Thermophilic and mesophilic enzymes from B. caldotenax and B. stearothermophilus: properties, relationships and formation.

1) The adaptive system of thermophilic bacteria, as demonstrated with B. caldotenax, seems to be suitable to produce thermophilic and mesophilic enzymes for comparative studies. 2) If it may be assumed that the extensive homologies in the N-terminal sequences of the LDHs also extend over the entire polypeptide chain, comparison of these sequences together with investigation on the 3-dimensional structure offer the possibility of elucidating those structural details which may be responsible for thermostability and the other thermophilic properties. However, the difficulty still remains that the latter may be obscured by differences not related to thermostability etc. Neverthless it may be hoped that comparison of the full sequences of not only the LDHs but also of a sufficient number of other enzymes of the same system will yield such details. 3) A further interesting goal with respect to the mechanism of enzyme adaptation would be reached if the differences in amino acid sequence of thermophilic and mesophilic LDH enzymes would throw light on the type of the amino acids always being exchanged. Here from the very hypothetical point of view the question arises as to whether the bacterial cell during the metabolic adaptation process or even by mutation/selection is able to modify just those few amino acid residues thermodynamically important for thermostability. Alternatively: does there exist a "rule" by which certain amino acid residues are invariably exchanged on a change for thermophilic to mesophilic enzymes? 4) Problems not mentioned here arise with B. stearothermophilus, which can be adapted poorly via the spores or on intermediate temperatures. Of great importance, but also  a special problem in these studies on thermophilic and mesophilic enzymes produced by the same bacterium are a) the characterization of the thermophilic (70 degrees or 55 degrees) and mesophilic (37 degrees) bacterial variants (in respect to type), b) the control of homogeneity of the bacterial culture (contamination, mixed population), c) proof of the genetic identity of the 70 degrees- (55 degrees-) and 37 degrees -variant of B. caldotenax and B. stearothermophilus, which differ greatly in their phenotypes, for example in their metabolism, cell- or colony merphology. The taxonomical-biochemical identity or also the identity of morphology of the sporangia, since this should be an expression of the temperature dependent phenotype, cannot be used unconditionally as criteria of identity. Criteria such as the presence of identical enzymes in both variants or the identity of the genome (use of genetic markers, anlaysis of the DNA) are more reliable. Experiments with both variants of B. caldotenax demonstrated an identically high content of cytosine plus guanine in their DNA: 62.2% in the thermophilic DNA and 66.8% in the mesophilic DNA. In the thermophilic B. stearothermophilus the C+G content of the DNA was 56.5% and in the mesophilic variant 57.1%...


Family planning program effects on the fertility of low-income U.S. women.

Under rigorous statistical controls, it has been shown that the larger the proportion of lower SES women enrolled in organized family planning programs, the lower their fertility. Program effects independent of other social, economic and cultural factors were shown for lower SES whites and blacks, and for most age groups. The potential of a fully implemented program to reduce fertility differentials between upper and lower SES groups was assessed, using 1969-1970 fertility rates and the estimates of 1969 program impact. Although we believe that the program's impact has increased in magnitude over time, even these estimates from an early point in U.S. program development provide impressive documentation that the program reduces fertility in the subpopulation served by the program, and, by implication, that there is a genuine need for organized family planning services, even in an industrialized nation like the United States. If there were no need, there could be no program effect. The family planning program was one of the major new health and social programs introduced in the mid-1960s. This study shows that, far from failing, the program was succeeding very well in attaining its objectives. The program works because it gives women of lower socioeconomic status access to modern and effective methods of contraception that they would not otherwise have. As a result, the rates of unwanted and mistimed pregnancy of patients are lower than those of comparable women who lack access to organized clinic programs.


Number and timing failures among legitimate births in the United States: 1968, 1969 and 1972.

More than one in 10 legitimate births that occurred in the United States during 1968, 1969, and 1972 were not wanted at all, and more than one-quarter of the births were timing failures. A substantial reduction in unwanted childbearing took place between 1968 and 1972. The proportion of legitimate births reported by their mothers to be unwanted ever declined from 13 percent in 1968 to eight percent in 1972. If, as reported in a number of cross-sectional surveys taken during this approximate period, there was a sharp reduction in wanted family size reported by married women, then these women would have remained at risk of having an unwanted birth for a longer period than when their wanted family size had been higher. Thus, these estimates of a decline in unwanted childbearing may be understated (although there was the countervailing trend of later age at marriage during these years). The decline in unwanted childbearing between 1968 and 1972 is only partially attributable to the shift toward lower birth orders that occurred. Declines in unwanted births occurred for almost all birth orders. There was no significant reduction in mistimed births. Because the decline in unwanted fertility during the study period was much greater for nonwhites than whites, the traditional racial differential in unwanted childbearing narrowed considerably between 1968 and 1972. In 1968, 12 percent of the white legitimate births were classified as not wanted, compared to 21 percent of the legitimate births to nonwhites. However, between 1968 and 1972, nonwhites experienced extremely sharp declines in unwanted childbearing. Thus, in 1972 only 9.5 percent of the legitimate births to nonwhites were reported as unwanted, compared to 8.1 percent of the white births. Mothers of higher parity were much more likely to report a birth as unwanted than those of lower parity. Mothers who had completed more schooling were less likely than poorly educated mothers to report births as unwanted. Income level seems unrelated to whether the birth is unwanted, but is inversely related to whether it is a timing failure. Births that resulted from premarital conceptions tended to be reported as timing failures. Viewed from the cross-sectional perspective of period rates of population change, the elimination of unwanted legitimate childbearing would have had a substantial effect on population growth in each of the study years even without decreasing marital mistimed births or illegitimate fertility. The data also suggest that eliminating unwanted marital childbearing could significantly reduce completed family size. However, this conclusion must be viewed with great caution, since we do not know the future variations in timing and spacing of births, and the extent to which the childbearing experience of the sampled mothers is representative of their birth cohorts.


The bad old days: clandestine abortions among the poor in New York City before liberalization of the abortion law.

In surveys of poverty neighborhoods in New York City conducted in 1965 and 1967, it became apparent that clandestine abortions were more frequently reported as occurring when the woman was married and had one to three children than before marriage or after three children had already been born. Knowledge of persons who could induce an abortion was not very common among the women interviewed, and most of those who were known did not have any specialized medical training. Physicians were involved in only two percent of the respondents' own reported abortion attempts and in six percent of those among their friends, relatives and acquaintances. There was a fairly large variety of methods known and used that were supposed to provoke an abortion. The largest proportion of these were substances taken by mouth--some of which, like turpentine, Chlorox and massive doses of quinine, are quite dangerous. The next largest group involved uterine insertions. Other types of methods like massage and baths were quite rare. The popularity of the oral route of administration may be relevant to biomedical researchers who are developing new fertility regulating methods and are concerned about their acceptability.


Synthesis of 3-aminothieno-(2,3-b)pyridine derivatives. II.

The 3-cyanopyridin-2-thiol and its alkyl derivatives give, with halogen derivatives having an electron attracting group in alpha-position, the 3-aminothieno (2,3-b) pyridine derivatives in high yields. The behaviour of 2-carboethoxy-3-amino derivates and its products of hydrolysis and acetylation are studied.


Surface activity of drugs: oximes of 3-formylrifamycin SV.

The surface activity of a series of oximes of 3-formylrifamycin SV, carrying an n-alkyl chain from C1 to C12 has been investigated. The oximes can be classified into two main groups, depending on the length of the chain and having different CMC, ageing effect and area/molecule values. Two different orientations of the rifamycin molecule at the surface are proposed for the two groups: the first one occurring in the oximes with ALKYL SUBstituents C1 to C3 and induced by the hydrophobic region located in the ansa of the base molecule, the second one occurring in the oximes with alkyl substitutents C1 to C12 and induced by the hydrophobic substituent itself. The oxime with the C8 chain is the most efficent surfactant of the series. Some biological implications are discussed for the inhibition of bacterial strains resistant to rifampicin and of viral RNA dependent DNA polymerases.


[Synthesis and evaluation of the antibacterial activity of benzothiazole derivatives of 1,3,4-thiadiazole and immidazo/2,1-b/1,3,4-thiadiazole].

The synthesis and chemical properties of some derivatives of 1,3,4-thiadiazole and imidazo (2,1-b) 1,3,4-thiadiazole are described. These substances were prepared in order to study their antimicrobial activity.


[3,4,5-trimethoxybenzamides. IV. - Synthesis of the new trimethoxybenzoyloxazolidine].

As a part of a systematic research on new heterocyclic 3,4,5-trimethoxybenzamides with potential C.N.S. depressant activity, some derivatives of methyl- or dimethyloxazolidines were prepared. The results of preliminary pharmacological screening are reported in comparison with those of the model compound (I).


[High pressure liquid-liquid chromatography: correlation between retention times and biological activity of 1,3,5-triazine derivatives].

An investigation has been made of the possibility of using the retention times t obtained by reversed phase high pressure liquid-liquid chromatography in the study of quantitative structure-activity relatiionships. Taking as an example a group of herbicides which inhibit the Hill reaction, it was found that log t is additive and can be used as the hydrophobic parameter in regression analyses. The characteristics, advantages and possible developments of the method are discussed and the analytical interest is highlighted.


The preparation of 5-spiro-7'-(bicyclo (4.1.0.) heptane)barbituric acid.

The 7,7-diethoxycarbonylnorcarane (III), obtained by a catalytic decomposition of diethyldiazomalonate (I a) in cyclohexene, was condensed with urea to give the 5-spiro-7'-(bicyclo(4.1.0.)heptane)barbituric acid (IV).


[Use of oximinoiminopyrrazoline esters in the synthesis of solids phase peptides: synthesis of bradykinin].

Since oximinyliminopyrrazoline ester (OPmp) present a peculiar characteristic in the omogenous peptide synthesis, the use of them, also in the synthesis of bradikinine by the solid phase technique, was duly taken into consideration and tried out. This synthesis was achieved by employing N-protected amino acid OPmp esters containing a methoxycarbonyl or a benzylaminocarbonyl as the acyl function in position 5 of the pyrazoline ring. No significant differences were found in the reactivity of such derivatives in respect of OPmp esters containing the benzyloxycarbonylglycyl moiety. The biological activity of the synthetized braikinine is similar to that of a sample of natural "standard".


