[Vater's papilla as an intra-operative problem].

A well-functioning major duodenal papilla is an indispensable condition for freedom from complaint in the region of the biliary tract and pancreas. Intraoperatively, the papilla is the problem of the surgeon. With appropriate morphological changes, transduodenal papillotomy is a necessary and irreplaceable procedure for curing the bile ducts and the pancreas. It should, however, be strongly emphasized that this surgical papillotomy is a major intervention bearing a number of possible risks. For this reason, only the sufficiently functionally disturbed and morphologically altered papilla is to be operated on.


[Particular causes of renovascular hypertension].

Besides 55 patients with renal artery stenosis in our department 5 occlusions of renal artery and some other rare but clinically very important causes of renovascular hypertension are reported. All these casuses of an angiotensin-renin mechanism given in general the indication for operative procedure. The very low risk of renovascular revascularisation justifies this operative indication.


[Suture materials in surgery. Significance of basic substance and construction of surgical suture material for utilization in vivo].

The paper is a review of all available suture materials (absorbable and non-absorbable threads). The tissue reaction to the various sutures is discussed and histologically demonstrated, as well as possible complication. It is described which suture material is best suited for the various tissues and suturing techniques.


[Polycythemia vera, clinical aspects and disease course].

The data of 140 patients with polycythemia vera during the period 1955--1975 were analyzed with regard to clinical signs and prognosis. The average age was 53,4 years. The sex ratio was 1.9:1 in favor of men. The most frequent symptoms were headache and vertigo. In more than half of the cases hepatosplenomegaly and hypertension were found. Besides typical changes in the blood count with elevated erythrocytes, hemoglobin, hematocrit, leukocytes and thrombocytes, increased levels of alkaline leukocyte phosphatase and uric acid were found. As to therapy, after 32P-medication the survival was two years longer than after phlebotomy. In 9 patients osteomyelofibrosis developed, and in 7 cases chronic myeloic leukemia. The mean age of death was 61 years.


[Acute intrauterine hypoxia].

It is most commonly caused by cord compression and decreased utero-placental perfusion. Among all diagnostic procedures cardiotocography is most effective. The dignity of the different pathologic heart rate patterns varies. By technical and organisational means such as central control panels and automatic alert systems registered data are continuously evaluated even if the staff is limited. A number of therapeutical procedures may be chosen instead of rapid delivery. To a certain degree acute intrauterine asphyxia can be prevented.


[Perinatal influences on blood coagulation in healthy newborn infants with special reference to vitamin K administration].

In a prospective study the daily milk intake and weight gain were recorded in 169 healthy newborn infants during the first week of life. Factor II, V and VII activities were determined on the fourth day using a capillary blood method with hematocrit correction factor. Late onset of feeding showed a major influence on factor II and VII activities. In full-term newborns factor II was correlated to the birth weight. Mode of delivery, color of amniotic fluid, umbilical cord round the neck, Apgar score and postnatal vitamin K prophylaxis showed no significant influence. In infants with abnormal cardiotocographic findings higher levels of factor II were determined. This can be explained by stress-induced liver maturation.


[Circadian periodicity and stomach ulcer. An animal experiment model for the detection of rhythm factors in the genesis of civilization diseases].

Against the background of clinical experience attesting to the role of the circadian and circannual rhythm stage in gastric ulcerogenesis, animal experiments provide a model where by circadian stage and sex are both revealed as determinants of gastric ulcerogenesis. Experiments on the genetically mesor-hypertensive Okamoto rat demonstrate the critical interaction of multiple loads in ulcerogenesis, in keeping with a report by Glavin and Mikhail. While stimulation by single loads of a certain intensity--immobilization, food deprivation or cooling--did not regularly lead to the production of gastric ulcers, the combination of these same loads did so as a function of circadian state at the beginning of exposure time.


[A system for the mechanized radioimmunological determination of digoxin].

Because of the increased number of samples to be processed in digoxin radioimmunoassay for clinical diagnosis and pharmacokinetic studies these analyses require mechanization to a certain extent. A newly developed modular analyzer system is described which is capable of mechanizing radioimmunoassays for digoxin, for example, independent on the kind of reagent kits as well as the separation technique. In dependence on the number of replicates from 60 to 240 samples per hour can be processed. The reaction vessels are placed in belts during the whole assay including centrifugation. The final separation of the liquid and the solid phase after centrifugation can be performed in two different ways: 1. If a conventional automatic gamma counter is used an aliquot of the supernatant is automatically dispensed into the counting vials which are to be closed manually and transferred into the counting device. 2. Further reduction of manual working steps can be achieved by employment of a newly developed discontinuous flow-through gamma counter which is part of the modular analyzer system. An aliquot of the supernatants is automatically flushed into a measuring cuvette installed into a conventional crystal detector. After measurement of the radioactivity and data output the cuvette is rinsed thoroughly. Thereafter the following sample is delivered.


[Obesity and cardiovascular risk].

Epidemiological studies on the relationship of obesity, morbidity and mortality revealed the following results: In life insurance studies, excess mortality of obese people was found with more than 30 percent overweight. Mortality was caused by cardiovascular disease and diabetes mellitus. Obesity at issue of the policy in younger age was a greater risk than in the older age group. In prospective studies with long follow-up periods (greater than 16 years) it could be shown that obesity alone was a risk factor for coronary heart disease, the risk being greatest for men and middle aged women. However, the prevalence of accepted risk factors in an obese population is so high that the question whether obesity alone is a risk factor for coronary heart disease is of little interest. The correlations between obesity and risk factors were of minor magnitude; therefore other factors, such as age or HDL-cholesterol, should be considered in the elucidation of the relationship between obesity and coronary heart disease. HDL-cholesterol appears to be a powerful independent protective factor which is diminished in obesity. Despite the fact that studies proving a prolongation of life by treating obesity are not available, the treatment of obesity may be beneficial for the patient by diminishing risk factors.


[Early diagnosis of neoplasms in young women. When should prevention of neoplasms start?].

Cervical cancer is seen in younger women more often than expected. In the literature up to 35% of the pre-stages--especially of dysplasia form--have been found in the age group under 30 years. By taking cervical smears in all women experiencing sexual intercourse we would detect these cases and prevent invasive forms of cervical cancer. Therefore, we strongly recommend to lower the age limit of 30 in performing general Pap screening.


[Geriatric gynecology. A contribution to geriatric gynecology with special reference to postoperative mortality].

A contribution to geriatric gynecology with special consideration of postoperative mortality. Almost imperceptibly, essential progress has been made within recent years in the field of surgical geriatric gynecology. The attempt was made, after enumerating the specific problems of geriatric gynecology, to deal systematically with surgical geriatric gynecology. From 1960 to 1969 in West-Berlin, 7151 major operations in 60-year-old women and older were performed in 17 gynecological hospitals. Complete records were available in 6658 cases. Evaluating them, we were able to substantiate effectively the clinical actuality of surgical geriatric gynecology as a component of geriatric gynecology.


[Cognitive performance in schizophrenics. A contribution to experimental psychopathology].

1. From the field of cognitive performances we investigated visual perception under varied acoustical conditions providing a certain amount of guidance. Ss: 108 (paranoid schizophrenics n = 34, nonparanoid schizophrenics n = 33, controls n = 41). All were acute patients. Stimuli were arranged in various perceptive stages by factor analysis. Analysis of variance of times of perception resulted in: conditions which did not show any deficits in schizophrenics; by increasing stimuli complexity different deficits were found in nonparanoid and paranoid schizophrenics; in a special pattern of stimuli constellation paranoid schizophrenics showed a reversal of attention tendencies. 2. The results of many important experiments which are found in respect of "psychological deficit in schizophrenia" are integrated into the edifice of clinical psychiatry as follows: by defining several aspects of attention which make it possible to employ the experimental results with no regard to hypotheses; by an extensive historical investigation; in the classical literature about 1900 we found many equivalent forerunners to modern American terms; our experiments are connected closely with clinical psychiatry with view to structural psychopathology. 3. The aim is an experimental basis of the performances of schizophrenics as a prior condition of systematical rehabilitation.


[Psychosomatic diseases in urology].

As in other medical fields there also exist psychosomatic diseases in urology which appear in the form of functional disturbances. Besides alterations of the diuresis, mainly an irritable bladder, symptoms of enuresis, urinary retention and additionally symptoms of chronic prostatitis and disturbances of sexual potency. In order to explore the psychic etiology usually a psychiatric examination is necessary with the aim to start adequate treatment.


[Treatment of distortions and non-traumatic conditions of pain and swelling. Double-blind trial with an analgetic and detumescent drug combination].

A combination of specifically detumescent and analgesic/antiphlogistic substances (Dolo Mobilat film tablets) was tested in a double-blind study against placebo. The active product brought about very good or good therapeutic results in approximately 78% of 50 patients suffering from distortions of joints and from painful inflammation and swelling of non-traumatic origin; the  corresponding percentage obtained with the placebo was 34%. Separate evaluations of pain and swellings most relevant for their homogeneity in distortions of joints showed rates of 80% and 31%, respectively. These differences as to efficacy are highly significant (p less than 0.001). There were no symptoms of intolerance except some sporadic mild gastric complaints. In comparison with the experience made with analgesics and antiphlogistics in oral therapy the action and tolerance were judged as very good.


[Complications due to soft hydrophilic contact lenses].

Soft hydrophilic contact lenses are widely favored thanks to their minimal ocular irritation. They may, however, also cause severe eye disease. In this report, allergies, hypoxia, tear film alterations, toxic effects and infections, as caused by soft lenses, are described, and their diagnosis, differential diagnosis and prophylaxis discussed. Moreover, it is pointed out that a misdiagnosis of "contact lens intolerance" may have serious consequences.


[Electronic image analysis in ophthalmology].

Based on experimental investigations a broad concept for the use of television image analysis in basic and clinical ophthalmology is given. This summary outline contents a short description of the technique and some examples for the clinical use of image analysis, like the measurement of corneal width and erosions, infrared pupillography, morphometry of the iris and quantitative fluorescence angiography. "Static" and "dynamic" image analysis are defined, the role of pattern recognition is mentioned. The results of the study demonstrate that television image analysis can be of great importance for the future of quantitative ophthalmology.


[Ultrasonic echography. Current and future tasks in the finding of intraocular foreign bodies].

