[Effect of phentolamine on the catecholamine output from the perifused pig adrenal medulla in response to infusions of acetylcholine (author's transl)].

The effect of phentolamine (regitine) on the in vitro release of catecholamines from adrenal medulla has been studied. Firstly, a continuous flow incubation (perifusion) system was developed in which secretory responses of adrenal medulla to acetylcholine were characterized by serial fluorimetric assay of catecholamine in the effluent medium. There was an initial massive release of catecholamine, which in the absence of acetylcholine, declined to a low basal level. The basal level was stable. Following 2.5 h preincubation, catecholamine release rose abruptly after addition of 10(-2) M acetylcholine to the medium and returned promptly to baseline after withdrawal. Pretreatment of pig adrenal medulla with 10(-2) M phentalamine blocked the increase of catecholamine overflow by 10(-2) M acetylcholine. It was also found that phentolamine, itself, caused no effect on catecholamine release from adrenal medulla. These results show that phentolamine blocked the catecholamine release from perifused pig adrenal medulla in response to acetylcholine infusion.


[High pressure liquid chromatography of corticosteroids: I. Preliminary report of the determinations of plasma corticosterone by HPLC combined with radioimmunoassay (author's transl)].

The analysis of corticosteroids (CDS) was preliminarily investigated using a DU PONT 830 High Pressure Liquid Chromatography (HPLC) equipped with a UV detector and a Permaphase column ETH. 1) Firstly, the best condition for the separation of mixed CS was investigated. In a linear gradient elution, ten authentic steroids, varying greatly in polarity (including native CS such as DOC, Corticosterone and Cortisol) were sharply separated in about 20 minutes. Recovery of the steroid injected into the column was 96 approximately 100%. 2) Standard CS added to the chloroform extracts from plasma or urine were also clearly separated in the same condition as above. In the experiment using predonisolone and estrone-propionate in different doses, the synthetic steroids were quantitatively separated, giving a linear calibration curve. 3) Sensitivity of the steroid determination was ng order photochemically in a plot study, but the method, using a UV detector, was not sufficient to apply to small amount of samples extracted with choloroform. To solve this problem, radioimmunoassay was applied to the eluate containing biological steroid, which was roughly separated using the synthetic steroid marker. As for the determination of plasma corticosterone using this method of HPLC combined with radioimmunoassay, the results were satisfactory for practical use; the mean based values and SD of 10 normal controls were 0.4+/-0.2 microgram/100ml for corticosterone, and they showed 4 to 5-fold increases to 250 microgram of synthetic ACTH injection.


[A simple method for the simultaneous analysis of urinary homovanillic acid, vanilmandelic acid and 3, 4-dihydroxy mandeli acid by mass fragmentography (author's transl)].

Gas chromatography-mass spectrometry makes possible the simultaneous measurement of homovanillic acid (HVA), vanilmandelic acid (VMA) and 3, 4-dihydroxy mandelic acid (DOMA) in 2ml urine samples. The equipment used was the Shimadzu LKB 9000 GC-MS (MID-PM). The TMSi derivatives of the compounds were analysed by the GC-MS system equipped with a 3ft. X 3mm column packed with 1.5% OV-1 and the temperature was programed from 130 degrees to 260 degrees C at 10 degrees C/min increments. The mass spectrum showed molecular ions at m/e 326, 414, and 472 which correspond to the TMSi derivatives of HVA, VMA AND DOMA respectively. The peaks at m/e 326 (HVA), 297 (VMA) and 355 (DOMA)  were applied to avail themselves of simultaneous multiple ion analyses by GC-MS. As little as 1pg of the compounds injected into the column could be measured reproducibly. The sensitivity is of the order of pg or ng, and the linearity of the response is maintained up to at least 200ng. The procedure was simpler and less time consuming than previous methods. It consists of extraction of the free acid into ether followed by complete silylation of the phenolic, alcoholic and carboxylic acid group with bis (trimethylsilyl) acetamide. Recoveried of HVA, VMA, DOMA added to urine were 93.8%, 71.2% and 23.6% respectively. The specificity of this method surpasses and cannot be compared to any other existing quantitative methods.


[An improved method for the simultaneous analysis of norepinephrine, epinephrine and dopamine at the picogram level by mass fragmentography (author's transl)].

Gas chromatography-mass spectrometry makes possible the simultaneous measurement of norepinephrine (NE), epinephrine (E) and dopamine (DA) at the picogram level. The equipment used was the Shimadzu LKB 9000 GC-MS (MID-MD. The TFA derivatives of the compounds were analysed by the GC-MS system equipped with a 3ft X 3mm column packed with 1.5%OV-1 and the temperature was programed from 135 degrees to 260 degrees C at 10 degrees C/min increments. The mass spectrum showed molecular ions at m/e 552, 566 and 440 which corresponds to the TFA derivatives of NE, E and DA respectively. The base peaks of NE, E and DA were m/e 109, 140 and 328 respectively. The peaks at m/e 126 (NE and DA) and 140 (E) were applied to avail themselves of simultaneous multiple-ion analyses by mass fragmentography. As little as 4pg of the compounds injected into the column could be measured with good reproducibility, and the linearity of the response was maintained up to 120 pg. The sensitivity was of the order of ng or pg which enable quantitation with 1ml of human serum and urine sample. The procedures were simpler and less time consuming than previously reported methods. Recovery rates of NE, E and DA from serum were 25.7%, 13.7% and 76.1%, whereas those from urine were 100%, 89.6% and 100% respectively. The specificity of this method surpasses and cannot be compared to any other existing quantitative methods.


[A simplified radioimmunoassay for serum aldosterone--non-extraction method with 125I-labeled aldosterone (author's transl)].

A simplified direct radioimmunoassay system for serum aldosterone measurement was developed by using radio iodine-labeled aldosterone and highly specific antiserum to aldosterone. 8-anilino-1-naphthalene sulfonic acid(ANS) was used to prevent the binding of aldosterone to serum proteins. Polyethylene glycol was used to separate the antibody-bound aldosterone from the free aldosterone as the precipitant. The minimum measurable concentration of aldosterone is 30pg/ml of serum by short incubation method (at 25 degrees C for 3hr incubation) and 15pg/ml of serum by long incubation method (at 4 degrees C for 20 hr incubation) respectively. Present radioimmunoassay eliminates extraction of the aldosterone from serum and chromatographic separation procedures, and requires only 0.1ml of serum sample for assay. The intra-assay precision was C. V. 6.9% (average of 4 samples) and the inter-assay precision was C. V. 10.7% (average of 4 samples). There is an excellent correlation between the extraction method and this direct method in serum aldosterone value obtained (correlation coefficient, 0.96). The normal value was 36.8+/-25.9pg/ml (recumbent) and 113.6+/-6.15pg/ml (upright).


[A simple method measuring plasma aldosterone by radioimmunoassay without extraction (author's transl)].

A radioimmunoassay method was developed to measure plasma aldosterone levels. Antibody was produced in rabbits by injecting aldosterone oxime coupled with bovine gamma-globulin once a month. Plasma aldosterone was measured simultaneously by two methods: the direct method without extraction and a method using paper chromatography. 125I-aldosterone was used in the first method and 3H-aldosterone in the second. The antibody had a high specificity adequate to show zero water blank in the first method. Adequate precision, accuracy and sensitivity were obtained in a direct method using 125I-aldosterone. Plasma aldosterone levels were 7.1+/-3.0ng/100ml (Mean +/-SD) in normal subjects and slightly higher after injecting ACTH-Z. The correlative coefficient between the first and the second method was significantly high (r=0.970, P less than 0.001, n=37). Plasma aldosterone was high (34.3+/-14.1ng/100ml, n=7) in primary aldosteronism, slightly high (14.2+/-2.6ng/100ml) in secondary aldosteronism, normal in Cushing's syndrome (10ng/100ml) and low in Addison's disease (1ng/100ml), hypopituitarism (1ng/100ml) and pseudoaldosteronism (2ng/100ml). From these results, it is concluded that the direct method without extraction was a very useful and reliable method for measuring plasma aldosterone. It was superior in simplicity and there is no need to use a liquid scintillation counter.


[Leucocyte migration inhibition test in diabetes mellitus (author's transl)].

The leucocyte migration inhibition test (LMT) using the agarose plate method introduced by Clausen is simple and highly reproducible. Using human pancreas extract and beef insulin as antigen, LMT was performed on ten patients with insulin dependent diabetes, twenty patients with insulin independent diabetes, and twelve healthy controls. The migration index was expressed as a percentage of migration calculated from the following formula. Migration index (MI) = average areas of migration in test suspension/average areas of migration in control suspension. Using human pancreas extract, the mean migration index for the insulin dependent diabetics (87.6 +/- 11.1) was significantly lower than in the normal subjects (99.3 +/- 6.3) (p less than 0.05). Using beef insulin as antigen for the insulin dependent diabetics and insulin independent diabetics, the mean migration indices (+/- SD) were 95.8 +/- 14.9 and 98.7 +/- 12.3 respectively. The corresponding values for the control group were 98.9 +/- 7.8. Cellular hypersensitivity to human pancreas extract was shown in the leucocyte migration inhibition test with insulin dependent diabetics, but a negative result was obtained with beef insulin.


[Studies on the role of high pressure baroreceptors in vasopressin (ADH) secretion. Effect of occlusion of common carotid and vertebral arteries on blood ADH level (author's transl)].

The role of baroreceptors in common carotid and vertebral arteries and arteries in the thoracic cavity in vasopressin secretion was investigated in this study. Effects of bilateral occlusion of common carotid and vertebral arteries on blood ADH level as well as mean arterial pressure were studied in common carotid arterial plexus-denervated dogs, cervically vagotomized dogs and intact dogs. Blood ADH titers were determined by bioassay technic before and 5 minutes after the occlusion of the arteries and were compared with the changes of mean arterial pressure (MAP). The following results were obtained. (1) Blood ADH titers and MAP were elevated by the occlusion of the common carotid arteries in both intact and vagotomized dogs, while they were not significantly affected in denervated dogs. Elevation of blood ADH titers was more pronounced in vagotomized dogs than in intact dogs. (2) Blood ADH titers and MAP were elevated by the occlusion of vertebral arteries in all groups of dogs. However, the elevation of blood ADH titers in denervated dogs was more pronounced than in intact dogs, but less than in vagotomized dogs. (3) The effects of the occlusion of common carotid arteries on blood ADH titers and MPA were more pronounced than those of the occlusion of vertebral arteries. These results may suggest that: a. baroreceptors involved in vasopressin secretion are present in vertebral arteries as well, and that b. the intrathoracic baroreceptors are dominant in controlling vasopressin secretion, while those in common carotid arteries are secondly and those in vertebral arteries thirdly dominant.