Synthesis of sulphonamidoquinoline derivatives.

In a research for new antimicrobial agents effective in therapy a new series of sulphonamidoquinoline derivatives have been studied. Their molecules, have got the feature of both 1-alkyl-1,4-dihydro-4-oxopyridine-3-carboxylic acid and sulphonamides. The structure of such compounds has been confirmed by chemical and physico-chemical methods and their antimicrobial activity has been tested.


Polymorphism of erythromycin studied by differential thermal analysis.

The polymorphism of erythromycin has been studied by differential thermal analysis. Three main forms, two crystalline (I and SI) and one amorphous have been characterized. Solvation and imbibition water can be differentiated. Solvates from 2-propanol (SII), trichloromethane (SIII) and tetrachloromethane (SIV) have been characterized. The physical stability of the various forms both in the dry state and in aqueous suspension are discussed.


Influence of side chain configuration on anti-inflammatory analgesic and anti-pyretic properties of 4-biphenylyl alkanoic acids.

A study on the influence of the number of carbon atoms in the side chain as well as side chain configuration on some pharmacologic properties of 4-biphenylyl alkanoic acids is presented. Unlike the chemical structure dependent anti-inflammatory properties, mild analgesic and anti-pyretic properties were neither dependent upon number of carbon atoms nor side chain configuration.


2-Adamantyl- and 2-adamantylidene-2-ethylamines.

The synthesis of 2-adamantyl-2-ethylamine, 2-adamantylidene-2-ethylamine and their N,N-dimethyl derivatives, starting from ethyl 2-adamantylidenecyanoacetate, is described.


[Preparation and study of phytotoxic activity of anilides of the (+/-) hydratropic acid].

A series of ((+/-)-hydratropanilides variously substituted in the aniline nucleus (substances I leads to XXXIX) were prepared. The substances were studied for inhibition of the Hill reaction and for phytotoxicity. Comparison of the results of in vitro and in vivo tests did not often show strict correlation of data: in particular it seems probable that in the hydratropanilide series substances active on the isolated chloroplast are hindered in vivo in the absorption and transport phases and thus cannot reach the receptor sites.


Andrenergic reactivity of the gastro-intestinal tract. I. Fundus of the rat's stomach.

The adrenergic receptors of the fundus of rat stomach are both type alpha and type beta. Activation of the alpha-adrenergic receptors gives a diphasic response in which inhibition precedes excitation. The beta-adrenergic receptors mediate exclusively inhibitory response; the beta-adrenergic component of the inhibitory response is clearly observed only when the alpha-adrenergic component is diminished. The beta-receptors can be assigned, with some reserve, to the betaalpha group.


An easy synthesis of ((+/-)-8,12-trans-delta5-en-cis-11-keto-14,15-yn-16-R,S-hdroxyprostanoic acid methyl ester.

A convenient synthesis of (+/-)-8,12-trans-delta5-en-cis-11-keto-14,15-yn-16-R, S-hydroxyprostanoic acid methyl ester (XI) starting from 2-propargyl-2-cyclopentenone (I) is described.


[Vesiculo-bullous erythrasma of the feet (author's transl)].

7 Cases of vesiculo-bullous erythrasma of the feet are reported. Wood's light, microbiology and histology permit to separate this entity from dysidrotic eczema and dermatophytosis.


Influence of lipophilic substances on fungal infections of the human skin. I. What constitutes a good lipid extractant?

A three-factor factorial experiment was performed to assess the efficiency of lipid extraction from the back of human volunteers. Chloroform-methanol (2:1 v/v) proved substantially superior to acetone or diethyl ether. The latter two solvents were also significantly more efficient than n-hexane. The implication of the findings is discussed with regard to the isolation and characterization of fungistatic and bacteriostatic agents on the surface of the skin.


[Alterations of the arrector pili muscle in a case of dermatomyositis (author's transl)].

We have observed great alterations of the arrector pili muscle in a case of dermatomyositis. These alterations were as follows: diminution and then loss of the staining properties of the smooth muscle fibres, perinuclear vacuolization, great heterogeneity in the degeneration of fibres, elective involvement of the cyto-fibrillary system with integrity of the other constituents of the arrector muscle and the surrounding dermis. This smooth myositis is nonspecfic and similar to the one observed in other internal diseases (scleroderma, chronic alcoholism).


[Eccrine-nevus (author's transl)].

The eccrine nevus is an exceptional entity, formed by well-differentiated adnexa which can be classified as hamartoma or organoid nevus. It is characterized by a high degree of structural maturation. The authors report a case of eccrine nevus observed in a 32-year-old woman and compare clinical and histological features of the lesion with literature data.


Condyloma-like penis carcinoma.

A squamous cell carcinoma is described which showed clinical and histological features of condyloma acuminatum on the glans penis of a 43-year-old man.


Magnesium content of the hair in alopecia areata atopica.

The magnesium content of hair from alopecia areata atopica patients, from nonatopic dermatological patients and from normal controls has been studied using atomic absorption spectroscopy. The two groups of patients had lower means and ranges than did the normal subjects, but the overlap was considerable. It is suggested that the lower levels found in the patients may be due to the nonspecific 'metabolic cost' of the skin diseases.


Pityriasis rubra pilaris. A clinico-pathological study with a special reference to autoradiography and histocompatibility antigens.

In a clinical study, 27 of 31 cases of pityriasis rubra pilaris (PRP) had two or more of the following clinical features: erythroderma, well-confined healthy islands inside the inflammatory areas, keratoderma of the palms and soles, or visible follicular hyperkeratosis. Histological features were: perifollicular parakeratosis in 26 cases, hyperkeratosis in 27 cases; the number of granular layers varied greatly from case to case and within one specimen; acanthosis was eczematous in 20 cases and psoriasiform in 8 cases. Erythroderma in PRP  in this study was self-healing, lasting 2-6 months with one exception, but PRP must as a whole be considered a mild, chronic disease lasting on average 5.7 years. Complete recovery occurred in only 8 patients and 5 of these had had an erythrodermic onset. Serum vitamin A level and tolerance test were normal. No immunological aberrations could be found. The HLA phenotype frequencies in PRP patients did not differ significantly from those in a Finnish control population. The autoradiographic study of the epidermal cells showed an increase in the cell production in the epidermis.


Transepidermal elimination of traumatically altered collagen. Report of three cases and considerations on the relationship between 'collagénome perforant verruciforme' and reactive perforating collagenosis.

Three cases of transepidermal elimination of traumatically altered collagen, including a case of 'collagénome perforant verruciforme' (CPV), are reported. On the basis of our own observations and on the data of the literature, CPV and reactive perforating collagenosis are considered as related, but different entities.


Epidermolysis bullosa hereditaria with junctional blistering in an adult.

A 38-year-old patient with epidermolysis bullosa is described, in whom junctional blister formation is revealed by electron microscopy. Clinical and ultrastructural differences from the recessive dystrophic type (Hallopeau-Siemens) and from the lethal type (Herlitz) of epidermolysis bullosa are discussed in detail.


Dermatopharmacology of salicylic acid. III. Topical contra-inflammatory effect of salicylic acid and other drugs in animal experiments.

The acute contra-inflammatory effects of salicylic acid, three standard dermatocorticoids and four contact antiphlogistics have been investigated by means of a UV dermatitis inhibition test in the guinea pig. The substances tested had a distinct inhibitory effect on the development of erythema and can be ranked in the following ascending order of activity (percent of maximum possible score): bufexamac = 36%, salicylic acid = 37%, hydrocortisone = 44%, acetylsalicylic acid = 48%, flumethasone pivalate = 51%, fluocinolone acetonide = 51%, phenylbutazone = 56%, and indomethacin = 58%.


Tonofilament-desmosome complex in induced regenerated epidermis in senile elastosis. An electron microscopic study.

This paper presents the ultramicroscopic structure of the epidermis in senile elastosis, and compares it with the structure of an induced regenerated specimen in the same layers. In the regenerated specimen it was found that tonofilament-desmosome complexes have been replaced by a regular twist of villous processes. Such a substitution influences the structure and function of keratinocytes. Newly-formed structures may be established even 10 years after the induction.


Biochemical and physiological parameters on the healthy skin surface of patients with common warts.

Biochemical and physiological examinations were carried out on the healthy surface of the skin of 24 test persons who had had contracted common warts during the 2 years prior to examination and on a control group of 46 healthy persons of the same age and sex. The following significant results were obtained: (1) There was a significant reduction in the percentage amount of squalene in the lipids of the skin surface in the patients with common warts as compared with the healthy control persons. (2) The alkali neutralization time in the patients with common warts was significantly shortened as compared with the healthy control group. (3) The degree of moistening of the skin with water was significantly less in the patients with common warts than in the control persons. These results indicate important predisposing factors for common warts.


Hypersensitivity to prilocaine.

A case of anaphylactoid reaction with late onset to prilocaine and a positive intracutaneous test is reported.


[Granulomas of axillae (zirconium?) (author's transl)].

Deodorant preparations containing Zirconium may induce axillary granulomas of allergic origin. The case of a 49 years old female patient is presented, who developed axillary granulomas after having used a deodorant preparation containing Zirconium.


Coexistence of peculiar pemphigus, myasthenia gravis and malignant thymoma.

An unusual vesculobullous disease and myasthenia gravis occurred concurrently with a malignant thymoma in a Japanese male. The bullous dermatosis had combined clinical and histological features of both dermatitis herpetiformis and pemphigus. Serum showed striated muscle antibodies and intercellular epithelial autoantibodies; the latter had been demonstrated even prior to the development of the skin lesions. Thus, immunologically, this dermatosis was confirmed to be a variety of pemphigus.


Position as a cause of deformity in children with cerebral palsy.

The asymmetrical deformities in 20 children with various types of cerebral palsy are compared with 20 children without cerebral palsy who have the so-called 'squint' baby syndrome (asymmetrical deformities of plagiocephaly, unilateral bat ear, facial and thoracic asymmetry, pelvic obliquity and apparent shortening of one leg). It is suggested that the 'squint' baby syndrome and the 'windswept' child syndrome in children with cerebral palsy are stages of the same syndrome and that in both the deformities are caused by the effect of gravity on an immobile growing child, rather than spasticity or muscle imbalance. Asymmetrical deformity should therefore be amenable to physiotherapeutic intervention, rather than trying to modify maturation of the damaged brain. As the 'windswept' cerebralpalsied child can develop some of the most severe deformities seen in cerebral palsy, it is important that asymmetrical deformities should be prevented.