Unlike most publications ultrasonography is not seen as an alternative concept to x-ray localization of intraocular foreign bodies but as supporting aid. It is primarily used for the rather simple measurement of the form of the injured eye and not so much for direct search of the foreign body. The latter is rather difficult to perform intraoperatively. The combined method is based on the Comberg localization using a mobile x-ray television unit. The x-ray imagery shows quickly, exactly and clearly the localization of the foreign body in the orbita. The eye itself cannot be seen on the monitor, but ultrasonic data allow to add its contours, corrected individually. This work is done by a computer. The measurement of coordinates and angles usually performed by the investigator is done by a computer, too. The linkage of both x-ray and ultrasonic equipment to a computer relieves the surgeon of the graphical tasks and ultrasonic search for the foreign body; it also gives information about the localization of the foreign body in the individual case during the entire operation.


[Scintigraphy of the lacrimal draining system].

A new scintigraphic method, the radionuclide dacryography, to evaluate lacrimal drainage and its disorders is described. A drop of 99mTc-pertechnetate is dropped onto the eyes and the transport of the nuclide is registered by a scintillation camera. By this method it is easy to verify, under physiological conditions, suspected obstructions of the lacrimal drainage system and to determine its localization. The absorbed radiation dose using radionuclide dacryography is very low as compared to radiological methods.


[The colonic carcinoma. Notes on clinical aspects and therapy].

1752 cases of colon carcinoma are reviewed. History and characteristics of these tumors are described and the results of operative therapy are shown. 50% of the curatively operated patients were still alive after five years, and it seems especially important to think of the possibility of such a carcinoma. Most of our cases have shown early symptoms. It is necessary to interrogate every patient in this respect.


[Therapy of chronic postprandia dyspepsia. Crossed double-blind study with Domperidon (Motilium)].

In a double-blind cross-over study over eight weeks two groups of 24 patients each with symptoms of chronic postprandial dyspepsia received during the first four-week period either 10 mg domperidon t.i.d. or placebo. After four weeks the medication was exchanged. Despite some improvement of symptoms under placebo, statistical analysis revealed a significantly higher improvement rate after domperidon.


[The psychiatric emergency in general practice].

Emergencies (conditions requiring immediate interference with putting aside all other obligations) in psychiatry are acute excitatory states and threats or attempts of suicide. In both situations systematic and prudent medical management is necessary. Taking into consideration the conditions in private practice, the principles of conduct and therapeutic procedure are outlined.


Fatty acid and lactate metabolism by heart homogenates from alloxan-diabetic dogs.

Myocardial homogenates from control of alloxan-diabetic dogs were incubated in the presence of lactate or palmitate as the sole substrate. The rate of lactate oxidation of the homogenates from diabetic dogs was less than half of the oxidation rate of homogenates from control animals. The incorporation of labelled palmitate into triglyceride was greatly enhanced in the heart taken from diabetic animals. The tissue concentration of l-carnitine was twice and that of triglyceride was three times as high in the diabetic animals as in their control counterparts. Thus the myocardium of diabetic animals exhibited both altered substrate utilization and increased rate of triglyceride synthesis.


Pancreatic hormones and plasma glucose: regulation mechanisms in the goose under physiological conditions. II. Glucose-glucagon and glucose-insulin feed-back mechanisms.

We have studied the pancreatic hormone-glucose feed-back mechanisms by infusing glucagon (G), insulin (I) and glucose into normal fasting geese. The controls received saline. Whilst a NaCl 9% infusion is devoid of effect, the pancreatic hormones, used at physiological doses, modify the plasma glucose level, glucagon being hyperglycaemic and insulin hypoglycaemic. In addition, a physiological increase in plasma glucose provokes a drop in plasma glucagon and a rise in plasma insulin, thus a marked decrease in the G/I ratio. The results show that the pancreatic hormone-glucose feed-back mechanisms are effective under physiological conditions.


Serum cholesterol esterification in hyperthyroidism and hypothyroidism.

The rate of serum cholesterol esterification was measured in twenty healthy subjects and compared to similar data obtained with seventeen hyperthyroid and ten hypothyroid subjects. No significant differences were noted in the rate of cholesterol esterification while differences in the fractional rates were highly significant (p less than 0.001); the hyperthyroid group being higher and the hypothyroid group lower than normal. There were no clear trends observed in the changes of the rate of cholesterol esterification upon therapy. However, the fractional rates always increased when hypothyroid patients became euthyroid and always decreased in hyperthyroid patients as the result of therapy.


Testosterone, LH and FSH in patients with treated testicular carcinomas.

Patients with testicular cancer were treated by semicastratio and in some cases by retroperitoneal surgery. The diminution of testicular parenchyma to about 50% results to a low serum level of testosterone, but elevated serum level of LH and FSH. 3 years after surgery and irradiation this is not a pathological finding but appears to be a typical pattern. As it is difficult to differentiate embryonal carcinomas and choriocarcinomas from pure embryonal carcinomas an estimation of serum level of LH and FSH may be of use by the diagnosis.


Genetically determined response to different ingested carbohydrates in the production of diabetes.

It has been shown that the metabolic responses to the ingestion of carbohydrates depend upon a) the type of the ingested carbohydrate and b) the genetic build-up of the recipient. In the non-susceptible animal, the ingestion of high sucrose, fructose or glucose diets will ensue in "normal" metabolic responses. In the susceptible animal the ingestion of these same carbohydrates will result in impairment of the carbohydrate and lipid metabolism, which will ultimately lead to the development of diabetes and diabetic angiopathy while their siblings with the same genetic build-up consuming starch, will not.


Effect of fasting, glucose, amino acids and food intake on in vivo insulin release in the chicken.

Insulin release was studied in vivo in the chicken using the radioimmunoassay previously described (Simon, Freychet and Rosselin 1974). An orally administered glucose load (2 g/kg b.w.) stimulated insulin release and was rapidly metabolized. A prolonged fasting period (65 hr) increased both initial plasma glucose and initial plasma insulin levels and highly impaired the glucose tolerance. A fasting-impaired insulin release and/or a fasting tissue "insulin resistance" accounted for this fasting-impaired glucose tolerance. An orally administered amino acid mixture (1 g/kg b.w.) stimulated insulin release to a very low extent. The effect was however sufficient to decrease the plasma glucose level. In combination with glucose, the oral amino acid load potentiated the effect of a dose of glucose on insulin release and highly improved the glucose tolerance. This synergism was still observed with the intake of a mixed and balanced diet. Therefore, except for some characteristics observed in the chicken which are discussed, the insulin regulation and the pancreatic beta-cell function are qualitatively similar in the chicken and in mammals.


Plasma glucagon, insulin and glucose responses to intravenous arginine infusion in the rat.

Plasma glucagon (IRG), insulin and glucose responses to intravenous arginine infusion in the rat were studied. Three doses of arginine hydrochloride were infused into fasted rats: 0.2 gm/kg b.w., 0.5 gm/kg b.w., and 1 gm/kg b.w. The 0.2 gm/kg dose did not result in significant elevation of plasma IRG or insulin. Both the 0.5 and 1 gm/kg doses produced a significant increase in glucagon and insulin levels within 5 minutes of starting the infusion. The 1 gm/kg dose was most effective in stimulating secretion of both hormones. This dose produced a 250% rise in the plasma IRG compared to 80% peak rise with the 0.5 gm/kg dose (p less than .01) and 1055% rise in insulin levels compared to a peak level of 225% above baseline with the 0.5 gm/kg dose (p less than .001). These results demonstrate the effectiveness of intravenous arginine in the stimulation of glucagon and insulin secretion in the rat.


[Synthesis of human [11-leucine]minigastrin I.--I. Preparation of the fully protected tridecapeptide amide (author's transl)].

The synthesis of the tridecapeptide amide corresponding to and 11-leucine analog of human minigastrin I is decribed. The fully protected peptide derivative was obtained by assembly of three suitably protected fragments corresponding to the sequences 1-6, 7-9 and 10-13 by the carbodiimide/N-hydroxysuccinimide method.


[Synthesis of human [11-leucine]minigastrin I--II. Purification of the synthetic tridecapeptide amide and isolation of a side-product (author's transl)].

The preparation of the pure 11-leucine analogue of human minigastrin I, a linear tridecapeptidaemide with full "gastrin activity", from the crude synthetic material obtained after deblocking of the overall protected tridecapeptide amide derivative by means of trifluoroacetic acid, is achieved by ion-exchange chromatography on DEAE-Sephadex A-25 and subsequent partition chromatography on Sephadex G-25. The isolation of a synthetic side-product and its identification as human [10-(Nin-tert-butyl-tryptophan),11-leucine]minigastrin I by means of spectroscopic (UV, fluorescence, 1H-NMR, MS), enzymatic and chromatographic methods is described. The pure tridecapeptide amides human [Leu11]minigastrin I and human [Trp(1'-But)10,Leu11]minigastrin I are isolated in overall yields of 37.4% and 4.6%, respectively (mol-% with regard to the overall protected tridecapeptide amide derivative).


Stilbene synthases and stilbenecarboxylate synthases, I  Enzymatic synthesis of 3,5,4-trihydroxystilbene from p-coumaroyl coenzyme A and malonyl coenzyme A.

1) Cell-free extracts prepared via acetone powder from rhizome of Rheum rhaponticum were found to be capable of converting p-coumaroyl-CoA and [2-14C]malonyl-CoA into a 3,5,4'-trihydroxystilbene, resveratrol. The product was characterized by repeated chromatography and by recrystallization to constant specific radioactivity. 2) The mode of condensation of the phenylpropanoid moiety with C2 units was determined by chemical degradation of the enzymatically formed product. 3) The enzyme system which catalyses the condensation of p-coumaroyl moiety with 3 malonyl units, the intramolecular aldol reaction and the subsequent decarboxylation was classified as stilbene synthase. It could be activated by dithiothreitol. 4) When the extraction of the rhizome was performed with aqueous grinding medium, a high percentage of this stilbene synthase activity was found to be membrane-bound.


The carbohydrate linkage site of cow colostrum trypsin inhibitor.

