Synaptonemal complex karyotyping in spermatocytes of the Chinese hamster (Cricetulus griseus). III. Quantitative evaluation. Relative length is a constant and distinctive characteristic for each autosomal SC, despite variations in absolute length from cell to cell. Arm ratio is distinctive for each SC except for two of the three sub-acrocentrics, and serves, together with relative length, for identification. The constancy of relative length and arm ratios indicates biological stability and lack of physical distortion in these spread preparations. There is a 1:1 relationship between relative lengths of autosomal SCs and mitotic autosomes: their arm ratios are similar. These close parallels provide strikingly similar SC and somatic karyotypes. Variability was observed in sub-acrocentric arm ratios and in lengths of unpaired X and Y axes, correlated with the presence of constitutive heterochromatin. - Utilizing progressive differentiations of the X and Y chromosomes for staging, it is demonstrated that autosomal SCs decrease in length from late zygotene to mid-pachytene, and then increase at late pachytene. Within a nucleus, synchrony of length changes is maintained. It is concluded that the factors governing autosomal SC length are regular for any given bivalent from cell to cell and may be related to those that control somatic autosome length relationships. - The X and Y axes differ quantitatively as well as qualitatively from autosomal SCs. The SC portion of the X and Y is constant in length through most of pachytene; the unpaired axes shorten and lengthen, but not in proportion to autosomal SCs. X and Y relative lengths ard arm ratios vary throughout pachytene and do not maintain proportionality with somatic values. The evidence suggests, but does not prove, that the long arm of the X is paired with the short arm of the Y.-Twists occur in autosomal SCs at increasing frequencies throughout pachytene but cannot account for length changes. The number of twists per SC is directly proportional to SC length. Intertwining of SCs is random and proportional to SC length. End-to-end associations of autosomal SCs appear to be random; however, the ends of the X and Y are less often involved in such connections. - The length of axial material in all chromosomes at pachytene, expressed as an equivalent length of DNA double helix, represents 0.013% of the diploid DNA complement.


A preliminary report on crime and addiction within a community-wide population of narcotic addicts. This paper discusses the criminal behavior of narcotic addicts and is based on a sample of males identified as narcotic abusers by a large urban Police Department in the United States over a twenty-year period (1952-1971). The records of 252 subjects (representing a 92% interview response rate) were analyzed to determine whether there were differences between blacks and whites with regard to criminality before first use and after first regular use of narcotics. The findings generally support previous ones in regard to the increase of criminal activity after the onset of narcotic addiction. In addition, this community-wide population of narcotic addicts revealed that black addicts tend to commit more crimes, and more serious crimes, than white addicts before first use of narcotics and after the onset of addiction. Further, weighted crime index scores of both the "before" and "after" segments appear higher for blacks who became addicted in the most recent years, while this appears to be true for the whites only after the onset of their addiction.


The effects of maternal drug dependence on neonatal mortality. Addiction in pregnancy has become an important health problem owing to the tendency of drug-dependent women to neglect general health care and to avoid seeking prenatal care. In addition, continued heroin administration during pregnancy carries additional risks for the maternal-fetal unit. Thus, there is an increased incidence of obstetrical and medical complications in these mothers, resulting in high incidences of prematurity, low birth weight and mortality in their infants. Therefore, there is a high neonatal mortality rate due to clinical conditions most commonly seen among premature infants. Data from three groups of drug-dependent women and their infants and one control group demonstrate that the high mortality rate, as well as the incidence of low birth weight, can be reduced to a rate similar to the control group in infants of mothers who receive comprehensive services that include prenatal care in conjunction with methadone maintenance.


Social stability on admission and success of in-patient treatment for alcoholism. The pre-treatment social stability score (combined economic-familial-residential scales), indicating whether the patients were comparatively integrated or disintegrated socially, was found to be of greater prognostic value regarding post-treatment drinking than was information about whether they received full, part or "no" treatment. There was a differential treatment effect for the first 3 months of the 12-month period only. Of the overall sample, one-third of the patients could be considered to have improved following treatment, but two-thirds drank as much, if not more, than they did prior to treatment. These two groups were significantly different in terms of social stability and different types of treatment appear necessary to accommodate these differences. Social integration/disintegration is most readily seen in terms of the number of previous treatments (or institutionalisations) the subject has received for alcohol-related problems.


[Anti-oestrogen treatment of metastasising carcinoma of the breast (author's transl)]. Within a period of four years 35 patients with metastatic breast cancer were treated with tamoxifen. One third had objective remissions, average duration of complete remission being 30.6 months and of partial remission 13.7 months. Mean survival time from start of tamoxifen treatment in five patients with complete remission was 30.6 months while in seven with partial remission it was 20.4 months. Nine patients with unresponsive metastases had a mean survival time of 24.3 months, the remaining 14 patients who deteriorated surviving for 11.7 months. Ten of the 12 patients who responded well were over 60 years old. Lymph-node and lung or pleural metastases were significantly reduced by treatment in four of eight and six of 15 cases, respectively. Satisfactory regression of bony metastases was never seen. Because of this, combined tamoxifen (10 mg twice daily) and methandrostenolone (1 mg twice daily) was given to an additional five patients, with one of them responding. Side effects included thrombocytopenia and hypercalcaemia.


[Biosynthesis of insulin. The Ferdinand-Bertram-Award lecture (author's transl)]. EEG recordings were done 1-3 months before and up to 5 years after shunt operations in 20 men and 7 women (aged 16 to 69 years) with liver cirrhosis, most of them of alcoholic aetiology, and with oesophageal bleeding. The EEG diagnosed encephalopathies before there were any clinical suspicions. Pre-operatively half of the patients (14) had EEG changes indicating encephalopathy. In only four patients who before operation had a normal EEG were there post-operative EEG changes indicating encephalopathy. In the other nine patients the EEG was normal before and after shunt operation. The abnormal EEGs which occurred post-operatively or got worse generally returned to pre-operative levels within 3-4 weeks. These studies indicate that in patients with pre-operative encephalopathy there is no improvement in the EEG after shunt operation. On the other hand, if pre-operatively there are no significant cerebral abnormalities, post-operative changes of encephalopathy are rare (14.8%).


The role of estrogen in the regulation of luteal progesterone secretion in the rat after day 12 of pregnancy. Pregnant rats, hypophysectomized-hysterectomized on day 12 (day 1=insemination), secreted progesterone (P) at about 50% of the day 12 level for 3-5 days. Daily treatment with estradiol 100 microng (E100) but not with E25 or E50, from day 12 to day 20, of such rats, restored P secretion until day 16 to that of intact pregnant rats; on day 17 a drastic permanent fall occurred. E100 had no effect after ovariectomy, and did not change the metabolic clearance rate of P. This E100 effect was absent in decidual tissue (DT)-bearing, or hysterectomized pseudopregnant (PSP) rats, and in pregnant ones before day 11. When pregnant rats were hypophysectomized-hysterectomized on day 10, and were treated with rat placental luteotrophin (rPL) (in the form of day 12 pregnant rat serum: "PRS-12") on days 10 and 11, however, E100 increased P secretion above that found with either PRS-12 or E100 alone. DT-bearing PSP rats, similarly operated on on day 12 and treated with PRS-12 on day 12, responded in the same way to E100. In these rats also the E100 effect lasted for four days. In the day 12 hypophysectomized-hysterectomized pregnant rat, the E100 effect could not be prolonged by single treatments with PRS-12 on either days 13, 14 or 16, but when PRS-12 was given daily from day 12 to 19, P was secreted until day 20 only slightly below the day 12 level; this treatment plus E100 raised P secretion, prolonged it to day 18, and led to a marked fall by day 20 similar to that of the intact pregnant rat at term. The marked increase in P secretion between days 12 and 15 of normal pregnancy may thus be a response to intraluteal estrogen; the pattern of P secretion from day 12 to term may reflect the effects of both estrogen and rPL. rPL probably induces this effect by generating luteal estrogen and LH receptors. The placenta may also secrete an LH-like hormone (rCG?) which, through the LH receptors, could stimulate intraluteal estrogen production.


An effect of estradiol and testosterone on the calcium pump activity and phospholipid fatty acid composition of rat liver microsomes. Castration of the male rat resulted in a 28% reduction of the specific activity of liver microsomal calcium uptake, three weeks after castration. Treatment of the castrated animals with testosterone during this period returned calcium uptake to control levels. Treatment with estradiol resulted in a reduction of calcium uptake to a level less than 25% of that seen in the normal male. Although testosterone treatment had only a small effect on the fatty acid composition of liver microsomal phospholipids in the castrated male, there were significant changes of linoleic acid (18:2) in phosphatidylcholines and of palmitic acid (16:0) in phosphatidylethanolamines, when compared to the untreated castrated male rat. Administration of estradiol to the castrated male rat resulted in a marked decrease of palmitic acid (16.0) and linoleic acid (18.2) in all three phospholipid fractions studied. Stearic acid (18.0) was significantly increased in the phosphatidylcholines and phosphatidylethanolamines by estradiol treatment. The phospholipid and calcium uptake changes seen after treatment of the castrated rat with testosterone or estradiol are consistent with the sex-related differences observed in the intact, adult rat liver microsomes.


Androgenic stimulation of progesterone production by granulosa cells from preantral ovarian follicles: further in vitro studies using replicate cell cultures. The influence of testosterone (T) on progesterone (P) production by isolated rat ovarian granulosa cells was studied in vitro using a new replicate culture technique. Preantral granulosa cells from ovaries of estrogen-primed hypophysectomized immature female rats were cultured in the presence of graded concentrations of T, diethylstilbestrol (DES), cyproterone acetate (CPA), flutamide and the hydroxylated derivative of flutamide, Sch 16423. The accumulation of P in medium collected from granulosa cell cultures was measured by specific radioimmunoassay. Maximal P production by cultured granulosa cells was attained during the second day of culture and declined markedly thereafter. The presence of 10(-9), 10(-8) or 10(-7)M T elicited increases in P production 2.4, 8 and 11 times that of controls, respectively, during the initial 48 h of culture. Each concentration of T elicited enhanced P production within the first 24 h of culture. Granulosa cells cultured in control medium for 2 days did not respond to 10(-7)M T during the subsequent 3 days. DES at a high concentration in the medium (10(-5)M) markedly suppressed the response to 10(-9) and 10(-8)M T. At a lower concentration (10(-9)M) DES significantly enhanced the stimulatory effect of 10(-9)M T but did not alter the response to higher concentrations of T. Neither high nor low concentrations of DES influenced P production in response to 10(-7) M T. The stimulatory effects of T on P production were suppressed in the presence of a 100-fold molar excess of the anti-androgens, CPA or Sch 16423. The present data indicate that androgenic stimulation of P production by preantral granulosa cells is a specific receptor mediated event which is modulated by the presence of estrogen in vitro. It is suggested that androgen-responsive P production is a functional capacity which granulosa cells acquire at a very early stage of hormonal differentiation and may be of physiological consequence in the intraovarian control of follicular maturation in vivo.


