were prepared and studied in vitro and in vivo. Only zinc sulfathiazole and zinc methoxazole were as effective as zinc sulfadiazine in animal studies. The sulfadiazines of aluminum, chromium, cobalt, copper and iron were prepared and compared in vitro and in vivo. Only cobalt sulfadiazine appeared comparable to zinc and cerium sulfadiazine in healing burn wounds in rats. Studies on the molecular structure of silver sulfonamides disclosed the polymeric structure peculiar to silver sulfadiazine which appears to account for its unique properties. It is not yet known whether other metal sulfadiazines have this attribute.


Clinical comparison of maphenide and silver sulphadiazine. A series of 645 consecutive burn injuries are analysed. There were 175 patients in the control group, 156 in the Maphenide (Sulfamylon) group and 314 in the Silver Sulphadiazine (S. S. D.) group. The Maphenide group and S.S.D. group are compared statistically with the control group. S.S.D. proved superior in relation to clinical infection rate and culture rate in reduction of Pseudomonas and Staphylococcus. Other culture rates were analysed. There were significant reductions in both groups for E. coli and Candida albicans. Pneumonias were significantly increased in both groups and the mortality rate reduced with S.S.D. Overall S.S.D. gave better results than Maphenide.


Clinical assessment of disease activity in rheumatoid arthritis. A new experimental design was developed to study the value of clinical parameters of disease activity in patients with rheumatoid arthritis. Ten patients with classical rheumatoid arthritis were examined by five senior doctors in a department of medical rheumatology. In spite of an attempt to make the clinical examination as uniform as possible the inter-observer variation among the doctors was greater than the variation among the patients, for the following parameters: joint pain at rest, joint tenderness and joint swelling. An acceptable inter-observer variation in relation to patient variation was found for 1) a combined registration of joint pain at rest or on movement, 2) duration of morning stiffness, 3) grip strength, 4) subjective well-being as indicated on a visual analogue scale, 5) fingertip--palm distance, and 6) maximum flexion-extension in elbows, wrists and knees. The variation from morning to afternoon and from day to day was negligible. It is concluded that registration of elaborated articular scores is useless in the daily routine in rheumatological departments when different doctors examine the patients.


Plasma salicylate levels in rheumatoid arthritis: a comparison between micro-encapsulated and conventional aspirin. Ten patients with rheumatoid arthritis were given identical amounts of conventional aspirin (Magnecyl) tablets and micro-encapsulated aspirin (Reumyl) capsules. Steady-state salicylate levels were determined after 4 days' treatment at 8 a.m., 12 noon, 4 p.m., 10 p.m. and again at 8 a.m. No difference was noted between the levels at 12 noon or 4 p.m. The 10 p.m. levels were slightly though not significantly higher and the last set of 8 a.m. levels were significantly higher during the capsule administration. A criterion for inclusion was good tolerance of Magnecyl. The clinical effectiveness was not evaluated, but the observed good absorption features of Reumyl indicate that this preparation may prove to be of value in long-term treatment.


Interobserver variation in the evaluation of radiologic changes of rheumatoid arthritis. The variation between four radiologists in the evaluation of hand, wrist, and foot radiographs of rheumatoid arthritis was examined. The recognition of individual radiologic changes varied considerably as judged by the findings of the different observers. Erosion and joint space narrowing were interpreted more uniformly than soft tissue swelling and osteoporosis. When the radiographs were graded from 0 to 5 using standard reference radiographs, more than 90% of them were graded uniformly or with a difference of only one grade. The investigation has shown that when applying grading of rheumatoid arthritis according to standard reference radiographs, the interobserver variation is considerably less than when pure individual radiological changes of rheumatoid arhtritis are considered.