Cow colostrum trypsin inhibitor (chromatographic form AIV[7])was subjected to basic conditions that favour beta-elimination of carbohydrates from O-glycosidic linkages. The unchanged carbohydrate composition and the unchanged values for serine and threonine indicate the presence of an alkali-stable N-glycosidic bond to asparagine. From a tryptic digest of S-aminoethylated inhibitor the glyco-decapeptide (residues 24 through 33) was isolated. The carbohydrate composition was identical with that of the S-aminoethylated inhibitor. Further degradation of this peptide by carboxypeptidase C (and aminopeptidase) produced the glycopeptide Asn(CHO)-Ser-(Thr) with the same carbohydrate composition. Thus, a single carbohydrate moiety is bound by a N-glycosidic linkage to asparagine-27 of the colostrum inhibitor. It is located opposite to the reactive site at the base of a pear-shaped molecule.


Effect of Na on bile acid uptake by isolated rat hepatocytes. Evidence for a heterogeneous system.

The effect of Na on cholate and taurocholate uptake was studied in isolated rat hepatocytes. Uptake of both bile acids can be divided into three components: a) a non-saturable component independent of Na, b) a Na-independent saturable and c) a Na-dependent saturable component. The two saturable components were inhibited by KCN, oligomycin and various other bile acids, which suggests carrier-mediated, energy-requiring processes. The relationship between Na concentration and the Na-dependent uptake rate was sigmoidal. The maximal uptake rate, rather than the Km, was affected by Na. These results suggest that more than one Na (probably two) are cosubstrates in the transport of one bile acid molecule and Na exerts a stimulatory effect on the translocation of the bile acid-carrier complex across the membranes. The Na-dependent uptake was inhibited by ouabain, suggesting that this uptake process is linked to the activity of membrane bound (Na-K)ATPase. Inhibition and competition studies suggest that cholate and taurocholate share a common Na-independent transport system while there are at least two Na-dependent transport systems for taurocholate, one of which is shared by cholate.


Inhibition of cholesterol synthesis in cultured cells by 25-azidonorcholesterol.

25-Azidonorcholesterol, a side chain analogue of cholesterol, inhibits cholesterol biosynthesis in BHK 21 cells in tissue culture; but 3-azido-5-cholestene, the azido analogue of cholesterol has no inhibitory effect. Cell growth was unimpaired by the azido analogue, which showed only a minimal uptake by the cell, compared with that of cholesterol or 25-azidonorcholesterol. 25-Azidonorcholesterol is incorporated into the membranes of BHK 21 cells in place of cholesterol as demonstrated by isotope experiments. The incorporation of radioactive acetate is strongly inhibited by the side chain azido substituted cholesterol derivative; the incorporation of radioactive mevalonate is, however, unimpaired. We conclude that the inhibition occurs at the hydroxymethylglutaryl-CoA-reductase step. Cell growth is not significantly altered.


New protein reagents. Synthesis and properties of halogenated maleimides and isomaleimides.

The title compounds were investigated as examples of potential hetero-bifunctional protein reagents having an electrophilic moiety in addition to a maleimide or isomaleimide ring. The synthesis of such products by cyclization of the corresponding maleamic acids gives lower yields in the maleimide than in the isomaleimide series, especially when the second function is labile, owing to the more drastic reaction conditions necessary to form the symmetric isomer. On the other hand, a comparison of the isomeric imides showed that despite some differences in reactivity, isomaleimides can be used instead of maleimides for chemical modification of proteins. Therefore, if the synthesis of new maleimide reagents containing a second fragile functional group is difficult, they can be designed in the isoimide form.


Studies on bovine insulin with methyl vinyl ketone. Isolation of crystalline A1-3-oxobutyl derivative of bovine insulin.

Reaction of methyl vinyl ketone with bovine insulin affords, amongst others, a crystalline A1-(3-oxobutyl)insulin. This retains full biological activity in the mouse convulsion assay. The presence of zinc ions changes the course of the above reaction, and illustrates the use of zinc as a "blocking function".


The stability of A1,B29-adipoylinsulin to chemical and enzymatic degradation.

The degradation of A1,B29-adipolyinsulin by partial hydrolysis, by disulphide-bond exchange, by chymotrypsin and by a cytosolic enzyme fraction of rat liver was measured and compared with that of A1,B29-diacetylinsulin and insulin. The cross-linked insulin is, in general, more resistant than insulin itself or the diacetylated derivative. However, in the case of enzymatic degradation, A1,B29-diacetylinsulin resembles more the cross-linked derivative than insulin. This provides evidence that the properties of A1,B29-adipoylinsulin could not in all circumstances be attributed to its 'proinsulin-like' structure.


Preparation and physical-chemical characterization of poly-N-vinylpyrrolidone-insulin.

In an attempt to modify the structure of insulin, the hormone was coupled by covalent linkage to poly-N-vinylpyrrolidone (PVP). PVP-insulin is soluble in aqueous solution and was purified by column chromatography. Special care was taken to check for a possible leakage of insulin from the synthetic polymer. The amount of bound insulin was determined by quantitative amino acid analysis after acid hydrolysis. After protection of the N-terminal glycine residue of the A-chain by citraconylation, a biologically active PVP-insulin was obtained. The molecular weight determined by analytical ultracentrifugation and column chromatography was 50 000-60 000. The biological activity of the coupled hormone was between 0.5 and 7% when compared with native insulin in the system in vitro. The immunological activity was about 20-50%.


A new method for the preparation of band 3, the main integral protein of the human erythrocyte membrane.

Band-3 protein from human erythrocyte membranes was isolated, without using detergents, by a two-step procedure: (1) The peripheral proteins were removed from the membrane by treatment with 10% acetic acid. (2) The remaining lipoprotein complex was solubilized in approximately 92% (v/v) acetic acid and then separated into its components by preparative zonal electrophoresis in a gradient made up of acetic acid, water and sucrose. Band 3 was recovered from the gradient at a yield of 60 - 70% and purity of about 95%. Approximately 25 mg of band 3 could be prepared in one run. The protein is soluble in aqueous solutions, even in the absence of organic solvents or detergents. In addition to band 3, the proteins stained by periodic acid/Schiff's reagent (the sialoglycoproteins) are also separated from the other proteins.


[Concentration and characterization of a liver cell proliferation factor from partially hepatectomized rat livers (author's transl)].

An extract of rat liver, made 12 h after partial hepatectomy, was injected into untreated rats. The synthesis of DNA in the liver cells of the injected animals showed a 3.3 fold increase in comparison with controls. A similar increase was observed in the mitosis index. Injection of liver extracts from normal rats showed no effect when compared with the injection of NaCl. The effect of the active extract was not altered by neuraminidase treatment. Trypsin-chymotrypsin treatment, howerver, removes the activity. The active factor must therefore be either a protein or a protein-like substance. The molecular weight of the factor was shown to be between about 30 000 and 50 000 by molecular filtration. The specific activity after molecular filtration was raised by a factor of 100. The factor is inert with respect to the proliferation of kidney and spleen. It is apparently not species-specific, however, since it also causes increased proliferation of liver cells in normal mice.


Management and programmatic constraints on community mental health services.

While the special needs of the mentally ill are discussed in detail by society in general and by federal and state governments in particular, it is the local mental health services that must develop, integrate, and manage resources from federal and state levels and must deal with the constraints and strings attached to those resources. The author divides the constraints into several categories--clinical, administrative, fiscal, and legal--and offers suggestions for dealing with them, drawing in several cases on examples from the state of California. He feels that the control of mental health services must be kept in the hands of those who are knowledgeable about and have an investment in the delivery of those services.


The role of a regional treatment center in a model mental health delivery system.

The author discusses the changes that have occurred at the Mendota Mental Health Institute in Madison, Wisconsin, in response to the growth of the community movement. He traces Mendota's evolution from a traditional state hospital to a regional center that offers specialized treatment services for those who cannot be cared for in community programs, and that places strong emphasis on education and consultation services and on research into treatment methods. He believes a major problem with the community mental health movement has been the expectation that community services should be able to meet all the needs of the people in their areas, an expectation that he considers impossible to fulfill. He proposes a mental health delivery system with primary, secondary, and tertiary levels of care (at the third level would be regional centers similar to Mendota), and a fourth level that would provide protective care.


Do community mental health centers underserve psychotic individuals?

An analysis of treatment statistics from three community mental health centers in California indicates that the centers provide treatment to a substantial proportion of the psychotic individuals in the community. Psychotic patients have a significantly higher number of inpatient, day treatment, and outpatient admissions than neurotics. Psychotic patients also receive significantly more treatment in all major service modalities than neurotics. The authors conclude that severely impaired individuals in the treatment population are neither ignored by the centers nor routinely transferred to a state hospital.


The psychiatric screening clinic at a VA hospital: making it work.

A psychiatric crisis and screening clinic in a general medical and surgical hospital has expanded psychiatric treatment available to general medical patients and has eliminated overcrowding on the psychiatry service. The authors describe admissions procedures and problems that existed before the clinic was developed and ways clinic staff found to deal with the bureaucracy, which include promoting personal responsibility for patient care. The clinic has met its initial goal of decreasing the amount of time patients have to wait for their first contact with professional staff. Feedback from wards indicates that staff have been successful in making appropriate dispositions.


EMS or HSA: which program model influences health delivery more?

The EMS and the HSA programs differ radically in concept of area of operation, agency structures, roles of consumers and health care professionals, method of funding, and control by the federal government. Both the government and providers should study the differing impact of the programs in order to determine which approach can more effectively change health care delivery.


Hospital remains in inner city by moving to recycled factory.

An urban hospital that needed an up-to-date physical plant renovated and moved into a nearby foundry building. By remaining in its inner-city neighborhood, the hospital continues its programs to help solve socioeconomic problems that affect the community's health and well-being and that may help stimulate the community's recovery from urban blight.


Professionals in 'alliance' achieve more effective discharge planning.

A general hospital's discharge planning program shows how patients' needs can be met more effectively when various health care professionals work in "alliance" rather than in more rigid modes, such as "the team." In alliance, professionals can perform nontraditional roles, compromise, and shift dominance and partnerships in order torespond to patients' needs with more flexibility and common sense.


Hospital libraries' consortium blunts impact of budget cuts.

Hospital libraries frequently are faced with increasing costs for journals and other educational resources, increasing demand for continuing education materials by health care professionals, and decreasing budgets to meet these needs. Several medical and hospital libraries in Illinois are providing continued, and possibly improved, services under budgetary constraints through a consortium that emphasizes sharing of resources, interlibrary loans, librarian consultation services, and cost-saving projects.


