Comparative follow-up study of conservative and surgical treatment of femoral shaft fractures in children. The guiding principles of treatment of femoral shaft fractures in children are discussed. Up to the age of six years a Bryant or Weber bandage was used. In older children surgical treatment was preferred. The indications are outlined. Between 1959 and 1974 100 children with femoral shaft fractures were treated in the Maasziekenhuis, 21 percent received surgical treatment. In 92 cases follow-up was possible. For detection of changes X-ray examination is preferred. Significant deformities were not found. An increase in length by more than one centimeter of the fractured femur was seen in 22 percent of cases after conservative treatment, in 53.8 percent of cases after treatment with a medullary pin and in 16.6 percent after treatment with an AO-pressure plate. For surgical treatment of femoral shaft fractures in children the AO-plate appears to be preferable.


An unusual scapular fracture.

An unusual scapular fracture. This paper describes a fracture of the scapula, extending around the coracoid process and through the glenoid cavity. No humeral subluxation developed in this case. The diagnosis, complications and treatment of scapular fractures are discussed with reference to data from the literature.


Costochondritis of the costal arch.

Costochondritis of the costal arch. Costochondritis is a rare and symptom-poor affliction which often remains unrecognized for a long time. The diagnosis depends upon the patient's history and the physician's acquaintance with the disease. Body temperature, X-ray examination including sinography, WBC count and bacterial examination may be non-informative. Local resection of the affected cartilage, excochleation, cauterisation, irrigation and antibiotic treatment most often lead only to recurrence of the ailment. The definitive treatment consists of total resection of one or both costal cartilaginous arches. The cases of two patients are described.


Photoallergic urticaria induced by visible light. Additional cases and further studies. Four patients with solar urticaria induced by visible light developed an urticarial wheal at the site of injection of their own serum, which previously had been exposed to light in vitro. The in vitro-irradiated patients' sera did not produce the urticarial response in normal control subjects. Direct passive transfer studies with the patients' sera yeilded positive results, while reverse passive transfer studies showed negative results. Based on the experimental data, the patients' conditions might be induced by an allergic mechanism in which a circulating photoallergen appears to be an etiologic factor. One of the patients demonstrated an urticarial reaction at the site of injection of in vitro-irradiated normal serum as well as his own serum. The urticaria formation was blocked by intradermal injection of epinephrine but not by local injection of antihistamines. The repeated exposures to light had a beneficial effect on wheal formation in all cases.


Fate of pemphigus antibody following successful therapy. Preliminary evaluation of pemphigus antibody determinations to regulate therapy. Six of 17 pemphigus patients (35%) treated during a six-year period with immunosuppressive agents and/or corticosteroids have had prolonged clinical and immunologic remissions off all therapy. All were treated until serum and tissue bound pemphigus antibodies could no longer be detected. The length of remission has ranged from 1 1/2 years to 4 years. Three of these six patients relapsed after being clinically and serologically free of pemphigus for 19, 20, and 48 months. Seven additional patients are clinically free of disease with insignificant pemphigus antibody titers of 10 or less. Therapy now is being discontinued gradually in these patients. This preliminary study demonstrates that (1) a large percentage of pemphigus patients may have a prolonged clinical and immunological remission after successful therapy; (2) maintenance therapy may not be required to preserve the remission; (3) monitoring serum and in vivo bound pemphigus antibody is of value in regulating therapy in pemphigus patients.


Treatment of keratoacanthomas with intralesional fluorouracil. Fourteen patients with 26 keratoacanthomas (KA) were treated weekly with intralesional injections of fluorouracil. Twenty-five lesions cleared in an average of three weeks (range, two to eight weeks) after an average of 2.8 injections. One KA failed to respond after five weekly injections and was excised. No recurrences or meaningful side effects were observed. It appears that treatment of KA with intralesional fluorouracil injections is a safe, effective, and convenient mode ot treatment yielding excellent cosmetic results.


Cutaneous plasmacytomas in myeloma. Relationship to tumor cell burden. Solitary cutaneous plasmacytomas may occur as benign tumors that are confined to the skin, whereas multiple lesions are generally associated with systemic plasma cell disease. Cutaneous plasmacytomas developed in two patients with documented multiple myeloma; this development occurred late in the course of their disease at a time when their systemic plasma cell tumor burden was large-approximately 3 kg in mass, which represented 2 to 3 x 10(12) cells. The occurrence of cutaneous plasmacytomas in patients with multiple myeloma is generally late in the course of the disease and should be considered as a bad prognostic sign.