Skin collagen biosynthesis in patients with rheumatoid arthritis treated with D-penicillamine. Collagen biosynthesis was measured in skin biopsies taken from 13 patients with rheumatoid arthritis before and after at least 6 months' continuous treatment with D-penicillamine, 1.0 g/day. There was a significant 36% reduction in mean collagen biosynthesis (p less than 0.0125) as assayed by 14C-hydroxyproline formation from 14C-proline during 24 h of tissue culture. The changes in 14C-hydroxyproline formation were correlated with the total doses of D-penicillamine taken (r = 0.71, p less than 0.01) and the falls in ESR (r = 0.72, p less than 0.01). No significant change in general protein syntehsis was observed. 500 microgram/mlD-penicillamine added to skil cultures in vitro inhibited both collagen and general protein synthesis (p less than 0.01). It is suggested that the clinical improvement induced by D-penicillamine could reflect an inhibition of collagen proliferation in the synovium.


[Treatment with 10% glycerin in acute ischemic cerebral infarct. Doubleblind study]. 56 patients with acute ischemic cerebral infarction were randomly allocated to intravenous treatment for 6 days with either 500 ml of a 10% glycerol solution or 500 ml of a 5% dextrose solution (placebo). The neurological status of the patients was evaluated by a blinded investigator before the beginning of the treatment, after 2 weeks and again after 6 months. According to the initial degree of neurological deficit, patients were stratified into a mild, intermediate and severe group (using a scoring system). After 2 weeks there was significantly less neurological deficit in the total glycerol-treated group than in the placebo group (2p less than 0.02). This favourable effect of glycerol was even greater in the patients with an initially intermediate degree of neurological deficity (2p less than 0.01). After 6 months there was no difference between the total glycerol-treated and the placebo group. A beneficial effect of glycerol treatment, however, was still demonstrable in the intermediate group (2p less than 0.05). Mortality was not influenced by glycerol treatment. No side effects of the glycerol treatment could be detected. Intravenous administration of 10% glycerol can thus be recommended in patients with acute cerebral infarction.


[The biological effect of purely synthetic human insulin in patients with diabetes mellitus]. Six patients with diabetes were treated with fully synthetic human insulin (CGP 12 831) for durations of 3 days (4 patients), 4 days and 13 days (1 patient each). In every case, clinical signs of hypoglycemia were registered and measured by blood sugar determinations. Two patients with insulin-dependent diabetes were maintained on synthetic insulin. Ketoacidosis was corrected in 1 patient. In a hyperglycemic diabetic with failing response to oral antidiabetics, synthetic insulin normalized the hyperglycemia. In 2 juveniles with recent onset of diabetes, every injection of synthetic insulin was followed by a fall in blood sugar. In a normal individual, hypoglycemia developed after a single injection of 8 units. The synthetic human insulin was well tolerated. The 6 diabetics showed evidence of full biological action of the fully synthetic insulin, as was expected from animal experiments.


[The effect of light physical work on the glucose formation in the liver in patients with liver cirrhosis]. In 7 normals and 7 patients with cirrhosis of the liver the influence of moderate physical work on glucose turnover was determined with 14C-glucose. Under resting conditions glucose turnover was 0.60 +/- 0.12 mmol/h/kg in the normals and 0.45 +/- 0.13 mmol/h/kg in the patients (mean +/- SD). During one hour's ergometer work of 45 +/- 12 watt, an increase of 90 +/- 42% (normals) and 53 +/- 29% (patients) was observed which resulted in a significantly lower turnover in the cirrhotics during work (normals 1.12 +/- 0.16, cirrhotics 0.68 +/- 0.14 mmol/h/kg). Serum concentrations of glucose, insulin and FFA remained constant in the normals, while in the patients a slight decrease in glucose and FFA was observed. Serum lactate levels were slightly higher and normalization lasted longer than in normals. It is obvious from these results that even fundamental liver functions, such as glucose production, are disturbed in patients with liver cirrhosis and show a reduced augmentation during physical work.