Ambulatory care survey  paves way to the future.

University of Utah Hospital collected data from patient visits to its ambulatory care clinics to determine how it should build its new facility. The new clinic is planned for 1985, and the survey data showed how to build today to meet tomorrow's needs.


Coordinating patient education in the hospital.

Hospital personnel discover that duplication of patient education efforts was occurring because of the absence of coordination. A Patient Education Committee was established to consolidate all the individual efforts that were going on in the hospital.


ABC analysis helps to determine which drugs to bid purchase.

The advantages of bid purchasing to both buyer and supplier are described and an explanation of how an ABC classification of inventory helps to determine which items should be bid upon is provided. The cost savings that resulted from bid purchasing of drugs by one hospital using an ABC analysis is also described.


System design of a clinical facility for diagnostic ultrasound.

This two-part report sets out the fundamental considerations that are necessary for the successful development and functioning of a clinical diagnostic ultrasound facility. Part 1, "Establishing a Clinical Diagnostic Ultrasound Facility," deals with the myriad details that must be considered when establishing such a facility. Part 2, "Managing a Clinical Diagnostic Ultrasound Facility," is concerned with the functioning of the facility once it is established.


Residents Council provides paint, provokes interaction.

The Residents Council of the Villa Maria Geriatric Center, Tucson, organized and carried out three mural-painting projects. The painting tasks actively involved many of the nursing home's residents and provided an interesting topic of conversation for others. Villa Maria staff consider the projects one example of how a residents council can truly function to improve the quality of residents' lives.


The trustee and the risks of persuasive leadership.

Boards of trustees are challenged to structure their leadership roles in such a way that they can help the institutions they lead to fulfill their potential. Coercion and persuasion are both tools that boards can use; but while coercion may be necessary in extreme situations, it is not useful for encouraging performance. Persuasion, as defined, is the means by which a board may guide an institution toward its highest possible performance level.


An applicant's checklist for assessing executive positions.

Job moves are expensive for the individual--they affect personal and family life, career development, and finances. Such moves are also expensive for the institution because of the impact the executive has on its operations. But sharing information, ideas, and concerns between employer and potential employee may improve the chances of a "successful match," a benefit for both parties.


Principles and techniques of time management.

Managing time efficiently is, or should be, part of the credo of every manager from supervisor to chief executive. For managers to take advantage of every  tip and technique available, they must be prepared to increase their self-discipline and adjust their work style each time they climb the organization ladder.


Management's response to the union phenomenon.

While management must be allowed to assert its right to govern, it must not neglect the dignity of the employee in the process. If management can satisfactorily handle employeees' grievances about poor upward communication and poor and unfair treatment, it might also prevent unionization in its institution.


Shared services in a small multihospital system.

The pressures of governmental regulation and the inevitability of NHI or catastrophic insurance programs will lead hospitals to multiinstitutional arrangements as means of survival. The experience of the Tri-County Hospital Group, Wooster, OH, suggests some optimal conditions for shared services organizations and stresses the advantages of quality and economy which may be reaped by hospitals participating in such plans.


The elderly as prophets.

An understanding of the biological, psychological, and social factors of aging is just one part of helping older persons to view their own aging as the fulfillment of living, since spiritual growth takes place in the context of these factors but transcends them. Younger persons can facilitate such growth for themselves and their elders by helping the aging to function as "prophets" for the younger.


Personalism in health care.

The practice of personalism in health care will not survive unless health care professionals uphold the inherently equal value of all persons and regard health care as a covenant between themselves and their patients. Respecting the dignity and rights of patients, especially those whose quality of life is severely diminished, demands increasingly great and even heroic efforts.


The impact of waiving compulsory retirement.

A variety of forces operated synergistically to bring about quick development and passage in April of amendments to the Age Discrimination in Employment Act of 1967. Consequently, administrators must reassess the age-related assumptions underlying personnel policies.


Right-to-die laws: creating, not clarifying, problems.

That living will, or natural death, legislation--which is currently being pushed in state assemblies nationwide--is unnecessary and may actually inhibit physicians in providing the best of care to dying patients is evident from an analysis of the statutes that have been passed. Whether the motivation behind such legislation is to take a step toward legalizing euthanasia is an open question.


The hospital library in transition.

The community hospital library has evolved to a current status of real importance because of advances in medicine and technology, rising expectations from better-informed consumers to be "well," health care specialization, legislation, and malpractice and licensure concerns. Some suggestions are offered to help the hospital library and librarian function in a broad range of roles, from a reservoir of information to public relations resource.


Professional energy audit points way to $100,000 annual saving.

St. Mary's Hospital, Troy, NY, as part of a general budget-trimming effort, had a professional energy audit conducted. The hospital's management expect to reap both short-and long-term energy and cost savings for the hospital and recommend such an audit by trained professionals.


Partial monosomy 13 and 21 due to a familial 13/21 translocation.

Two patients are described with a monosomy for the proximal part of the long are of chromosome 13 and for the distal part of the long arm of chromosome 21, due to an unbalanced 13/21 translocation.


A dynamic study in two new cases of X chromosome translocations.

The authors discuss the clinical and cytogenetic problems raised in two new cases of X-chromosome translocations. The first case involves a child who presented marked malformations at age 3 months. Chromosome analysis revealed the presence of a translocation between a 22 and X chromosome resulting in partial X monosomy and partial trisomy 22: 46,X,der(X),t(X:22)(q112;q13)mat. The balanced translocation form was detected in the mother. Dynamic study after 5-Brdu treatment revealed inactivation of the translocated X chromosome in the proband, while in the mother the normal X chromosome was inactivated. In addition to magnesium dependent hypocalcemia resulting from a specific absorption anomaly, Case 2 presented discrete malformations and psychomotor retardation. Chromosome analysis revealed an apparently balanced translocation between a 9 and X chromosome: 46,X,t(9;X)(q12;p22). Treatment with 5-Brdu demonstrated that the translocated X chromosome was inactivated but that inactivation did not extend to the translocated part of chromosome 9. Finally, a pericentric inversion of a 9 chromosome was detected in the father, grandfather, and brother of the proband.


Chromosomal aberrations in heavy smokers.

Lymphocyte chromosomes from 20 heavy smokers were analyzed from 48-h whole blood cultures for the frequency of dicentric chromosomes, ring chromosomes, and chromatid translocations. Compared to controls, these exchange type aberrations occurred more frequently in the smokers.


Four cases of chromosome changes detected in course of prenatal diagnosis and probably originating in vitro.

In a series of 1000 prenatal diagnoses, four cases were found with chromosome changes. The probable in vitro origin of these changes was demonstrated by starting several parallel cultured simultaneously and by repeating the amniocenteses and chromosome analyses.


Structural aberrations of the X chromosome in man.

Among 209 patients with Shereshevsky-Turner syndrome, 69 women with structural aberrations of X chromosome were detected: 46,X,i(Xq) - 11; 45,X/46,X,i(Xq) - 24; 45,X/46,X,r(X) - 14; 45,X/46,X,f(X or Y) - 10; 45,X/46,X,del(Xq) - 4; 45,X/46,X,del(Xp) - 2; 45,X/46,X,idic(X) - 2; 46,X,idic(X) - 1; and 46,X,t(X,2) - 1. All the patients with structural abnormalities of X chromosome were short in stature, but in no group was it as low on the average as in 45,X cases. Somatic signs were noticed in all structural changes of X, but they were less frequent and less pronounced. In some patients with r(X) and i(Xq), spontaneous menstrual bleeding and breast development was found. The structurally abnormal X chromosome appears to be functionally inactive, the phenotype of patients with structural rearrangements being close to the phenotype of patients with X monosomy. At the same time, the abnormal X might have certain effects in early embryogenesis which mitigated the further development of the Shereshevsky-Turner syndrome.


A new cytogenetic aspect of polycythemia vera.

The cytogenetic findings in a group of 15 polycythemic patients are reported. G and C banding techniques were used on bone marrow and peripheral blood preparations. Major chromosomal aberrations were found in four out of the 15 patients, an incidence similar to that found in other studies on polymorphism. The most interesting finding concerned the chromosomal polymorphism of the pair 19. A possible relation to the etiology of the disease is discussed.


Analysis of banding patterns and mosaic configurations in a case of ring chromosome 15.

Cytogenetic studies on lymphocytes from a 14-year-old mentally retarded girl with somatic anomalies suggestive of a chromosomal abnormality revealed a ring chromosome 15. The long arm of the defective chromosome is broken at band q24 or q25. The silver staining technique for nucleolus organizer regions showed that the ring had lost the achromatic stalk and the satellite. The chromosomal mosaicism resulting from the structural instability of the ring chromosome was analyzed and compared with 6 cases reported in the literature. It is proposed that the clinical manifestations in the different patients with ring chromosome 15 result from both the deficiency in the long arm and the mosaic configurations.


Analysis of the HLA-ABC linkage disequilibrium: decreasing strength of gametic association with increasing map distance.

1242 HLA-ABC haplotypes of the North German population (Hambrug) as deduced by family analyses are described. They are in perfect agreement with recently published data by Mayr (1977) from Austria (Vienna) in all parameters tested: frequency of the single HLA-alleles, haplotype distribution and linkage disequilibrium values. Gametic association studies revealed that 69.4% of the B and C genes (map distance 0.2cM) 36.9% of the A and C genes (0.6 cM), but only 23.2% of the A and B genes (0.8 cM) were significantly more often combined than expected due to their frequencies. From these findings it seems likely that the linkage disequilibrium within the MHC is rather due to a short evolutionary period than to selective forces. Some observations as to the most common European haplotype A1,B8 are discussed.


Inherited congenital normofunctional testicular hyperplasia and mental deficiency. A corroborative study.

Three 46,XY unrelated individuals out of 84 postpubertal male inpatients with severe mental deficiency in a psychiatric hospital were found to have megalorchidia and macrogenitosomia. One of the cases had a similarly affected brother. Endocrine studies were performed in two of the cases with similar results. Normal plasma levels of pituitary gonadotropins were found. A normal testicular function was demonstrated by the finding of normal: (a) baseline plasma testosterone levels and a significant rise following human chorionic gonadotropin administration, (b) sperm analysis, and (c) morphology and cell architecture of the testes. These results were compatible with normofunctional testicular hyperplasia confirming previous observations and allowing the definite individualization of a syndrome with mental deficiency probably due to an X-linked recessive mutation.