The impact of breast feeding patterns on the biometric analysis of infant mortality.

A major assumption of the biometric analysis of infant mortality as developed by Bourgeois-Pichat is that the age structure of infant deaths after the first month of life is virtually constant across time and cultures. Reanalysis of results from studies which compare the mortality of infants according to the type of feeding indicated that the relationship between mortality and age within the first year of life followed different patterns for breast fed and artificially fed infants. Historical data for populations with different breast feeding customs reveal similar differences in the age pattern of infant mortality. In populations where breast feeding was uncommon or of very short duration, infant mortality rises particularly steeply during the early months of the first year of life. The age structure of infant mortality in less developed countries where breast feeding is decreasing rapidly may bsimilarly affected. When substantial deviations from the linear relationship are evident, particular caution is required in applying the biometric technique, since in such situations the estimated endogenous mortality is very much affected by the particular set of data points within the first year of life which are chosen for the basis of the estimates.


What difference would it make if cancer were eradicated? An examination of the Taeuber paradox.

The immediate effect of discovering a way to cure cancer would be a reduction in the number of deaths in the United States by the number of people now dying from that cause. Within a short time, however, deaths from other causes would increase, and the net long-term effect would be relatively small. A parameter is derived that measures how much the expectation of life is increased by a marginal reduction in any cause of death. That parameter is additive in the several causes and has other advantages, though it does not avoid the assumption of independence.


Measuring the effects of race differentials in mortality upon surviving family members.

A model is developed to use marital history data from the U.S. Current Population Survey and mortality statistics from the federal registration system to estimate color differences in (a) the risk of widowhood among women in the working ages and (by the cumulative duration of widowhood. Color differentials in mortality among married males are thereby translated into person-years of dependent survivorship among women, in anticipation of our later estimating average and cumulative lifetime income losses for the survivors. Initial results of this model, dealing with the demographic aspects of survivorship, are presented.


The predictive validity of reproductive intentions.

On the basis of data collected in the 1975 National Fertility Study (NFS) in which continuously married white women interviewed in the 1970 NFS were reinterviewed five years later, the aggregate and individual validity of reported fertility intentions is evaluated. The main finding about aggregate prediction is that 1970 intentions overestimated 1971-1975 fertility to the same extent as the conventional 1970 total fertility rate. The conclusion is that intentions suffer all of the same vulnerabilities as other period measures. At the individual level, the validity of intentions is considerable in comparison with most other indicators.


Target fertility, contraception, and aggregate rates: toward a formal synthesis.

This paper develops a stock adjustment model relating total expected births to conventional aggregate fertility rated for married women over 25. Each year, cohorts bear about 20 percent of their additional expected births. Aggregate U.S. rates have been consistent with expectations as expressed in surveys between 1955 and 1975; indeed, total expected births may be inferred from aggregate fertility behavior. A peculiar empirical finding is that the additional expected fertility of nonterminators has not changed since 1955, despite the dramatic decline in total expected and actual fertility. The model leads to a dynamic expression for the duration pattern of current and cumulative fertility and for the proportion of couples who have terminated childbearing. The model is also used to analyze the effects of changing contraceptive failure rates on fertility patterns. For example, a decline in "timing" failure rates increases duration-specific fertility five years later.


Son preference and the demand for additional children in Pakistan.

This paper tries to take into account the sequential element in fertility decisions and continues an investigation originally begun by Namboodiri. We examine the extent to which the "desire to have additional children" can be explained by a variety of economic, sociological, and demographic variables. The probit maximum likelihood estimation procedure is utilized, and the analysis is based on cross-sectional data on 2,910 currently married women obtained from a national survey conducted in Pakistan in 1968-1969. The principal finding is the presence of a strong son preference both for the husband and for the wife.


Residential segregation in urbanized areas of the United States in 1970: an analysis of social class and racial differences.

Sociologists and urban commentators often portray metropolitan areas as highly segregated by social class and race. We measured the extent of socioeconomic residential segregation in urbanized areas of the United States in 1970, determined whether cities were as segregated as suburban rings, and compared levels of socioeconomic and racial residential segregation. We found moderate levels of residential segregation and socioeconomic groups. Levels of social class segregation varied little from one urbanized area to another and were about the same in central cities and suburban rings. Racial residentail segregation was much greater than the segregation of social classes within either the black or white communities. The extent of racial residential segregation does not vary by educational attainment, occupation, or income.


The dimensionality of the urban functional system.

This paper suggests that the formulation and testing of hypotheses relating the functional role of cities in a society to other urban structure and process variables might be facilitated by substituting a continous variable approach to the functional system for the prevailing discrete typologies. Using variables indexing the scope of economic activities in U.S. communities at two points in time, we elaborate a technique for identifying the dimensions underlying an existing typology, and the 56 largest SMSA's are ranked along these dimensions.


Sampling variability of own-children fertility estimates.

This paper develops methodology for estimating standard errors and confidence intervals for own-children estimates of age-specific birth rates and total fertility rates. The methodology applies to systematic samples of households, which are treated as simple random samples of women. The assumption of simple random selection, together with the treatment of sample subgroup size and reverse-survival ratios as constants instead of random variables, imply that sampling variability is slightly underestimated. The methodology is applied illustratively to fertility estimates based on the 1970 census of the Philippines.


Measuring the impact of child mortality on fertility: a methodological note.

Recent studies of the impact of child mortality on children ever born have used the "replacement factor" to measure mortality. When microlevel data are used, however, use of the replacement factor (or other variables which are nonlinear in the family's experienced child mortality rate) yields biased coefficients. An alternative model suggests a sequential, rather than a static, decision-making process to relate the decision to have an additional child to the reproductive experience to date. In this case, unbiased coefficients are obtained if the functional form is correctly specified. In the abscence of a priori knowledge of the functional form, it is difficult to untangle true effects from spurious ones.


Intradermal triamcinolone treatment of psoriatic onychodystrophy.

Intradermal injections of triamcinolone acetonide have used in the treatment of psoriatic onychodystrophies in seven patients. The therapeutic response initially is good but relapses appear inevitable. One patient developed rather persistent periungual hypopigmentation, thereby limiting the routine recommendation of this form of treatment.


[Does a circumscribed melanosis secondary to malignant melanoma exist?].

Regarding the rare phenomenon of diffuse melanosis of the skin secondary to widespread melanoma, the possibility of a circumscribed melanosis in melanoma patients is hypothetically discussed on the basis of a personal observation. Microscopically, such a circumscribed melanosis appears as clusters of melanin-laden macrophages.


Erythema dyschromicum perstans. A follow-up study from northern Finand.

Four patients with ashy dermatosis are described. Their ages varied from 8 to 12 years. Three had typical widespread macular eruptions and one had a linear lesion not described before. The follow-up investigation revealed that the eruption disappeared within 2 years in three of the patients. One patient could not be followed. The duration of the disease and the linearity of one lesion resembled lichen ruber planus.


Dermatofibrosarcoma of the face. Report of two cases from Nigeria.

Two Nigerian patients with dermatofibrosarcoma protuberans of the face are described. Both patients developed histologically typical tumours of unusual size. The condition is discussed in relation to previous reports of this unusual location and the frequency of dermatofibrosarcoma protuberans in Africa.


Evaluation in clinical practice of Dextrostix and the Eyetone Reflectance Meter.

Venous blood glucose concentration measured by Dextrostix-Eyetone Reflectance Meter method were compared with conventional enzymatic measurements of plasma glucose in the same 373 blood samples over the range of 0.55-22.2 mmol/l (10-400 mg/100 ml). Agreement between the two methods was good up to 5.5 mmol/l (100 mg/100 ml) but above 11.1 mmol/l (200 mg/100 ml) the Dextrostix-Eyetone method gave higher results for glucose concentration. The Dextrostix-Eyetone method is a reliable means of confirming or refuting the clinical diagnosis of hypoglycaemia and is useful in the day-to-day management of diabetes mellitus in situations where insulin dosage requirements are varying and where access to clinical laboratory facilities are not readily available.


Genetic heterogeneity in thyrotoxicosis patients with and without endocrine ophthalmopathy.

HLA antigens and humoral antithyroid immunity have been studied in 97 thyrotoxic patients [48 without and 49 with endocrine ophthalmopathy (EOP)]. A statistical significant increase of HLA-B8 frequency could be observed only in the thyrotoxic patients with EOP, whereas in patients without EOP B8 frequency was similar as to the one in the controls. The C locus antigen Cw3 was significantly different between both groups of patients: increased in those with EOP and statistically significantly decreased in those without EOP. Thyroid microsomal antibodies were found to be associated with HLA-B8 positivity and were noted with highest incidence in B8 positive EOP patients. No such association was observed for thyroglobulin antibodies. These data show a genetic heterogeneity in thyrotoxicosis patients with and without EOP. HLA-Cw3 positivity represents and increased risk to develop EOP in thyrotoxicosis, as frequency of this antigen was significantly decreased in thyrotoxicosis patients without any signs of EOP. The increased frequency for microsomal antibodies in thyrotoxic patients with EOP, especially in B8 positives underlines the genetically influenced autoimmune reactivity in that disorder.


A comparison of phenformin and metformin in the treatment of maturity onset diabetes.

A comparison of the effects of two dose levels of phenformin (50 mg once and twice daily) and metformin (850 mg twice daily and 1,700 mg twice daily) has been undertaken in 24 maturity onset diabetics whose diabetes had remained inadequately controlled with dietary measures alone. Both biguanides effectively reduced the fasting blood sugar and body weight of the patients, metformin apparently having a greater effect on blood sugar than phenformin. Serum triglycerides were lower on the larger dose of metformin than on either dose of phenformin. Both drugs in the larger doses reduced the serum cholesterol. Side effects were more common with metformin, particularly in the higher dosage and overall control of the diabetes was achieved in the same proportion of patients (33%).


Intra-HLA recombinations in juvenile diabetes mellitus.