Knee flexion deformity and patella alta in spastic cerebral palsy.

A study on spastic knee flexion deformity has revealed a recurrence rate of 32 per cent following attempted surgical correction on 170 knees (103 patients). This rate appeared to be unrelated to concomitant surgery for correction of hip and ankle deformity. An additional study demonstrated patella alta in 72 per cent of 100 spastic knees (50 patients) and only 2 per cent and 50 knees of a comparable group of 25 non-spastic patients. It is suggested that restoration of a normal patello-femoral relationship may reduce both the functional disability and recurrence rate of spastic knee flexion deformity when this disease is managed surgically.


The prevention of postprandial seizures in children.

Three boys are reported who showed typical autonomic manifestations of hypoglycemia in association with stupor or convulsive seizures two to four hours after eating a meal. During glucose tolerance tests all three children had high peaks in plasma glucose within the first hour and subsequently developed symptoms typical of their clinical disorders on at least one occasion. Two of the boys showed appropriate responses of plasma insulin to oral glucose loading; the third showed a delay in peak plasma insulin. All three children responded promptly and completely to simple dietary management.


Management of children with non-organic (hysterical) disorders of motor function.

Five children aged between 10 and 13 years are discribed whose disorders of motor function were found to have a non-organic (hysterical) cause. In most cases extensive investigations had been made to establish an organic cause before the hysterical basis was diagnosed. The three essentials of management of such cases are to limit further investigations to the essential minimum, to institute quickly a programme of graduated physical rehabilitation, and to establish and treat the underlying psychological problems.


Polyradiculitis (Landry-Guillain-Barré syndrome) with total external ophthalmoplegia: encephalo-myelo-radiculo-neuropathy.

Total ophthalmoplegia is described in an eight-year-old boy with polyradiculitis. The findings suggest central nervous system involvement. It is postulated that this case represents an entity intermediate between the Miller-Fisher and the Landry-Guillain-Barré syndromes, with features of brain-stem encephalitis.


Familial cerebellar degeneration with slow eye-movements, mental deterioration and incidental nevus of ota (oculo-dermal melanocytosis).

Four members of a family with an autosomal dominant form of cerebellar degeneration all had slow eye-movements, i.e. slow pursuit with absence of both nystagmus and rapid saccadic movements. Three showed progressive mental deterioration. One patient had nevus of Ota (oculodermal melanocytosis) and a history of grand mal epilepsy. In these four patients the symptoms first occurred between the ages of 10 and 31 years--the onset apparently appearing earlier with successive generations. Current studies implicate a brain-stem lesion of the paramedian pontine reticular formation in the pathogenesis of the oculomotor abnormality. The possibility of a neurocutaneous syndrome, specifically a 'melanophakomatosis', in the patient with seizures and nevus of Ota is discussed; however, absence of these findings in other affected relatives makes a fortuitous association more probable. The literature on nevus of Ota associated with neurological disease is considered.


Effects of keto analogues of essential amino acids in portal-systemic encephalopathy.

Keto analogues of five essential amino acids (valine, leucine, isoleucine, methionine, and phenylalanine) were given either parenterally or orally in varying proportions to 11 patients with portal-systemic encephalopathy and hyperammonemia. Plasma concentrations of amino acids corresponding to the infused analogues, including alloisoleucine, increased significantly after infusions. Plasma tyrosine and glycine, which were abnormally elevated in control samples, fell after the infusions. After one to five daily infusions, the ratio of essential to nonessential amino acids in fasting plasma was increased toward normal, suggesting improved protein nutrition. Arterial blood ammonia and glutamate did not change immediately after infusions, but a pronounced decrease in glutamine (42%) was observed. Eight nitrogen balance studies performed in 5 patients during 3 to 12 days of oral or intravenous keto acid therapy failed to show consistent improvement in balance as compared with control periods. After five courses of oral therapy there was again significant improvement in the ratio of essential to nonessential amino acids. No toxicity from keto analogue administration was found, and clinical improvement, as assessed by mental status and psychological testing occurred in 8 of 11 patients. These studies suggest keto analogues of essential amino acids are converted to the corresponding amino acids in patients with portal-systemic encephalopathy, and that such therapy may be of benefit.


Deoxycholate metabolism in alcoholic cirrhosis.

Deoxycholate is often absent in bile of patients with alcoholic cirrhosis. The purpose of this study was to define the mechanism for this abnormality in bile acid metabolism in alcoholic cirrhosis. Excretion and hepatic metabolism of exogenous [14C]deoxycholate were determined, quantitative and qualitative analyses of fecal bile acids were performed, and ability of fecal bacteria to metabolize cholate to deoxycholate in vitro was measured both in cirrhotic patients and in controls. There was no evidence for deoxycholate malabsorption or rehydroxylation. In cirrhotic patients without biliary deoxycholate, both in vivo levels of deoxycholate and lithocholate in feces and in vitro fecal bacterial conversion of cholate to deoxycholate were significantly decreased as compared to controls. The marked decrease in 7 alpha-dehydroxylase activity of fecal bacteria of some patients with alcoholic cirrhosis results in impaired conversion of cholate to deoxycholate and explains the lack of biliary deoxycholate in these patients.


Familial benign recurrent intrahepatic cholestasis. Interrelation with intrahepatic cholestasis of pregnancy and from oral contraceptives?

A family study was prompted by the presence of benign recurrent intrahepatic cholestasis in three members and probably in a fourth. Pruritus and/or jaundice occurred during pregnancy in nine members. Two additional members suffered from pruritus while using oral contraceptives. The literature on benign recurrent intrahepatic cholestasis since 1959 describes at least 57 cases. A familial form of this condition proved to be fairly common. There seems to be a relation to the intrahepatic cholestasis sometimes seen during pregnancy and during oral contraceptive use. The data of the family study are suggestive for an interrelation of the three types of intrahepatic cholestasis, although a common denominator remains obscure.


The abnormal hepatic scan of chronic liver disease: its relationship to hepatic hemodynamics and colloid extraction.

To help explain the characteristic hepatic scan pattern of chronic liver disease, the degree of scan abnormality (scan score, SS) after administration of technetium-99m sulfur colloid (Tc) was compared with data obtained at hepatic vein catheterization in 28 patients. Although SS showed a correlation with wedged hepatic vein pressure (r = +0.491), the scan abnormality was not directly due to portal hypertension because it remained unchanged when the latter was relieved by portacaval shunt. Also, the scan abnormality was found to be unrelated to a low hepatic blood flow. Scan abnormality was not attributable primarily to hyperactivity of the reticuloendothelial (RE) cells of the spleen and bone marrow since fractional clearance (K) of Tc from the blood was decreased rather than increased in patients with abnormal scans. SS was inversely correlated with K or Tc (r = -0.575) and with hepatic extraction efficiency for Tc (r = -0.673), showing that the basic abnormality was poor extraction of the colloid by the RE cells of the liver with a resultant increase in the amount available for extrahepatic localization. Indirect evidence suggests that this poor extraction of colloid is due to intrahepatic shunts bypassing hepatic RE cells.


The stimulation of albumin sythesis by methadone.

Elevated levels of serum albumin have been noted in patients on chronic methadone maintenance and in heroin addicts. This observation was investigated in rabbits maintained on daily methadone 4 mg per kg of body weight after a period of 3 months on increasing dosage to assure drug tolerance. Albumin distribution and metabolism were measured with tested lots of 125I rabbit albumin. Studies were made before and again after the attainment of the methadone maintenance state. Albumin distribution was altered markedly with a shift of intravascular albumin to extravascular sites. Associated with this change, the serum albumin level rose by an average of 0.5 g per 100 ml. Albumin degradation increased by 32% from 248 to 327 mg per kg per day. The total exchangeable albumin pool increased 35%, or 3.6 g. Since the exchangeable albumin pool increased in the face of an increment in albumin degradation, albumin synthesis must have increased even further to account for this change. Although the specific factors responsible for these alterations in albumin metabolism and distribution are not known at present, to date, this hyperalbuminemic hypercatabolic state is not produceable in any other clinical or experimental situation.


Hepatic functional deterioration after portacaval shunt in the rat. Effects on sulfobromophthalein transport-maximum, indocyanine green clearance and galactose elimination capacity.

The consequences of a portacaval shunt on liver function were studied in male Sprague-Dawley rats. Fourteen days after an end-to-side portacaval anastomosis the galactose elimination capacity and the plasma clearance of indocyanine green were reduced in proportion to the approximately 50% loss in liver mass. The biliary transport maximum for sulfobromophthalein, on the other hand, decreased by almost 70% from 153 to 52 nmoles per min per min per 100 g after portacaval anastomosis. This reduction of sulfobromophthalein excretion was accompained by a significant decrease in the hepatic conjugation of the dye to glutathione. Our findings demonstrate that a quantitative and qualitative functional deterioration of previously normal livers results from portal blood deprivation.


A method of cholecystography applicable to small laboratory animals.

A method of intraperitoneal cholecystography is described and was tested on mice with experimentally induced gallstones. The presence of stones in the gallbladder was predicted with an accuracy of 95.5%, using doses of 3 ml of 51.6% meglumine iodipamide (Cholografin) per kg diluted 10-fold, followed a few days later by a repeat dose of 5 ml per kg in cases of nonvisualization of the gallbladder. Pilot studies on guinea pigs and rabbits suggest that this method is applicable to these animals too, although a higher dose of contrast medium is required.


Lower esophageal sphincter pressure in women using sequential oral contraceptives.