Genetic markers in Malaysians: variants of soluble and mitochondrial glutamic oxaloacetic transaminase and salivary and pancreatic amylase, phosphoglucomutase III and saliva esterase polymorphisms.

Malaysians of Malay, Chinese, and Indian ancestries were electrophoretically phenotyped for Amy1 and saliva esterase region 1 (Set-1) from saliva, Amy2 from plasma, soluble and mitochondrial GOT and PGM3 from leukocyte and placenta. Kadazans and Bajaus, the indigenous people of Sabah, East Malaysia were surveyed for Amy2. Three types of variants were observed for Amy1, one type for Amy2. Only Indians were found to be polymorphic for Amy1. Two GOTs 2-1 and three GOTm 2-1 variants were found among 281 Chinese while three GOTm 2-1 variants were found among 311 Malays. Malaysian Malays, Chinese, and Indians were found to be polymorphic for Set-1 and PGM3. The gene frequencies in Malays are Set-1F=0.601 +/- 0.021, Set-1S = 0.399 +/- 0.021; PGM13 = 0.788 +/- 0.020, PGM23 = 0.212 +/- 0.020; in Chinese Set-1F = 0.497 +/- 0.028, Set-1S = 0.503 +/- 0.028; PGM13 = 0.745 +/- 0.24, PGM23 = 0.255 +/- 0.024; in Indians, Set-1F = 0.449 +/- 0.031, Set-1S = 0.551 +/- 0.031; PGM13 = 0.755 +/- 0.029, PGM23 = 0.245 +/- 0.029.


Chromosome analysis of bone marrow in mammals after treatment with isoniazid.

Cytogenetic investigations in bone marrow from animals treated with isoniazid (INH) were performed in seven different laboratories according to a standard protocol. The experiments were carried out in the Chinese hamster, the mouse, and the rat. In short-term studies INH was administered twice at an interval of 24 h in doses of 5, 25, and 125 mg/kg, and the animals were sacrificed 6, 12, 24, and 48 h after the second dose. In long-term studies doses of 25 and 125 mg/kg were administered thrice weekly for 12 weeks. As a rule, each group consisted of at least four animals, and 100 metaphases per animal were counted. Statistical analysis of the data showed that the incidence of chromosomal aberrations including gaps lay in the critical range for two groups in one laboratory and was significantly higher than in the control in three groups in another of the seven laboratories. From the results of both the short-term and the long-term studies in all laboratories, however, it may be concluded, that isoniazid does not induce gross chromosomal aberrations.


Analysis of chromosome aberrations in bone marrow cells of rats after treatment with isoniazid.

100 mg INH/kg body weight was administered to male Wistar rats five times, at 24 h intervals, either intraperitoneally or intravenously. In both experimental series the yield of chromosome aberrations in bone marrow cells was not increased as compared to controls.


Mutagenicity of isoniazid: testing for somatic chromosome aberrations in mouse embryos.

Isonicotinic acid hydrazide (INH) were given by peroral intubation to pregnant mice of strain C57BL/6Ffm on day 9 of pregnancy, INH was given in the following doses: 0, 5, 25, and 125 mg/kg solved in physiological saline. Cytogenetic analysis of homogenized embryos 6, 12, 24, and 48 h, resp., after treatment of the females did not show any increase of the rate of gaps or chromosomal aberrations.


Chromosome analyses in man in the course of chemoprophylaxis against tuberculosis and of antituberculosis chemotherapy with isoniazid.

Cytogenetic analyses were carried out in lymphocytes of 37 persons before and during a primary chemoprophylaxis or a preventive chemotherapy with isoniazid as well as of 30 patients suffering from active pulmonary tuberculosis before and during a chemotherapy with isoniazid in combination with two other antimycobacterial drugs. The results of the four participating research groups consistently reveal no indication for a chromosome damaging activity of isoniazid, of its metabolites in the human organism and of the administered drug regimens.


The effect of isoniazid (INH) on Chinese hamster and mouse spermatogonia.

Acute and chronic treatment of Chinese hamsters and mice with 5, 25 and 125 mg/kg isoniazid (INH) given by oral intubation did not enhance the chromosomal aberration frequencies in spermatogonia. The structural and numerical aberration rates remained in the range of spontaneous events even after the chronic treatment over 12 weeks with 3 x 125 mg/kg INH per week. This dose is much higher than normally used for prevention and therapy in man (3--16 mg/kg).


Cytogenetic study in spermatocytes of mice and Chinese hamsters after treatment with isoniazid (INH).

Meiotic chromosomes of spermatocytes from INH-treated male mice and Chinese hamsters were analysed for chromosome aberrations in diakinesis-metaphase I and metaphase II. The experiments were performed in two laboratories while a third laboratory participated in the chromosome evaluation. No enhancement of chromosome aberrations could be observed after acute treatment of early primary spermatocytes or chronic treatment of spermatogonia with INH.


Effects of isoniazid (INH) on the oogenesis of mice.

Mutagenic damages in female germ cells of mice have been tested with the dominant lethal assay and the cytogenetic analysis of unfertilized M II-oocytes. Concluding one can say that from the experimental data presented here do not show any mutagenic effect of INH on oogenesis of different strains of mice can be stated.


A balanced translocation t(11;16)(q13;p11), a cytogenetic study and an attempt at gene localization.

Members of three generations of a single family were examined and found to have a balanced translocation t(11;16)(q13;p11). Cytogenetic investigation and investigation of a number of gene markers is consistent with the current view that the Hp-alpha locus is situated in the proximity of band 16q22.


Timing of meiotic stages in oocytes of the Syrian hamster (Mesocricetus auratus) and analysis of induced chromosome aberrations.

The stages of maturation of oocytes (meiotic stages) in adult Syrian hamsters (Mesocricetus auratus) have been timed following superovulation treatment. Timing and superovulation were induced by an injection of pregnant mares' serum on the first morning of the estrus cycle, followed by injection of human chorionic gonadotropin (HCG) in the evening of the fourth day. The oocytes completed the prophase of the first maturation division 3 h after the injection of HCG. Ovulation began 9 1/2 h after the injection. A method of analysis of metaphase II chromosomes of Syrian hamster oocytes 16 h after injection of HCG is described. This method seems to be appropriate for the examination of the induction of genetic defects during oogenesis. Female hamsters were treated with 2,3,5-triethyleneimonobenzoquione-1,4. The induced chromosome aberrations were analysed. Dosis-dependent response could be demonstrated.


The effect of SH-SS transition in the structural organization of mitotic chromosomes.

Human lymphoid cell cultures were treated with 2,2'-dithiodipyridine, a thiol reacting agent which produces SS bridges inside the living cells. After 1 to 4 h treatment chromosome preparations were made. The chromosomes acquired a peculiar segmentation along the chromatids. The results suggest that the alteration might arise from a direct reaction of the agent with special chromosomal proteins. The resistance of treated chromosomes to alkali-heat treatment used in C-banding technique was different from that of untreated chromosomes. This prefixational procedure seems to be advantageous in analysing both the chromosome organization and the banding mechanism.


A case of ring Y chromosome.

Ring Y chromosome 45,X/46,X,r(Y) was identified by fluorescence in a child with ambiguous external genitalia, urogenital sinus, vagina, uterus, and Fallopian tubes. Testicular tissue was noted on gonadal biopsy.


Nucleus anomaly test in Chinese hamster and in rat after treatment with isoniazid.

Nucleus anomaly test in Chinese hamsters and in rats treated with isoniazid (INH) was carried out according to a standard protocol in two different laboratories. These comprised both short-term studies, in which the tests were performed on animals killed 6, 12, 24, 36, or 48 h after the second of two consecutive doses of 5, 25, or 125 mg/kg INH given at an interval of 24 h, and long-term studies in animals treated with 25 mg/kg INH thrice weekly for 12 weeks. As a rule, each group consisted of at least four animals, and 1000 cells from each animal were examined. In one of the laboratories, a slight, but statistically significant increase in the incidence of nuclear anomalies was observed in two experiments on animals sacrificed 24 h after treatment; in the majority of cases, however, the investigations yielded negative results. Two out of three long-term studies revealed a slight, but statistically significant increase in the incidence of nuclear anomalies.


Trisomy 9p with an isochromosome of 9p.

An 18 1/2-year-old female is described with moderately severe mental retardation, the phenotype of the trisomy 9p syndromy, and an isochromosome for the short arm of a chromosome 9, contained in an unique karyotype, 46,XX,-9,t(7q9q),+ iso 9p.


An HLA map of Europe.

HLA--A and B antigen frequencies from 65 different population samples (61 European and 4 non-European) have been tabulated. Pairwise genetic distances were calculated between some of the populations using HLA--A and B data. The distances obtained with these two series were very strongly correlated. Distances obtained with ABO blood groups (in part of the material) showed weaker but still highly significant correlation with those obtained from combined HLA--A and B data. In general, neighbouring countries had low distances, and of the populations studied, Essen would represent the 'middle' population in Europe. The supposedly inbred population of Sardinia showed the highest distances. The data may be useful for comparison in new HLA studies and can be used for further phylogenic studies.


Break points in human chromosomes.

Break points of structural rearrangements of human chromosomes can be identified by banding techniques. The present study attempts to analyze the randomness and the distribution of the reported spontaneous break points in the human genome. Reports of break points in structural rearrangements of human chromosomes from the published sources up to October 1976 were analyzed. Based on the assumption that each unit length of band has an equal chance of being broken, chi2 tests show that positions of breakage are highly non-random; that is, breaks are more frequent in the negative band areas and in the centromeric and terminal regions. In double-break rearrangements the same band types tend to rejoin. The distribution of breaks is not proportional to the chromosome length. The longer chromosomes (i.e., 1--12, X) have a lower number of breaks per unit length, while the shorter chromosomes (i.e., 13--22, Y) have a greater number of breaks per unit length with the exception of chromosomes 4, 9, 10, 16, 17, 19, 20 and X. Out of the whole genome, chromosomes 9, 13, 18, 21, 22 and Y have the most breaks per unit length and chromosomes 16, 6, 2, 3 and 19 have the fewest. 18p11, 21q22 and Yp11 are the three bands with most frequent breaks. There are 53 bands where no breaks have been reported.