Complete HLA and Bf typing of 18 families with juvenile diabetes mellitus (J.D.M.) showed that of 68 children, 9 bore recombinant haplotypes (13%). This frequency is significantly higher than the currently accepted 1.6% for intra-HLA recombinations with a p of 1.3 X 10(6) (binomial expansion) and may be related to the J.D.M. gene itself. Five of the nine crossovers were between HLA-A and B, and four between HLA-B and D. In one informative A/B recombination, Bf segregated with the HLA-B-D segment while in another two, it segregated in cis with HLA-A. This suggests the existence of two genetic sequences within the HLA region, one with Bf on the A site and a second one with Bf on the D site.


Temazepam (Euhypnos) as a hypnotic: a twelve-week trial in general practice.

One hundred and forty-seven patients requiring a hypnotic, took soft gelatine capsules containing 10 mg temazepam (Euhypnos) 10-30 mg at night, for up to twelve weeks. One hundred and thirty-three patients (90-5%) completed twelve weeks on drug. Hypnotic performance was rated Good or Very Good in 90% of their assessments and 93-2% of the assessments recorded no hangover effect. Adverse reactions were occasional headaches and nausea. There were no drug-related accidents. One hundred and forty-two patients (96-6%) said there was no adverse effect on their work. Seven patients who did not complete twelve weeks resumed normal sleep patterns and had no further need for hypnotics.


Temazepam (Euhypnos) as a hypnotic: a multicentre trial in general practice.

In a one week study of 236 patients, soft gelatine capsules containing 10 mg temazepam (Euhypnos) were evaluated as a hypnotic in general practice. Doses of 10-30 mg were generally well tolerated and performed satisfactorily in 76% of the patients. Seventy-two per cent experienced no hangover effect and 72% rated Euhypnos as good as or better than their previous hypnotic drugs.


Ticarcillin: pharmacokinetics in man according to different administration schedules.

The pharmacokinetic characteristics of ticarcillin, a semisynthetic penicillin more active than carbenicillin against Pseudomonas, were studied. Following a rapid intravenous infusion of 1 g, 2 g, 5 g and 10 g ticarcillin respectively the serum half-life was 72-4 minutes independent of the dosage administered. If ticarcillin is administered under steady-state conditions, e.g. continuous infusion of either 2g/hr or 1g/hr following a loading dose of 1g (total dose 5 g) the average steady-state serum concentrations are 125 microgram/ml and 105 microgram/ml respectively.


Lower respiratory tract infections treated with bacampicillin: a dose comparison.

In an open multicentre study of bacampicillin (Penglobe), a new orally well absorb ed prodrug of ampicillin, 516 patients with acute exacerbations of chronic bronchitis or pneumonia were treated by a group of Belgian pneumologists or internists. Bacampicillin was given in a dosage regimen of 400 mg or 800 mg three times daily. In patients with acute exacerbations of chronic bronchitis the clinical success rate was high, over 95% in both groups. An improvement in the sputum purulence score was seen in 93% of the patients with an initially purulent sputum and 69% had a normal mucoid sputum at follow-up. The clinical success rate in patients with pneumonia was also similar in both dosage groups with success rates over 96%. The total number of patients with adverse reactions was not more than 5-4%, of which the majority were considered mild or moderate. Each type of side-effect occurred in a frequency of 1-2% or less. There were no differences between the two dosage regiments as regards the frequency of side-effects indicates a remarkably good tolerance of bacampicillin also with the higher dosage.


Serum levels and urinary concentrations of kanamicin, bekanamicin and amikacin (BB-K8) in diabetic children and a control group.

Serum levels of kanamicin, bekanamicin, and amikacin were studied, after a single intramuscular dose of each antibiotic, in three groups of diabetic children, with their respective normal controls, paired by age, weight and sex. Lower serum levels were observed with kanamicin and bekanamicin in diabetic children compared to their controls. The difference in low serum levels was less noticeable with amikacin.


A clinical evaluation of pivampicillin in childhood pneumonia.

A clinical trial was done at the University Teaching (Children's) Hospital on 20 children suffering from clinical pneumonias with a specific drug regime with pivampicillin suspension. Every child was reexamined after 7-10 days of discharge from hospital. Only one chhild developed diarrhoea. There was no significant adverse drug toxicity shown in the biomedical investigations. Pivampicillin, three times a day at a dosage of 175 mg t.d.s. was found to be therapeutically effective in the treatment of childhood pneumonias.


Aladione (diftalone) in the treatment of subacute thyroiditis.

During 1974 and 1975 thirty patients with subacute thyroiditis referred to us were treated with diftalone (Aladione), a new non-steroidal anti-inflammatory drug, at a daily oral dose of 750 mg. The average treatment lasted 39 days (range 15-100), the mean age of the patients was 43-5 years (range: 22-70). The response to this therapy was prompt and excellent, in no patient was it necessary to switch to any other kind of treatment, such as the corticosteroids. The drug was tolerated very well although among our patients there were two diabetics on insulin and two patients with chronic duodenal ulcer. Following our experience in thirty patients we suggest that diftalone can be considered a treatment of choice in patients with subacute thyroiditis. We also think that during its prolonged administration leucocyte counts and transaminase levels should be regularly controlled.


Effect of beta-blockade on performance: use of beta-blockade in bowling and in shooting competitions.

The effect of oxprenolol on performance has been investigated on a double-blind basis in eight bowlers during a 30 hour continuous bowling competition ("marathon bowling") and in twenty-four pistol shooters in four internal competitions. An administration of 40 mg oxpernolol every six hours during the marathon bowling did not impair the scoring of the bowlers as compared with the subjects receiving placebo. Oxprenolol likewise exerted little influence on the subjective feelings of general tiredness as measured hourly during the bowling on a visual analogue scale. The beta-blockade effectively prevented metabolic changes, such as increases in plasma renin activity and in plasma free fatty acids, evoked by the prolonged physical stress. A single dose of oxprenolol (40 mg) given to pistol shooters 60 minutes prior to internal shooting matches resulted in a significant improvement of the scoring as compared on a double-blind basis with similar placebo matches. Some evidence was obtained to indicate that the latter improvement by oxprenolol might have been associated with a prevention of cardiovascular manifestations (mainly tachycardia) occurring during the shooting competitions. Unwanted effects were not recorded either in bowlers or shooters, by contrast, the beta-blockade appeared to produce a general feeling of well-being as frequently experienced by the shooters.


The use of disopyramide in resistant cardiac arrhythmias due to acute ischaemic heart disease.

Disopyramide, a new anti-arrhythmic drug, has been assessed in twenty-one episodes of cardiac arrhythmia secondary to acute ischaemic heart disease which failed to respond to more conventional suppressive therapy with lignocaine and other standard drugs. The intravenous administration of 100 mg of disopyramide resulted in suppression of two out of seven episodes of supraventricular arrhythmia, and eleven out of fourteen episodes of ventricular arrhythmias. Successful suppression correlated with blood levels of disopyramide in most cases of ventricular arrhythmias but not in the supraventricular arrhythmias. There were no adverse effects on blood pressure or cardiac function. There were minimal effects on conduction in the electrocardiogram. It is concluded that disopyramide, which probably acts by direct depression of myocardial irritability, is a useful new anti-arrhythmic drug in acute myocardial infarction, especially in those patients with ventricular arrhythmias resistant to more conventional anti-arrhythmic therapy.


Preparation of the large bowel for endoscopy.

After the use of a number of varied purgation regimens for precolonoscopy preparation of the bowel and use of X-Prep liquid for the purgation phase in 500 patients with a very high success rate and low side-effects, we have found that this preparation provides the best results, both for the patient and the endoscopist.


The use of betadine antiseptic paint in the treatment of Herpes simplex and Herpes Zoster.

Twenty-two patients with Herpes Simplex were treated with Betadine (povidone iodine) Antiseptic paint and seven with 5% idoxuridine in dimethyl sulphoxide, also one patient with bilateral lesions was treated with the two solutions, one on each side. The povidone iodine alcohol solution appeared to be at least as effective as the idoxuridine with minimal side-effects (some stinging in two patients). Good results were also obtained with this solution in twelve patients with Herpes Zoster.


Topically applied griseofulvin in the treatment of superficial dermatomycoses in Egypt.

One-hundred and fifty-five patients suffering from T. Capitis, T. Corporis, T. Cruris and T. Verisicolor participated in studies of topically applied griseofulvin. Various concentrations of the drug were prepared in an ointment form in a new solvent system. Successful results were obtained with the 2% preparation in cases of T. Corporis, T. Cruris and T. Versicolor. Failure of the therapy was observed in cases of T. Capitis. No side-effects occurred in any patient using the 2% preparation. In the opinion of the authors, topically applied griseofulvin in the new solvent system is safe and highly effective in the treatment of superficial dermatomycoses.


Phenylbutazone: factors influencing plasma concentrations.

The author points out that whilst the total metabolic fate of phenylbutazone in man is better understood, discrepancies between single and multiple dose half-lives, as shown in the studies described, still remain to be explained. It is concluded that the mechanism responsible for limiting the plasma concentration of phenylbutazone when doses are increased requires further study.


The effects of antacids on the absorption of enteric-coated phenylbutazone (butacote).

Phenylbutazone bioavailability from an enteric-coated formulation (Butacote) has been studied in normal volunteers following ingestion of a single 200 mg dose with water, aluminium hydroxide and magnesium trisilicate. No significant alteration in bioavailability of phenylbutazone from Butacote was noted in the presence of the antacids.


Investigation of phenylbutazone in synovial fluid.

1. Phenylbutazone was measured in the synovial fluid of 15 patients and found to be present in appreciable amounts which were related to plasma levels. 2. 80% of fluid levels were between 55% and 80% of those in plasma. 3. There was some evidence that in very actively inflamed joints phenylbutazone levels were lower. 4. There was no relationship to plasma or synovial fluid protein levels. 5. Phenylbutazone was found in one patient's synovial fluid three weeks after stopping the drug.


Have the anti-inflammatory drugs helped our understanding in rheumatology?

The author discusses the part that certain anti-inflammatory drugs have played in increasing our understanding of the pathogenesis of rheumatoid arthritis and in adding to our knowledge of the mediators of the inflammatory response. Increasingly, the therapeutic agents under discussion have directed attention to the role of the macrophage in inflammation. Closer examination of existing anti-inflammatory or anti-rheumatic drugs and their mode of action has more recently directed attention towards immunomodulation.