Acute changes in serum gonadotrophins and steroids following orchidectomy in the rat: role of the adrenal gland. Orchidectomy in male rats leads to a) an increase in serum LH and FSH within 9 h; b) a decrease in serum testosterone to baseline levels by 30 min; c) an increase in serum progesterone (for 30 to 120 min), in the presence of the adrenals. If adrenalectomy is performed simultaneously with orchidectomy, the LH and FSH rises at 9 and 12 h are abolished, and the rises at 24 h are attenuated or abolished. By 48 h, the orchidectomized-adrenalectomized rat has achieved a rise in serum LH and FSH equal to that found in gonadectomy alone. Two hypotheses are offered to explain the abolition of the early gonadotrophin rises after combined orchidectomy-adrenalectomy treatment: a) the early responses are due to increased serum progesterone, on a background of decreased testosterone; b) the early responses are abolished because of the missing corticosterone, which either forces competition between pituitary secretion of ACTH and LH/FSH, or is necessary for rapid gonadotroph-secretory response. The differences and similarities between male and female rats, in the response of LH and FSH to gonadectomy, in the presence  or absence of the adrenals, are discussed.


Hypothalamic areas involved in prostaglandin (PG)-induced gonadotropin release. I: effects of PGE2 and PGF2alpha implants on luteinizing hormone release. Ovariectomized rats had a cannula inserted unilaterally within various hypothalamic areas. Several days later they were primed with a sc dose of 10 microng of estradiol benzoate (Eb). Two days after priming they were etherized and an initial blood sample was drawn from the external jugular vein. An inner cannula containing PGE2 or PGF2alpha at its tip was inserted into the previously implanted outer cannula. Blood samples were drawn at 20, 40, 60, and 120 min following the implantation. PGE2 induced a 4-5-fold increase in plasma LH 40 to 60 min following its implantation in the arcuate nucleus-median eminence region (ARH-ME). Levels were already significantly elevated at 20 min. When PGE2 was placed slightly more dorsally, close to the ventromedial nucleus (VMH), LH titers rose to comparable levels but only after a delay of 120 min. PGE2 implanted in the caudal portion of the ARH-ME or dorsally in the VMH-dorsomedial nuclei, barely increased plasma LH, whereas its placement in the anterior portion of the ARH-ME clearly elevated LH titers. PGE2 implants located more than 1 mm lateral from the midline or outside the hypothalamus were ineffective. When PGE2 was placed in the preoptic area (POA) or anterior ventral portion of the anterior hypothalamic area (AHA), plasma LH levels rose strikingly, the first significant increase being observed at 20 min. PGE2 implants located in the vicinity of the paraventricular nucleus-dorsal portion of AHA were much less effective. PGF2alpha implanted in the ARH-ME or POA induced a small increase in plasma LH and the implantation of empty cannulae in the same areas was ineffective. Intrapituitary implants of PGE2 failed to alter plasma LH significantly. The results indicate that PGE2 acts at the ARH-ME region to induce LH release and that an even more effective site of action seems to be located in the POA-AHA. Since these are areas which contain LHRH, the results support the view that PGs can activated LHRH-secreting neurons in these regions.


Hypothalamic areas involved in prostaglandin (PG)-induced gonadotropin release. II: effect of PGE2 and PGF2alpha implants on follicle stimulating hormone release. The effect of unilateral intrahypothalamic implants of PGE2 or PGF2alpha on FSH release in ovariectomized, estrogen-treated rats was studied. Both PGs induced an equally small increase in plasma FSH following their implantation in the body of the arcuate nucleus-median eminence region (BARH-ME). Levels were maximally elevated 120 min post-implantation. PGE2 implanted in the caudal portion of the ARH-ME (TARH-post-ME) also induced a similar increase in plasma FSH, whereas its placement in the region of the ventromedial nucleus (VMH)-dorsomedial nucleus (DMH) did not significantly alter FSH titers. By contrast, PGE2 placed in the post-chiasmatic region (HARH-ME) clearly elevated plasma FSH as early as 40 min after implantation. Implants of PGF2alpha in this area were ineffective. PGE2 implants located more than 1 mm lateral from the midline or outside the hypothalamus were also ineffective. When PGE2 was placed in the preoptic area (POA) or anterior ventral portion of the anterior hypothalamic area (AHA), plasma FSH rose markedly showing the first significant increase between 40 and 60 min after implantation. PGE2 implants located in the dorsal portion of the AHA-paraventricular nucleus (DAHA-PVH) were also clearly more effective than implants in BARH-ME, but less effective than implants in the POA. PGF2 implanted in the POA evoked a smaller increase in plasma FSH than that induced by PGE2 implants in this region. Implantation of empty cannulae in the ARH-ME region or POA failed to increase plasma FSH levels significantly. Intrapituitary implants of PGE2 did not alter plasma FSH. The results indicate that PGE2 acts mainly on the POA-AHA region to induce FSH release and that PGF2alpha, although less effective, also stimulates FSH release in this area. The ARH-ME appears to be a less important site. The greater effectiveness in the POA-AHA region than in the ARH-ME may indicate that PGE2 is more effective in stimulating cell bodies of LHRH neurons than their axons. Although most of the sites at which PGE2 released FSH coincide with the distribution of LHRH, it is noteworthy that a relatively enhanced release of FSH took place from certain sites in the dorsal AHA-PVH and from sites in the post-ME, which suggests that PGE2 may act on neurons which secrete a specific FSH-RF as well as on neurons which release LHRH.


Growth hormone, somatomedin and cartilage sulfation in failure of catch-up growth after propylthiouracil-induced hypothyroidism in the rat. Male Long-Evans rats 36 to 39 days of age were fed a diet containing 0.1% propylthiouracil (PTU) for 17 to 20 days followed by the resumption of normal diet. Growth rates of body weight and tail length decreased during PTU treatment and increased during recovery; yet only slight catch-up (compensatory) growth occurred in either body weight or tail length. Although serum thyroxine and triiodothyronine concentrations (radioimmunoassay) decreased significantly during PTU treatment, they returned to normal by recovery day 14. Pituitary immunoassayable growth hormone (GH) content and concentration dropped during PTU-feeding. By recovery day 14 there was significant, but incomplete, repletion of the gland. Serum GH during ether anesthesia was increased significantly during PTU treatment; it remained elevated (NS) and showed greater variability during recovery than in controls. Bioassayable serum somatomedin (Sm) activity decreased during PTU treatment in one of two experiments but returned to a normal level by recovery day 7. The addition of PTU to normal rat serum in concentrations used during PTU treatment failed to alter Sm activity. The addition of L-triiodothyronine and/or L-thyroxine to hypothyroid serum also did not alter Sm activity. In vitro and in vivo cartilage sulfate incorporation decreased during PTU treatment but it rose to greater than control values during the recovery period. The difference in sulfate incorporation between treated and control rats was maintained throughout the observation periods. The results indicate that incomplete catch-up growth following transient hypothyroidism is the result of factors other than deficient GH or Sm production. The implications of the persistent changes in cartilage sulfate metabolism are not clear, but these findings during recovery suggest the possibility that a disturbance of intrinsic cartilage function is a limiting factor preventing full catch-up growth after PTU-induced hypothyroidism.


Evidence for depressed catecholamine and enhanced serotonin metabolism in aging male rats: posssible relation to gondotropin secretion. The steady state concentration of dopamine (DA), norepinephrine (NE), and serotonin (5HT) was determined and turnover estimated in several brain regions of young (3-4 months) and old (21 months) male Wistar rats. An estimate of DA and NE turnover was obtained by determining their depletion rates after treatment with alpha-methylpara-tyrosine, a tyrosine hydroxylase inhibitor. Serotonin turnover was estimated by determining its rate of increase after monoamine oxidase inhibition with pargyline. In old males, medial basal hypothalamic (MBH) DA concentration and depletion rate were significantly lower than in young males. DA concentration of the remaining hypothalamus also was lower in old than in young males, but depletion rates were not different. DA concentration and depletion rate in the olfactory tubercle were the same in both age groups. The steady state concentration of NE in the MBH and remaining hypothalamus, and the hypothalamic NE depletion rate, were significantly lower in old than in young animals. In both brain and hypothalamus, steady state concentrations of 5HT were the same in young and old rats, but by 30 min after monoamine oxidase inhibition with pargyline, hypothalamic, but not brain, 5HT increased more in old than in young males. This may indicate a greater turnover of 5HT in the hypothalamus of old than of young males. In non-drug treated (control) old male rats, serum LH and FSH were lower, serum prolactin was higher and serum TSH was the same in young male rats. These data suggest that a decrease in catecholamine and an increase in serotonin metabolism occur in the hypothalamus of old male rats. These changes may be related to the decrease in release of gonadotropins and increase in release of prolactin observed in these old male rats.


The effects of actinomycin D and puromycin on the induction of the cytosol enzymes involved in the androgen metabolism by testosterone in female rat liver. Induction of the cytosol enzymes involved in the androgen metabolism in the female rat liver by testosterone was studied. The treatment by testosterone propionate increased the production of 5beta-androstane-3alpha,17beta-diol in the 105.000xg supernatant when 4-14C-testosterone was used as a substrate. The conversion of 4-14C-androstenedione to labelled testosterone was increased by the injection of testosterone propionate into female rats. Actinomycin D or puromycin which was administered for four days with daily subcutaneous injections of testosterone propionate prevented the increase of these enzymes by testosterone propionate. Actinomycin D given once with the final injection of testosterone propionate blocked the induction of cytosol 17beta-hydroxysteroid dehydrogenase by the treatment of testosterone propionate, whereas puromycin given in the same manner as actinomycin D had no such a blocking effect on the enzyme. Both of these antibiotics given once with the final injection of testosterone propionate showed no preventing effects on the induction of cytosol delta4-5beta-reductase by testosterone propionate.