[The problem of the multifocal breast neoplasm]. Nowadays, it is accepted that mammary cancer does not represent a localized tumor only, but a bilateral disease of breast tissues. During a period of 6 years, bilateral manifestations of infiltrating cancer have been observed in 12.7% of all cases. 23.2% of all breast cancer patients had a unilaterial multicentric tumor. The implications of this phenomenon with regard to control and therapy are as follows: As early diagnosis of malignant breast tumors often is possible by means of mammography, this examination should be performed regulary in high-risk patients, especially in cases of known earlier malignancy of one breast. More radical surgery should have priority, in view of the frequently observed multicentricity of breast cancers.


[Congenital cystic dilatation of the intrahepatic bile ducts. Caroli's disease and its complications]. Two cases with congenital dilatations of the intrahepatic bile ducts are reported. The clinical, diagnostic and therapeutic aspects and possible complications of this rare disease are discussed. The well-known frequent occurrence of cholangiocarcinoma in Caroli's disease is illustrated by one of our patients. Because of the limited therapeutic possibilities, the prognosis of this illness remains unfavourable.


[Neurophysiological characteristics of early auditory waves of the brain stem and their clinical utilization]. The auditory brainstem electric response yields information on both the neurological and the audiological status of infants and adults. These early waves have particular properties as: non-habituation, absence of latency modifications between sleep, awake state, or under high doses of barbiturates. We have developed a procedure for extracting each type of information by measuring the latencies of wave I (auditory nerve) and wave V (inferior colliculus), then the speed of conduction between these two waves.


[Catamnestic studies in hemiplegics].

[Catamnestic studies in hemiplegics]. 61 patients with hemiplegia who had undergone hospital rehabilitation were examined 1 year later and 29 patients after an interval of 10--11 years. Special attention was paid to improvements and relapses with respect to walking ability, personal care, and social situation. The investigation showed that 62% of personal living on their own made progress in the activities of daily life; there were no relapses. 14% of those living in a family showed improvement while 29% relapsed. Of patients living in nursing homes only 5% showed improvement, while there were relapses in 42% of cases. The percentages of cases showing improvement (or relapses) with respect to walking ability are as follows: 20% (7.5%), 30% (22%) and 0% (21%). 32% of the patients had regular physiotherapy sessions. A change in the social situation had resulted for 50%; many of these were lonely and missed visitors. Persons looking after themselves showed the best prognosis following rehabilitation.


[Cardiac tamponade in malignant tumors]. Among 40 patients with cardiac tamponade observed over the years 1972--1978, 23 (57.5%) had a neoplasm as primary cause of illness. The most common etiology was bronchial carcinoma (13). In 9 cases cardiac tamponade was the first clinical symptom of the tumor. Evacuation of the pericardial fluid by puncture (3), surgical drainage (6) and left parasternal insertion of a plastic catheter (12) brought rapid relief from symptoms in all cases. Six patients survived 3--6 months, while another two have now been followed up for over 5 years. Diagnostic problems and therapeutic possibilities in malignant pericarditis are discussed.


[Indication for selective surgical excision of hepatic metastases]. 451 patients undergoing surgery for colorectal cancer showed synchronous hepatic metastases in 24.4% (110 cases). Survival of patients with hepatic metastases appears to depend on both the age of the patient and the site of metastatic deposit. A relatively good prognosis group with median survival of 14 months can be separated from the other patients with only 5 months survival. Survival of patients with hepatic metastases can thus be predicted and long-term survival (5 and 10 years) obtained by surgical excision of these metastases. Postoperative CEA determinations will also increase the rate of early surgery for hepatic metastases.