Generalized pustular psoriasis precipitated by lithium carbonate. Precipitation of generalized pustular psoriasis was manifested in a patient with previously stable psoriasis vulgaris following lithium carbonate therapy for manic-depressive psychosis. Methotrexate toxicity was observed during the acute stage of the illness, and photochemotherapy was the successful treatment. Further pustulation occurred when lithium carbonate therapy was reintroduced.


Delayed cutaneous reaction to phytonadione. A 63-year old man developed a delayed cutaneous reaction at the sites of intramuscular injections of a phytonadione (vitamin K) preparation. The patient was tested with the drug and its components by intradermal and epicutaneous application. Sensitivity to the pure phytonadione and not the other components of the preparation was documented by patch tests.


Cornoid lamella in pachyonychia congenita. A 13-year-old white girl was admitted with pachyonychia congenita, Kumer and Loos type 1. In addition to all nails being distally elevated, plantar keratoses and bullae, and a scalloped tongue, the patient also had keratotic papules on the elbows and knees. A cornoid lamella was identified in the histologic examination of keratotic papule. The cornoid lamella, widely regarded as pathognomonic for porokeratosis (Mibeli) and its variants, may not be specific. This histologic marker should be sought in other localized disorders of keratinization.


Allergic contact dermatitis to 1,4-bis(isopropylamino)anthraquinone. Caused by a felt-tip marker pen. Adult allergic contact dermatitis to the black ink of a felt-tip marker pen occurred in two adult subjects. In both subjects the cutaneous reaction did not require photoactivation. Patch testing with the ingredients in the black ink demonstrated cutaneous sensitivity to the black dye. Further patch testing with the components of the black dye revealed cutaneous sensitivity in both subjects to the blue component, 1,4-bis(isopropylamino)anthraquinone, commonly known as Colour Index Solvent Blue 36.


Failure of flat warts to recur in electrosurgically altered skin. Two men with recurring flat warts in the beard area have been observed for five and ten years, respectively. Both have depigmented patches at sites where flat warts had been removed by electrosurgical destruction. Crops of new warts appear periodically. These develop always on the normally pigmented skin and have never been found in the leukodermic areas. Flat warts have been observed repeatedly at the margin of depigmented and normal skin; these invariably enlarge toward the normal skin and never encroach on leukodermic skin. The failure of flat warts to develop in electrosurgically treated skin, if substantiated, would indicate that local tissue factors influence resistance to development of flat warts. Perhaps this phenomenon is similar to that reported in Darier's disease, where partial-thickness excision of involved skin has resulted in  resistance to recurrent disease.


Progressive interstitial lung disease from prolonged methotrexate therapy. Progressive interstitial fibrosis with roentgenographic honeycombing developed in the case of a psoriatic patient who had been on a regimen of methotrexate for 18 years. Examination revealed a combined restrictive and obstructive defect in pulmonary mechanics and severe compromise of gas transfer across the pulmonary alveolar-capillary membrane. Improvement in the level of arterial blood gases and pulmonary diffusing capacity occurred after discontinuation of methotrexate therapy. Interstitial fibrosis of the lung is a potential complication of methotrexate therapy for psoriasis.


Stimulation of lymphocytes in patients with psoriasis under photochemotherapy. A study of lymphocyte transformation. Lymphocyte-transformation by phytohaemagglutinine (PHA) was examined in 21 patients with generalized psoriasis during photochemotherapy (PUVA). Lymphocyte-transformation-tests (LTT) were performed before and after 8-methoxypsoralen (8-MOP) medication, before and after the initial irradiation and before and after the first maintenance irradiation four to six weeks later. Spontaneous and PHA-induced lymphocyte-transformation was not altered by 8-MOP alone or in combination with UVA irradiation.


[Electron microscopic investigation on cutaneous leiomyosarcoma (author's transl)]. A 61-year old woman developed a tumourous nodule in her left leg. Fifteen years ago a similar tumour had been removed in the same localization. Histological examination performed on biopsy material showed bundles of predominantly fusiform tumour cells with nuclear pleomorphism and many mitotic figures. Electron microscopic examination confirmed the diagnosis of leiomyosarcoma by demonstration of the ultrastructural characteristics of smooth muscle cells. Cellular differentiation showed various degree ranging from smooth muscle cell type to dedifferentiated edematous tumour cells with scanty myofilaments. An important finding was the demonstration of multiple accumulated centrioles.