Phenylbutazone: plasma concentrations and effectiveness in patients with rheumatoid arthritis.

Phenylbutazone in doses of 50, 100, 200 and 400 mg/day has been given for four periods of three weeks to seven patients with rheumatoid arthritis. The trial was double/blind and the order of administration of the doses was arranged to eliminate order and carry-over effects. Before and at the end of each period the patient's clinical state was assessed by measurement of the pain score, duration of morning stiffness, paracetamol tablet count, grip strength, digital joint size, articular index and overall patient preference. The plasma phenylbutazone concentration was measured by gas liquid chromatography and the expected concentration of phenylbutazone in plasma was also predicted from a knowledge of the antipyrine half-life in each patient. Phenylbutazone had a significant therapeutic effect, in some cases after only 50 mg/day. There was however no correlation between the plasma concentration of phenylbutazone and its therapeutic effect. The observed plasma concentration of phenylbutazone agreed well with that predicted at doses of 50 and 100 mg/day. However, at 200 and 300 mg/day the observed plasma concentration was significantly lower than that predicted, perhaps due to saturation of the protein binding sites.


Juvenile chronic polyarthritis: clinical sub-groups and response to medication.

Juvenile ankylosing spondylitis, as a clinical entity, is outlined. A double-blind trial compared Safapryn and Butazolidin, each given for 3 months, for 15 treatment periods in 11 patients. No differences were shown, but the study highlighted the problems of assessing this condition, and some comments are made, hopefully, to guide further investigators in this field.


Danazol treatment and follow-up of patients with endometriosis.

In conclusion, we find that danazol has proved to be highly effective as a treatment for endometriosis. On the dosage used, we have not achieved the freedom from side-effects which we had hoped for, but in general these have been much less severe than those with combined oestrogen progestogen preparations. We propose continuing the trial with a reduced dosage of 400 mg daily in the hope of further reducing the incidence of side-effects.


Offspring survival, development, and operant performance following maternal ethanol consumption.

Gravid Sprague-Dawley-derived rats received 35-40% of their total calories in alcohol during pregnancy or pregnancy and the 23-day nursing period. Ethanol was administered both as the sole fluid source in a .1% saccharin solution and by twice daily subcutaneous injections. Two gravid control groups were matched for caloric and fluid intake to the experimental groups and received injections of the saline vehicle. The offspring were monitored from birth to adulthood on a variety of vital, developmental, and operant measures. Littermates of the behavioral offspring were sacrificed  and necropsied at 1 and 12 months of age and the major organs examined for pathology. Differences between alcohol and control groups were found for maternal weight gain, length of gestation, number of neonatal deaths, growth retardation of offspring to postnatal Day 72, date of eye opening, distance traversed on Day 15, contingent performance in the 1st week on continuous reinforcement, fixed ratio, and timing appetitive schedules, and on number of shock initiations and ability to discriminate contingencies on punishment schedules. No gross abnormalities were observed in the major organs at necropsy.


Development of postural asymmetry in premature human infants.

The head position of 95 infants, born between 30 and 37 weeks gestational age, was observed every 15 min for 2 hr weekly from birth until 39 weeks conceptional age. At 35 weeks and increasingly thereafter, significantly more time was spent with the head to the right than to the left. By 39 weeks the infants were similar to term infants: almost 90% spent 80% or more time with their heads to the right. The increase appeared independent of intra- or extrauterine experience; neither age at birth nor time since birth was consistently related to head position. Unlike term infants, prematures were equally likely to turn left as right and have their heads left as right 15 min after release from a midline position. These findings suggest complex determinants of asymmetry including factors intrinsic to the fetus and those contributed by the uterine environment.


The role of motor learning and cage size in the early enrichment effect in mice.

Three experiments with C57BL/10J mice examined the possible roles of cage size and simple motor practice as factors responsible for producing improved performance of animals reared in enriched environments. Neither factor was found sufficient to improve subsequent performance in a food-seeking task. Mice reared in flat environments containing a variety of objects, but designed to prevent any climbing practice, out-performed nonenriched animals on a task requiring extensive climbing activity.


Measurement of "true" glucose production rates in infancy and childhood with 6,6-dideuteroglucose.

"New" glucose production has been measured in 54 infants and children for the first time by continuous three-to-four-hour influsion of the safe, nonradioactive tracer 6,6-dideuteroglucose. The use of combined gas chromatography--mass spectrometry with monitoring of selected ions allowed deuterium enrichment in blood glucose to be measured on microliter samples with an error of less than 2 per cent. In the young child, glucose production increased in a slightly curvilinear manner from 1 kg. to 25 kg. body weight, when it reached 140 mg. per minute, almost the adult value of 173 mg. per minute (2.28 +/- 0.23 mg./kg.-min., mean +/- S.E.). Normalized for weight, glucose production in premature infants was 5.46 +/- 0.31 mg./kg.-min., in term neonates averaged 6.07 +/- 0.27 mg./kg.-min., in children below the age of six years was 7.1 +/- 0.27 mg./kg.-min., and in late childhood averaged 5.4 +/- 0.28 mg./kg.-min. Relative to estimated brain weight, however, glucose production was essentially linear from the 1-kg. premature infant to the 80-kg. adult. These data, the first measurements of "new" glucose production in childhood, suggest that brain size may be a principal determinant of those factors that regulate hepatic glucose output throughout life.


Diminution of bone mass in childhood diabetes.

Photon absorption measurements of forearm bone density in 196 insulin-dependent patients, age 6--26 years, were compared with findings in 124 controls. Expected density, gm. Ca/cm.2 bone width (M/W), was calculated from regressions of M/W on ulnar length for white and black male and female controls. There were no significant correlations between M/W differences from expected and serum Ca, Mg, P, or alkaline phosphatase levels, estimated physical activity level, insulin dosage, or the presence of joint contracture. White females averaged 8.2 per cent (+/- 1 S.E.M.) loss of M/W, as against white male average loss of 4.7 per cent +/- 1 and black female loss of 2 per cent +/- 2 (p less than 0.001); the black male population was too small for separate analysis. M/W loss greater than 10 per cent was seen in 29 per cent of white males, 19 per cent of blacks, and 48 per cent of white females (p less than 0.02). When the groups were further divided into those with duration of diabetes less than or equal to five years and those with duration greater than five years, significant reduction in M/W average loss over time was seen with white females (10.6 per cent +/- 1.2 to 3.7 per cent+/- 1.5, p less than 0.0001). Expression of this defect in bone mineralization is controlled by race and sex acting independently of each other.


A study of factors promoting and inhibiting lactation.

The present series of studies, made between 1972 and 1975, has shown that existing routines in the maternity ward, such as weighing the baby before and after breast feeding, can inhibit the establishment of lactation and increase the number of early failures. Giving information to the father in the maternity ward may be an important factor in promoting breast-feeding, as judged from the findings on duration of breast feeding and from the mothers' comments. The greatest effect observed was that of skin-to-skin and suckling contact during the first hour after delivery, which increased the median duration of breast feeding by 2 1/2 months. These findings illustrate that existing routines during the neonatal period should be re-examined as to their influence in promoting or inhibiting breast feeding.


Skinfold thickness as an indicator of neonatal hypoglycaemia in infants with birthweights over 2500g.

Some full-term infants with birthweights over 2500g suffer neonatal hypoglycaemia. These infants often appear to be poorly nourished, due to decreased amounts of subcutaneous fat. 100 normal term infants with birthweights over 2500g who were nursed, apparently asymptomatically, beside their mothers were chosen at random for study. As an objective indicator of malnourishment, standard deviation scores of skinfold thickness as a function of birthweight were derived from standards for each infant. Those infants with low skinfold standard deviation scores had significantly lower plasma glucose levels at four hours of age, but the correlation between plasma glucose and skinfold standard deviation scores, although significant, was too low for use as a screening method. The importance of finding an objective measurement for predicting neonatal hypoglycaemia in term neonates weighing over 2500g at birth is discussed.


Neural-tube defects and mid-cycle abstinence: a test of the 'over-ripeness' hypothesis in man.

The prevalence of mid-cycle abstinence at the time of conception of infants born with neural-tube defects was found to be only 6-7 per cent (8/119) compared with that of 9-8 per cent (32/325) at the time of conception of non-affected siblings. This is suggestive evidence against mid-cycle abstinence--and, by inference, over-ripeness--as an important possible cause of neural-tube defects.


H. influenzae meningitis treated with ampicillin or chloramphenicol, and subsequent hearing loss.

Sensori-neural hearing loss after H. influenzae meningitis in children has been reported to occur more frequently after treatment with ampicillin than with chloramphenicol. In the present survey, hearing was assessed clinically and, in most cases, audiometrically in 47 children seen after H. influenzae meningitis. Three children were found to have some sensori-neural hearing loss. In no case was this severe or suspected prior to examination. One was among 27 children treated with ampicillin; one was among eight treated with ampicillin and chloramphenicol; and one was treated with chloramphenicol and streptomycin. Most of the children received ampicillin in a dose of 250mg/kg/day or less, but the two who were treated with ampicillin and developed hearing loss were among five children who received higher doses, suggesting that ampicillin may be ototoxic when given in very high doses.


Longitudinal study of bowel and bladder control by day and at night in the first six years of life. I: Epidemiology and interrelations between bowel and bladder control.

The development of bowel and bladder control by day and at night during the first six years of life in 320 Swiss children in the Zurich longitudinal study (1955--1976) is described in detail. A scoring system was used which included intermediate stages of control. With toilet-training started in 96 per cent of the children during the first year of life, bowel control was completed in 32 per cent at age one, in 75 per cent at age two and in 97 per cent at age three. Complete bladder control by day and at night were established in none of the children at age one, in 20 per cent at ages two and three and in 90 per cent at age four. Complete bowel control and complete bladder control by day and at night were found in 5 per cent at age two, in 11 per cent at age three, in 77 per cent at age four and in 91 per cent at age six. The significant relationships between bowel control, bladder control during the day and bladder control at night (p less than 0-001) demonstrate that the same developmental process acts in bowel and bladder control. Highly correlated to each other, first bowel control develops, then bladder control by day and finally bladder control at night. The relevance of these interrelations for toilet-training and for the management of enuretic and encopretic children is discussed.