Lower esophageal sphincter pressure, basal gastric pH, and fasting plasma gastrin were measured sequentially in female volunteers who were using oral contraceptives. No difference in basal gastric pH or fasting plasma gastrin was observed during any of the three selected periods studied. Lower esophageal sphincter pressure was the same during menses (20.8 +/- 1.7) when the volunteers took no medication during the phase of the cycle when the volunteers were ingesting ethinylestradiol (18.3 +/- 1.7). Lower esophageal sphincter pressure decreased significantly (P less than 0.01) to 9.4 +/- 1.2 during the phase of the cycle when the volunteer took the progestation agent, dimethisterone, as well as ethinylestradiol. It is therefore proposed that the progessive rise in plasma progesterone alone or in combination with estrogens that occurs during the course of pregnancy might be responsible for the increased incidence of symptomatic heartburn in pregnant women.


Lower esophageal sphincter function in children with and without gastroesophageal reflux.

Resting lower esophageal sphincter (LES) pressure was assessed in infants and children 2 weeks to 12 years of age. There were 62 control subjects and 35 patients with reproducible gastroesophageal reflux (GER) determined radiologically. In control subjects without GER: (1) LES pressure was well developed by 2 weeks of age; (2) in children less than 1 year of age, mean LES pressure (43.3 +/- 2.4 mm Hg) was significantly greater than mean LES pressure (30.6 +/- 2.3 mm Hg) children older than 1 year of age; (3) LES sphincter length increased with age; and (4) bethanechol 0.1 mg per kg subcutaneously caused a rise in LES pressure that increased in magnitude as LES resting pressures increased. In patients with GER: (1) only 16 or 35 children had LES pressures below the normal range for their appropriate age group; (2) LES length was shorter than control values in children beyond 6 months of age; (3) GER usually occurred in the absence of hiatus hernia; (4) clinical improvement was common and in patients with low LES pressure was associated with a rise in LES pressures to normal, even in the presenece of hiatus hernia; and (5) bethanechol caused a change and an absolute rise in LES pressure that were not significantly different from those observed in controls. These results indicate that in infants and children low LES pressure is not the sole determinant of GER, and that pharmacological stimulation of the Les could prove to be a useful adjunct to the medical management of GER.


Gastric acid hypersecretion in children with duodenal ulcer.

Rates of gastric hydrochloric acid secretion were compared in 10 children with active duodenal ulcer (DU) and 14 non-duodenal ulcer children. Duodenal ulcer was diagnosed by gastroduodenoscopy or by evidence of an ulcer crater on upper gastrointestinal radiographs. Duodenal ulcer disease was excluded in the comparison group by similar criteria. Basal acid output in DU children tended to be higher, but the difference was not statistically significant (P greater than 0.05). Maximal acid output was significantly higher in DU children than in the comparison group whether expressed as milliequivalents per hour (P less than 0.025) or as milliequivalents per kilogram per hour (P less than 0.005). Peak acid output also showed a statistically significant difference (milliequivalents per hour, milliequivalents per kilogram per hour, (P less than 0.05). These findings demonstrate that, on the average, hypersecretion of gastric acid does occur in children with duodenal ulcer disease.


Calcium absorption in Crohn's disease.

Calcium absorption and endogenous loss of calcium were measured in a group of patients with Crohn's disease, using a simultaneous metabolic balance and calcium isotope regimen. Calcium malabsorption resulting in negative calcium balance was found in only 4 of 31 patients with Crohn's disease. No elevation of endogenous fecal calcium or total secreted intestinal calcium was observed in 10 patients studied, regardless of the level of net or true calcium absorption. Correlation between calcium balance and serum protein loss was observed, but no association was noted with intestinal fat excretion, d-xylose absorption, bacterial colonization of the jejunum, or glucocorticosteroid therapy. The results indicate that in this group of patients with Crohn's disease involving different areas of the intestine, calcium malabsorption occurred infrequently and that the levels of calcium excretion correlated best with enteric protein loss.


A new technique for continuous sphincter pressure measurement.

The use of a constantly perfused side hole sensor (CPSH) for continuous measurement of maximal lower esophageal sphincter pressure (LESP) is associated with important but variable undermeasurement as a result of side hole displacement. A 5 cm long pressure sensor has been developed which measures maximal LESP continuously in the face of movement of the sphincter within the sensor length. This sensor, the perfused sleeve, is described, and validated by comparison with CPSH in man, the dog, and a model esophageal sphincter. The sleeve detects maximal LESP accurately, regardless of sphincter length, over the pressure range encountered in the lower esophageal sphincter. Continuous recording of LESP with the sleeve is unaffected by displacement that causes serious undermeasurement with CPSH.


Effects of antacids on gastric emptying.

Aluminum hydroxide gel delays gastric emptying in rats and man. This effect of aluminum hydroxide gel varies with the concentration of aluminum in solution in the stomach when pH, osmolarity, and anion content are held constant. Because aluminum solubility drops as pH is raised, those antacids which neutralize more effectively than aluminum hydroxide gel alone and which contain "nonreactive" aluminum hydroxide result in lower aluminum concentration and do not affect the rate of gastric emptying in animals or in man. By using [51Cr]sodium chromate and a gamma camera technique, half-emptying time in 6 subjects with no gastrointestinal disease was shown to be prolonged from 13.1 min after water ingestion to 48.0 min after three hourly doses of aluminum hydroxide gel. Conventional nonabsorbable markers, including phenol red, were found to be of limited use for studying gastrointestinal function in the presence of antacid gels, most of which adsorb dyes.


Further studies on prostaglandin E1-induced jejunal secretion of water and electrolytes in man, with special reference to the influence of ethacrynic acid, furosemide, and aspirin.

Perfusion studies were performed in 35 healthy volunteers to investigate further the secretory effect of prostaglandin E1 (PGE1), administered intraluminally, on the human jejunum. A perfusion system with a proximal occluding balloon and continuous aspiration of duodenal secretions was used. The influence of PGE1 (0.9 mug per kg per min) on glucose, fluid, and ion transport was entirely reproducible throughout a 6-hr perfusion experiment and was fully reversible 60 min after the end of PGE1 administration. The influence of ethacrynic acid (EA), aspirin (two agents previously reported to inhibit choleraic secretion), and furosemide was studied both on basal jejunal absorption and on PGE1-induced secretion of water and electrolytes. EA (2.5 mg per kg), administered in jejunal lumen, significantly reduced (P less than 0.001) the net secretory effect of intraluminal PGE1, and suppressed the PGE1-induced increase in plasma-to-lumen unidirectional flux of sodium. Intravenous or intraluminal aspirin (25 to 40 mg per kg) as well as intraluminal furosemide (1.5 mg per kg) did not modify the PGE1-induced secretion nor the basal absorption rates. Plasma immunoreactive levels of PGE1, calcitonin, and diverse gut hormones did not change significantly during PGE1-induced secretion. These results indicate that (1) aspirin, an inhibitor of prostaglandin synthesis, has no influence on the intestinal secretory effect of preformed PGE1; (2) EA, unlike furosemide, inhibits in man PGE1-induced jejunal secretion, an effect of EA similar to that observed in animals on cholera toxin- and cyclic AMP-mediated secretion.


The genesis of bowel sounds: influence of viscus and gastrointestinal content.

This study was undertaken to try to solve the controversy about the influence of gastrointestinal contents on the genesis of bowel sounds, and to probe the respective importance of the various abdominal viscera. Eleven healthy volunteers were intubated by mouth with a multiple-lumen tube. Bowel sounds were recorded for 10 min when the tube was in the stomach, the upper jejunum, and the cecum, while it was left intact in situ, or perfused with isotonic saline (15 ml per min), or with an equal (7.5 ml per min of each) mixture of isotonic saline and air. Using a previously developed method, a computer analysis was made of the recording without any human intervention during the treatment of data. An analysis of variance demonstrated that the effect of perfusion varied according to site, with 46% of counted sounds while the tube was in the stomach, 32% in the jejunum, and 22% in the colon (P less than 0.05). There were two types of sounds: some exceeded in amplitude a preset threshold, and thus were picked up by the computer, but their average absolute value for 20 msec remained inferior to another preset threshold. Their number was kept in memory (NS--sounds having an amplitude exceeding a threshold S1, expressed in number per 10 min). A second type of sounds also exceeded the present threshold but their average absolute value for 20 msec also exceeded another preset threshold. Their number (NE--sounds having an amplitude exceeding the thershold S1 but having also a 20-msec average amplitude above another threshold S2, expressed in number per 10 min) was also memorized. The latter group was composed of two types of sounds: some had a limited spectrum of low frequency (100 Hz) and were of high amplitude and short (congruent to 5 msec) duration (NE1); some others had a higher and more dispersed frequency centered around 300 Hz (NE2). Fifty per cent of high energy (NE) sounds appeared while the tube was in the stomach, 30% in the colon, and 20% in the jejunum (P less than 0.005). Short and high amplitude sounds (NE1) were counted more often (43%) when it was in the colon than in the stomach (38%) and the jejunum (19%) (P less than 0.025), and this was confirmed (P less than 0.005) by a study of the ratio of NE1/NE. On the contrary, higher frequency sounds (NE2) were present more often when the tube was in the stomach (59%) than in the jejunum (24%) and in the colon (17%) (P less than 0.005). There was no influence of the presence of the unperfused tube on the genesis of bowel sounds in different sites (P greater than 0.05). In the stomach and the colon perfusion of the air/saline mixture increased the number of sounds (P less than 0.025) and all types of sounds in the stomach (P less than 0.025), whereas in the jejunum it was the perfusion of saline which increased them (P less than 0.025). It is concluded that the stomach is the most active site of production of bowel sounds, followed by the colon and then the small bowel, that sounds differ in different sites, and that all this is influenced by viscus content.


Studies on the acid secretion that occurs during injury to the gastric mucosa.

When pouches of the oxyntic glandular mucosa in dogs were irrigated with 4mM dithiothreitol in acid solution the mucosa shed plasma and secreted acid. There was a linear relationship between the net addition of H+ to the lumen and the amount of plasma shed, suggesting that the mechanisms of acid secretion and plasma shedding were closely related. Atropine, metiamide, and PGE2 only partially inhibited the acid secretion. The three drugs also reduced the plasma shedding and may be useful in the management of protein-losing gastropathy in man.


Clearance rate, half-life, and secretory potency of human gastrin-17-I in different species.