Differential response of the ampullary and isthmic cells to ovariectomy and estrogen treatment: an ultrastructural study. Ultrastructural response of the ciliated and secretory cells from the ampullary and isthmic parts of the oviduct was studied in ovariectomized and ovariectomized plus estradiol dipropionate (EDP) treated rabbits. Ovariectomy did not significantly affect the cilia in the ampullary epithelium; degenerative signs, however, appeared overtly in the isthmic cilia. EDP at either 1 microng/kg or 5 microng/kg doses raised the number of cilia/cell in either tubal segments. For comparable change isthmic cilia seemed to require a higher dosage of the estrogen. Ovariectomy led to the depletion of the secretory granules (SGs) from the secretory cells of either tubal segments. EDP at both the doses induced formation of the SGs; this is more remarkable in the isthmic cells. Merocrine type of secretions were observed from the secretory cells of either segments but only at the high dose of estrogen. The findings are discussed in the backdrop of current knowledge.


Plasma testosterone response to HCG in normal men without and after administration of anabolic drug. In young, adult male volunteers Leydig cell function tests were performed consisting of i.m. administration of 1500, 3000 or 4500 IU of HCG on days 1, 2 and 3 and plasma testosterone determination by radioimmunoassay. The stimulatory effect of HCG known from the literature is reconfirmed. However, no difference between the effect of the three dosage levels was found and the first significant effect of HCG was observed 24 h after its first application. Testosterone levels on day 3 and 4 are higher but not different from each other. A depression of plasma testosterone after treatment with an anabolic steroid (1alpha, 17alpha-dimethyl-5alpha-androstan-17-ol-3-one) 20 mg daily for 14 days is described. Reactivity to HCG was sustained in these subjects, but testosterone response to HCG was diminished at all investigated time intervals.


Morphological and biochemical findings in the tissues of maldeveloped gonads in 45,XX females with early primary ovarian insufficiency. The gonads or excisions there of obtained from 13 cases of early primary ovarian failure in 46,XX females subjected to explorative laparotomy have been examined microscopically, histochemically and biochemically. Clinically, the cases were characterized by either primary amenorrhoea or by one or several spontaneous menstruations followed by amenorrhoea until operation. Roentgenologically and macroscopically, the gonads were characterized as either "steak" gonads or hypoplastic ovaries. There were no associated somatic anomalies except for slight dysplastic bone changes and/or osteoporosis. Based on morphological findings, the gonads were grouped as follows. Type A ("dysgenetic" or "aplastic") gonads characterized by a complete absence of follicular apparatus or its remnants were composed of ovarian cortical-like stroma. Some of them contained hilus cells and rete structures. Type B gonads were severely hypoplastic ovaries differing from the previous ones by the presence of various active, but predominantly inactive derivatives of the follicular apparatus, such as scarce primordial or growing follicles, corpora albicantia or atretica. Type C gonads were designated as hypoplastic sclerocystic ovaries showing a microscopical pattern similar to that of the "Stein-Leventhal ovaries", with follicles, follicular cysts and predominantly perifollicular hyperthecosis. Biochemical investigations were based on incubation studies with labelled precursors. They permitted to conclude that steroid biosynthesis was severely affected in all the gonads examined, differing most markedly from the ordinary ovarian steroid biosynthesis in the A-type gonads, and being rather similar to that observed in the "Stein-Leventhal ovaries" in the C-type ones.


Teratogenic activity and metabolism of primidone in the mouse. Primidone, 25, 50, 100, and 150 mg/kg, was administered orally to mice of the I.C.I. strain from days 6-16 of pregnancy. The fetuses were removed by caesarian section on day 19 and examined by dissection and alizarin staining for gross structural and skeletal defects. The most common abnormalities found were palatal defects with full-length or submucosal clefts. In the controls--25, 50, 100, and 150 mg/kg groups--the incidence of palatal defects was 0/85, 16/84, 18/117, 19/102, and 17/92 fetuses, respectively. Essentially no other major or minor drug-related abnormalities were found. The metabolism of primidone in the pregnant and nonpregnant mouse was also studied and shown to be similar to that previously reported in the rat. Peak blood levels of primidone were obtained after 1 hr; they fell to very low levels by 6 hr. and were completely cleared by 24 hr. The metabolites produced, PEMA and phenobarbital, are similar to those produced in other species including man. Blood levels following single oral doses of 5 to 150 mg/kg were dose-related so that no explanation for the lack of dose-related teratogenic effect was found.


Evidence of osteomalacia in an outpatient group of adult epileptics. A review of 50 adult epileptics who had taken anticonvulsant drugs for 10 or more years showed a decrease in the concentration of serum phosphate and calcium and an increase in the activity of alkaline phosphatase in 22% of the patients. Plasma albumin and gamma-globulin levels were higher than in control subjects. All the patients lived at home and the dietary intake of calcium and vitamin D was often borderline normal or low. Six patients were submitted to bone biopsy and of these, 4 showed histological osteomalacia. Gastrointestinal disease did not appear to be a significant factor. None of the patients had symptoms or signs attributable to osteomalacia which does not seem to be of serious significance. All the patients were taking at least two drugs and it was not possible to assess the relative importance of the various drugs. A prospective study is needed. Measurements of serum calcium, phosphorus, and alkaline phosphatase should be performed at intervals on patients who are receiving anticonvulsant therapy. Treatment with calciferol may be indicated.


Genetic study of infantile spasm with hypsarrhythmia. Infantile spasms (IS) appear to be a distinct syndrome complicated by heterogeneous etiology. Family data support a multifactorial model involving a polygenic determination of susceptibility to IS but requiring environmental factors such as anoxia, birth trauma, or immunization to precipitate seizures. The empiric recurrence risk among siblings was estimated to be 15 +/- 3 and for all first degree relatives as 7 +/- 5 per 1,000. These risks should be interpreted with caution since possible heterogeneity of IS may result in the occurrence of families in which cases are presumably totally environmental, and other rare families which may be segregating for an autosomal recessive disorder. Careful review of involved medical and family histories and a thorough physical examination should permit discrimination among these possibilities.


[Experiences with a cardiorecorder system for continuous 24-hour registration of heart rate]. Studies regarding to the continuous registration of the heart frequency by a transportable instrument, which can store the data of the heart frequency per minute up to 24h, are presented. It is a tape recorder the speed of which is geared down. Thus a normal tape cassette C 60 is sufficient for a registration of the heart frequency during 2 X 24h. The R-wave of the ECG is registered on the first channel of the tape as a biological signal. Moreover every minute an impulse of a clock is recorded on the second channel of the tape. With help of a second instrument the play back procedure for the 24-h-recording can be performed in about 15 min. The signals of both channels of the tape are transformed in digital rectangle impulses by an installed impulse-converter. The serial impulses are counted per minute with help of the time-mark by an interface in a counter. These data are at disposal in BCD-code. They can be passed on the following peripherals: digital printer, computer, pen-recorder and so on. A parallel standardized recording of the physical activity observed by the subject or by an experimenter allows a statistical evaluation and comparison of the physical activity with the corresponding heart frequency data. Some examples of the aread of occupational health, epidemiology and exercise physiology are discussed.


[Effects of adaptation to work in heat of rectal temperature evolution during recovery]. Evolution of rectal temperature (Tre) during recovery in different air temperatures was studied following different patterns of heat load before and after adaptation to work in heat (10 consecutive days). Three subjects have been exposed, after a 30 min rest period (Ta=28degrees C, Pwa=14 mb) to 4 heat loads, each producing 1 degreeC increase in Tre in approximatively 30 min (Co:Ta= 50 degrees C, Pwa = 60 mb, W = O watt; C1; 50 degrees C, 42 mb, 50 W on bicycle ergometer; C2;39 degrees C, 38 mb, 100 W and C3: 28 degrees C, 31 mb, 150 W). After of these heat loads, subjects were allowed to recover during 2 h at Ta = 28, 22 or 16 degrees C (Pwa = 14 mb). Results show that: (a) the cooler was the Ta, the faster was the recovery time; (b) before adaptation occurs, the evolution of Tre depended on the preceding heat load pattern; (c) the more intense was the work load, the more the adaptation reduced time for subsequent recovery. The interaction obtained between adaptation and intensity of preceding work load is discussed. The evolutions of leg skin temperatures suggest that a decreased local heat conductance (of inferior limbs) is associated with a local increase in external heat exchange. Adaptation to work in heat would take the form of a local re-adjustment of internal and external heat exchanges.


The response of endurance-adapted adults to intense anaerobic training. The effects of a 6 week program of intense, intermittent hill running was investigated in 5 endurance-trained men (34-37) years. Venous lactate responses averaged 10.7 mM X 1(-1) during training. Biopsies were obtained from the vastus lateralis before and after training for determinations of histochemical classification, phosphagen concentrations (ATP and CP) and activities of total LDH and selected LDH isozymes. Indices of aerobic and anaerobic capacity were also measured. Significant improvements (P less than 0.01) were noted in training distance and loads employed in leg presses, also part of the training: the treadmill test for anaerobic capacity improved by 16.7% and the terminal blood lactate level increased 14%(P less than  0.05). No changes occurred in VO2 max, body fat per cent or anaerobic power. Muscle ATP concentration increased by 14.8% (P less than  0.01) whereas the tissue level of CP remained unchanged. Total LDH activity and the LDH isozymes (LDH-1, LDH-5 and LDH-2, 3, 4) were not altered by training. No changes in fibre distribution were observed. That adaptations to the anaerobic training did occur is evident, but the cellular locus remains to be elucidated further.


The changes in hematocrit, hemoglobin, plasma volume and proteins during and after different types of exercise. A group of 7 healthy males was studied after maximal exercise and during and after prolonged exercise of two types (approximately at 40 and 67% of their VO2 max). Hematocrit, plasma proteins concentration, and hemoglobin were followed. Relative changes of plasma volume and total content of plasma protein were calculated from hematocrit changes. The mean corpuscular hemoglobin concentration was obtained by dividing hemoglobin by hematocrit. After maximal exercise, hemoconcentration with concomitant decrease of plasma volume (-13.0%) was found, with a corresponding increase in  protein concentration (+12.9%) and without any protein content changes. Later normalisation at the 30th min of the recovery phase was shown. During prolonged submaximal exercise (67% of VO2 max) the changes in hemoconcentration, plasma volume (-7.1%), and plasma protein concentration (+6.9%) reached the highest changes in the first 15 min of exercise, and no decrease in protein content was observed. After them the spontanious tendency to the normalisation was found. No changes were registered in prolonged mild exercise (40% of VO2 max). The ratio of hemoglobin to hematocrit remained unchanged during and after all types of exercise.