Longitudinal study of bowel and bladder control by day and at night in the first six years of life. II: The rôle of potty training and the child's initiative.

The rôle of potty training and the child's own initiative to use the pot were evaluated in 320 Swiss children in the Zurich longitudinal study (1955--1976). Initiating potty training in the first months of life has a short-term effect on bowel control, but no effect on bladder control by day or at night. Frequent daily prompting to use the pot results in a higher percentage of completely bowel-trained children, and of children partially but not completely dry during the day. It has no influence on bladder control at night. Asking for the pot is part of the maturation process of bladder control. A child who does not ask for the pot may not soil himself but is unlikely to be dry by day nor, especially, by night. The child's asking for the pot cannot be induced by frequent prompting.


Mothers' speech to young children: variation in context.

Recent research has demonstrated the importance of particular features of mothers' speech in influencing the rate of language acquisition in very young children. In the present study of 22 mother-child pairs, the occurrence of these features was examined in samples of mothers' speech to children (aged 18 to 29 months), obtained in unstructured observations in the homes. The features facilitating language acquisition were found to be more frequent in the context of joint attention to pictures or books; speech in other contexts showed social-class differences, with a higher frequency of 'facilitating' features in the speech of middle-class mothers. There was also a tendency for the relative frequency of these features to be positively associated with the children's linguistic ability.


Teaching medical students about mental handicap.

The care and management of mental handicap is a relatively increasing problem, and medical responsibilities for the prevention, detection, treatment and management of mental handicap are undergoing significant changes in emphasis. The present paper examines the current position of undergraduate medical training in this field in medical schools in the United Kingdom and in Eire. Although there are considerable training variations between different schools, the over-all style of presentation is not thought to facilitate appropriate learning in this subject for future doctors. There is a suggestion that medical students themselves would welcome more attention to this field. Greater co-ordination is needed within existing teaching programmes. The appointment of senior academics with multiple departmental attachments and a major commitment to the subject of mental handicap may be a valuable step forward.


Ablepheron macrostomia syndrome.

Two male children are reported with similar features, including absent eyelids, eyebrows, eyelashes and hair, fusion defects of the mouth, expressionless facies, rudimentary external ears (but normal hearing), ambiguous genitalia, absent or rudimentary nipples, coarse dry skin with redundant skin folds and delayed expressive language development. The relationship of this syndrome to previously reported cryptophthalmos syndromes is discussed.


Atelencephaly.

A 13 1/2-month-old boy with severe microcephaly was found to have nearly total absence of the telencephalon. The patient had marmorated skin, hypoplastic penis and undescended testes. Spastic tetraparesis was present. Moro, grasp and sucking reflexes were easily elicited. He could not sit or stand, but was able to raise and support his head. He had occasional convulsions and a tendency to hypothermia and vomiting. The EEG showed symmetrical low-voltage theta-delta activity. His psychomotor development was severely retarded. Bone age was normal. Head circumference was 28cm at six months and did not increase after this age. At autopsy the small cranial vault and meninges were found to be intact. Brain weight was 105g. The supratentorial part of the brain was extremely small, consisting of an irregularly lobulated mass about 3cm in diameter and without any median fissure or ventricular cavity. The telencephalon was severely involved and partly replaced by gliomesenchymal scar tissue, while the diencephalic structures, including the eyes and the optic nerves and chiasm, were comparatively well-developed. The cerebellum and brain stem were essentially intact.


Migraine and migraine equivalents in children.

Migraine is one of the most common disorders seen in paediatric neurological practice. It may present with an obvious diagnosis of 'classical migraine' or it may mimic acute neurological disease. It may require extensive investigation and, before the more classical full-blown features of migraine appear, there can be a worrying period of follow-up for the physician, wondering whether he has missed some serious pathology--especially in cases of hemiplegic and ophthalmoplegic migraine. Differentiation from epilepsy, particularly of psychomotor type, may be impossible. Migraine frequently presents as a stress reaction to school failure. If this underlying cause is unrecognised and uncorrected, the response to medication will be poor.


Effects of somatostatin and human gastrin I on the lower esophageal sphincter in man.

The influence of gastrin and somatostatin on the lower esophageal sphincter was investigated in a total of ten metabolically healthy volunteers and one patient with Zollinger-Ellison syndrome. It could be shown that only unphysiologically high concentrations of gastrin produce a rise in pressure in the lower esophageal sphincter, while somatostatin has neither an effect on the lower esophageal sphincter pressure, nor is it able to inhibit the pharmacological effect of exogenic gastrin administration. The results of this study demonstrate that normal levels of serum gastrin do not seem to have much effect of resting LES pressure, nor does somatostatin. (Gastrin, in fact, in pharmacologic dosage does have an effecton the tonicity of the lower esophageal sphincter.)


Bile acids in liver disease associated with inflammatory bowel disease.

To investigate the possibility that bowel-related liver disease is due to accumulation of abnormal bile acids in the enterohepatic circulation, bile acids have been measured in gall-bladder bile and portal blood of patients with chronic bowel disease, none of whom had liver disease. There was no difference in the composition and concentration of bile acids in bile and portal blood compared with control patients. In a second study, serum bile acid composition and concentrations were similar in two groups of patients with liver disease, whether they had bowel disease or not. In a further study, post-prandial serum bile acid concentrations were not elevated in a group of patients with chronic bowel disease, making it unlikely that subcliical liver disease was present. No evidence has been found to support the hypothesis that bowel-related liver disease in man results from the action of abnormal bile acids.


Intramural ganglion cell degeneration in inflammatory bowel disease.

Comparable histologic alterations of intramural nervous tissue were reported in various diseases of the small and large intestine. In 6 cases, an intestinal obstruction was present which led to secondary intramural inflammation. The obstruction was induced by the spastic segment in Hirschsprung's disease (3 cases), by rectal atresia (2 cases) and by postoperative ischemic damage to the intestinal wall (1 case). In 4 other patients, the inflammation was predominant. The diseases considered were necrotizing enterocolitis (1 case), membranous enteritis (1 case) and Crohn's disease (2 cases). On the one hand, inflammatory infiltration composed primarily of lymphocytes was observed histologically in various degrees proximal to the obstruction in all cases. On the other, comparable alterations were found in splittering of nerve fibers and deterioration of nerve cells (degenerative alterations) in the plexus myentericus as well as hyperplasia and hyperchromasia of ganglion cells. Schwann cell proliferation and fibrosis in nerve fibers (reactive alterations). Until now such alterations were only observed in Chagas' disease and in ulcerative colitis, especially complicated by toxic megacolon. It is suspected that the neurodegenerative alterations in these diseases are toxically induced.


Methylation of histamine in the gastric mucosa.

Methylation of histamine in the gastric mucosa of various species has been studied in vitro and in vivo. When gastric mucosal homogenates of rat, guinea pig, cat, dog, and pig were incubated with 14C-histamine in the presence of S-adenosyl methionine Ntau-methylhistamine was formed as the only methylated histamine derivative. Excessive concentration of Ntau-methylhistamine inhibited the formation of Ntau-methylhistamine. Pretreatment of guinea pigs with prednisolone, aminoguanidine, or pentagastrin neither influenced in vitro the formation of Ntau-methylhistamine significantly nor shifted the methylation reaction towards the side chain. Pretreatment of guinea pigs with the histamine H2-receptor blocker cimetidine significantly enhanced the formation of Ntau-methylhistamine in vitro. In pooled samples of guinea pig gastric mucosa histamine and Ntau-methylhistamine were found. Under none of these circumstances was Nalpha-methyl-or Nalpha,Nalpha-dimethylhistamine found. It is concluded that in rat (to a small extent), guinea pig, cat, dog, and pig gastric mucosa the formation of Ntau-methylhistamine is the only methylating pathway of histamine. In cases where other methylated histamine derivates (Nalpha-methyl- and/or Nalpha,Nalpha-dimethylhistamine) are found they must origin in sources other than the gastric mucosa.


Serotonin distribution in the canine gastric mucosa: acute response to feeding and pouch preparation.

The gastric mucosa of anesthetized dogs was examined for serotonin (5-HT) in all major stomach regions. In animals examined immediately after anesthesia induction, the proximal corpus or antrum had substantially more 5-HT than the pyloric canal. Histological studies in 4 animals reveal a general pattern of declining enterochromaffin cell populations, from proximal corpus to pyloric canal. Either antral distention or digestive activity was induced in different groups of dogs, and only the latter produced a demonstrable, albeit transient, change in 5-HT. In 6 animals prepared with gastric fistulas, a uniform distribution of 5-HT was found throughout the stomach, after secreting 0.4 ml/h for 4 h neutral gastric juice. Their 5-HT concentrations in most regions of the stomach were substantailly greater than in any other animals in this study.


Gastric ulceration associated with experimental vascular occlusion.

The left gastric artery was cannulated in 17 cats, and a single dose of microspheres was injected into the artery, after which it was ligated. Microspheres with diameters of 8-10 micrometer induced gastric mucosal erosions that healed within 1-2 weeks. Microscopic examination revealed that there were few microspheres in the submucosa, more in the muscularis and large numbers in the glandular layer. The muscularis mucosae was intact. After injection of 50 +/- 5 micrometer spheres a large gastric ulcer developed. The ulcers healed after 4 weeks. Microscopically, the ulcer penetrated through the muscularis mucosae, and many microspheres were seen in the submucosa and serosa beneath the ulcer.


Inhibition of gastric electrical and mechanical activity by intraduodenal agents in pigs and the effects of vagotomy.

Miniature pigs were chronically implanted with gastric electrodes, strain gauge devices allowing the measurement of circular contractions in the antrum and body of the stomach, and with a duodenal catheter through which duodenal infusions were administered. Inhibition of gastric motility by intraduodenal agents was measured before and after truncal vagotomy in conscious animals 20 min after feeding of a normal meal. The agents infused in the duodenum (10 ml/min, 4 min), were: HCl 75 mEq/l(A), glucose 100 g/l(G), olive oil 10% pH 7(L), amino acids (AA) and saline. Before vagotomy, motor activity during the first 5 min was inhibited 50-80% with respect to basal levels; the duration of action was G No. L greater than A; AA had very little effect, and saline no effect. Inhibition was on the whole similar in the antrum and gastric body. After vagotomy, the inhibitory effect of A was reduced from 80 to 20% in the antrum, and completely suppressed in the gastric body. Inhibitory effects of G and L were completely suppressed.