Effects of parental consanguinity on fertility, mortality and morbidity among the Pattusalis of Tirupati, South Indian.

The incidence of consanguineous marriages is very high in the Pattusali population. First cousin marriages are preferred mostly. The consanguinity effects obtained in this population are also mostly confined to these marriages only. The inbreeding coefficient for the population is 0.02997. The consanguinity on fertility, mortality and morbidity are discussed in the paper.


[Passive immunization against rabies (author's transl)].

Passive immunization has proven an important complementary method for protection of an infected organism against rabies in the very first phase after virus contact. Passive-active immunization is by far superior compared to vaccination only. A few cases of human rabies after serovaccination in due time might be due to interference (immunosuppression) of active antibody formation after vaccination by passiively administered performed heterologous rabies immune globulin. This "interference phenomenon" can probably be explained as an imbalance of antigen and antibody in vivo, i.e. antigen masking and, hence, blocking of the immune reaction on its afferent branch. Both, 19S- and 7S- antibody moleculars, are able to induce interference. Whereas the old heterologous antisera from horse or mule, in an extremely high percentage, provoked moderate or severe side effects of such as urticaria, serum sickness, immune complex nephritis etc., the now available homologous Rabies Immune Globulin of Human Origin (RIGH) is very well tolerated, of long-lasting effectiveness and does not interfere with active antibody formation after application of HDCS-tissues culture vaccine, when an amount of 20 I.U./kg bodyweight of RIGH and 6 diseases of HDCS-vaccine on days, 0, 3, 7, 14, 30 and 90 (Essen schedule postexposure vaccination) is used.


[Malaria: 4 case reports with "atypical" symptoms (author's transl)].

Four cases of malaria are described. Five to nine days elapsed between the onset of clinical symptoms and the beginning of the anti-malaria chemotherapy. One of the patients died under signs of massive and nearly synchronous hemolysis during the last two hours of treatment. The Malaria tropica disease of the first and the second patient were first diagnosed as common cold with enteritic symptoms; the third patient showed signs of abdominal thyphoid fever and developed symptoms of intravascular coagulation. With the fourth case-Malaria tertiana-it shall be remembered that, if chemoprophylaxis starts too late, the disease is not suppressed but can be delayed: incubation period lasted ten weeks. The diagnostic procedure for the clinician and the pathogenetic mechanism are discussed: massive hemolysis and the possible influence of the chloroquine therapy, the intravascular coagulation and the elevation of the IgE level.


Plating of fractures of the middle third of the clavicle.

Twenty mid-clavicular fractures are reported which required plate fixation. This technique gave relief from pain within 12 hours and resulted in bony union in every case. The indications for this operation are described.


Non-union of fractures of the clavicle.

Three cases of non-union of the clavicle were successfully treated by compression fixation using AO semitubular plates.


Autoradiographic studies of fracture healing using 99Tcm-Sn-polyphosphate.

Using 99Tcm-Sn-polyphosphate, macroautoradiographs were produced of 34 standardized, medullary-nailed, 1--10-week-old tibial fractures in the rat. The radioactivity was localized in the callus and epiphyseal growth plate. On microautoradiography the 99Tcm-Sn-polyphosphate was found diffusely scattered within the mineralizing part of the callus and the epiphyseal growth plate.


A method for the production of an undisplaced reproducible tibial fracture in the rat.

Forty inbred hooded rats sustained a fracture of the left tibia and 2 animals had an additional fracture of the right tibia (44 fractures in 42 rats). Before the fracture, medullary nailing was done with a 0.8-mm stainless-steel wire. Forty-one of the 42 fractures were transverse, 7 of the 42 nails bent more than 15 degrees. Radiological union occurred within 3--4 weeks.


Arthrography of the shoulder in anterior dislocation: a study of African and Asian patients.

Arthrography of the shoulder was performed in 16 consecutive cases of primary anterior dislocation and in 11 cases of recurrent dislocation. All the primary dislocations were in African Negro patients and showed an unusually high incidence of capsular rupture rather than labral detachment. It is suggested that this is due to stronger soft tissue attachment to bone in Africans, resulting in fewer labral detachments and thus accounting for the low incidence of recurrent dislocation in the African populace. The series of recurrent dislocations, consisting of African and Asian patients, confirmed the low incidence in Africans but demonstrated labral detachment and humeral head defects common to both racial groups.


Sagittal fractures of the cervical spine.

Two cases of sagittal fracture of cervical vertebral bodies have been studied. The findings indicate that the fractures were a consequence of forces directed forwards against the posterior surfaces of the vertebral bodies due to flattening of the vertebral rings in an anterior--posterior direction.


Displaced fat pads in trauma to the elbow.

A study was made of all the X-ray films of elbows taken in a casualty department in 1975, to determine the significance of posterior fat pad displacement. Posterior displacement was always found to indicate a fracture, whereas anterior displacement occasionally occurred without a fracture.


A useful procedure in the treatment of chronic olecranon bursitis.

An operation for chronic olecranon bursitis is described and the results of 11 cases reviewed. It is suggested that a number of patients with this condition have a prominent olecranon process or spur. The technique involves excision of the olecranon process only, the bursa itself is preserved. The overlying skin remains undamaged and this manoeuvre avoids the unpleasant sequelae that may follow its removal. The operation appears to give satisfactory results.


Acute rupture of the pericardium with delayed dislocation of the heart: a case report.

A case is presented in which the right side of the pericardium was ruptured as a result of a fall. The heart dislocated through the rent on the fourth day and was irreducible, having to be replaced surgically. The possible mechanism of the delayed dislocation is discussed.


Traumatic hemipelvectomy--the tenth survivor: a case report and a review of the literature.

This tenth survivor of traumatic hemipelvectomy was a young male involved in a collision between a car and his bicycle. As in previous cases, he sustained severe associated injuries to the genitourinary tract and rectum. Atypically he required secondary closure with autogenous skin taken from the severed lower limb, and in addition, he developed a compartment syndrome in the opposite leg.


Metabolic problems in the management of a traumatic pancreatic fistula.

A case of persistent, high output, traumatic pancreatic fistula, complicated by the development of a gastric fistula secondary to a pancreatic abscess, is described. The problems associated with the metabolic and nutritional management are discussed.


A curious gunshot injury.

The case of a victim of an unusual gunshot injury is described. The man had been 'knee-capped' and on arrival at hospital was found to have two bullets and a cartridge casing in the knee joint. These had entered through one entrance wound. A ballistic report describes how the incident occurred.


A possible new approach to the management of brain abscesses.

A report is given of effective non-surgical treatment with antibiotics in a patient with a large brain abscess.Non-surgical treatment of brain abscesses may be possible if massive doses of specific bactericidal antibiotics are used and the patients are followed up with frequent brain scans and computerized tomography.


Comparison of four dosage schedules in the treatment of giardiasis with metronidazole.

Sixty patients with parasitologically confirmed giardiasis were treated with metronidazole using four different regimens administered to four groups of 15 patients each. A seven-day course of 200 mg thrice daily successfully eliminated the organism in 11 patients. A repetition of the seven-day course after an interval of one week was successful in 14 patients, a single dose of 2400 mg in nine patients, and two 2400 mg doses on successive days in 12 patients. Late relapses, detected more than one month after therapy, were relatively common in the single-dose groups. Side-effects associated with the 2400 mg dosages were frequent but tolerable.


A comparative factor analysis of attitudes toward societal relations of the elderly.

The major objectives of this study were to explore the factorial dimensionality of forty-two additudinal items designed to measure attitudes concerning old people, and to compare these factor structures in two groups. Respondents were divided into a younger group (370 participants aged 30-65) and an older group (337 participants aged 70 and 75). Factor analyses were run independently for each group, providing obliquely rotated factors. Six pairs of factors were judged to be congruent and sufficiently reliable: Work, Welfare, Social Work, Dwelling, Gatherings, and Administratorship. One postulated factor emerged in the older group alone and was named Housekeeping, the conceptual counterpart of which split into two conjugate factors in the younger group. Second-order factor analyses yielded two comparable sets of three second-order factors: Social Activities and Self-Care Ability, whereas the third factor connected high welfare with age-segregated dwelling (and low welfare with age-integration).


Age differences in personality structure revisited: Studies in validity, stability, and change.

Construct validity and longitudinal stability evidence for three cluster dimensions of personality identified as Anxiety, Extraversion, and Openness is examined in a sample of adult males. Correlations with Allport-Vernon-Lindsay Value scales, Cornell Medical Index scores, Eysenck E and N scales, and factors from the SVIB are presented in support of the interpretation of the three clusters. Nine-year longitudinal evidence of stability is presented for Anxiety and Extraversion scores. Previous evidence for change in the structure of Openness to Experience is reconsidered in the light of eleven-year longitudinal data. While the earlier structural differences were not longitudinally replicated, a pattern of external correlates provided evidence for validity of an Openness dimension. Finally, the structural approach to personality development is illustrated by examining the differing relations between field-dependence and tendermindedness in younger and older men.


Social class and political involvement in age graded and non-age graded associations.

This paper examines the relationship between social class and political involvement after retirement and seeks to determine whether this relationship is differentially mediated by participation in non-age graded and age graded associational contexts. Controlling for the age structure of association memberships, the relationships between social class and political activity and several measures of political interest are examined for 304 retired people. Strong and moderate relationships were found for individuals without memberships and those with non-age graded memberships exclusively. No relationships were found for members of age graded associations only. The absence of a relationship between social class and political involvement for those individuals who confine their formal associational activity to age peers is explained by positing the existence of a generational community which insulates lower class older people from class related cross-pressures and invidious distinctions which depress political involvement in other contexts.


Structured group interaction: An intervention strategy for the continued development of elderly populations.

Structured group interaction, through an emphasis on pre-group structuring, didactic presentations, experiential learning, and evaluation, provides a flexible approach to achieving a variety of goals while compensating for many of the problem characteristics of an aged institutionalized population. Structured groups are characterized by adherence to a rigorous intervention planning methodology, with a high degree of pre-planned group structure, explicit behaviorally stated performance goals, and a concern for transferring group behavior to everyday settings. After a consideration of literature support and some of the limitations and hazards involved in the approach, it is concluded that structured groups represent a useful tool for the applied gerontologist.


Health, socioeconomic status and self-preception in the elderly: An application of the interpersonal checklist.