Studies of malformation syndromes of man VB: the hypertelorism-hypospadias (BBB) syndrome. Case report and review. We describe a boy with the hypertelorism-hypospadias (BBB) syndrome. His mother and his maternal grandmother showed minor manifestations suggestive of the syndrome. The BBB syndrome is a syndrome of multiple congenital anomalies with mental retardation due a segregating mendelian mutation, either X-linked or autosomal. This paper reviews the literature on the subject and emphasizes the problem of identifying females at high risk of transmitting the condition.


Glucosephosphate isomerase deficiency, a new variant in a Dutch family. Case report. The clinical course and the biochemical findings are reported from a patient suffering from glucosephosphate isomerase (G.P.I EC 5.3.1.9) deficiency type Nijmegen. This disorder decleares itself as a non-spherocytic hemolytic anemia, presenting in the neonatal period. In the patient hemolysis was of the same degree during the years. However, trivial infections could often trigger an increase in hemolysis requiring treatment by blood transfusions. Enzyme studies revealed that the GPI deficiency in this patient was caused by a double heterozygous state for two different GPI deficient alleles. The presence of one of these deficient alleles in the proband's parents and grandparents, was not accompanied by any sign of hemolysis, as for instance a shortened red-cell survival.


New chromosomal malformation syndromes. I. Partial monosomy 8p. An attempt to establish a new chromosome deletion syndrome. A mentally retarded 8-year-old boy with a de novo partial monosomy for the short arm of the No. 8 chromosome is described. Based on G-banding analysis, the patient's karyotype was identified in lymphocytes and skin fibroblasts as 46,XY,del(8) (pter leads to p21:). No chromosomal abnormalities were found in the phenotypically normal mother, father and sister of the propositus. Four further cases described in the literature indicate that partial monosomy of the short arm of the No. 8 chromosome might be associated with a syndrome characterized by the following stigmata: mental retardation, slow growth, high forehead, broad chest, wide-set nipples, pulmonary stenosis with atrial and/or ventricular septal defect, hypoplasia of the genitalia, dermatoglyphic stigmata.


The selenium state of healthy children. I. Serum selenium concentration at different ages; activity of glutathione peroxidase of erythrocytes at different ages; selenium content of food of infants. The selenium concentration of serum is age-dependent. The median value at birth (chi=50 X 10(-9)g/ml) amounts to half of the median value of adults (chi=102 X 10(-9)g/ml). After a decrease in early infancy to chi=34 X 10(-9)g/ml it steadily increases to chi=58 X 10(-9)g/ml in the second half of the first year, to chi=82 X 10(-9)g/ml in 1--5 year old children, and to chi=92 X 10(-9)g/ml in school children. The activities of the selenium containing enzyme glutathione peroxidase of erythrocytes are also reduced in early infancy (chi=7.2 +/- 0.36 U37/g Hb), whereas the enzyme activities of cord blood erythrocytes (chi=8.72 +/- 0.76 U37/g Hb) are in the same range as those of older children or adults. The selenium content of some commercially available milk formulas for infants are lower than those of human and cow's milk.


Quantification of melanin in hepatic and cardiac lipofuscin. Melanin pigment in liver and heart tissue, obtained at autopsy from patients, was isolated and quantified. The quantity of melanin extracted was directly proportional to lipofuscin granule counts. Infrared and electron spin resonance spectographs of the isolated pigments from liver and heart showed absorption characteristics identical to those of known melanins. The pigment was absent in fetal and neonatal life, increased in brown atrophy of the heart and liver, and diminished in livers with fatty metamorphosis.


Biochemical polymorphism and the 2,3-diphosphoglycerate in the sheep red blood cells. There was no significant difference in the level of 2,3-DPG in the red blood cells of sheep of different haemoglobin types (Hb A and Hb B) or potassium types (HK and LK). However, low glutathione (GSHL) sheep had significantly higher (p less than 0.01) level of 2,3-DPG in their red blood cells than high glutathione (GSHH) sheep. There was also significant effect of interactions between glutathione, haemoglobin and potassium types (p less than 0.05) and glutathione and haemoglobin types (p less than 0.01) on red cell 2,3-DPG levels.


X-ray induction of chromosome and chromatid aberrations in the same cells after treatment with hydroxyurea. Vicia faba root meristem cells treated for 24 h with 1.25 mM hydroxyurea and then X-irradiated contained a large number of cells with both chromosome and chromatid aberrations. X-irradiation 4 h after release from the hydroxyurea block yielded cells with almost exclusively chromatid aberrations.


Ba++ induced square-shaped potential waves in molluscan neurones. Rhythmic slow square-shaped potential waves lasting 20-50 sec are induced in Aplysia neurones when Ca++ is replaced by Ba++. During the plateau, the membrane is highly permeable to Ba++ ions, whereas in the interwave period the membrane resistance increases by 60 times. Analysis with slow current ramps suggests that the membrane properties of Ba-treated neurones and normally burst-generating neurones are similar.


Irreversible shock in rats after injection of microspheres into the renal artery. After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4-12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.


Non-uniformity of regional vasomotor activity indicating the existence of 2 different systems in the sympathetic cardiovascular outflow. In rabbits, 2 populations of sympathetic postganglionic fibres innervating the skin, heart, muscle and kidney could be classified by their different spike heights and their different susceptibility to noradrenaline and angiotensin amide. The ability of the 2 populations to respond to physiological stimuli in a highly differentiated manner leads to the assumption that 2 different systems in the cardiovascular sympathetic outflow exist.


Inhibition of growth in developing oocytes of the desert locust. The location of the terminal oocytes (T) in the ovary of the desert locust dictates whether the penultimate oocytes (T-1) will enter vitellogenesis -- as long as the T oocytes are retained within the ovarioles, vitellogenesis in T-1 oocytes is prevented. When the T oocytes are ovulated into the oviduct, growth of the T-1 oocytes (new T) resumes. Inhibition of vitellogenesis in T-1 oocytes is not due to low rates of JH biosynthesis since high rates of JH biosynthesis were observed in animals in which T oocytes were retained in the ovarioles.


Respiratory responses in heat-exposed rabbits: inhibition of tachypnoea offset by increase in tidal volume. Rabbits in which thermal panting has been inhibiting by previous cold exposure or by water deprivation respond to a raised ambient temperature with an increase in tidal volume. By so doing, they are able to maintain a minute volume appropriate to their thermoregulatory requirements.


The effect of vinblastin and vincristin on single nerve fibres. The perfusion of the node of Ranvier with vinblastin or vincristin reduces the amplitude of the action potential within a few seconds. Vincristins is 10fold more active than vinblastin. Upon withdrawal, the effect is promptly reversible and its is antagonized by acetylcholine.


Calcium and the contractile response to prostaglandin in the smooth muscle of guinea-pig stomach. In the longitudinal smooth muscle of guinea-pig stomach, verapamil (10(-5) M) which showed marked suppression of high K-induced contractures, did not suppress the contractile response to PGE1 (1.5 X 10(-9) to 10(-6) M) markedly. These results suggest that the contractile mechanism of PGE1 in guinea-pig stomach may mainly depend on a release of bound Ca in the cell and partly depend on a Ca influx from the extracellular origin.


Effects of tranylcypromine and pargyline on brain tryptamine. Tranylcypromine produces behavioral excitation while pargyline produces depression. Tranylcypromine increased brain tryptophan which led to an accumulation of tryptamine. The levels of tryptamine after tranylcypromine were found to be 3 times those found after pargyline.


3-Amino-1-(3,4-dichloro-alpha-methyl-benzyl)-2-pyrazolin-5-one (Bay g 2821), a potent diuretic from a new substance class. Chemistry, salidiuretic activity and mechanism of action of 3-amino-1-(3,4-dichloro-alpha-methyl-benzyl)-2-pyrazolin-5-one (Bay g 2821), a new diuretic, are described. Owing to the initial rapid onset of activity, the reserve in capacity and the additional long duration of activity, this substance represents a potent diuretic and antihypertensive agent.


[Synthesis of 2,3-diazaphenothiazine. X. 7- and 8-nitroderivatives of 1- keto and of 4-keto-2,3-diazaphenothiazine and their mixtures of oxidation on 5]. A description is given of the synthesis of 7- and 8-nitro-derivatives of 1-keto- and 4-keto-2,3-diazaphenothiazine, by cyclization with acids and hydrated alkaline sulfides (XIV) and (XV). Oxidation of these nitroderivatives (XI), (XII), (XVI) and (XVII) gives products corresponding to those obtained by oxidation of the heterocyclic S atom to sulfones (IV), (XIII), (VIII) and (XVIII). Nitration of 1-keto- and 4-keto-2,3-diazaphenothiazine (1) and (V) gives the 7-nitroderivatives with simultaneous oxidation of the sulfur to sulfoxide (II) and (VI); oxidation of these sulfoxides or sulfones gives the same products (IV) and (VIII) obtained by the methods described above. The same compounds are obtained also by nitration of 1-keto- and 4-keto-5,5-dihidroxy-2,3-diazaphenothiazine (III) and (VII).


[Optical resolution of N-acetyl-(R)(S)-p-methoxyphenylglycine by differential crystallization]. The optical resolution of the ammonium salt of N-acetyl-(R)(S)-p-metoxyphenylglycine was performed by differential crystallization producing the two enantiomeric forms with excellent optical purity. Hydrolysis with hydrochloric acid/hydrobromic acid yields the two enantiomers of p-methoxyphenylglycine and p-hydroxyphenylglycine respectively.


The effect of silybin on liver phospholipid synthesis in the rat in vivo. Female Wistar rats have been injected intravenously for seven days with various different doses of silybin, the main component of the drug silymarin, and the in vitro synthesis of phosphatidylethanolamine and phosphatidylcholine from their respective precursors, CDP-ethanolamine and CDP-choline has been examined in liver microsomal membranes. Appreciable inhibition of the incorporation rates of precursors into lipids has been noticed at dosage of 15-20 mg/100 g body wt., daily. No evident effect is exerted by similar silybin treatment on choline and ethanolamine incorporation respectively into liver phosphatidylcholine and phosphatidylethanolamine in vivo.


[Studies on 1,5-benzodiazepine. I. Derivatives of 4-amino-1,5-benzodiazepine]. Condensation of o-phenylendiamine and N,N-dialkyl-ethoxycarbonylacetamides in the presence of phosphorus oxychloride afforded 2,3-dihydro-2-oxo-4-dialkylamino-1H-1,5-benzodiazepines. These same compounds with a substituent in the 3 position were obtained when N,N-dialkylamino-alpha-ethoxycarbonyl-alpha-alkylacetamides were employed in the reaction. In a similar manner from N-phenyl-o-phenylendiamine the synthesis of 1-phenyl-2,3-dihydro-2-oxo-4-dialkylamino-1H-1,5-benzodiazepines was achieved. The formation of benzimidazole-2-acetic acid derivatives was observed in these reactions.