Aminoterminal extension peptides from type I procollagen normalize excessive collagen synthesis of scleroderma fibroblasts. Fibroblasts derived from a skin biopsy of a patient with scleroderma in the sclerotic stage were shown to have a higher rate of DNA synthesis, and to synthesize more collagen than fibroblasts from a healthy control. The addition of procollagen peptides to the culture medium of scleroderma fibroblasts almost normalized the collagen synthesis. This observation indicates that the mechanism for the regulation of collagen synthesis by feed back inhibition of prollagen peptides is functioning in this disease. It is suggested that the level of biologically active procollagen peptides is lowered.


Photoprotective effect of a psoralen-UVA-induced tan. To determine whether a tan produced by 8-MOP and UVA protects from subsequent solar light irradiation, volunteers were irradiated with unfiltered Xenon arc light before and 10 days after a 1 week's course of four 8-MOP-UVA treatments. Evaluation of the minimal erythema doses and of histological changes before and after 8-MOP-UVA treatment revealed that the 8-MOP-UVA induced tan protected against the erythemogenic and cell damaging effects of Xenon arc light. Unscheduled repair DNA synthesis, used as a measure for UVB-induced DNA damage and repair, was also investigated in skin irradiated with the Xenon arc before and after 8-MOP-UVA induced tanning. Both the number of grains per sparse labeled cell and the number of sparse labeled cells per 1000 cells, were found to be significantly lower in tanned skin; taking decreased unschedules repair DNA synthesis as a measure for decreased DNA-damage, these findings also demonstrate a photoprotective effect of the 8--MOP-UVA induced tan.


[Hexachlorbenzene (HCB) induced porphyria in rats. Influence of HCB-metabolites on the biosynthesis of heme (author's transl)]. Female adult Wistar rats were fed with a diet containing 0.05% hexachlorobenzene (HCB) or its metabolites, pentachlorobenzene (PCB) and pentachlorphenole (PCP). These chlorinated aromatic hydrocarbons produced an increase in the liver cytochrome P-450 content in about the same degree, however, only the application of HCB showed an extremely high rise in the P-450 enzymatic activity expressed in terms of the O-dealkylation of 7-Ethoxycoumarine. No alteration was observed in the urinary porphyrin excretion in the PCB and PCP treated animals, whereas 60 days after the beginning of the HCB application a high level of porphyrins could be detected in the urine of the animals. It seems unlikely therefore that the HCB metabolites (PCB and PCP) are porphyrogenic agents. In addition, although induction of the liver cytochrome P-450 system was observed after PCP pretreatment of the rats over a period of 40 days, the consequent application of HCB did not influence the establishment of the experimental porphyria.


[HLA antigen frequencies in patients with progressive systemic sclerosis and morphea (author's transl)]. Forty three patients with progressive systemic sclerosis and 24 patients with morphea are typed for 30 antigens of the HLA-A and B series. There is an increase of the frequency of HLA-B8 in patients with progressive systemic sclerosis (37% vs. 20% in controls: P less than 0.001, Pcorr. = n.s.). The increase of the HLA-B8 frequency seems to be most pronounced in patients with a diffuse form of progressive systemic sclerosis. 4 out of 5 patients are HLA-B8 positive (P = 0.00672). In patients with acrosclerosis is HLA-B8 only slightly increased (32%), but the increase is greater in male patients (44%) and in patients with an early onset of the disease (36%). With the exception of HLA-A1 there is no deviation of the frequencies of any other HLA antigen tested, especially not of HLA-Aw24. The number of patients with morphea is to small for statistical evaluation.


Collagen metabolism in granulating wounds of rat skin. Collagen metabolism in granulating wounds of rat skin was studied with biochemical, isotopic and electron microscopical methods. Deposition of collagen in rat skin wounds was not only the result of an increase in collagen synthesis but it was also caused by a decrease in collagen degradation. Our investigations showed significant differences in the collagen turnover at different times of wound healing. Decreased collagen catabolism at the early stages of wound healing contributed decisively to collagen accumulation in the wound area. At later stages, during wound contraction and remodelling of the scar, the rate of collagen degradation rose. The above-mentioned results are discussed in the context of general criteria of scar formation.