One-hundred and thirty-four men and women in the Bonn Longitudinal Study of Aging (BLSA) sample from sixty-two to eighty-one years of age were tested and re-tested a year later using the Interpersonal Checklist (ICL) to study the effects of health, sex, socioeconomic status and time of self perception. Preliminary item analysis justified the use of the ICL for older people. A multiple analysis of variance for repeated measures with the factors SEX, SES, and TIME yielded two interactions for "rebellious-distrustful (FG by sex x health) and "self effacing-masochistic" (HI by time x health) and three main-effects for "agressive-sadistic" (DE by sex), "self-effacing-masochistic" (HI by SES) and "docile-dependent" (IK by time).


Higher education in retirement: The Institute for Retired Professionals.

This paper indicates the failure of our society to educate its citizens in the "worthy" use of retirement leisure. It contends that educated retirees should be offered an opportunity to function in creative, dignified and self-directed roles on university campuses. It describes the program of the Institute for Retired Professionals at The New School for Social Research in New York City, which has been functioning since 1962 and now serves as a model for a growing number of university programs for retirees. At the IRP educated retirees have found a new way of spending their retirement years in dignified roles as teachers, leaders, administrators and participants in their own inner university.


Method for controlled establishment of steady-state plasma levels through multiple dosing.

A specific dosage schedule is designed for the case of multiple dosing with the aim of achieving the desired steady-state blood level in a predetermined time interval. The method is based on the administration of nonuniform doses at uniform dosage intervals during the saturation time. To calculate the doses a nonlinear equation must be solved. The theory is illustrated by a quantitative example (digitoxin).


Developing gerontology in a developing country: The case of Sao Paulo, Brazil.

This paper details the efforts of a team of professionals to establish a gerontology center in Sao Paulo, Brazil. The focus is on some of the problems of the emergent profession in Brazil: the uncertain labor market; the problems of recruiting; the problems of generating a knowledge base on aging drawn from Brazil rather than borrowed from the American or European context; the problems of visibility, legitimacy, and financial support for the new gerontology center; the competition of aging programs with other government priorities. The article concludes by citing some benefits that might accrue to the field of gerontology by underwriting the development of such centers on aging in the developing countries.


Pharmacokinetic study of rifampicin in biliary surgery.

Following the oral administration of 600 mg rifampicin, the concentration of antibiotic in serum, bile of the gallbladder and choledochus, cholecystic wall, and hepatic tissue was determined with the agar diffusion method in 23 patients undergoing surgery for cholelithiasis. After 80-340 minutes the average rifampicin concentration was 6.4 microgram/ml in serum, 78.4 microgram/ml in the bile of the gallbladder, 91.6 microgram/ml in the bile of the choledochus, 4.0 microgram/g in the cholecystic wall, and 23.3 microgram/g in the hepatic tissue. After 24 hours the level was significantly reduced in the serum and hepatic tissue. The rifampicin level in the bile of the gallbladder was twelvefold, in the bile of the choledochus fourteenfold, in the cholecystic wall 61.1% and in the hepatic tissue 364% of the serum level. In general, the rifampicin concentration obtainable in the bile and hepatic tissue is sufficient against bacterial strains causing infections of the biliary duct, and for this reason rifampicin will play in the future an important role in the treatment of infections of the biliary duct.


The bioavailability of commercial metronidazole formulations.

A bioavailability study of eight commercial pharmaceutically equivalent tablet formulations and a solution of metronidazole was conducted in groups of ten subjects with single oral 250 mg doses. Although the solution gave significantly lower extents of bioavailability, the commercial tablets were not significantly different from the (innovator) reference product. The slow rate of absorption for one formulation (F) was observed to be associated with long dissolution time. Individual elimination half-life differences (probably attributable to metabolism) were reflected in considerable intersubject differences in plasma metronidazole concentrations.


The bioavailability of alpha-acetyldigoxin from Card-Hydergin--a fixed combination of Hydergine and acetyldigoxin.

In six healthy volunteers the bioavailability of alpha-acetyldigoxin in solution and tablet form was compared with a tablet which in addition to alpha-acetyldigoxin contained the DH-ergot alkaloid Hydergine in identical galenic formulation. After a single dose, bioavailability was measured from the areas under the plasma level time curves and from the cumulative amount of digoxin excreted into the urine. The addition of Hydergine did not change the plasma level/time profile and the bioavailability of alpha-acetyldigoxin. When this parameter was compared to the solution, a relative bioavailability of approximately 80% could be calculated for both tablets. Relating this data to a previously published infusion experiment, their absolute bioavailabilities amounted to about 70%.


Alterations in macroscopically intact skin of children with juvenile rheumatoid arthritis.

Punch biopsies of macroscopic-intact skin were performed on 75 children with rheumatoid arthritis, aged 4--14 years. There was no significant correlation between the morphologic alterations and the sex and age of the children or the duration of the disease, but there was a positive relationship with the degree of activity of the rheumatoid process. It appears that punch biopsy of the skin in children with juvenile rheumatoid arthritis can facilitate determination of alterations of the connective tissue if the data obtained are regularly correlated with clinical and laboratory findings. In such a way, the results can reflect the effects of treatment, as well as the evolution and prognosis of the juvenile rheumatoid arthritis.


The pharmacokinetics of dihydroergotamine in the beagle.

After single 0.5-mg nad 1.0-mg i.v. injections, dihydroergotamine, as measured by a radioimmunoassay, disappeared quickly from the plasma of beagles, with a mean alpha-phase half-life of 1.32--1.91 min. This explains its effect of rapidly lowering the temperature of the ear of the dog. Its short beta-phase half-life (mean, 40.79--70.13 min), a moderately low volume of ditribution at beta-phase (mean 1.50--3.46 L/kg) and a rather high plasma clearance value (mean, 311.67--587.88 ml/min) indicate a rapid elimination of the drug from the organism. The 24-hr urinary excretion of dihydroergotamine was 2.7% of the 0.5-mg i.v. dose and 2.3% to 3.1% of the 1.0-mg i.v. dose. A measure of the amount of a 7.5-mg p.o. dose of the drug reaching the systemic circulation was obtained from the ratio of the area under the plasma curve after p.o. administration to that after i.v. administration, corrected for the different amounts given by the two routes. Only 1.2--1.4% of the 7.5-mg p.o. dose of dihydroergotamine reached the systemic circulation. There were no significant differences in the plasma levels of dihydroergotamine after a single dose of the two preparations tested, Vasogin (Leiras) and Orstanorm (Sandoz), given either by the oral or intravenous route.


Acute poisoning with melitracen--absence of ECG changes.

The clinical course of the first case of acute poisoning from melitracen, a tricyclic antidepressant, is described, whose symptomatology was characterized by the absence of cardiovascular changes (ECG, arterial pressure, cardiac frequency). Central anticholinergic effects of the drug, as excitement, hallucinations, space and time disorientation, regressed with the administration of diazepam.


Human-pharmacological investigations on the platelet adhesiveness- and aggregation-inhibiting effect of EMD 26 644, an oxazolyl-thio-propionic acid derivate.

EMD 26 644, a compound of novel chemical structure and with platelet aggregation-inhibiting properties, was investigated in 2 controlled clinical pharmacological studies involving 42 normal volunteers. In the first study with 22 subjects exhibiting normal or spontaneously increased platelet aggregation the influence of 1 X 250 mg EMD 26 644 p.o. on the platelet aggregation and adhesiveness was examined ex vivo. In the second study 20 subjects with and without a premedication of 1 X 250 mg EMD 26 644 were exposed an artificial climate with special platelet-irritating properties. A single oral dose of 250 mg EMD 26 644 markedly and significantly inhibited the platelet aggregation and adhesiveness over a period of several days.


Sisomicin: in vitro activity and pharmacokinetics.

In vitro activity of sisomicin and gentamicin was compared in serial dilution tests for 619 bacterial strains (Staphylococcus aureus, E. coli, Proteus mirabilis, Proteus vulgaris, Enterobacter, Klebsiella, Pseudomonas aeruginosa, Salmonella, Serratia marcescens). Mean MIC of sisomicin was lower by one geometrical dilution step compared with gentamicin for Pseudomonas, Proteus vulgaris, Klebsiella, and Serratia, while it was almost identical with the other species. Resistance (MIC greater than 5 microgram/ml) against sisomicin was observed in 2% of Pseudomonas strains, resistance against gentamicin in 8%. Ten healthy adult volunteers had serum peak levels (after i,m. injection of 40 mg and 80 mg sisomicin) of 2.7 and 3.2 microgram/ml. Urine recovery (in 24 hrs) was 76%. Continuous i.v. infusion of sisomicin or gentamicin (6.6 mg/hour in 7 healthy adult volunteers) yielded in serum levels of 0.64 and 1.03 microgram/ml respectively. Biological half-life (90 minutes), urine recovery (60% in the fourth hour), renal clearance and skin blister levels at the end of infusion were almost identical for both antibiotics; total clearance was somewhat higher with sisomicin than with gentamicin.


Clofibrate and enzymatic induction in man.

The oral administration of clofibrate, 1 g per day for 13 days, did not modify the half-life of antipyrine and urinary glucaric acid excretion in five volunteers. Despite the fact that clofibrate is a strong inducer of hepatic microsomal enzymatic activity in the rat, in man it does not increase, at these doses, the metabolism of antipyrine and the urinary elimination of glucaric acid. Rifampicin, 600 mg per day orally for seven days, decreases the plasma steady-state concentrations of chlorophenoxyisobutyric acid, a major metabolite of clofibrate. It seems that the metabolism of clofibrate depends upon inducible enzymatic activity. When rifampicin and clofibrate are administered together, it may be important to increase the dose of clofibrate used.


Factors influencing diazepam pharmacokinetics: age, sex, and liver disease.

Published data on the effect of cirrhosis on diazepam pharmacokinetics were reanalyzed to determine how age, sex, and body weight might have influenced the conclusions. Diazepam elimination half-life (t1/2beta) and weight-corrected volume of distribution (Vd) were significantly larger in patients with cirrhosis (n = 9) than in controls (n = 4). Weight-corrected diazepam clearance was significantly reduced in cirrhotics as compared with controls. Multiple stepwise regression analysis, however, revealed that age and liver disease were of approximately equal importance as determinants of t1/2beta. Age, sex, and liver disease all influenced Vd, but liver disease by far was the most important determinant of diazepam clearance. Thus age, sex, and body size can have an important influence on the pharmacokinetics of drugs, and should be included as independent variables in pharmacokinetic studies.


