Umbilical polyp: a report of two cases.

Two cases with umbilical polyp are reported. This rare malformation arises from remnants of the omphalomesenteric duct and may be clinically mistaken for a granuloma pyogenicum or other benign or malignant umbilical neoplasms. Histologically umbilical polyp shows branching glandular structures lined by intestinal mucosa in connection with the surface of the skin. When the umbilical polyp is not associated with any other types of underlying abnormalities, it may be treated by a simple surgical excision.


Miconazole nitrate in the treatment of dermatomycoses.

Miconazole nitrate was used topically in 83 dermatophytic and candidal infections. Complete cure was obtained in 81% of the cases. The in vitro studies made before, during and after treatment showed no evidence of resistance to the drug. The miconazole 2% cream and powder preparations were well tolerated. Only one case of sensitization was observed.


Influence of local triamcinolone acetonide on patch test reactions to nickel sulfate.

The influence of local application of triamcinolone acetonide on patch test reactions was investigated in patients with a contact allergy to nickel sulfate. In 15 patients the reaction to patch tests with a mixture of 5% nickel sulfate and 0.1% triamcinolone acetonide in petrolatum was compared with the reaction to 5% nickel sulfate in petrolatum. In eight patients the test area on the skin was infiltrated with triamcinolone acetonide or saline solution after which test were performed with nickel sulfate. In eight patients the test area was pretreated with 0.1% triamcinolone acetonide cream or the cream base alone before the patch tests with nickel sulfate were done. In general, all three methods gave partial suppression of the size of the reaction.


Pretibial epidermolysis bullosa: report of two families and review of the literature.

Two pretibial epidermolysis bullosa families, with a total of four cases directly examined and another eight cases known from references, were studied. Both families showed an autosomal dominant inheritance. In one family there was a case of "bullous epidermolysis albo-papular of Pasini". All cases were compared with those of the literature.


Inflammatory linear verrucose epidermal nevus.

A typical case of inflammatory linear verrucose epidermal nevus (ILVEN), with quite a psoriasiform histologic pattern, is reported. Intralesionally administered paramethasone acetate caused a temporary suppression of the clinical and histopathologic inflammatory features. The concept of ILVEN is briefly discussed.


Nature of the sweat glands in the hairy skin of the beagle.

The local pharmacology, the thermal response and the response to hypothalamic stimulation of sweat glands of the hairy surface of the beagle are described. The results, together with those of electron-microscopic examinations, support the idea that these sweat glands are apocrine and are not directly innervated. No clear relationship with thermoregulation could be found and a pheromonal function is tentatively suggested.


Elimination of circulating antibodies. Attempts to eliminate antibodies circulating in rabbits using a fraction of normal human epidermis.

Rabbits were immunised with a fraction of normal human epidermis to produce circulating antibodies. In each experiment, half of the immunised rabbits were given a dose of the same antigen intravenously and the changes in the titres of antibodies were recorded. Doses of the antigen used in different experiments varied from 0.09 to 3.5 mg protein per rabor the first 24 h, followed by a secondary rise. Administration of corticosteroids together with the antigen intravenously could check this secondary rise in antibody titre. Repeated intravenous injections of the antigen led to severe anaphylactic reactions, while subcutaneously administered antigen produced no significant effects.


Tritiated thymidine uptake in pig skin. Comparison of in vivo and in vitro techniques.

Tritiated thymidine (3HT) was used in one of three ways to label deoxyribonucleic acid replication in epidermal cells of miniature swine: (1) the radioactive material was injected intracutaneously in vivo; (2) the radioactive material was injected intracutaneously into biopsy specimens and the specimens incubated in vitro in Eagle's medium, or (3) uninjected biopsy specimens were incubated in Eagle's medium with added 3HT. The first two methods yielded the same proportions of labeled cells with uniform distribution of labeled cells. The third method resulted in labeling of cells mainly at the periphery of the biopsy specimens. The advantages of the in vitro over the in vivo technique of injection of 3HT includes the fact that injecting a biopsy specimen avoids the problems of large amounts of radioactive waste disposal in animal studies or the legal and ethical problems of tracer studies in humans.


Serum lipids in patients with psoriasis.

In 13 patients with psoriasis a lower total cholesterol (TC) concentration was found compared to healthy controls of the same population. No differences in the concentration of serum triglyceride (TG) or phospholipids (PL) were detected between these two groups. In the same patients, serum triglyceride fatty acid analyses showed a reduced concentration of linoleic acid and a raised level of palmitoleic and myristic acids. No differences were detected in the major phospholipid fractions. The increase in plasma free fatty acids (FFA) following intravenous heparin was comparable in the psoriatic patient and in the controls. It is concluded that no basic abnormality of serum lipids exists and that the changes described were due to a selective loss via the scales or due to malabsorption.


Genetics and dermatology.

An attempt has been made to show and discuss today's problems of genodermatology, mentioning the important groups of the heterogenous diseases and enzyme defects which are coupled with the skin diseases. Moreover, the chromosomes breakage syndromes are reviewed. To a great extent, these problems are of theoretical interest, but the genetic counselling is on the increase and already plays an important part in the daily routine of the large hospitals.


Behçet's disease: etiology and treatment.

The etiology and treatment of Behçet's diseases are still undecided. There are three principal etiological hypotheses: viral, autoimmune and defective fibrinolytic activity. Accordingly, antiviral, immunosuppressive and fibrinolytic enhancing agents have been tried. Corticosteroids, however, still consitute conventional therapy. Follow-up of cases has so far revealed that none of the above therapeutic measures fundamentally alters the course of the disease, and serious complications may occur and progress during their administration.


'Isopathic phenomenon' in leprosy.

Isopathic phenomenon of SAGHER was elicited in 21 proved leprosy patients (consisting of 7 lepromatous, 7 tuberculoid, 3 neuritic, 2 borderline, and 2 indeterminate types). The substances used to elicit the isopathic phenomenon were BCG lepromin, Indian ink and staphylococcal vaccine. Isopathic phenomenon was elicited in most of the cases and BCG was the substance which produced the most responses. The phenomenon could be used to classify difficult cases of leprosy.


[Focal dermal hypoplasia with keratoconus, papillomatosis of esophagus and hidrocystomas (author's transl)].

Focal dermal hypoplasia (Goltz's syndrome, Goltz-Gorlin syndrome), an uncommon malady belonging to the group of congenital poikloderma, is characterized by its broad spectrum of meso-ectodermal defects involving the skin as well as the eyes, skeletal system and teeth. The case represented her is identical with the one published by Naegeli 1926, and contains some additional findings that have not yet been reported, namely: multiple hidrocystomas, bilateral keratoconus, papillomatosis of esophagus, hiatus hernia.


[Epidemiology of contact dermatitis in Geneva (1,000 cases) (author's transl)].

Results concerning 1,000 cases of contact dermatitis with positive patch-tests are published and commented. The allergens which are responsible for about 50% of our cases are: turpentine, nickel, hexavalent chromium and mercuri-organic compounds. These results are compared with those of other countries. As in the industrial world there should be information given to the general public to decrease the cases of contact dermatitis.


[Value of screening for gonorrhea at a family planning consultation (author's transl)].

We report the result of an investigation carried out in the Gynecology Policlinic of Geneva. Systematic screening of 217 patients led to the detection of 2 cases of gonorrhea. Although of interest, it is not justifiable economically to screen for gonorrhea a group of patients in whom the chances of infection are small. However, the study of a larger population might lead to a revision of this conclusion.


Effect of glucose on the growth hormone response to L-dopa in normal and diabetic subjects.

The effect of hyperglycemia on the growth hormone response to oral L-dopa (500 mg.) was assessed in eight normal and eight insulin-dependent diabetic subjects. A peak growth hormone response of 21.0 +/- 4.0 ng./ml. (mean +/- S.E.M.), significantly above baseline (p less than 0.01), was achieved in the normal group following oral L-dopa. Glucose concentrations did not change and were approximately 80 mg./100 ml. throughout. Administration of 100 gm. oral glucose with the L-dopa, or thirty minutes thereafter, totally suppressed the growth hormone response in all eight and six of the subjects, respectively. A peak growth hormone response of 20.0 "/- 1.7 ng./ml. (mean +/- S.E.M.), significantly above baseline (p less than 0.001), was obtained in eight nonobese, insulin-dependent diabetics, in spite of prevailing hyperglycemia (mean plasma glucose 243-258 mg./100 ml.) throughout the test. Endogenous hyperglycemia was achieved in these patients by lessening the usual strict adherence to plasma glucose control for the purpose of the study. These results suggest an abnormality in the hypothalamus or pituitary of diabetic subjects allowing growth hormone responsiveness in spite of hyperglycemia.


Plasma immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) after evisceration with and without a functional liver.

Fed male Wistar rats were eviscerated by two procedures. The first group of eviscerated rats were left with a nonfunctional liver in situ while the second group were eviscerated by a newer technic, developed in this laboratory, that preserves liver function. The animals were maintained on a regimen of saline and antibiotic treatment, and abdominal aortic blood was drawn at intervals up to seventy-two hours postoperatively from animals with a functional liver and up to six hours postoperatively in those with nonfunctional liver status. Blood concentrations of glucose, immunoreactive insulin, and immunoreactive glucagon were measured. Our results indicate that even with a functional liver, totally pancreatectomized eviscerated rats maintained normal amounts of plasma IRI and IRG for more than twenty-four hours. IRI and IRG were measurable even at forty-eight hours postoperatively. At the same time, these animals developed abnormally high blood glucose levels, which were sustained despite the presence of "normal" IRI in plasma. It had been suggested that the presence of measurable IRI and IRG in the classically prepared eviscerated animal was due to a deficit liver destruction of these substances. To the contrary, our data suggest that even with a functional liver, the eviscerated preparation maintains a circulating level of insulin and glucagon-like materials forty-eight hours after the known sources of such substances are removed. The physiologic meaning of immunoassay results following pancreatectomy are thus difficult to interpret.


Substantial differences in the diagnostic criteria used by diabetes experts.

A survey of twenty diabetologists revealed that they employ diagnostic criteria differing quite substantially. In some populations, including the general population of the United States, these disparities would result in very major differences in the rates of "diabetes." Under certain common circumstances, some diabetologists would classify as normal more than half of the one- and two-hour values considered to be abnormal by other well-qualified diabetologists.