[Malignat non-Hodgkin Lymphoma in childhood. Therapeutic results in 47 patients]. A preliminary report is presented on survival in 16 children with non-Hodgkin's lymphoma treated since 1975, as compared with that in 31 similar children treated between 1962 and 1974. In the former group, 10 of 14 children (71%) survived one or more years and 5 of 9 children (56%) two or more years with no evidence of disease. In the latter group, the corresponding survival rates were 26% and 19% respectively. This improvement is due to the introduction of an aggressive multidrug chemotherapy combined with radiotherapy, similar to the LSA2-L2 protocol. Considerable toxicity was observed with the new treatment. 23 of the 46 patients with diffuse non-Hodgkin's lymphoma had a Burkitt-type tumor. Treatment failures occurred mainly in children with a Burkitt-type tumor with primary intraabdominal localization.


[Familial bradycardia: a family with sick sinus and atrioventricular block]. A kindred is described in which several members have evidence of sick sinus syndrome and of conduction disturbance. The data suggest that in this family the rhythm disturbances were transmitted as an autosomal dominant trait whose penetrance increase with age. The occurrence of Adams-Stokes episodes required pacemaker implantation in 6 patients. In one case the arrhythmia is associated with a cardiomyopathy of unknown origin. No pathological studies were conducted. In one case the His bundle electrogram was recorded.


[Value and limits of urinary protein electrophoresis with sodium dodecyl sulfate in the evaluation of glomerular nephropathies]. Qualitative analysis of urinary proteins is contrasted with histological findings of 45 renal biopsies performed in patients with chronic glomerulonephritis. Compared to electrophoresis on cellulose acetate and immunoelectrophoresis, a method using polyacrylamide gel after sodium dodecylsulfate treatment makes for more refined and objective differentiation of protein abnormalities. On the whole, proteinuria of the selective glomerular or physiological type predominates in the event of minimal change or membranous lesions. The non-selective type is found more frequently with diffuse proliferative or membranoproliferative glomerulonephritis (p less than 0.025). There are, however, too many exceptions to this rule to allow certainty, and a precise diagnosis of the particular type of glomerulonephritis is thus only possible histologically. Each type of histological involvement may cause almost any of the qualitative abnormalities of proteinuria. On the other hand, qualitative analysis of urinary proteins is useful for the detection of glomerulonephritis. A glomerular type of proteinuria may sometimes reveal involvement of kidneys at a time when, quantitatively, there is no proteinuria. In cases of orthostatic proteinuria a persistent glomerular type of tracing in recumbency suggests an organic kidney ailment. All patients in this series had a glomerular type of proteinuria when excretion was pathological, thus allowing a distinction from pure tubular involvement. 10 patients of the group, however, although they clearly had glomerular lesions (3 were diffuse proliferative glomerulonephritis) showed perfectly normal proteinuria both quantitatively and qualitatively. This was the case in systemic lupus erythematosus where kidney biopsy was performed without clinical suspicion of renal involvement. In summary, qualitative abnormalities of proteinuria call attention to underlying glomerulonephritis, although no distinction can be made between the various forms and there may be no detectable abnormality even in the event of major kidney involvement.


[Angioimmunoblastic lymphadenopathy. 3 cases with polyclonal gammopathy]. Three patients with an atypical lymphoproliferative disorder disorder and polyclonal gammopathy have been reviewed retrospectively. The clinical and histological findings are compatible with the recently described entity of angioimmunoblastic lymphadenopathy. Two patients died within 6 months after the first symptoms of the disease. Circulating immuncomplexes were demonstrated in the serum of 2 patients. In one patient with a nearly fourfold increase of IgG, persistent hyponatremia was found.


[Pregnancy following tumor therapy].

[Pregnancy following tumor therapy]. A report is presented on 9 patients who became pregnant and gave birth to 11 children after intensive or long-term tumor therapy. Eight patients had Hodgkin's disease and one patient metastatic choriocarcinoma. Two children had a birth defect probably related to the anticancer therapy: one child has hearing loss of the inner ear and one child a cleft lip and palate. Some general issues relating to pregnancy after tumor therapy are discussed.