[Structural and functional integration of the processes of membrane hydrolysis and transport ("permeome" hypothesis)]. It was suggested and experimentally proved that the transport system's input is a part of an enzyme-transport ensemble and an allosteric regulator of enzyme activity. In special experiments, a typical for cooperation sygmoidal kinetics of saccharose and maltose hydrolysis was shown, as well as of their hydrolysis products transport, if the enzyme is involved in the actively transporting intestine mucosa. On the contrary, it is the hyperbolic curve which is specific for isolated digestive enzymes and for glucose accumulation. Replacement of oxygen with nitrogen and specific blockage of the glucose transporting agent with floridzine leads to disappearance or sharp reducing of the sygmoidality. The term "ergome" is suggested for designation of the minimal ensemble of elements able to carry out an elementary physiological process, the term "permeome"--for the transporting ergome.


[Responses of neurons of the cat cochlear nucleus to 2-tone signals]. Two-tone stimuli were used with harmonic relation between their components (F1-F6). At equal intensities of the harmonics, one of which was the neuron best frequency and the other did not, evoke any impulse response, the neuron response as compared to that at the best frequency tone alone, was decreased in 50% of all cases, facilitated in 19% and not changed in 31% of cases. Harmonics nearest to the best frequency tone were most effective in the decreasing or increasing neuronal activity. With diminution of the intensity of the best frequency tone, F4 by 10-20 dB decreasing effects were less pronounced at all the side harmonics except F5, whereas facilitatory effects rose greatly at the lower harmonics F1-F3. Neuronal response, facilitatory or inhibitory, to a two-tone stimulus was also connected with the effects of the side harmonic on the neuron spontaneous activity and the neuron response value to F4. Statistical character of the relations observed seems to be due to the variety of interfering factors.


[Neurophysiologic analysis of visceral afferent systems]. Interaction of visceral and somatic afferents and changes of neuronal discharges in focus of maximal activity of cerebral cortex on repetitive stimulation of visceral afferents were studied in anesthetized immobilized cats. Habituation was shown to develop in the cortex. Visceral and somatic impulses appeared to converge on cortical neurons in the S1. Simultaneous stimulation of the visceral and somatic afferents revealed domination of visceral influences. The elements of cortex seem to have unequal plasticity which can provide premises for learning process.


[Functional organization of the ganglia of the myenteric plexus]. In myenteral plexus of isolated segments of the small intestine and colon, presence of spontaneously active and silent cells was shown. The former discharge in separate action potentials with variable interval or in periodic bursts with relatively long intervals in between. The silent cells have a major group of mechanosensitive neurons and the neurons responding to pharmacological agents or to biologically active substances. The simplest interneuronal relations are considered in the myenteral ganglion: the excitatory and inhibitory connections, signs of organization in the neuronal activity. On the basis of own and literature data, a hypothetical scheme of functional organization of the myenteral plexus' ganglions is suggested.


[Hemodynamics and oxygen balance during isometric muscle tetany under conditions of hypoxic hypoxia]. Arterial pressure, venous outflow from the isolated m. gastrocnemius, and oxigenation of arterial and muscular venous blood during and after the 7-sec contraction elicited by electrical stimulation of peripheral end of cut sciatic nerve (24/sec), were studied in anesthetized cats. Hypoxia was induced by artificial ventilation of lungs with 7% oxygen in nitrogen. The data obtained showed a conformity of levels of O2 consumption to the levels of blood flow and a closer connection of O2 consumption with the flow than with oxygen extraction from the blood. Dynamics of the flow recovery seems to correspond to the metabolic theory while the growing of hyperemia confirms the ideas of the hystomechanical hypothesis.


[Effect of depolarizing factors on the contractile activity of the smooth muscle of stomach vessels]. In isolated strips of the pig left gastral artery, potassium and electrical stimulation were shown to elicit gradual contractile responses of the contracture type. This effect was abolished by the blockage of calcium permeability of the membranes with manganese ions. Fast stretching evoked no contractile response, while the slow one potentiated the contraction. Activation of the smooth muscle contractile apparatus seems to be due to calcium extracellular ions coming into the cell during depolarization of membrane. Further functioning of the contractile mechanism and the final physiological effect depend on interaction of the membraneous and intracellular links of electromechanical conjugation controlling the intracellular concentration of the calcium ions.


Community satisfaction, expectations of moving and migration. A previous residential mobility model (Speare, 1974) assumes an additive relationship between residential satisfaction, desire to move, and mobility. This paper elaborates the model and applies it to intercounty migration. An interaction between community satisfaction and expectations to migrate is hypothesized which distinguishes four groups of decision makers. A survey in Durham, North Carolina and a unique mobility follow-up over eight years provide the data to test the model and the interaction. Furthermore, using various time periods for identifying migrants offers some methodological insights. Results support Speare's general formulation but only after the interaction is taken into account. A three-year migration interval is found to be appropriate.


Residential preferences and migration.

Residential preferences and migration. For some time now, public opinion polls have revealed Americans' strong preference to live in comparatively small cities, towns, and rural areas rather than in large cities. However, as Fuguitt and Zuiches (1975) have reported, the majority of people also want these places to be within commuting distance of a large metropolitan city. This research tests the hypothesis that size-of-place and urban proximity preferences are factors in the dispersal of population through migration. A one-year panel survey of Pennsylvania households indicates that only about one household in ten that moved actually attained its preference for a smaller-sized place or a location more distant from a large city. Preferences for smaller-sized places and proximity to a city were not correlated with where people actually moved when the size and proximity of the previous residence were taken into consideration.


Relative income and fertility.

Relative income and fertility. The present study examines the relationship between relative income (i.e., actual income in relation to the expected income of one's socioeconomic group) and fertility, using data collected by the 1967-1968 Canadian Family Growth Study (Balakrishnan et al., 1975). We broaden the tests of relative income beyond cumulative fertility to spacing behavior and then examine some of assumptions included in the relative income model of fertility. Results of the tests, in brief, are as follows: (a) Relative income is found to be more closely related to spacing than to cumulative fertility; and (b) the relationship between relative income and fertility is strongest among those couples who plan their life ahead and have a high level of education and occupation, and when temporal alignment is brought between the measures of relative income and fertility. For the relative income model to receive confirmation, it was specified that the following hypotheses must be confirmed: (a) that fertility behavior would vary positively with relative income but the fertility norm would show no relationship with relative income: and (b) that consumption norms and behavior would show no relationship with relative income. The outcome of these tests are in the expected direction, giving support to the relative income model.  In addition, there is some evidence of predictive capability of the relative income model for correlative behavior.


Family planning program activity and patient enrollment rates in the United States, 1969 and 1971. The effects of demographic characteristics, socioeconomic conditions, health care, and family planning program activity on patient enrollment rates are estimated for 1969 and 1971. Two program activity variables (agencies and clinic locations) have significant, positive net effects in both years. The effect of agencies changed little between 1969 and 1971, and it is the strongest effect in both years. The effect of clinic locations more than doubled between 1969 and 1971, partly due to increased demand. The direct effects of the demographic, socioeconomic, and health care variables are not large, but many of the demographic and socioeconomic variables have substantial indirect effects via health care program activity.


The relationship between Schoen's index of mortality and a log-linear measure. This paper discusses the mathematical relationship between Schoen's index of mortality and an index derived from log-linear models for making compositionally controlled comparisons of the occurrence of an event in a population. The merits of each and the contributions of the log-linear formulation are discussed.


Hormonal and metabolic effects of somatostatin in diabetic patients submitted to an i.v. arginine infusion. Hormonal and metabolic effects of a synthetic linear somatostatin were tested in insulin-dependent subjects submitted to an intravenous arginine infusion. Arginine alone induced a rise in plasma growth hormone (HGH) and glucagon (IRG) concentrations but did not affect the spontaneous diurnal decrease of plasma cortisol; blood glucose concentration rose while that of alanine decreased suggesting enhanced gluconeogenesis; concentrations of plasma free fatty acids (FFA) and 3-hydroxybutyrate decreased. Somatostatin, at three different dosages, markedly influenced these patterns: HGH response to arginine was suppressed by the lowest somatostatin dose; IRG response was progressively inhibited by increasing doses of somatostatin but never reached zero; cortisol level was not decreased but slightly increased by somatostatin. Substrate responses to arginine were also modified by somatostatin: alanine disappearance was impaired, this effect being dose-related; plasma FFA and 3-hydroxybutyrate concentrations showed a significant increase rather than decrease, consistent with somatostatin suppression of residual insulin secretion. Tolerance to somatostatin was good and no alteration of hemostasis was observed.


The importance of HLA genes to susceptibility in the development of juvenile diabetes mellitus. A study of 93 patients and 68 first degree blood relations. The importance of genetically determined antigens of the HLA system in etiology and pathogenesis of juvenile onset diabetes (JOD) was studied in 93 JOD-patients and 68 blood relations. A close association was found between JOD and B-locus antigens B8 and Bw15, and C-locus antigen Cw3. Patients positive for one of these antigens have a 2-3 times -- and those positive for both B8 and Bw15 -- a 8.6 times greater chance of developing JOD, Evidence for a genetic heterogeneity between childhood type and later onset JOD could be obtained. B8 seems to play a particularly important role in childhood-type diabetes, whereas in the later onset JOD the antigens Cw3 and/or Bw15 might possibly represent an additional predisposing factor. Family studies have revealed a close correlation between glucose intolerance and those genes associated with JOD in blood relations below age 35. HLA-B7 which could be detected in that group of blood relations, and which was found statistically decreased in JODs might even exert some protective role. Incidence of haplotye identity in glucose intolerant siblings was almost three times higher than expected. These data provide evidence for the existence of a genetic basis which determines the susceptibility to develop JOD.


HLA antigens in patients with juvenile diabetes mellitus, coeliac disease and both of the diseases. We determined the prevalence of 24 antigens controlled by the HLA-A and B loci in twenty patients with juvenile diabetes mellitus (JDM), in twenty patients with coeliac disease (CD), and in eight patients with both of these diseases. The prevalence of HLA-B8 was increased in JDM chi2 = 12.52, p = 0.00040) and in CD (chi2 = 26.47, p less than 0.000001) as compared to 900 controls. There was only a modest increase of Bw15 in JDM (chi2 = 8.86, p = 0.0029) and in patients with both diseases (chi2 = 2.72). The observed prevalence of phenotype HLA-B8, Bw15 was enhanced in JDM (chi2 = 16.03, p = 0;000063) and in patients with both JDM and CD (chi2 = 24.48, p = 0.00000074) as compared with controls. In the latter group the observed value was 2.2 fold to that expected. In family studies the children having both B8 and Bw15 were more disposed to develop diabetes than siblings with only one of these antigens. In conclusion, the inherited susceptibility to develop juvenile diabetes is markedly associated with HLA-B8 and slightly with HLA-Bw15, and that of coeliac disease with HLA-B8 in Finnish paediatric patients. The presence of both B8 and Bw15 simultaneously increases the susceptibility to have both JDM and CD.