Plasma lipid levels in diabetic children. Effect of diet restricted in cholesterol and saturated fats.

Plasma lipids, blood glucose, and urinary glucose excretion were measured in 270 juvenile diabetic children upon admission to and throughout periods of summer camping during which the effect of a usual and a modified diabetic diet was assessed. The usual diabetic diet contained 700-1,500 mg. cholesterol daily with a polyunsaturated/saturated (P/S) ratio of 0.1, while the modified diet limited cholesterol to 300 mg. daily with a P/S ratio of 1.0. Both diets maintained calories with 40 per cent as fat, 40 per cent as carbohydrate, and 20 per cent as protein. Analysis of fasting blood glucose, qualitative and quantitative glucose excretion, and body weight indicated that groups were comparable except for the diet used. Elevated mean levels of cholesterol and triglycerides were approximately equally distributed in diabetic children of both sexes upon admission to camp, with 24 per cent demonstrating hyperlipoproteinemia. Eleven per cent had type II, 10 per cent type IV, and 3 per cent type V hyperlipoproteinemia upon admission. After following the usual diet, 21 per cent were type II, 1 per cent type IV, and none type V, with no reduction in the over-all incidence of hyperlipoproteinemia despite lower triglyceride and glucose levels. After consumption of the modified diet, hyperlipoproteinemia was reduced to 5 per cent, with 4 per cent type II and 1 per cent type IV. Results of this study indicated that plasma lipids in juvenile diabetics were elevated when first observed and that the control of blood sugar levels along with a diabetic diet with lower cholesterol and increased polyunsaturated fat significantly reduced the incidence of hyperlipoproteinemia more effectively than control of blood sugar levels alone.


Decrease in myelin content of rabbit sciatic nerve with aging and diabetes.

Previous studies of the amount of peripheral nerve myelin have been based on histologic examination. In this study, myelin content was measured directly after quantitative isolation from sciatic nerve. There was a decrease in the amount of myelin beginning at nine months, the time of maximal myelin content in normal rabbits, and beginning at six months, the amount was decreased in diabetic as compared with control animals. Composition of myelin isolated from young (age three to four months) and old (age nine to thirteen months) rabbit sciatic nerves was also determined and is similar to that of other species. Although the composition was not affected by diabetes, with aging there was a significant decrease in the amount of cholesterol and an increase in glycolipid.


Inhibition of labile aggregation-stimulating substance (LASS) and platelet aggregation in diabetes mellitus.

Irreversible second-phase aggregation of platelets in diabetic patients is prevented in vitro by 5, 8, 11, 14-eicosatetraynoic acid (TYA), a competitive inhibitor of the labile aggregation-stimulating substance (LASS) which is formed from arachidonic acid. Thus, inhibition of prostaglandin synthesis inhibits platelet aggregation in diabetic subjects. These findings indicate that platelets from diabetics are subject to control by intracellular mechanisms operative in the regulation of platelet function in normal individuals.


Red cell 2, 3-diphosphoglycerate levels among diabetic patents with and without vascular complications.

There have been differences of opinion among authors concening in the levels of red cell 2,3-diphosphoglycerate (2,3-DPG) and nucleotides in nonacidotic diabetic patients. Our data suggest that abnormal levels of 2, 3-DPG in diabetic patients are related to the presence of vascular complications and not to the duration of the disease per sec. 2,3-DPG levels are normal in diabetic patients with no evidence of vascular complications (group A). In ambulatory patients with vascular complications (group B), significantly higher levels of 2,3-DPG are found than in normal subjects and patients in group A. In hospitalized diabetic patients with active peripheral vascular complications (group C), levels of 2,3-DPG are likewise significantly increased over those of normal subjects and patients of group A. 2,3-DPG was found to be significantly elevated in patients of group C as compared with group B. 2,3-DPG levels in venous blood from infected legs as compared with those of the peripheral venous blood were not significantly different, thereby ruling out local factors. There were no differences in the blood lactate levels in any of the group studied. The elevation of the 2,3-DPG levels may be a reflection of attempted red blood cell compensation for tissue hypoxia in the diabetic with vascular disease.


Renal substrate exchange in human diabetes mellitus.

Renal substrate exchange was examined in five male patients with insulin-dependent diabetes mellitus of several years' duration. Insulin was withheld for twenty-four hours prior to the study. A renal vein was catheterized from the femoral vein, and PHA-clearance was employed for the determination of effective renal blood flow. None of the patients was in ketoacidosis, but all were moderately hyperglycemic in the fasting states (16.8 +/- 1.5 mmol/L.) (225-384 mg./100 ml.). Nevertheless, no net release of glucose from the kidney was detectable. Instead, there was a significant net renal uptake of glucose (320 +/- 80 mumol/min.). In addition, there was a significant net uptake of glycerol and a net release of pyruvate. Renal amino acid exchange was similar to that reported for healthy subjects: glutamine, glycine, proline, and citrulline were taken up and serine, alanine, cystine, tyrosine, and threonine were released by the kidney. It is concluded that (a) in nonketoacidotic diabetics there is no net production of glucose by the kidney; (b) renal amino acid exchange in diabetics is similar to that of healthy individuals; and (c) the kidney is not an important gluconeogenic organ in human diabetes.


Arginine-stimulated acute phase of insulin and glucagon secretion. I. in normal man.

To document and characterize the immediate phase of glucogen secretion as detected in peripheral blood in man, we have given pulses of L-arginine (0.1 gm. to 10.0 gm.) intravenously over twenty to thirty seconds to twenty-three healthy young men. Peak glucagon and insulin levels averaging four and five times basal levels respectively were reached two to five minutes after arginine administration and had returned to baseline levels by fifteen to thirty minutes. Computing the area above basal for the initial ten minutes after arginine stimulation established a dose-response relationship for the acute phases of glucagon and insulin secretion. A maximal glucagon response was elicited by doses of arginine of 5.0 gm. or greater, whereas for insulin, the plateau was reached at 2.5 gm. of arginine. Sequential 5.0-gm. pulses of arginine administered every thirty minutes showed that there was no augmentation or attenuation of the timing, magnitude (area 0-10 minutes) or absolute peak values reached for either the glucogon or insulin responses. The effect of induced hyperglycemia on the acute phase of insulin and glucagon secretion was assessed by administering the arginine during marked elevation of ambient glucose concentration achieved by the intravenous administration of glucose. This resulted in marked suppression of the acute glucagon response and dramatic accentuation of the insulin response.


Lactic acidosis associated with phenformin therapy. Evidence that inhibited lactate oxidation is the causative factor.

Using uniformly labeled 14C L-lactate, we have studied the turnover and oxidation of lactic acid in a patient who presented with a mild lactic acidosis while on phenformin medication. As with other cases of lactic acidosis associated with phenformin therapy, this subject had impaired renal function as evidenced by serum creatinine levels of 2 mg./100 ml. and BUNs of 40 mg./100 ml. Comparison of the rate of lactate oxidation relative to the rate of lactate turnover in this subject while on and off phenformin therapy suggests that a prime factor leading to the elevated lactate levels in this situation in impaired peripheral aerobic metabolism. Although lactate oxidation was increased in the presence of phenformin, the control studies clearly demonstrate that aerobic metabolism was not keeping pace with the increased level of anaerobic carbohydrate metabolism brought on by the drug. It is concluded that it is this imbalance in lactate metabolism that is responsible for the lactic acidosis that accompanies phenformin therapy.


Serum proinsulin in children and adolescents with chemical diabetes.

Proinsulin levels (PLC) in serum were determined after gel filtration on specimens obtained during oral glucose tolerance testing (OGTT) in seven patients with repeated abnormality in OGTT and in a group of seven control subjects matched for age. Fasting and thirty-, sixty-, and 120-minute postglucose venous samples were analyzed for glucose (PG) and immunocreactive insulin (IRI) as well as PLC, PG and IRI mean concentrations were greater at all testing times in the patient population, but the mean IRI/PG was significantly higher in the patients only at fasting. PLC mean levels were higher in the patients but not to a level of significance. Percentage of total IRI atributable to PLC at each time point was identical between the two groups. The apparcent diminished effectiveness of circulating insulin in chemical diabetes cannot be attributed to an abnormal proportion of proinsulin.


Effect of physical exercise on secretion of growth hormone, glucagon, and cortisol in obese and diabetic children.

The effect of muscular exertion of moderate intensity on blood sugar (BS), plasma levels of growth hormone (GH), glucagon, and cortisol (F) has been studied in endocrinologically normal children with short stature and compared with children with clinical diabetes mellitus and obese children with normal and diminished carbohydrate tolerance. In diabetic children, physical exertion induces a rise in plasma GH levels comparable to that in controls; in obese children with normal or with diminished glucose tolerance, the rise is considerably smaller. Physical exertion caused no change in F levels in the groups tested, although basal level in the obese children was significantly higher than in the controls. Basal glucagon levels were similar in all groups and showed no change on physical exertion. The behavior of GH and glucagon in diabetic children was comparable to that in the controls even where blood sugar level was high.


Glucagon response to arginine after treatment of diabetes mellitus.

To investigate the aminogenic glucagon response in diabetes mellitus, arginine infusion tests were carried out on twenty-four diabetic patients before and after treatment. Eleven healthy men served as a control group. Plasma glucagon was measured by radioimmunoassay using an antiserum, G21, specific for pancreatic glucagon. Out of twenty-four patients, five were treated with diet alone, eight with sulfonylurea, and eleven with insulin. In all these diabetic groups, the glucose tolerance improved after treatment for diabetes mellitus, while the insulin response to the glucose did not show any remarkable change. The fasting levels of the plasma glucagon did not differ from that of the normal subjects both before and after treatment. Hyperresponsiveness of the plasma glucagon to arginine infusion was observed in all diabetic groups, in comparison with that of the normal controls. The exaggerated response of the plasma glucagon to arginine was lowered following appropriate treatment in each diabetic group. However, as far as the changes in glucagon area during the arginine test are concerned, the aminogenic hyperresponsiveness of the plasma glucagon was reduced prominently in the diabetic group treated with sulfonylurea. The relationship between the response of glucose and plasma insulin and between glucose and glucagon to arginine was investigated, and the importance of the changes in the insulin:glucagon ratio was emphasized. Moreover, the possibility that long-term administration of a sulfonylurea may reduce an exaggerated glucagon response to arginine was discussed.


Age-adjusted analysis of insulin responses during normal and abnormal glucose tolerance tests in children and adolescents.