[Decompressive craniotomy in herpes simplex encephalitis]. Two patients with herpes simplex encephalitis (HSE) underwent decompressive craniotomy with brain biopsy. The indication for the procedure was in both cases computertomographic finding of a large, space-occupying process situated in the temple lobe with clinical picture involving febrile state, progressive hemiparesis, and subconsciousness. The patients were treated with standard doses of Ara A and methylprednisolone immediately after operation. In both cases, the improvement was very impressive. The massive neurological deficits -- in one case even including subtotal aphasia -- disappeared almost completely in the weeks following operation. 6 months later both patients underwent cranioplasty. These observations show that decompressive craniotomy with dilatation of the dura represents a decisive therapeutic approach in the case of HSE when the pressure of the brain cannot be brought under control by medical treatment. Computertomography proved to be of particular diagnostic value and assists in taking decisions for meaningful surgical treatment.


[Severe colitis with eosinophilia].

[Severe colitis with eosinophilia]. A 23-year-old woman from the French Antilles was successfully treated for intestinal and hepatic schistosomiasis, as evidenced by the normalization of immunofluorescence titers and many negative histogogical controls. She presented, however, persistent colitis with marked eosinophilia (eosinophils in excess of 50,000/mm3). No precise diagnosis could be established in spite of all parasitological, allergological, hematological and gastroenterological investigations. The colon was the only organ involved and showed colitis of a type unclassifiable both endoscopically and histologically. Massive infiltration by eosinophils was present. Temporary relief was achieved with steroids but the clinical condition of the patient became dramatic. Three years after the onset of the illness total colectomy was performed, sparing the rectum. After surgery all manifestations of disease disappeared and for ten months the number of eosinophils was normal. Ileorectal continuity could be re-established. Ten months after reanastomosis there was recurrence of bleeding from the rectum and eosiophils once again reached levels of 2340/mm3. The differential diagnosis of this colitis associated with eosinophilia is discussed. To our knowledge it does not correspond to any clinical entity described so far.


Antibody-selective membrane electrodes.

Antibody-selective membrane electrodes. Direct antibody-sensing membrane electrodes have been developed by immobilizing ion-carrier immunogen conjugates in a liquid membrane matrix. The resulting potentiometric probes measure specific antibodies with high selectivity over nonspecific antibodies in the physiological pH range. The electrode response is shown to arise from the selective interaction of the antibody with the membrane-bound immunogen.


A synthetic pentapeptide with biological activity characteristic of the thymic hormone thymopoietin. The pentapeptide arginyl-lysyl-aspartyl-valyl-tyrosine, corresponding to amino acid residues 32--36 in thymopoietin, was synthesized. In vitro, this pentapeptide induced the differentiation of murine prothymocytes to thymocytes and inhibited differentiative induction of cells of the B lineage. This combination of actions is presently unique to the parent molecule thymopoietin. In vivo, the pentapeptide reduced the high numbers of autologous rosette-forming cells normally present in the spleens of athymic mice; this also is a property of thymopoietin. These results suggest that this readily synthesized pentapeptide corresponds to an active site of thymopoietin and might serve as a therapeutic substitute for thymopoietin.


Evidence for extra-renal 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in pregnancy. The kidneys are thought to be the only organs capable of 1 alpha-hydroxylation of vitamin D and its metabolites. We have examined the in vivo conversion of 3H-(25,26)-25-hydroxyvitamin D3(25OHD3) to 3H-(25,26)-1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in vitamin D-deficient, pregnant and nonpregnant rats. As expected, nephrectomy of nonpregnant, vitamin D-deficient rats prevented the conversion of 25OHD3 to 1 alpha,25(OH)2D3. In contrast, nephrectomy of pregnant, vitamin D-deficient rats reduced but did not abolish the formation of 1 alpha,25(OH)2D3 from its precursor. The identity of the radioactive metabolite formed from 3H-25OHD3 which circulated in nephrectomized, pregnant rats was established as 1 alpha,25(OH)2D3 by comigration with synthetic 1 alpha,25(OH)2D3 on high-pressure liquid chromatography. The simultaneous absence of 1 alpha,25(OH)2D3 in the fetal kidneys indicated that the site of 1 alpha-hydroxylation after nephrectomy of the pregnant rat was probably extra-renal in origin. Two sites of 1 alpha-hydroxylation of 25OHD3, one renal and the other extra-renal, either fetoplacental or maternal, may exist in the pregnant, vitamin D-deficient rat.