The clearance rates of synthetic human gastrin-17-I were measured in man, dog, and cat. Half-life of disappearance and acid secretory potency (D50) were also measured in man and dog. The clearance rates in dog and cat were, respectively, 3 and 8 times more than in man. Accordingly, the half-life of gastrin-17 in the dog (3.5 min) was 3 times shorter than in man (9.5 to 10.5 min). The D50 for acid secretion was proportional to the clearance rate and yielded approximately similar increments of serum gastrin, indicating an equal sensitivty to gastrin-17 at cellular level in the three species. An inverse allometric relation between clearance rate and body weight was consistent with the known greater efficiency of metabolic and eliminatory processes in species of small size. Recent studies of the disposal of other gastrointestinal hormones indicate that the concepts developed theoretically for secretory stimulants and confirmed experimentally for gastrin-17 may have wider applicability.


Regulation of rat proximal intestinal glycolytic enzyme activity by ileal perfusion with glucose.

Specific activities of the glycolytic enzymes fructose-1-phosphate aldolase, fructose-1,6-diphophate aldolase, and pyruvate kinase, are higher in rat duodenum and jejunum than in ileum. Whether this gradient reflects the failure of dietary sugars to reach the ileum in high concentrations is unknown. Rats were first fed a carbohydrate-free diet for 3 days, which virtually removed the proximal-distal gradient of enzyme specific activities. Twenty percent glucose was then perfused directly into either the duodenum or the ileum for 3 days. Both proximal and distal glucose perfusion restored the normal gradient of all three enzymes. Ileal pyruvate kinase was also increased by ileal glucose perfusion, but ileal aldolases were no higher after distal perfusion than after duodenal perfusion. The low ileal aldolase levels normally found in fed rats therefore are an intrinsic property of distal intestine and are not due to failure of dietary sugar to reach this portion of the gut. Furthermore, adaptation of duodenal and jejunal glycolytic enzymes to ileal glucose perfusion suggests a humoral and/or neural mechanism rather than a direct local luminal effect of the sugar itself.


Distribution and arteriovenous shunting of gastric blood flow in the baboon: effect of epinephrine and vasopressin infusions.

The effects of 60-min intraarterial infusion of vasopressin (0.005 U per kg-min) and epinephrine (0.05 mu per kg-min) on gastric hemodynamics were studied in anesthetized baboons. Total gastric blood flow was measured electromagnetically and radioactive microspheres (15 +/- 5 mu) with three labels were used to determine regional distribution of gastric blood flow and arteriovenous shunting. Control flow was 55 +/- 8 ml per min, with 77.4 +/- 2.7% of flow going to the gastric mucosa and 1.7 +/- 0.4% of injected spheres appearing in the liver. Epinephrine infusion resulted in a sustained vasoconstriction to 18 +/- 5 ml per min with no autoregulatory escape and no changes in arterial pressure or cardiac output. Vasopressin resulted in a decrease in flow to 14 +/- 3 ml per min with no excape. Whereas cardiac output did not change, there was a singificant hypertensive effect during the vasopressin infusion. There was neither redistribution of flow nor change in arteriovenous shunting with either epinephrine or vasopressin. Transmucosal electrical potential difference was 62 +/- 8 mv and did not change significantly with either infusion.


Appendix helicus: a unique anomaly of the vermiform appendix.

A unique anomaly of the vermiform appendix is described from a child in which the appendix is helical in configuration. Its form brings to mind the symbol of the profession of medicine.


Effect of liquid diet on serum protein binding and prednisolone concentrations after oral prednisone.

After prednisone (two 5 mg tablets) was given to each of six normal volunteers with water or with a liquid meal, standard pharmacokinetic parameters of prednisolone metabolism were similar, except that peak serum prednisolone concentrations occurred later after the meal. We conclude that prednisone can be given with a meal without significantly affecting the metabolism of prednisone or prednisolone.


[The value of routine lymphadenectomy in radical Wertheim hysterectomies (author's transl)].

In 1959 Rauscher and Spurny questioned the advantages of routine lymphadenectomy in radical Wertheim operations compared to selective lymphadenectomies. Our present review disagrees with the above mentioned doubts. Rauscher and Spurny base their results on clinical staging of cancer of the cervix in cases from 1947 to 1950, and in cases from 1950 to 1953. Our results are quite different in two groups of patients from the years 1946 to 1949 and 1951 to 1953 with the staging done by histological methods. In the later period of 1965-1969 the results were further improved, probably due to the extent of the lymphadenectomy. The routine lymphadenectomy showed improved results not only in all cases but also in the cases with carcinoma of the lymph nodes.


[Determination of the gestational age in late pregnancy by sonography (author's transl)].

In 219 normal pregnancies between 28 and 42 weeks the relationships of different ultrasound measurements of the fetal head and the fetal body to the gestational age were determined in order to improve the accurate diagnosis of fetal maturity during the last trimester of pregnancy. With the A and B ultrasound apparatus of Kretz, the biparietal diameter was determined by the A mode, the fronto occipital plane and the largest abdominal diamter were determined by the B scan. The following ultrasound measurements were taken: the two horizontal and transverse diameters, the circumferences and the planes. The abdominal measurements showed a higher rate of growth, compared to the cranial measurements a lesser rate of growth retardation and a higher variation of the normals. The correlation of the abdominal measurements with the gestational age was worse than that of the cranial measurements. Wth the exception of the biparietal diameter in the A mode, the mean diameters of the cranial and abdominal measurements gave better results than the single diameters. Circumference and surface measurements showed no advantages. The best results were obtained by combined fetal head and body measurements using the summation of the biparietal diameter in the A mode and the mean abdominal diameter in the B scan.


[Conization of the uterine cervix in prevention and diagnosis of cancer (author's transl)].

The result of conization of the uterine cervix in 446 cases was reviewd regarding the diagnostic and preventive therapeutic value of the procedure with special attention to post-operative complications. Conizations for benign lesions of the cervix in 33 patients resulted in a well formed cervix with squamous epithelium covering of the ectocervix in 32 patients. There was only 1 failure. In 413 diagnostic conizations with extensive microscopic work-up the lesion was only completely removed in 62% of the cases. In spite of careful colposcopy and Schiller iodine marking the external margin of the cone biopsy material went through the atypical lesion in 51% of the cases. It is therefore necessary to extend the limits of the cone biopsy specimen in all cases as far to the periphery and upwards into the canal as feasible. The incidence of early and late complications was 10.9%. In 133 conizations with hemostasis by cauterization the complication rate was 22.6%. This rate was reduced to a complication rate of 5.2% in 261 cases with hemostasis by suture. The commonest early complication was cervical bleeding. The only late complication was stenosis of the cervical canal. After conization of the cervix 18 of 22 pregnancies were uncomplicated. The increased incidence of cervical dystocia following conization of the cervix is significant and was the indication for Caesarean Section in 6 cases. For the prevention of cancer, the indication for conization of the cervix should be diminished in favor of an increase of the indication for hysterectomy because of the high failure rate of conization to prevent cancer (37%) and because of the relatively high incidence of complications of conization.


["Menouria", a symptom of vesico-cervicalfistulae (author's transl)].

In the paper rare clinical picture is presented as a possible clinical manifestation of vesico-cervical fistulae, the cardinal symptom being cyclic vesical haematuria - "menouria". The author discusses the cause being at the bottom of the symptomatology, and elaborates on the differential diagnosis. The author considers operative treatment necessary in all cases, and prefers the abdominaltransperitioneal access for the operation.


[The optimal diagnosis of recurrence and metastases in female genital cancer by needle biopsy (author's transl)].

The "true-cut" disposable biopsy needle was used for 95 needle biopsies in 42 patients who were suspected to have a recurrence or metastases of low lying gynaecological cancer. Up to 3 biopsies per patient were obtained. In 21 patients the clinical suspicion of malignant was verified by microscopic examination. The needle biopsies were done as often by the vaginal as by the rectal route. Because of the low incidence of complications the needle biopsy was recommended for the definite diagnosis and follow-up examination of suspicious low lying gynaecological tumors.


The initial manifestations of acute myocardinal infarction.

A review of 132 consecutive patients 65 years of age and older who had a myocardial infarction showed that two-thirds of them experienced pain at onset. Pain was the only symptom leading to bedside diagnosis in one-fourth of the patients. Pain at onset combined with sudden or increased dyspnea was present in one-fifth of the patients and pain associated with other symptoms in one-sixth. Dyspnea unaccompanied by pain heralded onset of infarction in one-fifth of the patients, and in almost 7 percent, onset was marked only by other symptoms. Cerebral symptoms dominated onset in one-tenth of the patients. Preexisting coronary heart disease, hypertension, or diabetes was not predictive of painless infarction. To avoid pitfalls and facilitate bedside diagnosis of infarction, physicians should be aware of the different clinical presentations of painless infarction in the aged, which occurred in over one-third of the patients in this cohort. They also should suspect the possibility of myocardial infarction in any patient in whom symptoms are not clear, even when they are mild and unobtrusive. Questioning of the elderly patient, his family, or others around him as early as possible after the onset of an acute attack is likely to elicit a history of pain, which may lead to the correct diagnosis.


Cervical spondylosis: most common cause of position and vibratory sense loss.

At present, spondylosis of the cervical spine is the most common cause of loss of position and vibratory sense. The loss is asymmetric in regard to location and degree of involvement and results from intermittent contusion of the posterior columns against the lamina in persons having congenital narrow spinal canal. Subluxation of the vertebrae, reversal of cervical lordosis, and a hypertrophic ligamentum flavum further compromise the canal. Measurement of the anteroposterior diameter of the spinal canal is meaningful, as a narrow canal correlates best with the clinical symptoms. Not all patients with a narrow sagittai diameter have clinical signs, but all patients with clinical signs have a narrow sagittal diameter. Immobilization of the cervical spine in partial flexion with a light collar is the proper treatment in the absence of spinal fluid block.


The value of endoscopic study of the bile ducts and the pancreas in the elderly.