This report analyzes age-specific glucose (PG) and immunoassayable insulin (IRI) responses during oral glucose tolerance testing (OGTT) and examines test results in children and adolescents with OGTT abnormality using the age-appropriate control data. Controls' (n = 93) and patients' (n = 63) results were compared on the basis of statural age (SA) at the time of testing. Control tests (n = 101) showed significant positive correlation of fasting and four-hour postingestion PG with SA (p less than 0.001), but mean area under the PG curves did not vary between the SA groups (I--18.69 months, II--70-131 months, III--132+ months). The absence of differences of other sampling times permits uniform diagnostic criteria for this age group. IRI was positively correlated with SA at all testing times, and mean levels differed significantly between each SA group at every sampling time; the mean areas under the IRI curve also differed significantly between SA groups as did the mean ratios of IRI area to PG area (group I--0.2639 +/- 0.0175 S.E.M., group II--0.3864 +/- 0.0235, group III--0.6262 +/-0.0491). Patient tests (n = 110) were separated into normal (N), borderline (B), and chemical-diabetic (C) for each SA group. IRI means were above control data for each test type in each SA group at all sampling times; one fourth of these differences were significant. IRI responses also increased within each SA group from N to B to C tests. Mean IRI areas and IRI area to PG are mean ratios were higher than in controls, and this difference was greatest with the  most abnormal (C) test type in each SA group. A subgroup of three patients who had low IRI responses from the outset and developed overt diabetes in one to three years was excluded from the analysis. In contrast to apparent relative insulin inefficiency with normal maturation and with chemical diabetes, they had exceptional responsiveness to their low IRI levels. Variable involvement of alpha as well as beta cells in the pathophysiology of diabetes is suggested as one explanation for these paradoxic observations. Changing receptor affinity might also be implicated.


Plasma renin activity in juvenile diabetes mellitus and effect of diazoxide.

Low plasma renin activity (PRA) has been reported in patients with long-term diabetes mellitus complicated by hypertension and nephropathy. We have assayed PRA in twelve normal subjects and in eight age- and sex-matched juvenile diabetics of greater than twelve years' duration without hypertension and nephropathy under control conditions and following stimulation with diazoxide. During control conditions PRA did not decrease with time in the diabetics as it did in the normals. Following diazoxide infusion, PRA increased in both groups, and although the levels were often higher in diabetics than in normals, the mean differences were not statistically significant. The findings are consistent with the suggestion that PRA is normal or possibly elevated in clinically uncomplicated insulin-dependent diabetes mellitus and decreases with establishment of hypertension and nephropathy.


Immunoreactive glucagon responses to intravenous tolbutamide in chronic pancreatitis.

The effects of tolbutamide infusion (1 gm. over forty minutes) on plasma pancreatic glucagon-like immunoreactivity (PGLI), serum insulin, and blood glucose were studied in six patients with chronic pancreatitis and six matched controls.asal PGLI levels were significantly higher in the patients, despite higher fasting glucose concentrations. Tolbutamide infusion had no significant effect on mean PGLI levels in controls but was associated with significant elevation in pancreatitis patients, despite higher circulating glucose levels in the latter. The data suggest that chronic calcific pancreatitis patients hypersecrete immunoreactive glucagon, possibly from a nonpancreatic source and that this immunocreactive material may be stimulated by sulfonylureas.


Factitial panniculitis and necrotizing fasciitis in juvenile diabetes.

A fifteen-year-old diabetic girl developed multiple inflammatory areas on the extremities and abdominal wall at the site of insulin injection. The bizarre clinical manifestations led to great difficulties in determining both its etiology and its treatment. However, three months after her initial hospitalization, we found that the lesions were probably secondary to self-injection with a chemical agent rather than a result of insulin allergy. If idiopathic recurrent dermal infection is observed, then factitial origin should be suspected.


Marked hyperthermia as a manifestation of hypoglycemia in long-standing diabetes mellitus.

Hyperthermia has recently been recognized as a manifestation of hypoglycemia. We describe two episodes of hypoglycemia associated with nausea, vomiting, chills, and impaired consciousness which were followed by marked hyperthermia. We suggest that the hyperthermia may result from excessive reaction to preceding hypothermia caused by the hypoglycemia. We would like to alert the clinician to the possibility of a previous, severe hypoglycemic episode in any diabetic patient with hyperthermia and coma.


Diphenylhydantoin-induced gingival hyperplasia: its response to changes in drug dosage.

Changes in gingival hyperplasia were studied in 48 patients treated for epilepsy with diphenylhydantoin (DPH) over a two-year period. During this time changes in the dose of DPH were made in some patients in order to increase control of seizures or decrease side-effects: in 27 patients the dose was increased, in nine it was decreased and in 12 the dose remained unchanged. It was found that the severity of gingival hyperplasia varied directly with both the dose and serum level of the drug.


Mechanical efficiency in bicycle ergometer work of young adults with cerebral palsy.

This study used a method specifically adapted to motor handicap, one which measured pedaling rate and basal oxygen consumption. Its aim was to investigate whether bicycle ergometer work could distinguish any difference in mechanical efficiency between two groups with cerebral palsy. 10 patients aged between 18 and 30 years (six dyskinetic/ataxic, four spastic) were studieed. Six non-handicapped young adults formed a control gorup. The results showed a highly significant difference between the dyskinetic/ataxic group and the spastic group. Results for the dyskinetic/ataxic group and the control group did not differ significantly from those obtained for normal population. The observed difference between the two groups with cerebral palsy seems to be the result of the greater amount of energy required to be expended by the spastic group in order to overcome the constant increase in muscle tone during the bicycle egometer test.


Electromyographic studies on flexor hypertonia of the extremities of newborn infants.

In order to investigate flexor hypertonia of the extremities in newborns, a neurological examination and superficial electromyogram (EMG) recordings were carried out on 50 full-term infants both before and after the first 48 hours of life (the 'birth-shock period). EMG amplituds on the flexor side of the upper arm in the traction response were low during the first 48 hours despite flexion of the elbow (hypertonia); after the first 48 hours EMG amplitudes increased in a large percentage of the infants although elbow flexion decreased (hypotonia). This finding suggests that the frflex response to passive movement (traction) is weaker during the first two days of life than after this time. Flexor tone of the upper arm in recoil of the forearm increased during the first 48 hours in spite of low EMG amplitudes; after the first 48 hours the amplitudes increased although flexor tone of the upper arm decreased. The popliteal angle was more than 90 degrees in 27 infants and less than 90 degrees in 23 infants during the first 48 hours; after this period the angle was more than 90 degrees in 11 infants and less than 90 degrees in 39 infants. EMG amplitudes on the flexor side of the thigh in most cases increased after the first 48 hours for both groups of infants, i.e. those with an angle more than 90 degrees and those with an angle less than 90 degrees. It is suggested that flexor hypertonia of the extremities in newborn infants is not a result of muscle contraction (i.e. real muscle strength) but rather is residual from the infant's position in utero.


The setting-sun eye phenomenon in infancy.

In a longitudinal study, 19 infants who displayed the setting-sun eye phenomenon were observed during the first year of life. Nine of the infants showed no signs of illness, eight had an evident increase in intracranial pressure requiring surgical relief, and two had transient signs of increased intracranial pressure which resolved spontaneously. The setting-sun phenomenon could be elicited both by alteration of the infant's position and by removal of light, and it also occurred spontaneously. The effectiveness of the eliciting mechanism depended on the age of the infant. The component parts of the phenomenon consist of downward rotation of the eyeballs and retraction of the upper eyelids, sometimes accompanied by raising of the brow. The phenomenon can be observed in healthy infants, and its value in early recongnition of increased intracranial pressure is limited. The response might indicate increased intracranial pressure if it can be elicited by alteration of position in infants older than four weeks of age or if there is a marked response to removal of light in infants younger than eight weeks or older than 20 weeks of age, especially if the response is combined with constant or intermittent strabismus or undulating eye-movements.


Early hospital admissions and later disturbances of behaviour and learning.

This study provides strong and unexpected evidence that one admission to hospital of more than a week's duration or repeated admissions before the age of five years (in particular between six months and four years) are associated with an increased risk of behaviour disturbance and poor reading in adolescence. The children who have experienced these early admissions are more troublesome out of class, more likely to be delinquent and more likely to show unstable job-patterns than those who are not admitted in the first five years. They include a high proportion of poor readers, though this is partly explained by poor application to work in the classroom. In contrast, nervous, shy or withdrawn behaviour is not more frequently reported in adolescence among children who have had early hospital-admissions. The association of troublesome and socially difficult behaviour with early admissions is explained neither by the initial selection of children for hospital nor by the physical disabilities they sometimes carry in later life. The interpretation of this association is complicated by the fact that some pre-school children appear to benefit from hospital stay. The children most vulnerable to early admission are those who are highly dependent on their mothers or who are under stress at home at the time of admission. There is evidence that early admissions to hospital are more frequent today than 25 years ago and that re-admissions are more frequent. Although the length of stay has been greatly reduced, the proportion of children who experience 'long or repeated' admissions is no less than in 1946 and may be greater.


Optimal developmental appraisal.

The six components considered to be essential for obtaining an optimal developmental profile of a child are described. It is emphasised that, in order to plan appropriate services for children, the consideration of these components should be made routine in developmental assessment.


Name-printing as a test of developmental maturity.

An attempt to derive a practical scoring technique for name-printing by children in kinderten (age-range 5 1/2 to 6 1/2 years) as a quick test of skills and maturity is reported. The relationship of the Print-Your-Name test scores to other established tools of developmental assessment is examined. Teachers' assessments of the study children's readiness for academic promotion and of those children with school problems tended to correlate with the test scores.


Neonatal disseminated herpes simplex virus infection with encephalitis treated with cytosine arabinoside.

Herpes simplex encephalitis was diagnosed by immunofluorescence and histology of a brain biopsy on the 19th day of life in a neonate in whom symptoms had begun at 12 days. Treatment with steroid, diuretic and cytosine arabinoside was begun and initially there was dramatic improvement in the symptoms. This improvement was not sustained, however, and the infant developed evidence of severe brain-damage. Disseminated herpes simplex virus infection is discussed and available therapy for this severe disease is outlined.


Unilateral arhinencephaly in goldenhar-gorlin syndrome.