Role of nuclear size in cell growth initiation. Swiss 3T3 cells arrested in B0 (quiescent state) by reducing serum content of the medium all contain the same amount of DNA but vary in nuclear volume over approximately a twofold range. By use of flow microfluorimetry, scatterplots of nuclear volume versus DNA content were obtained in intervals after serum stimulation. The earliest cells to enter DNA synthesis were those with the largest nuclei, whereas cells with the smallest nuclei were among the latest. Regulation of cellular transit from G0 to the S phase was therefore, at least in part, deterministic, since all G0 cells did not have equal probabilities of entry into S at a given moment. All cells having the same nuclear volume did not initiate DNA synthesis at the same moment; therefore, factors other than nuclear volume must also influence this timing. Nuclear volume correlated with the maximum rate at which cells could enter S. The kinetic model of the cell cycle postulating a probabilistic event as solely responsible for entry into S thus appears too simple.


Linkage of loci controlling alloantigens on red blood cells and lymphocytes in the horse. A system of equine lymphocyte alloantigens designated ELA, is identified, and it is shown that the locus or loci controlling these markers must be closely linked to the locus controlling markers in the A system of horse blood groups. Among 29 offspring in two stallion families there was evidence for one recombinant. Lod scores for linkage between the A and ELA loci in the two families were 3.61 and 3.33, respectively, for theta equal to 0.


Rhythms in human performance: 1 1/2-hour oscillations in cognitive style. Performance on verbal and spatial matching tasks was assessed every 15 minutes for 8 hours. Significant 60- to 100-minute oscillations were observed for each task. These oscillations were 180 degrees out of phase, supporting the hypothesis that in humans the basic rest activity cycle involves alternating activation of processing systems residing in the two cerebral hemispheres.


Development of the capacity for tactile information transfer between hemispheres in normal children. The hypothesis of less direct interaction between hemispheres in young children was supported by a behavioral test. Fabric samples were compared with either the same hand (same hemisphere) or with opposite hands (between hemispheres). Crossed errors were a significantly larger proportion of total errors in 3-year-olds than in 5-year-olds.


Perception of echo phase information in bat sonar. Echolocating bats (Eptesicus fuscus) can detect changes as small as 500 nanoseconds in the arrival time of sonar echoes when these changes appear as jitter or alternations in arrival time from one echo to the next. The psychophysical function relating the bat's performance to the magnitude of the jitter corresponds to the half-wave rectified cross-correlation function between the emitted sonar signals and the echoes. The bat perceives the phase or period structure of the sounds, which cover the 25- to 100-kilohertz frequency range, as these are represented in the auditory system after peripheral transformation. The acoustic image of a sonar target is apparently derived from time-domain or periodicity information processing by the nervous system.


On the specificity of kainic acid.

On the specificity of kainic acid. The specificity of the neurotoxic agent, kainic acid, for destroying cell bodies while sparing terminals and fibers of passage was examined by infusing this agent into the axons of the dorsal noradrenergic bundle and measuring the degree of depletion of noradrenaline concentrations and the reduction in noradrenaline uptake in cortex and hippocampus. Extensive neuronal loss and gliosis were observed around the injection site. In addition, a significant and consistent 25 percent depletion of hippocampal-cortical noradrenaline was also obtained. The results suggest that although kainic acid has its greatest destructive action on neuronal perikarya, a significant amount of damage to axons of passage may also occur.