Barbiturate-induced choleresis: possible independence from microsomal enzyme induction.

The influence of four barbiturates, phenobarbital, barbital, thiopental, and pentobarbital, on bile secretion and on the hepatic microsomal system was studied in anesthetized rats. The barbiturates were injected intraperitoneally for 4 days and the animals were studied on the 5th day. It was found that: (1) phenobarbital, barbital, and thiopental, but not pentobarbital, significantly increased liver weight, cytochrome P-450 concentration in the liver, decreased pentobarbital sleeping time and induced a hypertrophy of the smooth endoplasmic reticulum in the hepatocytes at electron microscopy; (2) in contrast, the four barbiturates, including pentobarbital, significantly increased bile flow; this increase was attributed to an increase in the bile acid independent bile flow. There was no correlation between the increase in bile flow and the cytochrome P-450 concentration in the liver. It is concluded that the increase in bile flow observed after barbiturate treatment in the rat is possibly independent of the hepatic microsomal enzyme induction produced by these drugs.


Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark.

The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970-1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27%. A marked peak of incidence was found at 12-14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May-July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.


Biological activity of synthetic human insulin.

The biological activity of human insulin, prepared by total chemical synthesis, was compared in various tests in vivo and in vitro with that of natural human or pork insulin. The potencies of the synthetic and natural hormone, as determined by the mouse convulsion assay, by hypoglycaemic effect and diaphragm glycogen increase in fasted rats in vivo, or by stimulation of 14C-glucose metabolism in fat cells and binding to anti-insulin serum in vitro, did not differ significantly. It is concluded that this synthetic human insulin is biologically equivalent to the natural hormone.


Lipids in the pulmonary artery and the lungs of severely diabetic rats. A histochemical and chemical study.

To investigate the effect of diabetes on the lipid composition of the lungs and of the pulmonary artery, 43 streptozotocin diabetic rats and 43 control rats were examined. Triglyceride deposits were observed by a histochemical method in the branches of the pulmonary artery in 10 diabetic rats but in none of the controls. In the pulmonary tissue of the diabetic rats the total lipid content was not different from that of control animals, but the relative amount of phospholipids was decreased (p less than 0.001), and that of non-esterified fatty acids (p less than 0.001) and triglycerides (p less than 0.05) increased as compared to the control rats. These results indicate abnormalities in the lipid metabolism of the pulmonary artery and lungs during insulin deficiency.


Does glucagon play a role in the insulin resistance of patients with adult non-ketotic diabetes?

Using a constant intravenous infusion technique we have measured in vivo insulin resistance in 17 normal subjects, five patients with chemical diabetes, and 13 non-ketotic diabetic patients with fasting hyperglycaemia (FBS greater than 120 mg/100 ml). All of the diabetic patients were non-obese. The results demonstrated that the diabetic patients were insulin resistant compared to normals and that the degree of insulin resistance was greater the more severe the diabetes. No differences in plasma glucagon levels were found among the different groups during the infusion studies. These results demonstrate that non-obese, non-ketotic diabetic patients are insulin resistant and that abnormalities in plasma glucagon concentrations do not account for this insulin resistance.


Mortality from cardiovascular diseases among diabetics.

A retrospective analysis of a cohort of 5210 diabetic patients revealed a mortality rate 1.3 times higher than in the general population of Warsaw. The higher death rate in the cohort under study was mainly due to an excess mortality from coronary heart disease and cerebrovascular disease. The excess mortality was greater in men than in women. Th risk of death from cardiovascular diseases was higher among the patients with early onset diabetes. Mortality from cerebrovascular disease was highest in patients treated with insulin, intermediate in the group treated with oral drugs, and lowest in the group treated only with diet. The mortality ratio from coronary heart disease in men was not related to the method of hypoglycaemic therapy given at the onset or during the course of the diabetes. In women, the highest mortality was in the group treated with insulin, intermediate in the group treated with oral agents, and lowest in the group treated with diet only.


Plasma insulin and glucose levels in maturity onset diabetics treated with chlorpropamide.

19 diabetic patients taking various doses of chlorpropamide were studied throughout a normal day. Plasma chlorpropamide levels were related to the daily dose of the drug and were relatively constant throughout the day. Blood glucose concentration was highest and the plasma insulin concentration lowest in patients taking the largest dose of chlorpropamide. Patients on a small daily dose of chlorpropamide were well controlled and had higher than normal insulin levels. --12 patients were restudied 10 days after stopping chlorpropamide. Although diabetic control deteriorated in all patients, plasma insulin concentration did not change significantly. This suggests that the long-term hypoglycaemic action of chlorpropamide is not dependent on an effect on the concentration of insulin in peripheral venous blood.


["Pericarditis epistenocardica" as as a marker of extensive myocardial infarction. Clinical, electrocardiographic and enzymatic study (author's transl)].

Pericarditis may complicate the early phase of myocardial infarction (MI). It occurs when necrosis involves the epicardial surface. To verify if pericarditis may be regarded as a marker of extensive MI, 60 patients with anterior or inferior MI admitted to the Coronary Care Unit within 6 hours from onset of symptoms, were studied by clinical, electrocardiographic and enzymatic parameters. 20 patients developed left ventricular failure (LVF) assessed by clinical, radiologic and hemodynamic indexes (15 mmHg has been considered the upper normal value for mean wedge pulmonary pressure). 9 of the 11 patients with pericarditis (PP) had LVF, versus 11 of the 49 non PP group (P = 0.002). Life threatening arrhythmias (ventricular tachicardia and fibrillation) appeared in 5 of the 11 PP versus 7 of the 49 non PP group (P = 0.04). No significant difference has been found between the two groups concerning the inhospital mortality. In a follow-up of 3 to 18 months, no difference in mortality was observed, while the functional recovery in the PP group was significantly worse (I and II versus III and IV New York Heart Association classes P = 0.003). Higher sigmaST values were found in precordial maps of the PP group, on admission (P = 0.03). After a deep spontaneous fall, sigmaST showed a reelevation which was similar in the two groups. SigmaR showed a greater % decrease however not statistically significant in PP. Creatinekinase enzymatic infarct size was significantly higher in PP group (P = 0.0002). It is concluded that pericarditis is a clinical marker of extensive MI and may be useful in evaluating prognosis and effectiveness of therapeutic interventions in MI.


[The specificity of the CPK MB enzyme kinetic test for the diagnosis of acute myocardial infarction (author's transl)].

The clinical usefullness of the CPK MB test (spectophotometric method) was evaluated on 139 patients admitted to a Cardiovascular Diseases Department with a diagnosis of suspected myocardial infarction. Serial determinations of serum MB isoenzyme creatine kinase, total creatine kinase, lacate dehydrogenase and hydrossibutirrate dehydrogenase were made at 1st, 2th, 3th, 4th, 5th, 6th, 7th day. Incidence of CPK MB false positive and false negative data were also determined and correlated with the electrocardiogram pattern and serum levels of other standard enzymes. Results indicate that the CPK MB kinetic test is highly specific (94%) and promptly available in the early diagnosis of acute myocardial infarction.


[Blood and plasma viscosity during the various phases of the acute myocardial infarction (AMI). Preliminary study (author's transl)].

In a group of 29 infarct cases, the behaviour of the same blood and plasma viscosity at the initial stage and two weeks after the AMI was. At the same time as the rheological tests, we evaluated a few parameters of the lipid (cholesterol-triglyceride), proteic (fibrinogen) and glycoproteic (haptogloben-alpha1 acid GP ceruloplasmin) balance. Though noting significant variations of all the parameters studied, the correlation between the viscosity of blood and plasm and the other humoral parameters is of little significance. In fact except for the good correlation between the blood viscosity with hematocrit and with the fibrinogen (only on 7th day and at high gradient) the other correlations, when present, are occasional or of little significance. It is our intention to continue the research undertaken, considering either the utility of the early diagnosis of a rheological change or the possibility that the latter may be a further parameter to be related to clinical, hemodynamic and humoral parameters useful for determining the prognosis of the AMI.


[Electrophysiological mechanisms of tachyarrhythmias associated with the sick sinus syndrome (author's transl)].

Atrail programmed stimulation (APS) and His bundle recordings were performed in 24 patients with assessed sick sinus syndrome, 14 of whom had previously suffered from bouts of spontaneous paroxysmal tachycardias (Group I) and 10 with no history of previous similar complication (Group II). APS reproduced re-entry arrhythmias in 13 cases of Group I (92%). In 6 cases, junctional reciprocating tachycardia was elicited and the atrioventricular node function curve showed a typical steplike profile, consistent with longitudinal dissociation of the node itself as a cause of reciprocation. In 7 cases with previous paroxysmal atrial tachycardias, APS elicited intra-atrial re-entry arrhythmias. Absolutely no arrhythmia was elicited by APS in the 10 cases of Group II. High incidence of basal prolongation of conduction intervals was observed in both Groups (11 cases in Group I, 6 cases in Group II). Intra-atrial and/or atrio-nodel conduction delays were recognized in all the cases with intra-atrial re-entry arrhythmias. These results suggest that so called bradycardia-tachycardia syndrome should be regarded as an independent clinical form from the sick sinus syndrome, sharing with the latter the sinusal disfunction only. Re-entry mechanisms seems to be mainly responsible for the inititation of paroxysmal tachyarrhythmias: re-entry in the atrium, based on stable conduction delays, is probably correlated with scattered lesions of the same degenerative process affecting the sinus node. On the contrary, the frequent association of sick sinus syndrome with junctional paroxysmal tachycardia and its comples dissociation mechanism of the a-v node, raises the suspicion that, in such cases, two completely different processes are merely coexisting: a degenerative lesion of the sinus node and an anatomical or functional anomaly of a separate portion of the conduction system.


[Mitral valve prolapse in patients with coronary artery insufficiency. Report of two unusual cases (author's transl)].

The authors illustrate two peculiar cases of mitral valve prolapse in patients with coronary artery disease. The first case reports a mitral valve prolapse that, absent in basal conditions, is unmasked by a premature ventricular beat. In the second case concerns about the manifestation of a mitral valve prolapse developed during the course of retrosternal chest pain.


[Unfavourable effects of the sublingual isosorbide dinitrate. Osbervations on nine personal cases (author's transl)].