The post-mortem examination of the brain of a 2 1/2-year-old girl with clinical featutes of oculo-auriculo-vertebral dysplasia and hemifacial microsomia (Goldenhar-Gorlin syndrom) revealed a unilateral absence of the olfactory foramina of the lamina cribrosa of the ethmoid bone and ipsilateral absence of olfactory bulb and tract. Other cerebral abnormalities were also present. In this report, unilateral arhinencephaly in this disorder has been documented for the first time and an attempt has been made to correlate various nosological, clinical and pathological aspects of the case with previously reported instances of arhinencephaly. It is concluded that unilateral arhinencephaly occurs in a variety of cranial and facial abnormalities and is not specific for any particular syndrome.


Cerebellar hypoplasia in Werdnig-Hoffmann disease.

The case of an infant with Werding-Hoffmann disease, who died at the age of 4 1/2 days, is reported. At autopsy there was severe cerebellar hypoplasia, associated with degenerative changes in the brain-stem nuclei. This case supports the concept that cerebellar hypoplasia may develop as a manifestation of the neuronal abiotrophy of Werdnig-Hoffmann disease. A similarity has been noted between the cerebellar lesion found in the child reported here and that produced by viral infection in experimental animals.


Increased sulfation of lithocholate in patients with cholesterol gallstones during chenodeoxycholate treatment.

Chenodeoxycholate was administered to 13 patients with cholesterol gallstones. During the treatment period the bile composition changed markedly. Chenodeoxycholate increased from 42.9% of the total bile salts before treatment to 79.3% after 8 weeks of treatments. Ursodeoxycholate increased from 2.3 to 12.6% and lithocholate from 1.1 to 3.3%. In contrast, cholate decreased from 40.3% of the total bile salts to 3.1% and deoxycholate decreased from 12.5 to 2.5%. Less than 5% of chenodeoxycholate, ursodeoxycholate, cholate and deoxycholate in bile were sulfate esters. In contrast, considerable amounts of lithocholate were sulfated. The sulfation of lithocholate increased from 32.8% of the total lithocholate before treatment to 73.9% after 8 weeks of treatment. Sulfated lithocholate is more rapidly eliminated in feces and urine than the nonsulfated compound. Furthermore, sulfated lithocholate is less toxic. Therefore, the increase in the sulfation of lithocholate observed in most of our patients represents a protective mechanism.


Transport studies in the small bowel obstruction of the rat.

In the mechanically obstructed small bowel of the rat the decrease of passive transport of antipyrine was found to be equal after 24 and 48 h. The active transport of glucose was found to be progressively inhibited after occlusion.


Effects of citrate and tiadenol on physicochemical equilibrium of bile in rats.

A diet containing citrates increased bile salts and phospholipids concentration in the rats' bile, while a diet containing a hypolipemic factor (tiadenol) decreased cholesterol. No potentiation was obtained when the diet contained both factors.


New method for the isolation and crystallization of human liver alkaline phosphatase.

A new and simple method for the purification of human liver alkaline phosphatase using butanol extraction, acetone and ammonium sulfate precipitations, anion exchange chromatography and gel filtration is described.


Hepatic, vascular and biliary responses to infusion of gastrointestinal hormones and bile salts.

The effects of secretin, cholecystokinin, synthetic pentagastrin, sodium dehydrocholate and sodium taurocholate on hemodynamics of the canine liver were studied in a total of 57 dogs. Bile flow was also measured. Dehydrocholate and cholecystokinin significantly decreased systemic arterial pressure while the other substances did not. Hepatic arterial vessels were dilated by pentagastrin and the bile salts; however, flow was not increased in the latter case. Intraheptic portal venous resistance was decreased by pentagastrin and increased by the bile salts. Portal flow was decreased by the bile salts and increased by pentagastrin. Apart from this, mean changes in portal venous flow and portal pressure were not statistically significant. All were potent choleretic agents except pentagastrin which produced only a relatively small transient increase in bile flow.


Effect of pentagastrin on small bowel structure and function in the rat.

Since chronic pentagastrin stimulates pancreatic and proximal duodenal growth (15), we studied jejunal structure and function following subcutaneous pentagastrin (2 mg-100 g-1 day-1). After 15 days, macroscopic enlargement was confined to the proximal duodenum with a significant increase in wet weight (from 231 +/- SEM 6 to 308 +/- 13 mg) but there was no significant difference in wet and defatted dry intestinal weights, histological measurements of villous height and mucosal thickness or in glucose absorption per unit length of distal duodenum and proximal jejunum. Since chronic pentagastrin causes parietal cell hyperplasia and hypersecretion of gastric acid, the results suggest that the adaptive changes seen in the jejunum after ileectomy are neither mediated by gastrin nor by factors present in gastric secretions.


Treatment of haemorrhoids by rubber band ligation.

Outpatient treatment of haemorrhoids by elastic band ligation without anaesthetic was performed in 75 patients. Clinical review showed that 65 returned to work within 24 h of ligation, 8 in 48 h and 2 after 48 h. No patient required hospitalisation for either rectal bleeding or pain after ligation. In the first week after treatment 36 were completely symptom-free, 26 had minimal discomfort and 13 had moderate pain with a sense of imcomplete evacuation in the rectum, and some frequency of call to stool lasting up to 7 days in 1. Follow-up at 8-26 months (mean 10 months) showed that 59 were symptom free, only occasional rectal bleeding occurred in 7 and more frequent irregular bleeding in 2. Religation of residual haemorrhoids was performed in 7 and 2 and a haemorrhoidectomy. For the majority of patients hospitalisation and loss of work were avoided.


The enteral insulin-stimulation after Whipple's operation.

The insulin response to oral and intravenous glucose was measured in ten patients after resection of antrum, duodenum, proximal jejunum, and the head of pancreas (Whipple's operation). Compared to matched normal subjects the operation reduced neither the total nor the gut hormone induced part of the insulin response to oral glucose. The results suggest, that hormones from the first part of the intestinal tract are not necessary as incretins.


An experimental postoperative metastasis system using Yoshida sarcoma inoculated subcutaneously into footpad.

When Yoshida sarcoma cells were inoculated subcutaneously into the left footpad of Donryu rats, the weight of the left lumbar lymph nodes increased proportionally to the number of the inoculated cells. Resection of primary implants the day after the inoculation of 5 x 10(6) cells failed to rescue the host rats and they died of metastases within 12 days. There was no significant difference in mean survival days between the rats (8.9 days) whose primary implants were resected on the 5th day after inoculation and the control rats (8.6 days) bearing the primary implants. Mitomycin-C, a highly effective drug against Yoshida sarcoma cells, produced many long survivors (over 30 days) in the treated rats whose primary implants were resected the day after inoculation, but failed to do so when resected 5 days after inoculation. All of them died of metastases within 20 days. Based on these results, this present system is discussed for its usefulness as a screening and evaluation model for antitumor agents.


Transplantable adenocarcinomas from color-rectal tumors induced by infusion of N-methyl-N'-nitro-N-nitrosoguanidine in ACI/N rats.

Two transplantable strains of adenocarcinoma were established from the carcinomas of the colon and rectum induced by infusion of N-methyl-N'-nitro-N-nitrosoguanidine in inbred ACI/N rats, The tumors are solid type, not converted to ascite form yet, either papillary or tubulo-papillary adenocarcinomas, and particularly grow slowly, showing 2 to 4 months of survival in animals transplanted subcutaneously. Besides histological resemblance of the tumors to human adenocarcinoma of the large intestine, marked mucin production in tumor was noted in one of these strains.


Surgical correction of reflux. An effective therapy for esophageal strictures.

An effective antireflux operation, posterior gastropexy with cardiac calibration, was performed on 24 patients with well established peptic strictures of the esophagus. Without intraoperative or postoperative dilation, the diameter of the strictures went from a mean of 6.3 mm to a postoperative mean diameter of 13.0 mm. Significant increases in sphincter pressure were recorded and endoscopic evaluation showed a return to normal. Preoperative dysphagia was relieved. It is concluded that an adequate antireflux operation will obviate the need for postoperative dilations or more formidable operations such as interposition.


Reversibility of pyloric sphincter dysfunction in gastric ulcer.

To investigate both the cause and reversibility of pyloric sphincter dysfunction in patients with gastric ulcer, pyloric sphincter pressures were measured in 10 normal subjects and 13 patients with gastric ulcer before and during gastric acidification. Fasting serum gastrin concentration was significantly higher in patients with gastric ulcer than in normal subjects. Compared to normals, patients with gastric ulcer had significantly lower pyloric pressures in response to intraduodenal amino acids and sodium oleate. However, during gastric acidification, these same patients demonstrated normal pyloric responses to these stimuli. Serum gastrin concentrations did not change during gastric acidification. These studies show that: (1) in patients with gastric ulcer the pyloric sphincter does not respond normally to intraduodenal stimulation; (2) fasting serum gastrin concentration is elevated in patients with gastric ulcer; and (3) in these patients, pyloric sphincter dysfunction can be reversed by gastric acidification. The mechanism of pyloric dysfunction in patients with gastric ulcer remains unknown.


Gastric operations and glucose homeostasis. II. glucagon and secretin.

Alimentary hyperglycemia in patients who have undergone gastric operations may be due, in part, to altered intestinal signals for glucose disposition. We measured glucose, immunoreactive insulin (IRI) pancreatic glucagon (IRG), and glucagon-like immunoreactivity (GLI) after oral glucose in patients with prior antrectomy or vagotomy and pyloroplasty and in normal individuals. All subjects had normal assimilation coefficients for intravenous glucose, which suggests that the responsiveness of the pancreatic beta-cells had not been altered by the surgical procedures. The early hyperglycemic response to oral glucose and the associated elevation of plasma GLI were much greater and the IRI levels slightly higher in both experimental groups in comparison to normal subjects. A decrease in the level of IRG, albeit not statistically significant, was noted in all groups after the ingestion of glucose. In gastrectomy patients, secretin infusion during repeated oral glucose tolerance tests partially corrected the hyperglycemia and lowered plasma GLI and IRI levels. The responses of the vagotomy and pyloroplasty patients and of the normal subjects were not altered by secretin infusion. We conclude that the intolerance or oral glucose after gastric surgery may be related to elevated GLI levels, and that the beneficial effect of secretin may be due to its ability to decrease these levels.


Effects of an orally administered prostaglandin analogue (16, 16-dimethyl prostaglandin E2) on human gastric secretion.