Endoscopic retrograde cholangiopancreatography was performed in 46 patients age 60 or older with various suspected pancreaticobiliary or duodenal diseases. Thirty-one patients (67.4%) had diagnostically satisfactory opacification of a duct system. Pathologic conditions obstruction injection of the contrast medium prevented opacification in eight patients (17.4%). Seven cannulations  (15.2%) were technical failures. There was one complication, a Gram-negative septicemia that was successfully treated. The procedure is of value in the geriatric patient because it may provide preoperative evidence of pancreatic or biliary disease that cannot be diagnosed by any other technique. In jaundiced patients, identification of the site of obstruction facilites the surgical approach and thus reduces operating time. If the common bile duct is shown to be patent, the patient is spared exploratory surgery or a prolonged hospital stay for observation. Although a normal pancreatic duct does not exclude cancer of the pancreas, it should influence the physician to search for other explanations for abdomianl pain or weight loss befror proceeding with abdominal surgery.


Aging of human bone and articular cartilage collagen: changes in the reducible cross-links and their precursors.

The age-dependent changes in reducible collagen cross-links, Schiff bases and their precursors were followed for human bone and articular cartilage throughout the whole life span from 3 to 89 years of age. With aging, the reduced Schiff bases dihydroxylysinonorleucine remarkable decreased, wheras hexitollysine peaks increased significantly in both collagens. Dihydroxynorleucine, the precursor of the cross-link, was found to increase slightly with age. But the changes in hydroxylysinonorleucine and lysinonorleucine were comparatively small. These changes were discussed in relation to the increased insolubility observed in both collagens at higher age.


Surface labelling of senescent chick fibroblasts by lactoperoxidase-catalysed iodination.

Cell surface of chick fibroblasts were labelled by a short treatment with 125I in presence of lactoperoxidase. A glycoprotein (220,000 molec. wt) was iodinated and was present in a more exposed position or in greater amounts at the surface of old phase III cells compared to young phase II cells. The findings extend our previous observations on cell surface modifications in in vitro senescing fibroblasts.


The origin and nature of pseudo-synovium appearing around implanted Silastic rods: an experimental study.

The pseudo-synovium appearing around Silastic rods is a labile layer made up of a range of cells from undifferentiated fibroblast precursors through to mature fibrocytes. Various factors influencing their behaviour are discussed. The optimum time for grafting into a rod-induced sheath would seem to be in excess of four months.


The assessment of hand function: Part III--the final analysis.

Some common surgical procedures, practised to improve the function of the rheumatoid hand, have been subjected to a prospective and objective evaluation. This analysis has been based on the concept of the assessment of hand function by measurement of individual digital forces and the results clearly justify surgical intervention. In addition, function is improved in those digits belonging to the hand operated upon but not themselves undergoing surgery.


Further observations on the anatomy of the ulnar nerve at the wrist.

A review of the anatomy of the course of the ulnar nerve at the wrist, in the pisohamate tunnel. The exit from this tunnel is the most likely place for compression of the ulnar nerve at the wrist.


Tendon plasticity-a property applicable to reconstructive surgery of the hand.

A study carried out by light and electron microscopy of the behaviour of different tendons when subjected to lateral stretching and longitudinal splitting. Tendons like the FDS are more resistant to lateral stretching and show greater shredding. The structure of the tendon shows criss-crossing of the fibrils, necessary to stand up to the greater stress to which the tendon is normally exposed.


Treatment of a case of macrodactyly of the thumb.

An unusual association between macrodactyly of the thumb and a severe abnormality of the thenar eminence is presented. A reduction of the soft tissues and opponens transplant gave a satisfactory cosmetic and functional result.


Early tendon transfer for radial nerve transection.

A retrospective comparison of twelve patients with radial nerve transection treated by nerce repair, and thirteen similar patients treated by tendon transfer only, showed an average time to recovery of 7.5 months after nerve repair, and eight weeks after transfer. In view of this, a policy of early tendon transfer instead of radial nerve suture is advised. Results are reported in nine patients who had tendon transfers at an average of thirteen days after nerve injury.


Extensor indicis proprius transfer to supplement replacement arthroplasty of the rheumatoid hand.

A new procedure is described to cope with the rotation deformity so often seen after replacement arthroplasty of the destroyed metacarpophalangeal joints in rheumatoid arthritis. The same procedure, in combination with a similar transfer to the ring and little fingers, but using extensor digiti minimi as the motor, can be used as a suspension procedure to stabilise the early unstable metacarpophalangeal joint. Thirty hands have been treated with the longest follow-up of two-and-a-half years; so far the results have been encouraging.


Intraosseous ganglion of the pisiform bone.

A case report of a ganglion in the pisiform bone, accompanied by pain and instability in the wrist joint.


Sarcoidosis presenting as a wrist tumour.

A forty-year-old male with a painless, indurated mass on the volar surface of the wrist, was proved to have Boeck's Sarcoid. The surgery and pathology of the mass is described and the literature reviewed.


Bracelet burn-an unusual electric burn.

A car mechanic sustained a deep partial thickness burn of the wrist when his metal watch strap short circuited the battery of a car upon which he was working.


Carpometacarpal dislocation of the little finger.

A case is reported of dislocation of the base of the fifth metacarpal treated by manipulation and percutaneous fixation with a Kirschner wire. Visualisation by the image intensifier confirmed the reduction. A lateral view is important to control the volar displacement.


Use of chemically preserved tendon allografts in hand surgery.

The origin of the use of tendons preserved in Cialit is reviewed and the results of a series of thirty-seven flexor tendon grafts which were performed by this method are discussed.


Closed acute traumatic rupture of extensor pollicis longus tendon-a report of two cases.

Two cases are presented of closed rupture of the extensor pollicis longus due to rotational trauma to the forearm. Case 1 was successfully managed by indicis proprius transfer and the operative findings are described. The rarity of this injury is stressed by a review of the sparse relevant literature.


Transposition lengthening of a digital ray after multiple amputations of fingers.

Matev's principle of gradual distraction has been applied to the problem created by multiple digit amputation where the thumb is normal.


Oedema of the hand after fasciectomy with or without tourniquet.

Two groups of patients with Dupuytren's disease were treated by limited fasciectomy. A tourniquet was used for one group, and an elevated hand table without tourniquet for the other. Taking into account other factors controlling oedema it was discovered over a post-operative period of twenty-eight days that "Tourniquet" hands remained significantly increased in volume compared to "Non-Tourniquet" hands. Other facts of clinical interest also emerge from the trial and are discussed. It is concluded that the use of the elevated hand table without tourniquet, not only allows an unlimited and uninterrupted period for hand surgery, but also reduces the subsequent oedema.


Ulceration of a ring into a phalanx.

A case is described in which a ring ulcerated into a finger, until only the setting could be seen. The patient reported when the finger began to swell. The injury recovered after removal of the ring. Previous reports of ring and rubber band constriction are reviewed.


High pressure injection injuries of the hand. A clinical, chemical and histological study.

Although high pressure injection injuries of the hand are frequently described, little is known about the mechanism of tissue necrosis. A case is described which led to digital amputation and the clinical features are discussed in relation to others reported. The digit was examined histologically and a sample of liquid drained from the palm was subjected to organic chemical analysis. The findings of widespread vessel thrombosis, absence of fat from fat loculi, and coagulative necrosis of skin and subcutaneous tissue becoming less marked the more proximal in the digit suggest a chemical inflammatory cause. This is supported by chemical analysis revealing a fat solvent as the chemical agent and fat degradation products in the palmar liquid.


Purification of canine gut glucagon-like immunoreactivity (GLI) and its insulin releasing activity.

In order to clarify the nature of the biological action of gut glucagon-like immunoreactivity (GLI), GLI was extracted from the mucosa of the canine intestine and purified by gel filtration and affinity chromatography. 1500 gm of the mucosa yielded approximately 7 gm of crude extract of GLI. This crude extract was applied to a column packed with Sephadex G-50 or Bio-Gel P-10 and two peaks were obtained, Peak I and II. Each peak was purified with affinity chromatography, bound to gamma-globulin of anti-glucagon rabbit-serum. In this step, the GLI was purified approximately 80 times in comparison with the crude extract. Peak I or Peak II, as well as pancreatic glucagon, was infused successively into the pancreaticoduodenal artery of the anesthetized dogs. When buffer solution or the Peak I GLI was infused, the plasma immunoreactive insulin in the pancreatic vein did not change significantly. In contrast, both the Peak II and pancreatic glucagon promoted insulin secretion from the pancreas. The results obtained in this experiment demonstrate the promotion of insulin release from the pancreas and suggest an important role of gut GLI in the absorption and metabolic processing of nutrients.


Decreased pituitary growth hormone content in rats treated neonatally with high doses of L-thyroxine.

Growth hormone and thyrotrophic hormone content have been measured by specific radioimmunoassays in anterior pituitaries of 22 day old rats. These animals were injected with saline or very high doses of L-thyroxine during the neonatal period in order to induce the "neo-T4" syndrome. Growth of such animals is known to be affected. It was found that not only TSH but also GH content of the T4-treated animals was significantly lower than that of the saline-injected controls.


A comparison of the effects of altered thyroid and parathyroid function on reproduction in the rat.

Mild maternal hypothyroidism produced by surgical thyroidectomy resulted in significantly reduced food intake along with retarded reproductive performance in rats. Hyperthyroidism increased food consumption above the control level along with an increase in fetal resorptions which was the only parameter of reproductive performance altered by the twenty-second day of gestation. In animals which underwent pregnancies, reproductive performance suffered a further decline in the second gestation due to increasing duration of the hypothyroidism. Food restriction alone failed to duplicate these adverse effects on fetal development. Serum gonadotropins (LH and FSH) were not significantly altered by mild maternal hypothyroidism of hypoparathyroidism. The hematocrit and total blood volume of hypothyroid but not hypoparathyroid rats was significantly reduced from normal. Maternal hypoparathyroidism alone did not affect fetal development grossly.


Critical issues in mental health service delivery: what are the priorities?

The director, one other professional, and one para-professional in 515 community mental health centers and 193 state hospitals throughout the United States were asked to rate 57 critical issues in mental health services as to their importance now and five years from now. Issues judged most important now are services for children and for adolescents; five years from now children's services still top the list. Answers to two other questions revealed that respondents placed research on prevention at the top of a list of needed research areas, and that the most useful NIMH service to agencies was person-to-person assistance such as consultation and workshops.


Evaluating the effectiveness of innovative design for a community mental health center.