Nine among our patients have shown some phenomena of intolerance owing to the engagement of the sublingual isosorbide dinitrate. Even if these troubles are comparatively rare (no more than 10% of the cases we have examined), nevertheless we deem it necessary to exhort to some prudence in the administration of this drug, at least for the first time.


Host origin of lymphoid cells in thymomas developed from subcutaneous thymus grafts in Buffalo rats.

Ten out of 31 male Buffalo rats developed thymomas, 18 months after birth, from the subcutaneous thymuses grafted neonatally either from female or male litter mates. Most of them were of lymphoid cell type and contained numerous lymphoid cells within the network composed of neoplastic epithelial cells, as mediastinal thymomas. Lymphoid cells in the subcutaneous thymomas had normal diploid karyotype and were of host type with the Y chromosomes. These facts may indicate that lymphois cells intermingled in the network of neoplastic epithelial cells are non-neoplastic in nature.


Measurement of tritiated thymidine labeling index by incubation in vitro of surgically removed cervical cancer.

Autoradiographic study was made on 24 cases of uterine cervical tumor, including 22 cases of squamous cell carcinoma, using a technique of in vitro labeling of surgical specimens with tritiated thymidine (3H-TdR) under hyperbaric oxygen. Labeling index of the cervical cancer ranged from 8.7 to 30.4% and was well correlated with the histological subtypes (spinal, transitional, and basal cell types). The upper limit of the growth fraction was also estimated from the general relationship between phase lengths. The necessity of sufficient oxygen tension for the S-phase cells to effect synthesis of DNA was stressed.


Effect of diethylstilbestrol on the cell kinetics of subcutaneous growth of diethylstilbestrol-induced renal carcinoma.

A response to diethylstilbestrol (DES) of DES-induced renal carcinoma in Syrian hamster was studied by comparing subcutaneous growth of this tumor in DES-treated and untreated animals with respect to the growth curve, cell cycle time, Tc, growth fraction, GF, and cell loss factor, phi. In both conditions the tumor growth followed the Gompertz curve, but the latent period was 14 days longer without DES than with DES. In the untreated animals, Tc was 80% longer due to increases of TGl and TS. However, phi was not changed significantly and GF rather increased without DES. It was concluded that DES-dependency of this tumor growth was manifested in the prolongation of Tc.


Inhibitory effect of mepitiostane on the growth of mammary tumor of a rat.

Mepitiostane (2alpha,3alpha-epithio-5alpha-androstan-17beta-yl 1-methoxycyclopentyl ether) is an orally active anti-estrogenic and anabolic-androgenic steroid compound. Mepitiostane administered orally suppressed the growth of transplanted estrogen-dependent mammary tumor in rats. This result was compared with the oral administration of fluoxymesterone, which is widely used orally for treatment of advanced breast cancer. Experimental result showed that Mepitiostane has a more dominant antitumor activity than fluoxymesterone. Therefore, this new compound may be useful for clinical treatment of breast cancer.


Induction of squamous cell carcinoma in the lung of C57BL/6 mice by intratracheal instillation of benzo[a]pyrene with charcoal powder.

Squamous cell carcinomas were readily induced in the lung of C57BL/6 mice by repeated intratracheal instillations of benzo[a]pyrene with charcoal powder suspended in saline solution. Intratracheal instillations were performed once a week for 8 weeks, and the observation period of the experiment was 40 weeks. Some of the tumors were highly keratinized and others were moderately keratinized squamous cell carcinomas. At a later period of observation, poorly differentiated squamous cell carcinomas were found. Invasion into blood vessels was occasionally seen but metastasis to regional lymph nodes or distant metastasis was not found. One tumor from the mouse killed on the 280th day was successfully transplanted subcutaneously into C56BL/6 mice. This mouse, killed on the 84th day after the first tranplantation, had a pulmonary metastasis.


Comparative study on radiosensitivities of cultured cell lines derived from several human tumors under hypoxic condition.

Three human cell lines, Burkitt lymphoma cells (P3HR-1), epidermoid carcinoma cells (HeLa S3-1), and melanoma cells (HMV) were irradiated with 200 kV X-rays under three different oxygen conditions. The values of D0 and D10(-2) were estimated for survival curves, and then the dose-modifying factors (DMF) were calculated, for the oxygenated and hypoxic irradiations. These DMF values for oxygenation were not different for each cell line, but those for hypoxia revealed considerable difference for cell lines. From the comparison of modifications due to variable oxygen concentrations on the survival curves of Burkitt lymphoma cells with those of other resistant cells, it is concluded that the shoulder of the survival curves becomes larger primarily with lowering of the oxygen tension, and then D0 value increases followed by a decrease in n value, while in oxygenation, the decrease in D0 value takes place after n value becomes close to 1.


Cancer in colitis: assessment of the individual risk by clinical and histological criteria.

The cancer risk among 229 patients with extensive ulcerative colitis observed during January 1, 1966 to February 29, 1976 is correlated with the length of history and the histological findings in rectal and colonic biopsies. Five patients are known to have developed carcinoma. No carcinoma was observed in 578 patient years of follow-up within 10 years of onset of the colitis, but the risk in the second decade was approximately 1 in 200 patient years and in the third, 1 in 60 patient years. Severe epithelial dysplasia was rare and found in 32 biopsies from 13 patients. No carcinoma has occurred during the period of follow-up in patients without dysplasia. It has not been possible to follow the development of dysplasia in sequential biopsies. Seven patients with consistent severe dysplasia on biopsy have been treated surgically; carcinoma confined to the bowel wall (Dukes' A) was found in 4. A scheme of management for patients with extensive colitis, including regular rectal and colonic biopsies, is proposed. Our results suggest that such a program will isolate a small group of patients who require surgical treatment for established precancerous change or carcinoma with a high likelihood of cure.


Effects of arginine vasopressin on capillary filtration in the cat ileum.

The effect of local intraarterial infusion of arginine vasopressin was studied in a vascularly perfused segment of cat ileum. Systemic arterial pressure (Pa), superior mesenteric arterial pressure (Pma), superior mesenteric venous pressure (Pv), blood flow (QB) and intestinal volume (V) were continuously monitored. Intestinal lymph flow (QL), lymphatic protein clearance (LPC), isovolumetric capillary pressure (PC), capillary filtration coefficient (KF,C) and vascular resistances were also determined. A dose-response relationship was obtained for several parameters and a dosage of 17.5 mU per kg per min was chosen for more extensive study. At this level vasopressin was found to increase both systemic (Pa) and local (Pma) arterial pressures while decreasing superior mesenteric venous pressure (Pv), capillary pressure (PC) and blood flow (QB). Precapillary (Ra), postcapillary (Rv), and total (Rt) vascular resistance were all increased during the vasopressin infusion; however, a greater effect was demonstrated on the precapillary vessels as indicated by an increased pre- to postcapillary resistance ratio (Ra/Rv). Vasopressin infusion also reduced the capillary filtration coefficient(KF,C), intestinal volume (VT), lymph flow (QL) and lymphatic protein clearance (LPC). The results of this study clearly establish an effect of vasopressin on transcapillary and lymphatic volume flows in the small intestine.


Value of a single forceps biopsy of colonic polyps.

The accuracy of colonoscopic biopsies in predicting the histological diagnosis of colonic polyps removed at colonoscopy or at laparotomy was studied. Forty-two patients were colonoscoped before the removal of 50 polyps. A single fractional biopsy was obtained from each lesion with the standard endoscopic biopsy forceps and was compared to the final histological diagnosis of each excised lesion. Thirteen (26%) of the singular fractional biopsies did not demonstrate the significant histological features of the excised polyps. These tiny biopsies do not adequately represent the entire polyp. Moreover, the 2- to 3-mm size of the biopsy does not permit the study of the central submucosal area of the polyp stalk, the critical area for assessing invasive malignancy. Histological examination of a completely excised polyp is essential for accurate diagnosis and appropriate therapy.


Duodenal ulcerogens, cysteamine and propionitrile, stimulate serum gastrin levels in the rat.

Cysteamine and propionitrile are members of a family of compounds which induce the formation of acute duodenal ulcers in fasted and fed rats. Gastric acid secretion is increased by both agents, and acid hypersecretion appears to be required for ulcer formation. To determine the role of gastrin in the ulcerogenic mechanism, cysteamine and propionitrile were administered to fasted rats and their effect on fasting and food-stimulated serum gastrin levels was studied. Intragastric administration of cysteamine caused a 3- to 4-fold increase in fasting serum gastrin levels over the values of controls. Propionitrile was a less effective stimulant of gastrin release, causing a 1.5- to 2-fold increase in gastrin levels over matched control rats. The food-stimulated rise in serum gastrin levels after either a chow meal or intragastric instillation of a peptone solution was markedly enhanced by cysteamine pretreatment. Three hours after feeding the serum gastrin levels of cysteamine pretreated rats were 6 times higher than those of fed controls. The high serum gastrin levels of cysteamine-pretreated fed rats could not be explained solely by the additive effects of cysteamine and food, indicating that a potentiating interaction may exist between the two stimulants of gastrin release. The importance of this drug-induced stimulation of gastrin release, under both fasted and fed conditions, in the ulcerogenic process has yet to be ascertained.


Studies of esophageal epithelial cell proliferation in patients with reflux esophagitis.

Accelerated cell turnover has been held responsible for the basal zone thickening of the esophageal squamous mucosa of patients with reflux esophagitis. We have studied the in vitro proliferative activity of the basal zone in suction biopsy specimens obtained from normal subjects, from patients with medically treated esophagitis, and from patients who had previously undergone anterior fundoplication. In patients with severe esophagitis, the basal zone showed a significantly elevated [3H]thymidine labeling index in contrast to that of mild esophagitis patients and that of normal subjects. When esophagitis was associated with mucosal lesions at endoscopy, the labeling index was higher than that seen in esophagitis patients without endoscopic abnormalities. Significantly increased thymidine labeling was found only in patients with the most severe changes of papillary length or basal layer thickening. We therefore conclude that there is an increased basal zone uptake of [3H]thymidine in severe esophagitis which suggests increased cell turnover as the mechanism for basal zone hyperplasia. Present techniques for measuring mucosal uptake of [3H]thymidine, however, do not permit the distinction of mild degrees of esophagitis from normal epithelium.


Krebs cycle, pentose phosphate pathway, and glycolysis in the uninvolved gastric mucosa of peptic ulcer and gastric cancer patients.