The secretory response to 16, 16-dimethyl prostaglandin E2 (DMPG) administered orally in 4 different dosages and to placebo was evaluated in healthy volunteers over a 2-hr period. During stimulation of gastric secretion by histamine, DMPG at the highest dosage (1.5 mug per kg) reduced volume by 47% and acid output by 79%. Pepsin concentration was not affected. At the same dose, DMPG inhibited basal secretion by 54% and 99% for volume and acid output, respectively. There were no side effects secondary to DMPG administration, which indicates that this compound may be useful in treating peptic ulcer disease.


Ileorectal anastomosis for Crohn's disease of the colon.

Sixty-six patients underwent ileorectal anastomasis for Crohn's colitis sparing the rectum between 1957 and 1972. Excellent results were achieved in 26 patients and satisfactory results in 12. Unsatisfactory progress necessitated further surgery in 21 patients. Seven patients with diversionary ileostomies and ileorectal anastomoses never had their ileostomies closed. No anastomotic leaks developed. Five patients died from causes not directly related to the ileorectal anastomosis. These results indicate that ileorectal anastomosis is a safe and useful procedure for selected patients with Crohn's colitis.


Experimental animal studies of the etiology and pathogenesis of Crohn's disease.

Nineteen New Zealand White Rabbits were inoculated intramurally into the intestine with a 100- or 0.2-mu filtrate of homogenate of fresh ileum or colon from each of 6 patients with histologically confirmed Crohn's disease and compared with 22 animals injected with homogenates of normal ileum or colon from each of 5 patients; 4 sham controls were also included. The animals receiving Crohn's homogenates put on less weight than the controls; mucosal ulceration, ileal thickening, and abscess formation were seen in 8 animals and granulomatous changes evolved in 9. No significant macroscopic abnormalities or granulomatous changes were present in any of the 22 control inoculated rabbits. Successful first passage was achieved from 6 of 11 rabbits. The results of these experiments therefore confirm and extend those of our earlier reports and demonstrate that the transmissible agent or agents responsible must approximate to the size of a virus or be capable of being deformed to pass through a 0.2-mu filter.


Experimental gastroesophageal reflux in the Australian brush-tailed possum.

It has been suggested that the lower esophageal sphincter (LES) plays an important role in preventing gastroesophageal reflux. This study was designed to determine if abolition of the LES alone is sufficient to induce gastroesophageal reflux and esophagitis. Studies were performed in the Australian brush-tailed possum (Trichosurus vulpecula) which has a lower esophagus resembling that of man. Esophageal manometry, esophagoscopy, and contrast radiography of the lower esophagus and stomach were performed before and after surgery in a group of animals undergoing cardioplasty and in a group of sham operated control animals. In the animals undergoing cardioplasty, LES pressure fell from a preoperative level of 12.6 +/- 1.3 mm Hg to 0 mm Hg. This was followed by the development of gastroesophageal reflux and esophagitis. Sham operation did not alter LES pressure or result in either gastroesophageal reflux or esophagitis. In 4 of 5 animals undergoing cardioplasty, LES activity returned after 10 weeks, and this time gastroesophageal reflux ceased and esophagitis healed. It is concluded that abolition of the LES alone can induce gastroesophageal reflux and esophagitis.


Protective effect of Pepto-Bismol liquid on the gastric mucosa of rats.

Pepto-Bismol liquid (primary active constituent, bismuth subsalicy-late) protected the gastric mucosa of rats against the formation of hemorrhagic lesions or erosions in response to cold + restraint stress, to a combination of aspirin and cold + restraint stress, and to ethyl alcohol. The protective effect of Pepto-Bismol in these studies was clearly demonstrated. Although the mechanism of action of Pepto-Bismol was not delineated, there was a suggestion that the degree of coating of the gastric mucosa was related to protection.


Three layers of the opossum stomach: responses to nerve stimulation.

The three muscle layers of the opossum stomach were compared in their responses to electrical field stimulation. Strips were cut from the muscular wall of the stomach with their longer axes in the direction of the longitudinal, circular, and oblique muscle layers and stimulated at 1-min intervals with 20-sec trains of 1-msec pulses at 10 Hz and supramaximal strength at 500 ma. Strips either contracted, relaxed, or did not respond during the stimulus trains. Responses were abolished by tetrodotoxin, 10(-6) M. Contractions, but not relaxations, were abolished by atropine, 10(-6) M. Relaxations were not antagonized by propranolol, tolazoline, or phenoxybenzamine. Thus, the responses represent excitation of both cholinergic excitatory and nonadrenergic inhibitory nerves. In strips cut longitudinally, cholinergic contractions occurred more frequently than in the other two kinds of strips. After atropine treatment, the incidence of relaxation was greater in strips cut in the direction of the oblique layer than in the other two groups. The results suggest that, of the two kinds of nerves, the cholinergic excitatory innervation is usually dominant in the longitudinal muscle layer, and that the nonadrenergic inhibitory innervation is more complete in the oblique muscle layer.


Gastric emptying and its relationship to antral contractile activity.

Gastric emptying and antral contractile activity were simultaneously measured in 3 dogs with gastric and duodenal fistulas. Contractile activity was monitored by two force strain gauge transducers on the serosal surface of the antrum of 2 dogs and a single strain gauge transducer on the serosal surface of both the antrum and fundus of the 3rd dog. Both the frequency and force (motility index) of antral contractions were determined for each 1 min period. Gastric emptying and contractile activity were recorded and compared minute by minute with test meals (154 mM saline) of 60, 120, 240, and 480 ml. Although the rate of gastric emptying increased with the frequency and force of antral contractions, up to 67 ml min-1 (mean 6.9 ml min-1) were emptied without measurable antral contractile activity and 0 to 96 ml min-1 (mean 19.4 ml min-1) were emptied during maximal antral activity (minute motility index greater than 119 mm). Antral contractile activity increased with the size of the test meal and decreased expoentially with the rate of gastric emptying. Fundal contractile activity was generally absent during the test meal. These studies suggest that although the antrum has a significant role in the emptying of liquids, other undefined factors may modify its effect on gastric emptying.


Electrical stimulation of small intestinal electrical control activity.

The small intestinal electrical control activity (ECA) was driven by an electrical stimulus and the resultant effects on the frequency and the phase relationships of control waves recorded. The small intestinal ECA can be driven from all sites from which it could be recorded. The mean maximum driven frequency (MDF) was the highest near the pylorus and it decreased distally, but at any given site it was the same before and after dividing the small intestine into small segments. The length of the frequency plateau decreased and phase lag per cm increased with an increase in plateau frequency. The direction of phase lag was orad proximal to a stimulation site and aborad distal to it. Intravenous atropine (up to 100 mug per kg) or reserpinization of dogs before an experiment had no effect on the MDF in the frequency plateau region. The study confirms the validity of an array of bidirectionally coupled relaxation oscillators as a model of small intestinal ECA and shows that the frequency and the phase relationship of small intestinal control waves can be altered by electrical stimulation. The study also points out some differences between the small intestinal and gastric ECA's at the cellular level.


Hepatic cholesterol metabolism in patients with gallstones.

Relative rates of cholesterol and bile acid synthesis were estimated in patients with cholesterol gallstones and biliary obstruction by determining the hepatic activities of 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7 alpha-hydroxylase, the respective rate-determining enzymes for cholesterol and bile acid synthesis. As compared with eight control studies, 3-hydroxy-3-methylglutaryl-CoA reductase activity was 27% higher in 12 gallstone subjects, but 75% lower in 5 subjects with biliary obstruction. Cholesterol 7 alpha-hydroxylase activity was reduced in the gallstone (47% lower) and biliary obstruction (78% lower) subjects. Liver cholesterol concentrations were 56% higher in the gallstone and 53% higher in the biliary obstruction subjects than the control group. These findings suggest that the pathogenesis of gallstones is related to both increased cholesterol synthesis and decreased bile acid formation, whereas cholesterol accumulates in biliary obstruction because of defective removal since cholesterol production is low.


The hepatic lesion in Reye's syndrome.

The hepatic lesion in Reye's syndrome (acute encephalopathy with fatty degeneration of viscera) was studied by light microscopy of sequential biopsy specimens obtained in 49 children. The hepatic lesion is a morphologically characteristic, rapidly evolving, and reversible toxic hepatitis. In specimens obtained with 48 hr of onset of neurological deterioration, the severity of the diffuse microvesicular steatosis is best appreciated in frozen sections stained for lipid content. Variation in severity of hepatocyte glycogen depletion in early biopsies correlates with other histological measures of severity, and with the occurrence of hypoglycemia, severity of the encephalopathy at the time of admission, and mortality rate. Histochemical studies suggest that the hepatic lesion is attributable to mitochondrial injury and other evidence that supports this hypothesis is briefly reviewed. The etiology of the syndrome and its relationship to the viral disease which usually precedes it are unknown.


Studies of renin and aldosterone in cirrhotic patients with ascites.

Plasma renin activity and aldosterone metabolism were investigated in patients with cirrhosis and refractory ascites. All patients initially showed marked elevations of plasma and renin activity and plasma aldosterone. Although metabolic clearance of aldosterone was reduced, increased secretion rate was the major factor leading to elevated plasma levels. The elevated plasma renin activity and plasma aldosterone were only minimally affected by posture, dietary sodium restriction, and diuretic administration, suggesting a near-maximal degree of secondary aldosteronism. In most patients plasma renin activity and plasma aldosterone returned to normal when spontaneous natriuresis appeared. However, in 2 patients during spontaneous diuresis and in all 3 given aminoglutethimide, sodium excretion was poorly correlated with plasma renin activity and plasma aldosterone, suggesting that other tubular and/or vascular factors are important in the intense sodium reabsorption found with cirrhosis and ascites.


Bile salt metabolism in the human premature infant. Preliminary observations of pool size and synthesis rate following prenatal administration of dexamethasone and phenobarbital.