Clinical experimental evaluation of the effect of dibromotyrosine on thyroid function.

In order to evaluate the effects of dibromotyrosine (DBT) on the thyroid function (already demonstrated in animals), thyroid tests were performed in 10 subjects with functional signs of thyroid hyperfunction, before and after administration of 1800 mg (600 X 3) of DBT for 10 days. The results show a mild decrease of the RAI uptake, but no significative interference on the thyrodal hormonogenesis. According to the author, the DBT seems to act on the hypothalamic centers regulating the thyroid function, due to its peculiar molecular components. It is therefore particularly suitable for the treatment of patients with involvement of the C.N.S.


Pharmacokinetics of papaverine hydrochloride and the biopharmaceutics of its oral dosage forms.

The pharmacokinetics of completely metabolized papaverine hydrochloride were characterized by a linear sum of three exponentials on intravenous administration with respective 1.5, 19 and 107 min apparent half lives. There was a time-dependent partition from plasma water into red blood cells with an apparent half life of 1.5--3 min. The partition coefficient normally ranged between 8 and 15 at therapeutic levels but approached unity at high plasma concentrations to indicate a saturable partition. Apparent compartmental volumes of distribution referenced to total concentrations in the plasma were 4.3--4.8, 11--13 and 20--25 liters. Protein binding was 91--95%. The hepatic clearance of blood was 960 ml/min, corresponding to a hepatic efficiency of 69%, and indicated that the clearance of protein-bound drug was consistent with the observed first pass metabolism of 70% for oral solutions. No dose dependency was observed on intravenous administration or on oral administration of solutions and tablets. Tablets with release lag times of 10--15 min showed relative bioavailabilities of 52%. Two different lots of sustained release capsules showed 68 and 89% relative bioavailabilities. Release lag times among capsules ranged between 0 and 170 min. Loo-Riegelman calculations and analog computer fittings were consistent with a half life of absorption from oral solutions of 19 min and zero order release rates from tablets and sustained release capsules. Chronic studies of tablets q.i.d. and capsules b.i.d. confirmed lack of accumulation. An appropriately designed 300 mg sustained release capsule, b.i.d., for an arbitrary plasma level of 0.200 microgram/ml should have one tenth the release rate of the studied capsules.


The influence of ethacrynic acid, hydrochlorothiazide and clopamide on the renal excretion of chloramphenicol and its metabolites.

Simultaneous administration of chloramphenicol (1 g orally) and ethacrynic acid (150 mg orally), hydrochlorothiazide (25 mg orally) or clopamide (40 mg orally) increased the urinary excretion of chloramphenicol and its metabolites (aryl amines and total nitro compounds). The administration of diuretics did not change the time course of serum concentrations of substances under study. Since the urinary excretion of chloramphenicol and its metabolites is a urine flow-dependent process, the influence of the tested diuretics can be explained as a consequence of decreased tubular water reabsorption.


The effect of papaverine on the contraction of the human gallbladder.

In a double-blind study, 40 mg of papaverine (Group I) or the same amount of placebo (1.0 ml of physiological saline, Group II)was injected intravenously in 19 patients to study the effect of papaverine on the contractility of the gallbladder in connection with routine oral cholecystography. In both groups a standard contraction meal (200 ml of cream) caused a significant contraction of the gallbladder (at 30 minutes). Thereafter, intravenously administered papaverine significantly inhibited further contraction caused by the fatty meal, but no significant dilatation was observed. This difference between the two groups lasted throughout the whole study period to 60 minutes after the drug administration. This time period mainly consisted of the distributional alpha-phase of the drug concentrations determined by gas chromatography in the serum. Because no dilation effect on the gallbladder was found, the clinical spasmolytic response to papaverine during an acute attack of pain in a patient with gallstones seems to be questionable.


The effect of crystal size, gastric content and emptying rate on the absorption of nitrofurantoin in healthy human volunteers.

The effect of four crystal sizes, gastric contents, and gastrointestinal motility on the absorption and excretion of nitrofurantoin was studied in three separate cross-over studies on 10 healthy volunteers. Microcrystal preparation gave an early and high serum peak. The greater the crystal size was, the smaller was the peak serum concentration. Correspondingly, microcrystal preparations gave initially very high nitrofurantoin concentrations in urine. Macrocrystal preparation had a not significantly longer excretion time than the other preparations. Food did not increase the serum nitrofurantoin concentrations, but excretion during 4 to 6 h was considerably greater than after fasting. In contrast, antacid and the use of a delayed-release preparation greatly worsened the biovailability of nitrofurantoin. An increased gastric emptying rate induced by metoclopramide significantly worsened the absorption of nitrofurantoin, but atropine only retarded the absorption and the principal excretion in urine occurred during 4 to 8 h.


Effectiveness of analgesics evaluated with the tourniquet technique.

The analgesic effectiveness of acetylsalicyclic acid, noramidopyrinium methane sulfonate sodium, pentazocin and codeine phosphate was studied in 19 healthy male and female subjects between 25 and 65 years of age by means of two variants of the tourniquet technique. Compared with placebo, no differences in effectiveness were found using a double-blind approach; primarily because of the low reliability of the method.


Indomethacin esters acting as anti-inflammatory and immunosuppressive drugs.

Administration of indomethacin and ten different indomethacin derivatives led to a variable depression in the mice immume response to sheep red blood cells (SRBC) as shown either by direct hemolytic-plaque assay or hemagglutination tests. Compounds with a lower toxicity than indomethacin and predominant immunosuppressive or anti-inflammatory activity were obtained. According to the variations in the primary immune response and to their variable anti-inflammatory actions, the structure-activity relationships are documentted and some possible explanations, relative to their immunodepressive effect, are discussed.


Clinical and laboratory evaluation of 8-methoxypsoralen toxicity.

Twenty-seven patients with vitiligo took (Meladinine 8-methoxypsoralen) for 2 to 12 years. They were selected from those patients who, in an attempt to get a more rapid repigmentary response, exceeded the advised doses by ingesting from 7-16 tablets (equivalent to 70-160 mg) per day. These regimens were well tolerated. Hepatic and renal function were not affected.


Photochemotherapy of psoriasis.

Orally administered 8-methoxypsoralen followed by irradiation with longwave ultraviolet light (UVA, 320-400 nm, maximum 365 nm) resulted in 90-100% clearing in 24 of 26 psoriasis patients. Recurrence could be prevented by maintenance treatment. The treatment was tolerated well; no serious side effects were observed. A moderate increase of serum transaminase values was observed in 6 patients; in 5, these values became normal in a short time. The connection between these enzyme increases and the treatment is uncertain. At completion of the treatment the skin is universally, evenly hyperpigmented-a side effect considered positive by the patients.


Malignant change in a verrucous nevus.

A 41-year-old man developed squamous-cell carcinoma within a verrucous nevus of linear distribution of a long duration. Controversial cases have been reported in the literature. Such malignant change in verrucous nevus is extremely rare.


Treatment of psoriasis: trioxalen and sunlight.

Eighteen psoriasis patients were treated alternately with 40 mg of trioxalen and sunlight on the right side and sunlight only on the left side. Improvement was apparent faster on the psoralen-exposed side.


A simple model for protein thermal denaturation.

Whether proteins denature in all-or-none fashion or in a continuous fashion is as yet an unresolved problem. The all-or-none process implies that while the process of denaturation is going on, only two kinds of protein molecules can exist. One is completely unchanged and the other is altered. The altered protein molecules are indistinguishable. Underlying the 'continuum' models is the assumption that all the chains in a protein globule undergo similar changes so that it is enough to consider a single chain.


Empirical calculations on cyclic dipeptides. Conformations of serine, threonine and histidine residues.

Empirical conformational energy calculations were carried out for the dipeptides cyclo-(L-Ser-L-His) and cyclo-(L-Thr-L-His). Various DKP structures have been investigated to study side chain conformations through the DKP ring deformations, and prevalent conformers of monosubstituted and disubstituted dipeptides are discussed. The most stable conformations occur when both side chains are folded over a planar DKP ring, the imidazole ring being in the epsilon-tautomeric form. Theoretical results are consistent with those obtained from n.m.r. and crystallographic studies.


Studies on polypeptides. XXVI. Synthesis of the N-terminal 1--23 peptide sequence of rat pancreatic ribonuclease; enzymatic activity of the hybrid complex with bovine S-protein.

A description is given of the synthesis by fragment condensation of the peptide Gly-Glu-Ser-Arg-Glu-Ser-Ser-Ala-Asp-Lys-Phe-Lys-Arg-Gln-His-Met-Asp-Thr-Glu-Gly-Pro-Ser-Lys corresponding to the 1--23 amino acid sequence of rat pancreatic ribonuclease. This rat peptide combined with bovine S-protein yields a fully active ribonuclease S' analogue.


Location of disulfide bridges in cardiotoxin from the venom of Formosan cobra (NAJA NAJA ATRA).

The location of the four disulfide bridges in cardiotoxin from the venom of the Formosan cobra, Naja naja atra, was determined by isolating cystine-containing peptides from the enzymic and partial acid hydrolyzates of the intact toxin. The results indicate that the disulfide bridges are formed by half cystine residues 3--21, 14--38, 42--53, and 54--59. The amino acid sequence at the position 48--49 was revised to -Leu-Val- instead of Val-Leu- as reported previously.


Solid phase synthesis of apamin, the principal neurotoxin in bee venom. Isolation and characterization of acetamidomethyl apamin.

The synthesis of apamin, the principal neurotoxin in bee venom, has been accomplished by the solid phase method on a benzhydrylamine resin, 2-Phenylisopropyloxycarbonyl amino acids were used throughout the synthesis except for the C-terminal histidine. Improved yields in the coupling steps in the N-terminal part of the molecule were obtained by coupling each amino acid both in dichloromethane and dimethylformamide. The use of acetamidomethyl as an S-protecting group for cysteine made it possible to isolate and purify the linear peptide. The deblocked and oxidized peptide was fractionated by ion-exchange chromatography (Bio-Rex 70) to obtain a highly purified apamin with full biological activity and with the same physical and chemical properties as the natural peptide. Circular dichroism (CD) spectra of the synthetic and natural apamin were identical.