Perceptuo-motor dysfunction in the child with hemiplegia. Eighteen children with hemiplegia were examined by means of standard neurological and other, specialized, sub-tests to define the extent of their perceptuo-motor dysfunction. Particular attention was paid to auditory language function, praxis, visuo-spatial skills, body schema, tactile defensiveness and inattention. The side of the hemiplegia was not found to predispose to any specific dysfunction, with the exception of inattention which was seen only in those with left-sided hemiplegia. Children with a history of familial sinistrality had a higher incidence of speech problems, particularly in the area of auditory language and speech delay. The results are discussed in the light of therories of plasticity and cerebral organization.


Recurrence risks in families of children with symmetrical spasticity. This study was undertaken to evaluate the recurrence risks for sibs of patients with symmetrical spasticity (either quadriplegia or diplegia) in the absence of factors known to cause spastic cerebral palsy (e.g. pre-term birth, perinatal hypoxia). Among 669 children in the West Midlands with spastic cerebral palsy, 24 had symmetrical spasticity and normal birth histories. This group was clinically and genetically heterogenous. Among their 55 sibs, six had a spastic disorder similar to that in the index patient, and one further sib, who had died young, had been mentally retarded. Of particular interest were two families with an autosomal recessive condition of post-natal microcephaly, myoclonic epilepsy and spastic quadriplegia; and one family, and possibly a sporadic case of X-linked athetoid cerebral palsy. The recurrence risk in this series of approximately 1 in 9 suggests that about half the children with symmetrical spastic cerebral palsy and a normal birth history may have a recessive condition.


Verbal auditory agnosia in children.

Verbal auditory agnosia in children. Four (possibly five) boys are described with a profound comprehension deficit for acoustic language, leading to severe or complete abolition of expressive speech. One boy had presumed megalencephaly from birth but was of superior intelligence. He had a severe articulation deficit from early childhood, with delayed acquisition of speech. Another boy is thought to have a small angiomatous anomaly in the depth of the left parietal lobe. No brain lesions are known in the other three. Evidence for bilateral brain dysfunction consists of minor motor abnormalities in three boys, oromotor deficits in two boys, and bilaterally synchronous diffuse or independent focal paroxysmal discharges in the EEG of three, possibly four, of the boys. Seizures have occurred in only three boys, and have been easily controlled with anticonvulsants. One boy with a grossly abnormal EEG has had no clinical seizures to date and has not benefited frome one year of anticonvulsant therapy. Two of the boys are brothers, including the boy in whome the diagnosis is questionable since speech was never normal and since he has had neither seizures for an abnormal EEG. The severity of EEG abnormalities did not correlate closely with the course of the language deficit. The relationship of this syndrome to acquired aphasia in children, to Wernicke's aphasia and pure word deafness in adults, and to developmental lagnuage disability with predominantly receptive deficits, is discussed. One child illustrated the close association between writing and phonologic encoding and decoding operations, and two children the preservation of linguistic skills provided the acoustic channel was by-passed and language presented visually. This latter point has been emphasized because of its implications for the remedial education of children with this syndrome.


Recovery after electrical injury.

Recovery after electrical injury. A 14-month-old boy was seen following an accidental electrical injury received from a faulty domestic appliance. After initially showing marked clinical and electroencephalographic signs of cerebral damage, after one month there was a dramatic and continued improvement in both motor and sensory function. The importance of prolonged and optimistic resuscitation is stressed.


Atelencephalic microcephaly.

Atelencephalic microcephaly. A two-month-old child born with marked microcephaly (head circumference 17cm) was found at autopsy to have gliomesodermal tissue replacing the telencephalon (atelencephaly). This finding, together with genital anomalies and hypoplasia of the extremities, suggests arrest at the fifth week of fetal life. The clinical and pathological features are described and the pathogenesis is discussed.


Bilateral obstruction of the vertebral arteries in a three-year-old child. A three-year-old boy developed gait instability, nausea, vomiting, cranial nerve disturbances, hypotonus and dysarthria. Angiography of the four main cranial arteries showed complete obstruction of both vertebral arteries at the level of C1 to C2. Abundant collateral circulation was observed, which by-passed the obstruction to the vertebral arteries before their enterance into the posterior cranial fossa. The left vertebral artery was hypoplastic and both internal carotid arteries showed coiling in their extracranial portions. A high erythrocyte sedimentation rate at the beginning of the disease suggests an inflammatory alteration of both dysplastic vertebral arteries. The child recovered completely one month after the onset of symptoms. All other reported cases of childhood vertebro-basilar obstruction are reviewed and it is emphasized that the site of arterial obstruction has an important bearing on the clinical outcome.


Frequencies of circular units of nucleolar DNA in oocytes of two insects, Acheta domesticus and dytiscus marginalis, and changes of nucleolar morphology during oogenesis. The organization of the extrachromosomal nucleolar material in oocytes of two insect species with different ovary types, the house cricket Acheta domesticus (panoistic ovary) and the water beetle Dytiscus marginalis (meroistic ovary), was studied with light and electron microscopic techniques. Stages early in oogenesis were compared with fully vitellogenic stages (mid-to-late diplotene). The arangement of the nucleolar material undergoes a marked change from a densely aggregated to a dispersed state. The latter was characterized by high transcriptional activity. In spread and positively stained preparations of isolated nucleolar material, a high frequency of small circular units of transcribed rDNA was observed and rings with small numbers (1--5) of pre-rRNA genes were predominant. The observations suggest that the 'extra DNA body' observed in early oogenic stages of both species represents a dense aggregate ofnumerous short circular units of nucleolar chromatin, with morphological subcomponents identifiable in ultrathin sections. These apparently remain in close association with the chromosomal nucleolar organizer(s). The observations further indicate that the individual small nucleolar subunit circles dissociate and are dispersed as actively transcribed rDNA units later in diplotene. The results are discussed in relation to principles of the ultrastructural organization of nucleoli in other cell types as well as in relation to possible mechanisms of gene amplification.


Types of neural tissues induced through the presumptive notochord of newt embryo. Neural induction through the presumptive notochord was tested by means of the sandwich method. The result disclosed that the notochord was a potent inducer of neural tissues not only in the ectoderm of gastrula but also in the ventral ectoderm of neurula and early tail-bud embryos. Structures formed by the induced neural tissue varied greatly. They can be classified into three types. (1) Tubular: the neural tissues induced in explants containing abundant mesenchymes always formed long tubular structures. The shapes of these neural tubes showed considerable variation; moreover, they were atypical and none formed the regular structure of the spinal cord. This type was most frequent, being found in about 50% of the explants. (2) Inverted: this type was produced when the explant contained mesenchymal component. Consequently, the epithelium of explants was missing. Nevertheless, a considerable mass of neural tissue was always induced. It was noticed that the induced neural tissues were invariably inside out; this type was found in about 30% of the explants.(3) Archencephalic: this was the only type to form the regular structure, i.e., the archencephalon. Formation of the archencephalon was limited solely to those explants containing only a few mesenchymes; this type was found in about 20% of the cases. As described above, it was found that the neural tissues induced by the same inducer of the notochord were not uniform but varied in type. Further it was shown that the types of neural tissue differed according to different quantities of the surrounding mesenchyme. Based on these facts, it is to be concluded that it is not the inducer of notochord, but the surrounding mesenchyme that is of primary importance for the determination of the types of neural tissue.


[Hematic and plasmatic viscosity in cyanotic congenital heart diseases (author's transl)]. 57 patients with cyanotic congenital heart diseases were studied. 39 patients presented t. of Fallot, 18 patients had patent ductus arterious with pulmonary hypertension and right to left shunt. The average whole blood viscosity in patients with t. of Fallot was 6.86+/-0.32 cps. This parameter was correlated with hematocrit, fibrinogen, euglobulin lysis time, pulmonary output, systemic output, and O2 saturation. The value of "r" resulted as statistically significant only for the correlation between viscosity and hematocrit and between viscosity and fibrinogen (t=13.22, p less than 0.0005; t=3.35, p less than 0.001 respectively). The average value of plasma viscosity in patients with t. of Fallot was 1.61+/-0.024 cps. The correlations of this parameter with fibrinogen, euglobulin lysis time, pulmonary output and systemic output did not result as statistically significant. The average fibrinogen value was 256.10+/-20.63 mg%, whereas that of euglobulin lysis time was 12,67+/-1.50 hours. In patients with patent ductus arteriosus the average blood viscosity was 6.65+/-0.56 cps. Such parameter was correlated with hematocrit, fibrinogen, euglobulin lysis time, pulmonary output, systemic output and O2 saturation. The value of "r" resulted as statistically significant only between blood viscosity and hematocrit and between blood viscosity and O2 saturation (t=9.30, p less than 0.0005; t=5.800, p less than 0.001 respectively). The average value of plasma viscosity was 1.61+/-0.04 cps. This parameter was correlated with fibrinogen, euglobulin lysis time, pulmonary output and systemic output. The correlation index "r" never resulted as statistically significant. The average fibrinogen value was 299.20+/-20.30 mg. The average euglobulin lysis time was 16.02+/-2.73 hours.


[Particular aspects of cardiomyopathy in Landouzy-Déjérine's progressive muscular dystrophy. Study of a family (author's transl)]. In the study of a family affected by progressive muscular dystrophy (DMP) of facio-scapulo-humeral type (f.s.o.) the myocardial involvement has been found to be constant and of moderate degree. The myocardial component has been found to appear in the adult age with initial and prevalent atrial involvement. In one case the myocardiopathy was not associated with appreciable clinical signs of skeletric myopathy. Possible causes of the pecuationship between the DPM type f.s.o. associated myocardiopathies and familial idiopathic cardiomyopathies are outlined.