Bile salt synthesis and bile salt pool size were determined by isotope dilution in two groups of healthy premature infants, utilizing nonradioactive deuterium-labeled bile salts. All 9 infants were between 32 and 36 weeks of gestation; however, in one group (4 infants), the mothers had received either dexamethasone or phenobarbital prior to delivery. The total bile salt pool averaged 20 mg for the infants of untreated mothers and 79 mg for the infants of treated mothers; similarly, the bile salt synthesis of 8 mg per day in the untreated group was increased to 27 mg per day for the treated group. Expressed per sq m of body surface, the cholic acid pool for the treated group was 321 mg per sq m, and the cholic acid synthesis rate equaled 98 mg per sq m per day; values equal to those for full term infants and nearly 4 times those for the untreated prematures. The intraduodenal bile salt concentrations obtained during meals were also low in the untreated group, equaling 1.2 mM as compared to 5.3 mM for the treated group. The reductions of bile salt pool size, synthesis, and intestinal concentration establish that the functional maturity of the liver, and possibly the gastrointestinal tract, is reduced in premature infants. The results further suggest that this maturity may be dramatically influenced by medications administered to the mother prior to delivery.


Fatty liver induced by tetracycline in the rat. Dose-response relationships and effect of sex.

Dose-response relationships, biochemical mechanisms, and sex differences in the experimental fatty liver induced by tetracycline were studied in the intact rat and with the isolated perfused rat liver in vitro. In the intact male and female rat, no direct relationship was observed between dose of tetracycline and hepatic accumulation of triglyceride. With provision of adequate oleic acid as a substrate for the isolated perfused liver, a direct relationship was observed between dose of tetracycline and both accumulation of triglyceride in the liver and depression of output of triglyceride by livers from male and female rats. Marked differences were observed between female and male rats with regard to base line (control) hepatic concentration of triglyceride and output of triglyceride. Accumulation of hepatic triglyceride, as a per cent of control values, in response to graded doses of tetracycline, did not differ significantly between male, female and pregnant rat livers. However, livers from female, and especially pregnant female rats, were strikingly resistant to the effects of tetracycline on depression of output of triglyceride under these experimental conditions. These differences between the sexes could not be related to altered disposition of tetracycline or altered uptake of oleic acid. Depressed hepatic secretion of triglyceride accounted only for 30 to 50% of accumulated hepatic triglyceride, indicating that additional mechanisms must be involved in the production of the triglyceride-rich fatty liver in response to tetracycline.


Scanning electron microscopy of the rat liver. Studies of the effect of taurolithocholate and other models of cholestasis.

The normal surface anatomy of rat hepatocytes, sinusoids, and bile canaliculi was examined by scanning electron microscopy following finger fracture of tissues that were perfused via the portal vein and fixed with 2.5% glutaraldehyde. These normal findings were contrasted with several models of cholestasis, including infusion of sodium taurolithocholate (TLC), bile duct ligation, and ethynyl estradiol treatment, in order to examine the effects of cholestasis on morphology of the bile canaliculus. TLC-induced cholestasis was associated with specific dilation and disruption of canalicular membranes, which corresponded to evaginations of pericanalicular ectoplasm observed by transmission electron microscopy, and suggested a direct toxic effect of the bile salt on membrane structure. Infusions of lithocholate sulfate or simultaneous infusions of TLC and sodium taurocholate prevented these severe abnormalities from occurring. Bile duct ligation produced progressive canalicular dilation (from 1 to 96 hr) and loss of microvilli, but did not result in the type of membrane changes produced by TLC. No significant changes in canalicular morphology were observed following ethynyl estradiol treatment. These studies demonstrate that scanning electron microscopy is a useful technique for the evaluation of both normal and abnormal hepatic surface morphology, and indicate that TLC produces a distinctive abnormality in the structure of the canalicular membrane, which was not seen in other models of cholestasis.


Benign gastric ulcer in a patient with pernicious anemia.

This is the report of the presence of a benign gastric ulcer in a patient with achlorhydria and documented pernicious anemia. The pernicious anemia was established by a Histalog-fast achlorhydria, a Schilling test of 2.1% excretion of tagges vitamin B12 in a 24-hr urine, and reticulocytosis after administration of cyanocobalamine. Following Histalog (1.5 mg per kg of body weight), the gastric volume was 40 ml, there was no acid, and the pH was 8.1. The ulcer demonstrated by gastroscopy was confirmed at gastrectomy. Histological examination of the ulcer and the remainder of the stomach showed no malignancy. The principal conclusion of this paper is that the patient did not have an acid-produced ulcer, but that bile regurgitation coupled with alcohol ingestion produced the lesion. Surgical investigation of the ulcer seemed mandatory because of the known increased incidence of gastric carcinoma in patients with pernicious anemia.


Nodular regenerative hyperplasia of the liver.

Nodular regenerative hyperplasia of the liver, an uncommonly reported and poorly defined clinicopathological entity, obscured clinical diagnosis and was misdiagnosed on hepatic biopsy in a recent case. Approximately 19 cases are recorded in the English literature. Six patients had Felty's syndrome, about 12 patients had congestive heart failure, and the patient under discussion had subacute bacterial endocarditis. Light- and electron-microscopic examination was utilized to define nodular regenerative hyperplasia pathologically. Features common to all reported cases are discussed but elucidation of the pathogenesis of nodular regenerative hyperplasia must await further investigation.


67Gallium accumulation in hepatic actinomycosis.

A case of actinomycosis involving the liver is reported. The liver scan with 99mTcS colloid showed multiple areas of focal abnormalities. 67Gallium citrate liver scan showed these areas to concentrate intensely. This pattern of differential hepatic scintigraphy is seen in pyogenic abscesses as well as malignancy of the liver. Actinomycosis may mimic the clinical picture of a malignant neoplastic process, making the differential diagnosis of 67Ga-positive lesions of the liver more difficult.


Increased sulfobromophthalein clearance in a patient receiving phenobarbital and other anticonvulsant drugs.

A marked increase in bromosulfophthalein, dibromosulfophthalein, and indocyanine green fractional clearance was found in a patient who had received phenobarbital for 30 years and other anticonvulsant agents for 6 years. This was related to a marked increase in hepatic blood flow, while hepatic extraction remained normal. These changes were associated with signs of hepatic microsomal enzyme induction (in particular a 2-fold increase in liver bilirubin UDP-glucuronyltransferase activity and hypertrophy of the smooth endoplasmic reticulum in the hepatocytes). Drug administration (especially phenobarbital) should be considered as a possible cause of increased bromosulfophthalein clearance in man.


Abdominal ultrasonography in a mesenteric cyst presenting as ascites.

A case of a mesenteric cyst presenting as the sudden onset of bloody ascites is reported. The diagnosis was suggested by abdominal ultrasonography.


[Measurements on the grade of the human skull base and angle determinations].

1. The angle between the Os sphenoidale and the Clivus has been determined on 106 skulls. The mean was 117.68 degrees. 2. The altitude of the Foramen magnum with respect to the Frankfort plane was determined at -1.96 cm on the average. 3. The angle of inclination of the Foramen magnum to the Frankfort plane was determined from the altitude of the Basion and Opisthion and from the length of the Foramen magnum. The mean was -13.71 degrees. 4. In the inner base of the skull the altitudes of following structures have been determined: Planum sphenoidale (mean 2.34 cm), ground of the Fossa hypophysialis (1.32 cm), ground of the middle cranial fossa (-0.03 cm), ground of the posterior cranial fossa (-2.30 cm), upper edge of the Os petrosum (1.12 cm), Tuberculum jugulare (-0.21 cm), ground of the Meatus acusticus internus (0.45 cm). 5. In order to provide numerical data for the step-like building of the inner base of the skull, the differences between the altitudes of important structures from the inner base have been determined: Margo superior partis petrosae - Tuberculum jugulare (mean 1.35 cm). Opisthion - ground of the posterior cranial fossa (0.11 cm), Planum sphenoidale - ground of the middle cranial fossa (2.38 cm), ground of the middle cranial fossa - ground of the posterior cranial fossa (2.27 cm), Margo superior partis petrosae - ground of the posterior cranial fossa (3.35 cm), Margo superior partis petrosae - ground of the middle cranial fossa (1.15 cm).


[Histological, histochemical and histophysiological changes of the exocrine pancreas and stomach fundus in Anguilla anguilla L. in the course of postlarval development].

During the postlarval development of eels exocrine status of pancreas and fundus was investigated. Therefore results of histomorphological, histophysiological and histochemical tests were interpreted. The conclusion is that there is no secretory activity till stage I. No relation exists between secretory activity and food-supply.


Some observations on the histology of oesophagus of crimsonbreasted barbet, Megalaima haemacephala, and whitebreasted kingfisher, Halcyon smyrnensis.

Histological observations were made on the oesophagus of 2 birds showing different feeding habits. The birds taken for study included frugivorous form, M. haemacephala and H. smyrnensis, which is primarily piscivorous. Various histological modifications such as relative development of mucosal folds, mucous-secreting glands and musculature have been shown to be correlated with the specific feeding habits of the birds.


[Sex differences in the human sternum].

We investigated 14 male and 14 female breast-bones of adult human beings by measuring 2 parameters of length, 2 of breadth and 2 of thickness and estimated their frequency distributions. They overlap more or less. Therefore we made a discriminant analysis in order to differentiate male and female skeletons by means of a-l 6 measures of the breast-bone. The result was satisfying. The received discriminant function may be used in the sex diagnosis in forensic osteology, especially, if the more reliable criterions of the pelvic measures are missing.


The hypothalamo-hypophysial vascular relationship in Indian fresh-water goby, Glossogobius giuris (Ham.).920u.

The hypothalamo-hypophysial vascular relationship and intra-hypophysial vasculatisation have been described in order to understand the regulatory mechanism of hypothalamic control over the functions of the pituitary gland. In Glossogobius giuris, the disposition of the blood vessels in the head region is on typical teleostean pattern with certain modifications. The nucleus preopticus is supplied through the nucleus preopticus artery, a small blood vessel arising from the anterior branch of the posterior cerebral artery, whereas the pituitary gland receives blood through a pair of hypophysial arteries. The blood from the pituitary is drained off by the pituitary veins whch pour their blood into the supra-orbital sinus. The anterior cerebral vein after taking the blood from anterior part of the brain including the hypothalamus and the nucleus preopticus joins with the supra-orbital sinus. The hypothalamo-hypophysial portal system is absent in this fish. The saccus vasculosus receives blood from the posterior cerebral artery through a small blood vessel and is collected by a prominent saccus vasculosus vein which pours blood into the supra-orbital sinus before it joins the infra-orbital sinus to form the heat vein. There seems to be no physological connection between the saccus vasculosus and pituitary gland. The highly vascularised neurohypophysis interdigitate with the pars intermedia and extends upto the proximal pars distalis. The blood vessels are restricted to the neurohypophysial extensions only. However, in the rostral pars distalis the blood vessels are present but the neurohypophysis does not extend to this part. The blood capillaries enter the rostral pars distalis from the capillary network on the surface of pituitary gland along with the connected tissue covering of the pituitary. The neurohypophysis shows a greater vascularisation in comparison to that of the other glandular part of the pituitary gland. In the present study of Glossogobius giuris, though an extensive ramification of neurohypophysis occurs with the pars intermedia and the proximal pars distalis, the neurosecretory axons do not innervate the endocrine cells of the pituitary gland and the blood vessels are found restricted to the neurohypophysial extensions except that of the rostral pars distalis. The neuro-vascular way of hypothalamic control over the functions of the pituitary gland seems to be justified as the neurosecretory fibres have been found associated with the blood vessels.