Uninvolved gastric mucosa from duodenal ulcer, gastric ulcer, and gastric cancer patients was incubated with [1-14C]glucose and [6-14C]glucose in order to assess the relative contributions of the pentose phosphate pathway and Krebs cycle to glucose metabolism. [14C]Glucose counts retained by the tissue, glycolysis, and pyruvate formation were also measured. Tumor tissue from the cancer patients was included in the study. Less than 1.2% of the glucose entering the tissues was metabolized via the pentose phosphate pathway; suggesting that this pathway plays a minor role in energy production from glucose. The major determinant of energy production was the Krebs cycle. Its contribution to glucose metabolism was greatest in the body mucosa of duodenal ulcer patients, less in the uninvolved body mucosa of gastric ulcer patients, and lower still in the corresponding body mucosa of gastric cancer patients. The low levels of Krebs cycle activity seen in the latter tissue resembled those of uninvolved antral mucosa. The smallest Krebs cycle contribution was seen in tumor tissue. [14C]Glucose counts retained by the tissue and glycolysis both tended to vary inversely with Krebs cycle activity among the tissues studied. Thus, both were small in the body mucosa of noncancer patients and somewhat larger in the body mucosa of cancer patients, in uninvolved antral mucosa and in tumor tissue.


Proliferation rate and transit time of mucosal cells in small intestine of the diabetic rat.

Streptozotocin-induced diabetes in the rat alters intestinal function, causes hyperphagia and arrests body growth, but stimulates intestinal growth, particularly in the mucosa. Therefore we measured several indices of epithelial cell proliferation to gain insight on possible factors responsible for the increased mucosal cell mass in the small intestine. We examined epithelial cell proliferation in upper jejunum and terminal ileum of weight-matched control and diabetic rats pair fed or eating ad libitum. Cell proliferation was measured two ways: (1) isolating whole crypts 1 hr after injection of [3H]thymidine ([3H]TdR) and calculating disintegrations per minute per crypt (dpm per crypt), and (2) autoradiography of mucosal sections to obtain labeled cells per crypt, total cells per crypt-villus column, and cell migration rates. Autoradiography showed diabetes: (1) increased cell number of crypt-villus columns and increased labeled cells per crypt section, primarily jejunum, and (2) did not alter cell migration except for an increase in the ileum of diabetics eating ad libitum. Cell proliferation measured as dpm per crypt virtually doubled in diabetics in both segments regarless of dietary regimen. Dpm per crypt is a three-dimensional measurement based on the whole crypt. The increase in cell number and labeled cells per crypt in jejunal sections is also consistent with increased cell division, but shows a much smaller effect. The nature of the histological technique (two-dimensional) limits its usefulness for measuring morphological changes, and this may explain the discrepancy. Hence, the primary effect of diabetes is increased DNA synthesis (dpm per crypt) and this appears to be the main explanation for stimulated mucosal growth.


Myogenic and neural control systems for esophageal motility.

The role of myogenic and neural control systems in esophageal motility was studied in anesthetized opossums by applying electrical pulses at 20 to 40 v, and 100 to 400-msec pulse width directly to muscle layers, by cervical vagal stimulation (10 to 25 pulses per sec, 0.5 to 5-msec pulse width, 10 to 40 v), and by balloon distention. Direct muscle stimulation resulted in a propagated contraction in 13 of 22 opossums (proximal propagation from a distal stimulation site and vice versa). The velocity of propagation was of the same order of magnitude as that of a spontaneous swallow (less than 5 cm per sec). The propagated contractions were not blocked by intravenous or close intraarterial atropine and hexamethonium or by intraarterial tetrodoxotine. Smooth muscle depolarization by intraarterial KCl or tetraethylammonium brought about propagated contractions in those oppossums that did not show this in the first place. Generally, these propagated contractions could also be intiated in these opposums by applying 2 to 3 stimulating pulses 1 to 1.5 sec apart. The propagated contractions in response to direct muscle stimulation were observed in all opossums 2 to 20 min after death. Cessation of vagal stimulation and balloon relaxation produced "off-responses" which were blocked by tetrodotoxin. The propagation of off-responses was much faster than the swallow-induced peristaltic contractions. In conclusion, the myogenic control system in the esophagus is capable of producing propagated contractions independently which resemble normal esophageal peristalsis in propagation velocity, and may be the underlying system responsible for it. This system may, however, be modulated by the extrinsic and intrinsic nerves.


Individual bile acids in portal venous and systemic blood serum of fasting man.

The serum concentrations of cholic acid (C), chenodeoxycholic acid (CD), and deoxycholic acid (D) were determined in peripheral venous and portal venous blood from 10 otherwise healthy patients undergoing elective cholecystectomy. A highly specific and accurate gas chromatographic-mass spectrometric technique was used. Peripheral venous serum contained 0.49 +/- 0.16 (mean +/- SEM) mumole per liter of C, 1.55 +/- 0.32 mumoles per liter of CD, and 1.44 +/- 0.57 mumoles per liter of D. Arterial serum, obtained from 5 of the subjects, did not show any differences in bile acid concentrations compared to venous serum. In contrast, the portal venous content of each bile acid was several-fold greater, 6.14 +/- 1.20 mumoles per liter of C, 8.40 +/- 1.84 mumoles per liter of CD, and 6.18 +/- 2.27 mumoles per liter of D. The hepatic uptake of C was estimated to be about 90%, whereas that of CD and D was lower, about 70%. This difference in hepatic uptake between the individual bile acids was reflected in the relative composition of the total bile acids, which was 30:39:31 (C:CD:D) in portal venous serum and 13:50:37 in peripheral serum. Compared to common duct bile obtained simultaneously, the portal vein contained a greater proportion of CD. The relevance of the data obtained to our present concept of the enterohepatic circulation of bile acids is discussed, and it is suggested that the higher fasting level of CD compared to C in peripheral serum results from the combination of a lower fractional hepatic extraction and a higher portal venous input to the systemic circulation.


Giant mitochondria in hepatocytes: a diagnostic hint for alcoholic liver disease.

One hundred and sixty-five coded liver biopsy specimens were studied by light microscopy to evaluate the occurrence and diagnostic significance of giant mitochondria, which have been identified as periodic acid-Schiff-negative globular hyaline cytoplasmic inclusions of regular outline, clearly distinguishable from Mallory bodies. In 4 cases, electron microscopy confirmed that these globules were in fact enlarged mitochondria. The incidence of giant mitochondria was significantly higher in patients with high alcohol consumption (72%) than in those with low or no alcohol intake (10%). Their presence was related to the amount of daily ethanol consumption and to the shortness of abstinence before the biopsy. It was independent of other changes in the liver, and was detected with similar frequency in biopsies showing different alcoholic liver diseases. Our study emphasizes that giant mitochondria may be detected by light microscopy in a high proportion of alcoholics, and rarely in nonalcoholic liver diseases. Although less specific, they are much more frequent than Mallory bodies. Consequently they should be considered as a diagnostic hint of recent and heavy alcoholsm.


Disposition of nafcillin in patients with cirrhosis and extrahepatic biliary obstruction.

Nafcillin, a semisynthetic penicillin effective against penicillinase-producing staphylococci, is eliminated largely in man via the liver. This study assessed the effect of cirrhosis and extrahepatic biliary obstruction in man on the pharmacokinetics of nafcillin. The plasma clearance of nafcillin controls was 583 +/- 144.2 ml per min (mean +/- SD) and fell strikingly to 291 +/- 147.6  and 163 +/- 56.3 ml per min in patients with cirrhosis and extrahepatic obstruction, respectively (P less than 0.001). In the latter two groups nafcillin excreted in urine increased from about 30 to 50% of administered dose (P less than 0.02), suggesting that renal disease superimposed on hepatic disease would further decrease over-all nafcillin clearance. The depression of nafcillin clearance with hepatobiliary disease did not correlate with any conventional liver laboratory test. The initial volume of distribution of nafcillin (V1) was unaltered but at steady state (Vd()) there was a significant reduction in the distribution volume in the patients with liver disease. Accordingly, the impairment in drug elimination, as assessed by its clearance from plasma, was underestimated by the prolongation of the nafcillin elimination half-life (t1/2(beta)) which was 1.02 +/- 0.20 hr in controls, and 1.23 +/- 0.31 (P greater than 0.05) and 1.73 +/- 0.44 hr (P less than 0.03), respectively, in patients with cirrhosis and extrahepatic obstruction.


Endoscopic papillotomy.

Obstruction of the common bile duct can now be relieved by endoscopic electrosurgery. This report describes our experience with 267 patients. In 192 of 222 patients with choledocholithiasis all calculi were evacuated by endoscopic papillotomy (EP). The remaining patients had EP because of papillary stenosis. Complications of EP included nine instances of pancreatitis, seven of bleeding, and two perforations. In 2 of 32 patients having EP for papillary stenosis, restenosis has appeared on follow-up. The two fatalities were attributable to purulent cholangitis and acute bleeding. This required to manage these situations. The endoscopic method requires less hospitalization and recuperation. EP and stone extraction are the methods of choice for managing common duct obstruction in high risk patients before cholecystectomy, for retained or reformed stones after cholecystectomy, and for papillary stenosis.


Absence of mucosal atrophy in human small intestine after prolonged isolation.

Light and electron microscopic evaluation of segments of human jejunum (bypassed for 3 1/3 years in treatment of morbid obesity) and ileum (bypassed for 6 years as a Thirty-Vella fistula in treatment of postsurgical fistula) showed no obvious evidence of widespread mucosal atrophy. The findings contrast with those reported in experimental animals and in most human patients with ileal urinary conduits, where atrophy of the isolated segment is the rule. Perhaps nonluminal factors in the human subject are sufficient to maintain small intestinal mucosa for long periods in the absence of intestinal chyme.


Mucinous biliary obstruction associated with a cystic adenocarcinoma of the pancreas.

Obstruction of the biliary tree by large amounts of mucinous material is reported in a patient with a mucin-producing cystic adenocarcinoma of the pancreas invading the common bile duct. Although preoperative endoscopic retrograde cholangiography suggested bile duct invasion, mucinous obstruction, as in the previous cases in which it has been reported, was not suspected. Mucinous obstruction, although unusual, should be considered in patients with cystic carcinomas of the pancreas in the presence of jaundice or episodes of cholangitis.