[Ecographic results of mitral commisurotomy (author's transl)]. Echocardiographic studies were performed both before and after commissurotomy on fifteen subjects affected by non-calcified mitral stenosis. The amplitude CE of the anterior leaflet dis placement, the slope of the CD and EF intervals, the amplitude of the A-wave, the ratio FA/DE and the reciprocal position of the anterior and posterior leaflet echoes were measured on the echographic records. These data were compared with the values obtained in ten normal subjects. After commissurotomy, the slope of the CD interval and most evidently that of the EF interval increased (the last one by a factor of 3), and the area of the mitral opening was found to be more than 9% larger. The A-wave reappeared clearly in 30% of the operated patients, and the outline of the posterior leaflet was no longer inscribed in the anterior leaflet diastolic curve in all cases; the amplitude CE was unchanged.


[Phonocardiographic and auscultatory patterns in patients with normally functioning Lillehei-Kaster aortic prosthesis (author's transl)]. 42 patients who had undergone aortic valve replacement with the Lillehei-Kaster prosthesis were studied. Phonocardiographic and physical examinations were carried out on these patients to determine the typical auscultatory pattern of this prosthesis. In the majority of the cases, the first sound was slight. The second sound was made up of two components, both produced by the artificial valve. A prosthetic opening sound was also detected. Moreover, a sistolic ejection murmur was present in all of the patients, and a diastolic murmur in 25%.


Presentation and course of asymptomatic primary biliary cirrhosis. Twenty patients without symptoms of hepatobiliary disease were diagnosed as having asymptomatic primary biliary cirrhosis. In every patient liver histology was diagnostic of, suggestive of, or compatible with the diagnosis. Eighteen had a positive serum mitochondrial antibody, 18 had raised serum immunoglobulin M, and 17 had markedly raised serum alkaline phosphatase values. A mean of 4.5 years after diagnosis, 10 of the patients had not developed hepatobiliary symtoms; 4 of these 10 patients have survived 6 to 10 years. Ten patients developed symptoms after a mean of 2.2 years from initial diagnosis; 7 are still alive but 3 have died of liver failure. The development of symptoms could not be predicted by either serum biochemical tests or hepatic histology. It is concluded that the diagnosis of asymptomatic primary biliary cirrhosis is compatible with 10 or more asymptomatic years.


Effect of D-penicillamine on copper retention in patients with primary billiary cirrhosis. As part of a double blind, randomized trial evaluating D-penicillamine in primary biliary cirrhosis, we monitored urinary copper excretion and hepatic copper concentration during the 1st year of therapy in 46 patients with this disease. The retention of copper in primary biliary cirrhosis was confirmed by finding abnormally high levels of standard copper measurements in almost all patients before treatment. The hepatic copper was elevated in 43 of 45 patients, the urinary copper in 42 of 46, and the ceruloplasmin in 46 of 46. Urinary copper excretion correlated with the hepatic copper concentration (r = 0.68, P less than or equal to 0.001). No significant correlation occurred between hepatic copper and ceruloplasmin. Hepatic copper concentrations greater than 400 microng per g of dry weight were found almost exclusively in patients with advanced histological disease (P less than or equal to 0.01). Therapy with D-penicillamine and a low copper diet sustained increased urinary copper excretion for 1 year in almost all patients (P less than or equal to 0.001). Among patients taking placebo, the median hepatic copper concentration increased 13 microng per g of dry weight after 1 year. In contrast, among the patients taking D-penicillamine, the median hepatic copper concentration decreased 99 microng per g of dry weight (P less than or equal to 0.02). Continued observation of this therapeutic trial may help to clarify the relationship of copper retention and liver injury in primary biliary cirrhosis.


Effect of phenobarbital on biliary lipid metabolism in normal man. The efficacy of phenobarbital in altering biliary lipid composition in normal man was investigated by determining parameters of biliary lipid metabolism in 8 human subjects without biliary tract disease before and after oral phenobarbital administration at a dose of approximately 3 mg per kg per day for 25 to 54 days. In 8 subjects studied, phenobarbital did not produce any statistically significant changes in the following parameters: bile lipid composition, cholesterol saturation index, total bile acid pool size, daily fractional turnover rate of cholic acid, hepatic secretion rates of cholesterol, bile acids, or phospholipids, and the fraction of the total bile acid pool represented by individual bile acids. Therefore, phenobarbital is not an effective agent, at least when used alone, in inducing changes in bile lipid composition during a short term of administration in normal man. This would indicate that phenobarbital would not be a useful modality in the prevention of the development of cholesterol gallstones, but its prophylactic value in subjects with bile of higher lithogenicity cannot be predicted from these studies.


Biliary secretion of copper in healthy man. Quantitation by an intestinal perfusion technique. A duodenal perfusion technique which permitted a normal daytime eating pattern of three liquid meals and an overnight fast was used to measure the 24-hr output of copper in bile in 19 studies in 14 persons with normal hepatic and gallbladder function. Daily biliary output was also determined by direct measurement on four 24-hr bile collections obtained from 3 patients with complete biliary diversion, and in 4 patients measurements of dietary copper intake and fecal copper output were also made. A mean bile copper output of 25 +/- 13 microng per kg-day (1.7 mg +/- 0.8) (mean +/- SD) was obtained in 19 perfusion studies; the range was 9.0 to 53.0 microng per kg-day. The values in the 24-hr bile collections were similiar to those obtained using the perfusion method. Biliary copper output was similar during the day and night, and there was no correlation between hourly rates of copper output and hourly rates of bile acid output, nor was there any correlation between daily copper output and daily bile acid output. The similar values for dietary intake, biliary output, and fecal output provide additional support for the current view that in healthy man copper balance is maintained by biliary secretion and subsequent fecal excretion of copper which has been absorbed in the stomach and proximal duodenum.


Upper gastrointestinal fiberoptic endoscopy in pediatric patients. One hundred and forty-two pediatric patients between age 1 month and 20 years had 163 endoscopic procedures. Of 66 with chronic abdominal pain, 21 had a source identified endoscopically that was seen in only 15 by esophagogram and upper gastrointestinal series. Of 31 with nausea, vomiting, dysphagia, and/or odynophagia and retrosternal pain, endoscopy demonstrated the source in 19 patients and radiographic studies in 14. Of 34 with hematemesis and/or melena, 26 had a bleeding site identified endoscopically but only 4 of 28 had an identified source by radiographic studies. Duodenal and gastric ulcers and hemorrhagic gastritis were the commonest cases of upper gastrointestinal bleeding and organically of chronic adbominal pain. Functional abdominal pain was the commonest cause of chronic abdominal pain in those endoscoped. Foreign bodies were removed from the esophagus and stomach of 6 patients and dislodged in 2 others. Caustic ingestion was recognized in the esophagus and stomach of 2 patients who did not have mouth burns. The GIF-P2-prototype with four-way tip control and ability to retroflex 180 degree up, 60 degree down, and 100 degree right and left was superior to GIF-P1 and CF-P-prototype for visualization of the entire esophagus, stomach, duodenal bulb, and postbulbar area in patients less than 10 years old. Visualization of the duodenal bulb was possible in 28 of 29 pediatric patients, and of the postbulbar area in 25 of 26 in whom it was attempted. Infants who weighed as little as 3 to 5 kg were successfully examined. Retroflexion was possible in 29 of 30 to see the fundus and cardioesophageal junction. Patients older than 10 years were better examined with the GIF-D because of its increased ability to transmit light. Sedation for the school-age child with 0.5 to 1.0 mg per kg of diazepam and 1 to 2 mg per kg of meperidine given intravenously provides excellent sedation in most instances. General anesthesia is preferable for the preschooler and infant. Minor complications occurred in 2 patients who received less than adequate sedation and in 1 patient with general anesthesia.


Intestinal lactase deficiency in Ceylon (Sri Lanka). Lactose tolerance tests (LTT) in 200 normal adult Ceylonese have shown that 145 (72.5%) had a flat LTT, indicating a population prevalence of lactase deficiency of 66.2 to 78.8%. Jejunal lactase estimations in a smaller sample (41) confirmed this. Twelve of 55 subjects (21.8%) with a normal LTT had intestinal symptoms after lactose and intestinal lactase was low in most of them. It is suggested that little lactase is required to elevate the blood sugar but that more may be required to prevent diarrhea. On the other hand, 65.5% had no symptoms despite a flat LTT, and the possible reasons for this are considered.


Influence of amylase assay technique on renal clearance of amylase-creatinine ratio. The influence of amylase assay technique on the renal amylase/creatinine clearance measurement was determined by analysis of serum and urine specimens obtained from 10 normal subjects. CAm/CCr averaged 2.19 +/- 0.18% with a saccharogenic technique, 1.52 +/- 0.2% with an iodometric technique, and 0.80 +/- 0.08% with a chromogenic technique. Each of these values differed significantly (P less than 0.05) from the other two. Recovery studies were carried out by adding partially purified human salivary or pancreatic amylase to human newborn serum or urine (which contain minimal endogenous amylase). Equal amylase activity was recovered from serum and urine by the saccharogenic technique whereas recovery from urine was less than 50% of that from serum using the iodometric and chromogenic techniques. The accuracy of the chromogenic technique is markedly improved by the addition of albumin to the urine assay system. Although it appears that only the saccharogenic method provides an accurate estimate of CAm/CCr, each assay technique distinguished the elevated CAm/CCr of patients with pancreatitis from the normal range established for that technique. Accurate clinical interpretation of CAm/CCr measurment requires knowledge of the amylase assay technique used.


Increased serum gastrin concentrations and gastric acid hyposecretion in the immediate newborn period. Thirty-two infants and their mothers were studied to determine the source of elevated serum gastrin concentrations in umbilical blood and to learn whether neonates hypersecreted acid in response to hypergastrinemia. Gastrin concentrations in the umbilical artery and vein were similar. Both were significantly higher than maternal gastrin concentrations. No significant amount of gastrin could be measured in placental extracts. These results suggest that the increased neonatal gastrin concentrations were fetal in origin. Continuous basal acid secretory studies done for 4 hr in 32 infants and for 8 hr in 9 infants demonstrated hyposecretion of gastric acid for the first 5 hr of life. Acid secretion from hour 6 to 8 was similar to that in older children. Increased gastrin levels were still present at hour 8 and were associated with normal gastric acid secretion.