The testicular cycle of a percoid teleost--Nandus nandus (Ham.).

Small paired testes of Nandus nandus are situated posteriorly in the body cavity. They open posteriorly in a common sperm duct. A urinogenital sinus is present. Each testis consists of a large number of seminiferous tubules extending from the periphery towards the centre. The seminiferous tubules are separated from each other by a layer of interstitial tissue. 6 different stages of spermatogenesis are recognised. On the basis of morphological and histological changes in the testes during different months of the year, the reproduvtice cycle has been divided into post-spawning (October to December), pre-spawning (January to March) and spawning (April to August) periods. The monthly volume of testes is in direct correlation with the monthly changes in water temperature. Statistical observations indicate that the process of spermatogenesis is very active during pre-spawning period. The relative number of spermatozoa is maximum in July (69.89%), suddenly decreases in August (54.28%) and continues to decrease upto October (49.66%) indicating the maximum spawning in July and August.


[Ontogenesis of the spine-free initial zone of apical dendrites; studies in cortical pyramidal cells of albino rat].

1. In Golgi-Cox-impregnated coronal sections of albino rat brains at 1, 4, 26, 24, 30, 60 and 90 days it is presented the evolution of the spine-less, bare initial zone ("nude zone", NZ) at the proximal apical main dendrites of the layer V pyramidal neurons in the somatosensory and anterior limbie cortex. The quantitative results are analyzed by statistical methods. 2. The NZ is comprehended as a morphological correlate of the endodendritic neuroplasmic flow (Weiss 1944, Globus, Lux and Schuberl 1968, Kreutzberg 1973). The observed changes of the percental frequency and the average length of NZ increases rapidly. 3. The NZ occurs at first in the (12th) 16 postnatal day, thus in a time, when the organs of hearing and the eyes are differentiated completely. Between 16th and 24th day the percental frequency as well as the longitude of NZ increases. During this time the rats will be independent of the mother animals. With the full differentiation of the urogenital tract and especially with the sexual maturity the percentage frequency of NZ increases only at pyramidal cells in the anterior limbie cortex between 24th and 60th day. During 3rd month the NZ is occuring percental more frequently in the anterior limbic cortex than in the somatosensory cortex. At this time the average length of NZ is shorter in the limbic cortex. 4. As to the enriched, vivid movement of the animals and the playing impulse of the young rats the average length of NZ will be extended at pyramidal neurons in the somatosensory cortex during 2nd month, as well as the pattern of spine distribution will be changed along apical dendrites (Schlerhorn, unpublished). During the following (3rd) month the NZ will be shorteded in the somatosensory cortex, obviously caused by new formation of spines at the proximal main dendrites. 5. These newly formed spines in the initial zone of apical dendrites may be inhibitory spines. The inhibitory spines are stained only when using the mercury chromate impregnation according to Golgi-Cox, but not when using the silver chromate methods according to Golgi-Kopsch or Golgi-Bubenaite. The different tingibility of these spines by different Golgi techniques is discussed by Doedens, Nagel and Schierhorn (1974). The pyramidal neurons in the somatosensory cortex possess a longer average length of NZ (Lnz = 7,3[mum]) than the pyramidal cells in the anterior limbic cortex (Lnz = 6.2[mum]). As to NZ the differences between silver and mercury chromate stained pyramidal neurons are greater in the somatosensory cortex than in limbic cortex (see Tab. 7). Therefore we assume that there are in the initial zone of somatosensory pyramidal neurons more inhibitory spines than at the pyramidal neurons in the anterior limbic cortex. 6. The regional differences in the percentual frequency and in the average length of NZ between somatosensory and limbic cortex are new identifying marks of architectonic differentiation of the pyramidal neurons in cortical regions of phylogenetically different ages.


Longevity, growth rate and related traits among strains of Tribolium castaneum.

Longevity of eight laboratory strains of the flour beetle Tribolium castaneum, with various geographic backgrounds, was studied under constant laboratory conditions of 33 degrees C and 70% relative humidity in standard medium (95% whole wheat flour and 5% dried yeast) during a period of 227 days starting from the egg stage. The eggs were collected from the same parents, first a few days after emergence and afterwards at intervals of 13, 9, 10 and 11 days. Mean survival time (MST) was found to be strain-specified. It ranges from 128.6 days for KJ (Kyoto, Japan) to 174.2 days for ES (Edinburgh, Scotland). MST was highly correlated with the percentage of adults alive after 227 days, which did not change the ranking order of strain longevity. Parental age had no effect on longevity. The mean adult longevity of the strains was correlated with the available data on adult weight, growth rate, viability and productivity. There was no relationship between adult weight and longevity. LIfe span was found to depend on growth rate (measured as 13-day larval weight), percent viability (from 13-day larvae to adulthood) and productivity. Developmental time was also found to influence adult life span within certain limits (two extreme strains deviated). The data suggest that ageing and death in T. castaneum is under genetic control and support the idea that ageing, allied to development, is genetically controlled.


[Disc electrophoresis of collagen protein (author's transl)].

The composition of proteins extracted from tendon collagen is investigated by disc electrophoresis. No qualitative differences can be demonstrated between young and old collagen. The action of formaldehyde and methionine on the tendons has no effect on the electrophoretic picture.


The effect of age on mitochondrial ultrastructure.

The ultrastructure of perfused livers and of mitochondrial fractions from 6-month-old and 30-month-old C57/BL mice were studied. In old mice the liver cell mitochondria were enlarged and rounded with a light 'foamy', vacuolated matrix, short cristae and a loss of dense granules. Quantitative studies showed a 60% increase in the mean size and an increased proportion of larger mitochondria in intact 30-month-old perfused livers. Endothelial and Kupffer cell mitochondria were smaller than those of the parenchymal cells. Mitochondria in pellets prepared from 6- and 30-month-old livers were rounded and condensed, although there were a few larger and 'foamy' mitochondria in the preparations from old mice. Up to 47% of large mitochondria in the old livers were lost during cell fractionation.


Alternatives in the management of varices.

When surgical treatment of varicose veins is not indicated or is withheld because of associated problems of greater magnitude, other therapeutic measures may be considered. These include elastic support, elevation of the legs, exercise to strengthen the calf musculature, and sclerotherapy. Each of these measures, independently or in combination, provides considerable relief of signs and symptoms of the venous problems in many patients. In difficult venous stasis problems in which the optimal treatment remains in doubt, a therapeutic trial of elastic support is safe and often helpful in defining the role of chronic venous insufficiency in the patient's symptom complex.


Craniofacial serial dimensions related to age, sex, and cleft-type from six months of age to two years.

The first two postnatal years are a time of rapid craniofacial growth. We selected 30 cleft lip/palate children, each seen at 6, 12, 18, 24 months, at which time lateral X-ray headfilms were taken. There were five boys, five girls, in each of three cleft-types: cleft palate only (CP), unilateral cleft lip/palate (UCLP), and bilateral cleft lip/palate (BCLP). Three dimensions were selected: 1) anterior cranial base (S-N); 2) upper face height (N-Pt.A); 3) maxillary depth (Pt.A-Ptm). All were in the midsagittal plane. This is a repeated measures study on the factor patient age, so that for each combination of sex and cleft-type the same subject was measured at the four levels of patient age. The multiple comparison technique utilized was the Newman-Keuls Procedure. There is no significant joint effect in the 6-24 months period. The factors seem to operate singly. There is no main effect due to the factor sex. Dimensions N-Pt.A. and Pt.A-Ptm show a significant main effect due to the factor cleft-type. There is a highly significant main effect due to the patient age factor.


Nutritional correlates of child development in southern Tunisia. IV. The relation of deciduous dental eruption to somatic development.

Deciduous dental eruption in a group of 658 children below 3 years of age in Southern Tunisia was found to be correlated with the general somatic development. On the other hand, this association was less close than that among the different components of somatic growth, suggesting that dental eruption is less affected by the factors which delay somatic growth in that area. Attempts were made to obtain methods of estimating the ages of children using the number of erupted deciduous teeth, both by means of regression equations and by a table of the median age of children with different numbers of pairs of teeth. In both cases the estimates obtainable are not accurate enough to do more than divide the children into coarse age groups. It is concluded that in anthropometric work there is no substitute for accurately known chronological ages.


Control of the pattern of perithecium development in Sordaria fimicola on agar medium.

In a Sordaria fimicola (Rob.) Ces. and de Not. colony grown on agar medium in a petri plate, perithecia developed in a narrow band around the plate edge after the colony margin reached the edge. Physical wounding of the colony carried out shortly before or during the time perithecia were developing around the plate edge stimulated perithecium development in the wound area. Diffusion barriers were created by cutting small trenches in the agar parallel to the plate edge. The trenches were made at several different positions between the plate center and edge using cultures of several different ages, and the resultant distribution of perithecia along the trench edges suggested that the colony center and periphery produce diffusible inhibitors of perithecium development. These inhibitors may be responsible, in part, for the observed pattern of perithecium development in the colony.


On the non-hormonal control of the termination of regeneration.

Simultaneous amputation at three different anterior and three posterior levels in the earthworm Eisenia foetida did not produce any measurable effect on the number of segments regenerated posteriorly compared to controls with intact heads. In every group, the number of segments formed depended only on the level of the posterior cut, declining by ten every time the level of the posterior cut was moved ten segments further from the head end. Repeated anterior amputation to prevent regeneration of the brain and subpharyngeal ganglia was without effect. No consistent differences were observed in the anterior neurosecretory cells either at the start or the end of regeneration. These results are discussed in relation to the "progress zone theory," the limited clonal cell life theory, and the theory of "sequential cumulative inhibition." It is concluded that the information determining the number of segments regenerated posteriorly resides in the tissues adjacent to the cut surface.