The effectiveness of the design of the inpatient and day patient areas of a community mental health center was evaluated in 1969, soon after the center was opened, and again in 1974. The focal area is a large, irregularly shaped communal space; it opens onto a wide, encircling corridor ringed with bedrooms, multiuse rooms, and offices. The center was designed to encourage different behaviors and varied uses of space, to promote interaction, and to stimulate and challenge patients. In 1974 the evaluators found the design still worked well for the unit that still operated the same kind of program the center was designed for, a therapeutic community, even though the unit admitted sicker patients than planned. The design did not work as well for the second unit, which had become a crisis intervention program for patients who were often highly agitated, suicidal, or determined to escape; security and surveillance were major problems.


Using peer-group intervention with problem students in a secondary school.

Twenty adolescent girls whose records showed poor academic performance and frequent truancies and referrals to the guidance office were selected to participate in a pilot project to provide a peer-group experience for students having difficulty at school. Half the students were placed in a control group and received regular services from the school. Students in the experimental group attended 12 discussion sessions held during the school day. A one-year follow-up showed that seven in the experimental group and one in the control group had improved.


Combining activities and group psychotherapy in the treatment of chronic schizophrenics.

The author reviews literature relating to the use of activities in the treatment of chronic schizophrenia, citing several programs that combined activities and psychotherapy to produce effective modes of treatment. He also describes a program in which he used collage-making to help a group of schizophrenic women improve interpersonal relationships, reality-testing, and self-image as well as to help them express problems and develop feelings of autonomy. The author believes that such combined programs help meet the basic needs of schizophrenic patients and alleviate their tendencies to withdraw from their surroundings.


Applying psychiatric techniques to patients with cancer.

A patient with cancer frequently experiences significant stress in adjusting to his disease. The authors feel that cancer patients who are receiving physical care in a general hospital may benefit from psychiatric techniques used regularly by mental health professionals. They describe weekly group meetings in which newly diagnosed cancer patients talk with the hospital staff, consultants from a psychiatric institute, and more experienced cancer patients about problems in adjustment, misconceptions about cancer, reactions of family and friends, and problems in relating to their physician. To date approximately 2000 patients have attended the meetings. In most cases their anxiety has decreased as they talk with other cancer patients who have learned to live with their disease, and as they see alternative methods for dealing with their problems.


Study points to the potential of arbitrating malpractice claims.

The Southern California Arbitration Project has demonstrated that arbitration may be applied successfully within the hospital segment of the health care industry. Although results are inconclusive at this time, arbitration may be a feasible alternative to litigation in securing expeditious and inexpensive resolution of malpractice cases. Of course, arbitration, in and of itself, is no panacea for the critical malpractice problem currently experienced throughout the nation; however, its potential for substantive contribution toward the resolution of malpractice claims is worthy of extensive experimentation and evaluation.


Circuit librarian serves five hospitals in shared program.

There is increasing emphasis on continuing education of hospital personnel, who need and want access to information in order to be aware of advances in health care. Small hospitals cannot afford to duplicate extensive collections. Personnel of hospitals that are remote from urban centers often do not have opportunities to visit a resource library on a regular basis and do not have experience in searching the medical literature through the use of reference tools. It is increasingly evident that the circuit librarian program has served as a catalyst in establishing relationships between the hospitals and the university health sciences center. The director of the CHSL has consulted with the deans of the nursing and the medical schools and with various professors. They have promised that the schools will try to address identifiable continuing education needs or requests from the hospitals. Moreover, the circuit librarian meets with individual hospital personnel and then obtains information for them from the CHSL and its staff. The circuit librarian program is one way to meet community hospitals' needs for access to health sciences literature and to initiate peer interaction for information exchange.


Pharmaceutical group purchasing cuts costs, expands knowledge.

The CHA-CSHP pharmaceutical group purchasing program has provided several benefits to participating hospitals and related institutions in Connecticut. The program is run by pharmacists and staffed by individuals knowledgeable in good purchasing techniques. Pharmacist compliance has been good because of maximum input into program decisions by all participating pharmacy departments. Pharmaceutical industry participation has been excellent, because each bid invitation includes information on the previous year's purchases by participating hospitals and on the committed volume for the contract period. In addition, the program is self-supporting. Thus, larger hospitals, which would often be able to obtain good pricing independently, are not obliged to support the bulk of this program, as is often the case when participating institutions pay dues based on their bed size. As a result of the pharmaceutical group purchasing plan of the Connecticut Hospital Association, hospitals have received significant benefits in cost savings and shared drug information.


Chief cell hyperplasia in the human carotid body at high altitudes; physiologic and pathologic significance.

The area occupied by parenchymal cells, in sections comprising the entire half of the surface of the carotid body, is significantly greater in people born and living at 14,350 feet than in those at sea level. The enlargement and increase in weight of the carotid bodies observed at high altitudes can thus be attributed to hyperplasia of parenchymal tissue. The proliferated cells have the morphology of type I chief cells and display marked vacuolation and depletion of yellow-green, naturally fluorescing, bioamine containing granules. Although unimportant variations in size and weight in relation to age occurred at sea level, it was found that the magnitude of the carotid body enlargement increased with age at high altitudes. The augmented carotid body size and weight in relation to age at high altitudes are associated with progressive chemoreceptor insensitivity. The physiologic and pathologic significance of these findings is discussed.


The pathology of the heart in progressive muscular dystrophy: epimyocardial fibrosis.

The gross and microscopic appearance of the hearts from eight patients with Duchenne's progressive muscular dystrophy are described. Seven hearts had gross evidence of myocardial fibrosis, five of these demonstrating distinctive fibrosis of the epimyocardial portion of the free wall of the left ventricle, often with a striking band-like appearance. On the basis of mapping studies of the myocardial fibrosis, a theory regarding the progression of myocardial fibrosis in Duchenne's progressive muscular dystrophy is presented. Correlation of the pathologic anatomy, electrocardiograms, and vectorcardiograms in these patients and the family studies of others suggests that Duchenne's progressive muscular dystrophy represents a generalized cardiomyopathy that has its gravest and most distinctive effect on the epimyocardial portion of the free wall of the left ventricle.


The carcinoid endocardial plaque; an ultrastructural study.

Ultrastructural studies disclosed that the plaque-like endocardial thickenings in three patients with the carcinoid syndrome were composed of smooth muscle cells embedded in a stroma that was rich in acid mucopolysaccharides, collagen, and microfibrils, but devoid of elastic fibers. The smooth muscle cells contained variable numbers of myofilaments and cisterns of rough surfaced endoplasmic reticulum, and their basement membranes were greatly thickened, reduplicated, and arranged in layers. The endocardial plaques appeared histologically and ultrastructurally similar regardless of their location in the heart. The smooth muscle cells in these plaques appear to have been derived from primitive mesenchymal cells, which normally are present in the subendocardial endothelial space. These observations are interpreted as indicating that the plaques develop as a result of healing of a superficial endocardial injury, which may be initiated by release of bradykinin from hepatic metastases of a carcinoid tumor.


Endobronchial plasma cell granuloma (xanthomatous pseudotumor); a light and electron microscopic study.

Plasma cell granuloma (xanthomatous pseudotumor) is polymorphic at light as well as electron microscopic examination. At light microscopy the endobronchial variant of this entity was rich in plasma cells and interwoven, whorl-like, or concentrically arranged spindle cells. Foamy histiocytes and macrophages usually abundant in the intrapulmonary variant were rare. At electron microscopy particles 20 to 50 nm. in size were found at the bronchial mucosal surface but not elsewhere in the lesion. Plasma cells near the bronchial surface contained cytoplasmic fibrils, mitochondria with concentric cristae, and inclusions that bore a close resemblance to adjacent extracellular crystallized hemoglobin. Those in the center of the lesion ordinary round inclusions and none of the other changes. Spindle cells in the interlaced areas were mostly fibroblasts or myofibroblasts, whereas those whorled around capillaries resembled pericytes with basement membranes and nuxes-like intercellular junctions. Year rings like multilayered basal laminae were frequently present between the pericyte-like cells and the endothelial cells of the capillaries. The ultrastructure of plasma cell granuloma, like the histologic and clinical aspects, differs from that of sclerosing hemangioma, pseudolymphoma, and malignant plasma cell tumor affecting the lung.


Intestinal lesions in immune deficiency.

The descriptive studies of intestinal lesions in immune deficiency and the research that has been done in order to explain their pathogenesis are reviewed. Current knowledge in this field is inadequate, and some of the intriguing phenomena described defy reasonable explanation, including the special role of Giardia lamblia and the rarity of gastrointestinal lesions in isolated IgA deficiency. Several hypotheses have been proposed regarding these phenomena.


Calcification in the renal medulla; a classification based on a prospective study of 2261 necropsies.

Kidneys from 1864 necropsies performed in Brisbane, Australia, and from 397 necropsies performed in Christchurch, New Zealand, were examined macroscopically and microscopically. Three zonal and three focal patterns of renal medullary calcification were defined: (1) Outer medullary cortical calcification seen in hypercalcemic conditions. (2) A band of calcification at the boundary of the inner and outer medullar associated with degenerative changes and correlated with aging and arteriolar disease. (3) Calcification concentrated around the loops of Henle in the papilla, sometimes a striking finding in children and common at all ages. Heavy calcification in this region was injurious to the loops. (4) Fine focal calcification in random distribution throughout the medulla. This lesion was seen in virtually all adult necropsies to some degree. (5) Coarse focal deposits in the papillary region, more common in males and in a hotter climate. (6) Randall's plaques also were common in males and in a hotter climate.


Reproducibility of the mitosis count in the histologic diagnosis of smooth muscle tumors of the uterus.

In order to ascertain the reproducibility of the mitosis count in histologic tumor diagnosis, a reference set of 10 microscopic slides from smooth muscle tumors of the uterus was shown to six different pathologists, who were asked to record the number of mitotic figures per 10 high power fields in the most active region of each slide. The results, when tubulated, revealed considerable observer variation in this supposedly objective and quantitative diagnostic criterion. The diagnosis of benignity or malignancy, based on this criterion alone, were unamimous in only four of the 10 cases, whereas the diagnoses based on a constellation of histologic criteria were unanimous in all cases and correlated well with the subsequent clinical evolution of those cases with follow-up data. Possible reasons for the lack of reproducibility of the mitosis count are discussed. We conclude that a qualitative estimation of mitotic activity is helpful as one of the diagnostic and prognostic criteria in the assessment of uterine and other smooth muscle tumors, but that it cannot be used as the sole criterion for distinguishing benign from malignant tumors.