Human rectal mucosa: proctoscopic and morphological changes caused by laxatives. To determine whether laxatives alter the proctoscopic and morphological appearances of the human rectum, 10 normal subjects were studied prospectively, and the following manipulations were assessed in a randomized, blinded manner: no treatment; oral mannitol to induce diarrhea; isotonic saline enema; Fleet's Phospho-Soda enema; and bisacodyl (Dulcolax), 10 mg, by enema or suppository. The rectal mucosa after mannitol-induced diarrhea, or after saline enema could not be distinguished from untreated rectum by proctoscopy, light microscopy, or scanning electron microscopy. Fleet's enema, and bisacodyl invariably changed proctoscopic appearances, and frequently altered light and scanning microscopic aspects. Both Fleet's enema and bisacodyl caused sloughing of surface epithelium. In addition, bisacodyl decreased the uptake of hematoxylin and eosin by crypt epithelial cells so that the affected cells had a partially erased appearance (16 of 25 biopsies examined by light microscopy). The lamina propria of 3 of these 25 biopsies contained polymorphonuclear cells. Transmission electron microscopy revealed that the abnormal crypt epithelial cells contained fewer cytoplasmic organelles and less nuclear chromatin. All lesions resolved within 7 days. Fleet's enema and bisacodyl by rectum may mislead the proctologist and the pathologist by altering normal rectal mucosa.


Acute and chronic effects of ethanol on fluid transport in the human small intestine. The effect of acute and chronic administration of ethanol on jejunal and ileal water and electrolyte transport was studied in healthy volunteers by the triple lumen intestinal perfusion technique. The acute perfusion of a glucose-free electrolyte solution containing 2 to 10 g per 100 ml of ethanol in the jejunum or ileum did not cause any significant alterations of sodium or water transport. In contrast, the administration of a folate-deficient diet and ethanol for 2 weeks produced a marked reduction in sodium and water absorption or a small net secretion (control, mean +/-SE: H2O = 0.91 +/- 0.06 ml per min, Na = 130 +/- 8 micronEq per min per 30 cm of intestine versus H2O = -0.13 +/- 0.14 ml per min, Na = -20 +/- 29 micronEq per min per 30 cm, P less than 0.001). These changes were not accompanied by a reduction in serum folate levels. The administration of ethanol with a folate-supplemented diet also produced significant but less pronounced changes in sodium and water transport control: H2O = 1.33 +/- 0.2 ml per min, Na = 185 +/- 34 micronEq per min per 30 cm of intestine versus H2O = 0.48 +/- 0.17 ml per min, Na =65 +/- 16 micronEq per min per 30 cm of intestine, P less than 0.05). From this study it appears that the diarrhea seen in chronic alcoholics can be explained in part by the effect of ethanol on intestinal sodium transport, without any accompanying changes in serum folate levels.


The continent ileal pouch: absorptive and motor features. In 8 patients, 6 to 40 months after proctocolectomy and construction of a continent ileal pouch, selected absorptive and motor functions of the pouch were assessed. Test solutions of 100 or 200 ml, containing a nonabsorbable marker, were placed in the pouch and sampled serially for 1 hr; an oro-intestinal tube was used to prevent contamination of the pouch by endogenous secretions. Sodium, chloride, and water were absorbed in a fashion similar to that reported previously for normal ileum. Similarly, the resting mucosal potential difference and its response to glucose were like those of normal ileum. The pouch also absorbed vitamin B12 that was instilled together with intrinsic factor. The distribution of primary and secondary bile acids in duodenal content suggested that decreased dehydroxylation of bile acids, also seen after conventional ileostomines, occurs in pouch patients. The pattern of motility in pouches was consistent with that reported previously for normal ileum. Thus, the functions of the mucosa and smooth muscle of the continent ileal pouch are quite similar to those of normal ileum.


Purification of hog gastric intrinsic factor by a simple two-step procedure based on affinity chromatography and a selective guanidine hydrochloride gradient. Monocarboxylic acid derivaties of vitamin B12 were covalently coupled to 1,6-hexanediamine-substituted Sepharose by using a water-soluble carbodiimide resulting in 1.32 micronmoles of B12 coupled per ml of Sepharose. After a source of crude hog intrinsic factor (IF) was passed over the column, a selective linear gradient of guanidine HC1 (0 to 4.0 M) was used to remove IF and 4.0 to 7.5 M to elute NIF (a vitamin B12-binding glycoprotein not active in promoting vitamin B12 absorption). Anti-IF antibodies blocked 99% of the B12 binding by the isolated IF and only 1% of the B12 binding by NIF. Passage over a hydroxyapatite column resulted in IF 99% pure with a specific activity of 29.8 microng of B12 binding per mg of protein. IF so isolated exhibited one homogeneous band on polyacrylamide gel electrophoresis and corrected B12 malabsorption in a patient with pernicious anemia.


Eosinophilic gastroenteritis with esophageal involvement. A patient with a lifelong history of asthma and hay fever was investigated because of symptoms of esophageal spasm. Esophageal biopsies revealed elongated papillae and basal zone hyperplasia of the epithelial layer with eosinophilic infiltration of the lamina propria and muscularis mucosae. There was no evidence of reflux. Small bowel biopsies revealed a flat mucosal pattern with absent or blunted villi, tall columar surface epithelium, and eosinophilic infiltration of the lamina propria. He did not respond to a gluten-free diet. This patient is thought to have eosinophilic gatroenteritis with esophageal involvement, the first such case reported.


[Ultrasonics of ovarian changes under gonadotrophine stimulation (author's transl)]. It is known that there are difficulties in timing of ovulation induction under gonadotrophines. The reason is that investigation parameters used so far only permit indirect quantitative statements. Ultrasonics permit the direct presentation of ovaries, cystic structure-follicles, registration of their number and size as well as control of the further development. Using an typical case, possibilities with ultrasonics are demonstrated. Ovulation was induced when one follicle (0 23 mm) dominated over two others (0 17 mm), and a corpus-luteum-cyst and the pregnancy were observed. Two gestational-sacs perished during bleedings in the 9th week of pregnancy. The normal pregnancy was controlled with ultrasonics until delivery. Ultrasonic equipment was Vidoson 635 S by Siemens and Diasonograph NE 4102/B by Nuclear Enterprises.


[The optimal treatment of carcinoma in situ of the uterine cervix (author's transl)]. The results of treatment of carcinoma in situ of the uterine cervix in 380 patients seen between January 1, 1966 and December 31, 1973 are reported. There were 134 women age 40 or less. There were 246 patients age 40 or older. In 334 patients a total hysterectomy with removal of a vaginal cuff was carried out (87.9%). A large therapeutic cone biopsy was done in 46 patients (12.1%). In the 334 patients treated by hysterectomy, 2 recurrent carcinomas in situ of the vaginal vault were observed (0.6%). In 16 of the cases treated by conization later suspicious colposcopic and/or cytologic findings made hysterectomy necessary. In 5 of these cases a recurrent carcinoma in situ was likely. The postoperative morbidity after total hysterectomy was low. There was no postoperative death. The total vaginal hysterectomy with removal of a vaginal cuff is recommended as treatment for carcinoma in situ of the uterine cervix in order to avoid the diagnostic difficulties in the follow-up after treatment by conization and because of the low recurrence rate after hysterectomy. Conservative treatment should only be employed in patients who desire later child bearing. tthe psychological stresses of the continually required follow-up examinations after conization should not be underestimated.


[Placental metastases from a maternal angioblastic sarcoma of the vagina (author's transl)]. Metastasizing maternal tumors during pregnancy with spread to the placenta are spontaneous attempts of malignant tumor transplantation to the Fetus. Because of the resistance of the Syncytiotrophoblast to metastases, carcinomas do not appear to transgress the placental barrier wheras malignant melanomas and sarcomas may do so in some cases. In the described case of maternal angioblastic sarcoma the lack of resistance to tumor spread of the epithelial trophoblast was compensated by resistance of the fetal stroma of the chorionic villi against invasive spread of the tumor. The infant was delivered by Caesarean Section and showed no evidence of a malignant tumor acquired by transplacental spread at the age of 2 1/2 months.


[The diagnosis and removal of obscure intrauterine devices (author's transl)]. When the thread of an intrauterine device cannot be seen in the cervical canal a diagnostic procedure to insure continued contraceptive effectiveness is mandatory. Hysteroscopy is the method of choice for localization of an intrauterine device even during pregnancy. Hysteroscopic removal is possible even during pregnancy. With this method we removed 16 obscure intrauterine devices and 7 devices during pregnancy. The advantages and disadvantages of other diagnostic and therapeutic methods are discussed.


[Microcalcifications in squamous cell carcinoma of the cervix (author's transl)]. The findings presented indicate that localized calcifications can sometimes develop within squamous cell carcinoma of the cervix. Apparently, these deposits develop via calcium salt loading from epithelial necrosis within the cell complexes of the tumor. This means that, with microcalcifications in a metastasis of a squamous cell carcinoma, the pathologist evaluating biopsies should also consider the possibility of metastases of a tumor from the area of the cervix.


[Quantitative IgM-testing and prenatal rubella infection (author's transl)]. Cord blood of 686 newborns was tested for IgM-levels in connection with an epidemic occurrance of rubella infection in Bonn and its vicinity. In 17 samples IgM was higher than 30 mg/100 ml and in 102 samples higher than 20 mg/100 ml. In 121 cases the cord blood was examined for rubella antibodies and in 85 children it was also checked for the persistence of rubella antibodies at the end of the first six months of life. No unexpected prenatal rubella infection was found. Two children of this group had clinical and serological criteria for rubella embryopathy at birth. In addition 39 cases of verified rubella infections during pregnancy were investigated. In 13 cases abortion was performed during the first trimenon following a rubella infection; the presence of rubella virus embryotic tissue could be proven in 9 cases. A prenatal rubella infection became apparent by illness of the mother during the pregnancy and/or embryopathy of the newborn in 26 children. In 16 of these children prenatal rubella infection was confirmed by the detection of rubella specific IgM which was associated in all instances with elevated levels of IgM, and/or the persistence of rubella antibodies after the sixth month of life. The remaining 10 children had neither clinical nor serological signs. The mothers of 9 of these children had been ill after the 16th week of pregnancy. In at least 21 cases (81%) of 26 maternal rubella infections during the first trimenon of pregnancy the virus passed the placenta. In 13 cases the pregnancy was interrupted; of the remaining 13, 6 children (46%) had embryopathy.


[On the optimal clarification of suspicous findings on the cervix uteri (author's transl)]. In the period 1972--1975 432 conizations were performed. 76,6% of all patients were dismissed healed after conization without necessity of hysterectomy; the duration of stay in hospital after operation was in uncomplicated cases 7,9 days, in complicated cases 9,9 days. In 13,9% complications were registered, mainly bleedings (10,9%). In more than half of the cases with not totaly removed carcinoma in situ the uterus showed rests of the malignant lesion. That indicates that in such situations a hysterectomy should be done in every case. If there was a suspicion of invasive carcinoma an excochleation was performed instead of cone biopsy. The high rate of false negative results in such cases confirms that the conization at the moment seems to be the method of choice in clarification of positive cytologic or colposcopic findings.