Amino acid profile of bovine bone during growth.

The amino acid profile of bovine bones at 2, 25 and 130 months of age was examined and the data were expressed as amino acid residues per 1000 total amino acid residues recovered. As age advance proline and hydroxyproline significantly increased in whole bone (P less than .01), while valine, tyrosine, methionine and histidine decreased (P less than .01). To a lesser extent phenylalanine and glutamic acid decreased with increasing age (P greater than .05). A substantial increase (P less than .05) in glycine and arginine, and a considerable decrease (P less than .05) in valine, tyrosine, methionine and histidine occurred between young (2 months) and intermediate (25 months) age bovine bone. The largest differences in amino acid distribution during growth were observed in bones from the young and intermediate age groups. Lower amounts of glycine were present in lumbar vertebra (P less than .05), whereas the highest amount of glycine was found in sacral vertebra when vertebra, ribs and femurs were compared. Proline and hydroxyproline residues were highest in the rib and femur. Vertebrae often contained higher levels of threonine, arginine, histidine, lysine and aspartic acid than either the rib or femur.


A canonical discriminant analysis of post-embryonic development in Notonecta Maculata fabricius (Insecta:Heteroptera).

A multivariate method, canonical discriminant analysis, was used to discern a pattern of growth in Notonecta maculata. A stepwise procedure reduced the 11 metrical characters measured on individuals of both sexes, from the 1st larval stage to the adult, to 4 significant variates which were used in the canonical analysis. The four canonical variates accounted for the meaningful part of the variablity. Relying on bivariate allometry and on an experimentation with a juvenile hormone analogue, each independent direction of variation was related to combined effects of such biological factors as a general growth trend, sex and juvenile hormone.


The effect of cold stress on muscle growth in young chicks.

The effect of cold stress on muscle growth in young poultry stock has been examined during an experiment involving one hundred and eight chicks. They were divided into two groups, namely the control group and the cold stress group. The newly-hatched chicks of broiler type were chilled at a temperature of 10 degrees C for a total of four hours. The breast and thigh muscles of one side of each bird were analyzed for fat, protein, potassium, magnesium, calcium, and sodium during the two weeks after hatching. In the stressed chicks, body weight, breast and thigh muscle weight were consistently lower over the fortnight than in the controls. The body weight of the stressed birds was increased by two-fold, whereas, in the controls, the increase was there and a half times. The breast and thigh muscle weights of the stressed chicks increased by seven times and two times, respectively. In the normal birds breast and thigh muscle weights were enhanced fifteen times and four times, respectively. The protein content of the breast muscle in the normal birds was enhanced by thirty-fold and that of the thigh muscle by five-fold. In the stressed chicks the increase in the protein content in the breast muscle was twelve-fold and that of the thigh muscle was two-fold. Muscle fat content was lower in the chilled birds than in the controls. Levels of potassium and magnesium were also lower in the stressed chicks than in the normal birds.


Sexual dimorphism in dentition mineralization.

This study determined for 121 boys and 111 girls of the serial experimental group of the Burlington Growth Centre the age, time interval and age sequence of 14 stages of mineralization of all tooth types. The two sexes differed significantly in the age at which the stages of tooth mineralization appeared, and in the length of the interstage intervals. In the canines, there was maximum sex difference in mineralization, which was almost 20 per cent and resulted from a delay in the boys. Changes in sequence of mineralization were due to delay rather than to acceleration. Sex differences in tooth mineralization manifested themselves before puberty, and mineralization was not accelerated at puberty. In contrast, post-pubertal mineralization of third molars appeared to be accelerated in both sexes and occurred earlier in the boys.


Gastric emptying following vagotomy and antrectomy and proximal gastric vagotomy.

Gastric emptying of solid meals labelled with 129Cs was studied in patients for up to one year after vagotomy and antrectomy or after proximal gastric vagotomy. Significant delay was found one month after vagotomy and antrectomy but this had returned to normal by six months. No delay was found after proximal gastric vagotomy. The effect of posture on gastric emptying was also studied in the same subjects. No significant differences were found between gastric emptying in the supine or sitting positions after solid meals.


Electronmicroscopic observations on the effects of orally administered aspirin and aspirin-bicarbonate mixtures on the development of gastric mucosal damage in the rat.

The effects of administering a single dose of (200 mg to 50 mg/kg body weight) aspirin or an equimolar mixture of aspirin (200 mg/kg body wt) with sodium bicarbonate on the fine structure of the rat gastric mucosa were investigated in order to establish the role of particles of the drug in the development of gastric damage. The sequence of cellular events involved in the development of a lesion and the influence of short-term starvation were also investigated. Aspirin-bicarbonate solutions produced much less damage in starved rats than aspirin suspensions given at low (50 mg/kg body weight) or high therapeutic doses (200 mg/kg body weight). Also, when non-starved rats were given 200 mg/kg aspirin, only slight damage was observed. The presence of particles of the drug in intimate contact with the mucosa is thus important in the development of gastric damage. A sequence of events with time involving direct physical exfoliation of mucosal cells and selective structural damage to parietal cells followed by structural damage indicative of a disturbance to oxidative and biosynthetic functions in cells near the developing erosion was observed. The implications of these results on the development of aspirin-induced lesions are discussed.


A search for a transmissible agent in Crohn's disease.

Controversy exists as to whether a transmissible agent is responsible for Crohn's disease. Previous reports have suggested that sarcoid-like granulomas can develop in animals following inoculation of homogenates derived from bowel affected by Crohn's disease. This study involved the injection of Crohn's tissue homogenates into experimental animals under a variety of conditions which might be expected to favour the demonstration of such an agent. Homogenates have been inoculated into the ileum of rats, mice, and rabbits and also given inoculated into ileum and footpads of rats which have previously been rendered lymphoedematous by surgical interruption of the draining lymphatics. Bowel homogenates from a total of 17 patients with Crohn's disease have been injected into 91 experimental animals. No macroscopic or microscopic changes indicative of Crohn's disease were detected. Thus study does not support the suggestion that a transmissible agent is present in Crohn's disease.


A case of  'Crohn's carcinoma'.

A case of adenocarcinoma of the ileum, occurring in an area concomitantly the site of Crohn's disease, is described. Examination of the literature suggests that there are certain characteristics of the small bowel carcinoma which arises in Crohn's disease. These include invisibility of the tumour on macroscopic inspection, dysplasia in the surrounding mucosa, and a peculiar endometriosis-like pattern of invasion. The finding that these tumours have certain characteristics is taken as evidence that carcinoma is a complication of Crohn's disease of the small bowel.


The immune response of phiX 174 in man. III. Evidence for an association between hyposplenism and immunodeficiency in patients with coeliac disease.

The ability of patients with coeliac disease to produce primary and secondary antibody in response to a new antigen has been tested. Eight patients with coeliac disease were injected intravenously with the coliphage phiX 174. Antibody levels were measured throughout the primary response. On day 28 a second injection was given and the secondary response was also studied in detail. The production of antibody in the primary response is lower than in a group of normal subjects. The secondary response is severely reduced and the difference between the coeliac group and controls is highly significant. The secondary response in the coeliac patients contains a much higher proportion of IgM antibody than normal. These abnormalities correlate approximately with clinical status and with hyposplenism. It is concluded that in patients with coeliac disease the ability to produce antibody is impaired, with a defect in switching from IgM to IgG antibody.


Regional differences in oxalate absorption by rat intestine: evidence for excessive absorption by the colon in steatorrhoea.

Clinical studies suggest that steatorrhoea can be associated with excessive absorption of dietary oxalate. We examined the influence of bile salts, Ca++, and long-chain fatty acid on the absorption of oxalate and water by rat intestine in vivo. Absorption was measured under steady-state conditions during single-pass infusions. Each intestinal segment served as its own control. In jejunum, 10 mM taurocholate, the principal salt in rat bile, depressed absorption of oxalate and water. Absorption was not depressed further by Ca++ or linoleic acid. In ileum, 10 mM taurocholate did not inhibit absorption. Linoleic acid, 2 mM, depressed absorption of both oxalate and water. In colon 10 mM taurocholate decreased absorption. Net water transport was depressed further when linoleic acid was added to the infusion, but oxalate absorption was enhanced. Ca++ negated these effects of linoleic acid. It is concluded that long-chain fatty acids may enhance the absorption of oxalate from the rat colon. This observation may be relevant to understanding hyperoxaluria in patients with steatorrhoea.


The relative potency of the Crick-Harper-Raper unit and the GIH clinical unit of secretin.

A reinvestigation of the relationship between the Crick-Harper-Raper (CHR) and the GIH clinical units (CU) of secretin has been undertaken in anaesthetized cats with the knowledge that for some time before 1970 the CHR standard used by The Boots Company to assay secretin had lost some specific activity. One clinical unit of GIH secretin (batch no. 17421) is 3-8 times more potent than 1 Crick-Harper-Raper unit of restandardized Boots secretin (batch no. 142) in increasing the flow rate of pancreatic juice, and four times more potent in increasing the amount of bicarbonate.


[Blood parasites of small wild mammals in Czechoslovakia].

The author investigated 4,853 specimens of wild living small mammals (43 species: Insectivora, Chiroptera, Lagomorpha, Rodentia, Carnivora) from Czechoslovakia for blood parasites. Trypanosomes were found in Talpa europaea, Sorex alpinus, Crocidura suaveolens, Myotis myotis, Apodemus sylvaticus, Apodemus flavicollis, Mus musculus, Rattus norvegicus, Clethrionomys glareolus and Microtus agrestis. Babesia was detected in Myotis emarginatus, Myotis myotis, Clethrionomys glareolus, Microtus arvalis and Microtus agrestis. Grahaemella was found in Talpa europaea, Sorex araneus, Neomys fodiens, Neomys anomalus, Myotis emarginatus, Myotis myotis, Apodemus sylvaticus, Apodemus flavicollis, Apodemus microps, Apodemus agrarius, Mus musculus, Clethrionomys glareolus, Arvicola terrestris, Pitymys subterraneus, Microtus arvalis, Microtus agrestis, and Microtus oeconomus. Spontaneous Bartonella-infection was ascertained in one Microtus arvalis and, in erythrocytes of one Sorex araneus, parasitic organisms very similar to Bartonella were found.