On the origin of the so-called tumorlets of the lung.

A light and electron microscopic study of multiple tumorlets in a 66 year old female is presented. Clinically the patient had had chronic obstructive lung disease with bronchiectasis of the right upper lobe. Aside from severe bronchiectatic alterations, the resected lobe showed typical tumorlets. On electron microscopic study, these were shown to consist of cells containing large numbers of a neurosecretory type of granule, which was identical to those present in the bronchial counterpart of the intestinal argentaffin (Kulchitsky) cell, as well as in pulmonary carcinoid and oat cell carcinoma cells. Our studies suggest the possibility of a histogenetic relationship between tumorlets, bronchial carcinoid tumors, and oat cell carcinoma, the cell of origin in each case being the bronchial counterpart of the intestinal argentaffin cell.


Aspartylglucosaminuria: unique biochemical and ultrastructural characteristics.

The observation of vacuolated lymphocytes in a coarsely featured two year old female with hepatosplenomegaly, mitral insufficiency, and mild psychomotor retardation led to the first diagnosed case of aspartylglucosaminuria in the United States. Although physical characteristics and bone roentgenograms were consistent with a mucopolysaccharide disorder, analysis of the urine showed no mucopolysaccharide elevation. The chromatographic, enzymatic, and ultrastructural studies confirming the diagnosis are presented.


Formal genetics of Fanconi's anemia.

The formal genetics of Fanconi's anemia were investigated on the basis of 21 families from different European countries, and of 69 families from the literature. 1. The result of segregation analysis is compatible with the hypothesis of a simple autosomal recessive mode of inheritance. 2. The number of sporadic cases is not greater than expected. 3. Among the affected siblings in the sibships analyzed, males are somewhat more frequent than females. However, this sex difference is also found among the unaffected siblings, and it is not statistically significant. 4. Contrary to assertions made in the literature, there is no clustering of affected in the sequence of siblings, no maternal age effect, and no preference of higher birth orders. 5. A high intrafamilial correlation for age at onset, and (very probably) number and severity of malformations points to genetic heterogeneity. Apart from the standard type, an especially mild type with late onset, few malformations, and a relatively benign course seems to exist. Its counterpart is possibly an especially severe type with early onset, many malformations, and a malignant course. However, definite conclusions on the special character of this heterogeneity will require application of additional methods.


Mental retardation and congenital malformations associated with a ring chromosome 9.

A 46,XY,r(9) (p24q34) complement was observed in a 35-month-old boy with multiple congenital anomalies. The main clinical features included intrauterine growth retardation, dwarfism, microcephaly, peculiar face, undescended testes, seizures and severe psychomotor retardation. It appears that 4 reported cases of r(9) can be divided into two groups. Three of them, including the present case, share clinical features with those of cases with 9p--. On the other hand, one case showed a different combination of malformations.


Fusion of two apparently intact human X chromosomes.

Cytological studies have been presented from a 15-year-old girl with short stature and failure of puberty. Buccal mucosa preparations revealed X-chromatin mass approximately double in size of that of a normal female. Leukocyte metaphases suggested a two cell line composition of the patient. One population of cells conformed with 45,X chromosome distribution. The chromosome complement of her other cell line had a modal number of 46. In this cell line a "C" chromosome was replaced by an exceptionally large submetacentric chromosome. This abnormal element exhibited late DNA replicating pattern. G-banding study revealed that the abnormal chromosome was produced as a result of fusion involving telomeric ends of long arms of 2 intact X chromosomes. This translocation X was bearing 2 C-banded areas; one around the centromere and the other at the distal end of the long arm. The distal C-band area did not show any evidence for centromeric function. It appears that a centromere becomes latent in the presence of another centromere in a translocation bearing 2 total chromosomes. Such a change of state in the additional centromere is vital for the stability of the translocation chromosome.


Localization of the human GLO gene locus.

Data on the linkage relation between the GLO locus and the HLA, Bf, and PGM3 loci are presented. The family material includes 49 GLO/HLA-B (and/or Bf) segregating matings with 134 children informative on 199 parental meioses. Of phase-known meioses, 3 are recombinants and 75 nonrecombinants; linkage is therefore proven. From the total material a distance of 2.5 cM between GLO and HLA-B/Bf is calculated; and from the segregation in some informative family groups it is shown that GLO is situated between PGM3 and HLA-B/Bf.


Significance of a new type of human fetal hemoglobin carrying a replacement isoleucine replaced by threonine at position 75 )E 19) of the gamma chain.

A new type of hemoglobin F, in which isoleucine in position 75 (E 19) of the gamma chain is replaced by a threonine residue, has been found in 29 out of 32 homozygotes for beta thalassemia. The amount of this hemoglobin ranges from traces to 40% of the total Hb F. The same gamma75 Thr chain is also present in the Hb F of 40% of normal newborns and premature infants examined, of one 14-week-old fetus and in one out of 3 patients with aplastic anemia and raised levels of Hb F. Our results strongly suggest that the synthesis of this new chain is under the control of a gamma gene nonallelic with those coding for Agamma and Ggamma chains.


The human leukocyte test system. VIII. DNA synthesis and mitoses in 3-day cultures stimulated with pokeweed mitogen.

In human leukocyte cultures set up with Ham's F-10 medium and stimulated with pokeweed mitogen (PWM), DNA synthesis and mitotic indices were analyzed by means of (3H)TdR autoradiography and cell counting. The results show a very similar pattern of DNA synthesis and mitotic indices to that found in cultures set up with TC medium 199 and stimulated with phytohemagglutinin (Obe et al., 1975 a).


Evidence for an association between ABO blood group and goitre.

A medical and genetic study on KarKar Island, Papua New Guinea revealed a significant association between ABO blood group status and susceptibility to goitre with O individuals more susceptible than non-O. The association is found in a number of separate villages on the island which indicates that it is not due simply to chance concordance in geographical patterns of genetic and disease variations.


A family with a high risk of segregation for an autosomal unbalanced reciprocal translocation.

A family with autosomal reciprocal translocation t(4;13) (q25;a31) with a sibship comprising 2 children with unbalanced karyotypes, der(13) partial trisomy 4q, 1 child with the balanced translocation, and 2 abortions were studied. The segregation risk of unbalanced derivation in reciprocal translocations is discussed. The clinical picture of the 2 children with partial trisomy 4q is compared with similar cases.


Hereditary retinoblastoma: penetrance, expressivity and age of onset.

Analyses of family data published in Japan concerning 29 kindred with 2 or more cases of retinoblastoma revealed that, in the children who received the gene from a carrier parent, both penetrance and expressivity increase with increasing degree of expressivity in the parent. The estimate for the average degree of penetrance varies from 0.7 to 0.9, depending upon the method employed. The value will be increased with increasing number of survivors of hereditary retinoblastoma. Data were presented to indicate that in the hereditary form of retinoblastoma onset tends to be later in unilateral than in bilateral affection, though in the non-hereditary form onset will be further delayed. No effect of birth order was detected. It was suggested that suppressor genes at other loci play a significant role in manifestation of the major dominant gene for retinoblastoma. Implications of these findings were discussed.


Inherited congenital normofunctional testicular hyperplasia and mental deficiency.

Four 46,XY siblings with congenital bilateral megalorchidia, marcogenitosomia, and severe mental deficiency were investigated. The testicular size was significantly larger than age-matched normal males. A normal hypothalamic-pituitary gonadotropin function was demonstrated by the finding of normal levels of luteinizing and follicle-stimulating hormones in blood samples drawn at frequent intervals and by normal responses to gonadotropin-releasing hormone and testosterone administration. A normal testicular function was shown by the finding of normal (a) plasma testosterone and estradiol levels, (b) gonadal response to human chorionic gonadotropin, (c) sperm analysis, and (d) morphology and cell architecture of the testes. Adrenal function was found to be within normal limits. These results demonstrated the existence of normofunctional testicular hyperplasia. The family studies suggested that this distinct congenital disorders is inherited as an X-linked recessive trait.


Isochromosome X in man: different DNA replication patterns in the long arms.

An X isochromosome for the long arm was studied in 3 patients with Turner's syndrome using the BrdUrd-Hoechst 33258-Giemsa method and C-staining. In all 3 patients studied, the long arms of the i(Xq) were asymmetrical with respect to chronology of DNA synthesis. The most striking asynchrony of DNA replication was observed in large early replicating segments adjacent to the centromeric region. Two C bands of similar appearance were observed localized symmetrically in both arms. The data are interpreted in accordance with two possible origins of an abnormal X which is known as i(Xq).


Gene dosage effect in human triploid fibroblasts.

The activity of 13 cytoplasmic enzymes has been determined in fibroblast extracts from 9 triploid and 13 control lines. The results show a high activity for 2 X-linked enzymes, glucose 6-phosphate dehydrogenase and phosphoglycerate kinase. These data, together with cytogenetic observations, support the contention that 2 X chromosomes were active in the triploid lines.


Genetic polymorphism of C3 and serum levels of immunoglobulins, C3, C4 components of complement and C3-proactivator in four different populations of Afghanistan.

The C3 phenotype distribution was studied in 4 different populations from Afghanistan. The gene frequencies of C3S allele were: Tajiks (0,8547), Pushtoons (0.8812), Hazaras (0.9036) and Osbeks (0.8530). These values were significantly higher than in European populations studied previously. No significant differences were found between the mean serum levels of C3, C4 and C3-proactivator among 4 population groups. A higher concentration of IgG, IgA and IgM was observed in Afghanistan sera than reported for Europeans.


Complex translocation t(9;21)(9;22)(q12p13)(q12q11) in the family of a child with 9p trisomy syndrome.

A case of partial trisomy 9 is described in a mentally retarded and dysmorphic child, confirming that this chromosome unbalance results in a characteristic clinical entity. This trisomy arose through aberrant segregation of translocation chromosome during meiosis in the patient's mother, who is a balanced heterozygote for a complex translocation involving chromosomes 9, 21 and 22. The phenotypically normal sister of the proposition is also carrier of the same complex translocation.