Long-term NO2 exposure of mice in the presence and absence of vitamin E. I. Effect on body weights and lipofuscin pigments. Mice on diets deficient in vitamin E, normal diets, diets with high supplements of vitamin E, and diets supplemented with N, N'-diphenyl-p-phenylenediamine (DPPD) were continuously exposed to 0.5 ppm or to 1.0 ppm nitrogen dioxide (NO2) or to filtered room air from weaning to 18 months of age. The effects of NO2 exposure on body weights, tissue weights, survival rates, and tissue organic solvent soluble lipofuscin (age) pigment concentrations were examined. Vitamin E deficiency resulted in lower body weights by 18 months of age; exposure to NO2 further increased this weight loss. With the exception of the kidney, tissue weights were not affected by NO2 exposure. Mice exposed to NO2 had lower survival rates than unexposed control animals. Tissue organic solvent soluble lipofuscin pigment (LFP) concentrations in the uterus, lung, spleen, kidney, liver, brain, and heart were not afffected by NO2 exposure. Only in the liver did vitamin E deficiency lead to an increase in LFP concentration; it did not occur in any of the other tissues examined.


Long-term NO2 exposure of mice in the presence and absence of vitamin E. II. Effect of glutathione peroxidase. One hundred and twenty female mice fed diets containing various levels of vitamin E were continuously exposed to 0.5 ppm, 1.0 ppm nitrogen dioxide (NO2), and filtered air for 17 months. Blood, lung, and liver tissues were assayed for glutathione peroxidase (GSH-peroxidase) activity. Exposure to 0.5 ppm NO2 did not affect blood and lung GSH-peroxidase activity; 1.0 ppm NO2 exposure, however, caused suppression of the enzyme. A combination of vitamin E deficiency and 1.0 ppm NO2 exposure resulted in the lowest GSH-peroxidase activities in the blood and lung. High levels of vitamin E in the diet resulted in elevated GSH-peroxidase in the blood and lung. Liver GSH-peroxidase activity was unaffected by either dietary vitamin E or NO2 exposure. No inverse relationship was found between GSH-peroxidase levels and concentrations of organic solvent soluble lipofuscin pigments present in tissues.


Increased blood lead levels in mentally retarded children in Greece. In 60 children with mental retardation of unknown etiology, the whole blood lead, as well as the activity of the red cell delta-aminolevulinic acid dehydratase (delta-ALAD), was measured. Thirty normal children and 30 with mental retardation of known etiology were used as controls. The lead values were found significantly higher in the study patients compared with both control groups  (P less than 0.001). The delta-ALAD activity in the 14 patients with blood lead levels greater than or equal to 40 microgram/dl, was significantly reduced compared with the normal controls (P less than 0.001) and the mentally retarded controls (P less than 0.01). In more than 20% of the patients with mental retardation of unknown etiology, indications of significant exposure to lead were found. There was no difference in blood lead values between children from cities and those from rural areas. The possible role of lead in the etiology of mental retardation is discussed.


Urinary delta-aminolevulinic acid as a biological indicator throughout penicillamine therapy in lead intoxication. A group of 121 patients with occupational lead exposure was studied. Saturnism was confirmed in 42 of them. Patients were given D-penicillamine in doses of 0.75 and 1.5 g/day. Urinary delta-aminolevulinic acid was selected as a toxicity biological indicator; its concentrations were quantified daily during therapy. Urinary delta-aminolevulinic acid is considered a good biological indicator throughout penicillamine therapy and also in the detection of lead intoxication. Likewise, the chelating test is considered an excellent method to confirm the diagnosis of lead poisoning.


Log normal distribution of ovarian and placental steroid values in early human pregnancy. Concentrations of estradiol, progesterone, 17OH-progesterone were measured by radioimmunoassay in individual serum samples obtained from a group of 304 women with normal gestations between the 4th and 17th week of pregnancy. Values obtained underwent statistical analysis in order to determine the arithmetic mean and the 95% normal range (+/- two standard deviations). It was noted hereby that the spread of values above the mean was greater than that below the mean, and that very often the mean minus two standard deviations was either close to zero or negative. Therefore, the data for each hormone were analyzed for normality of the distributions by the chi-square test. For each hormone the chi-square test was significantly different (p less than 0.001) from the normal distribution (Gaussian). Subsequently, linear transformation by rankit analysis revealed the log-normal distribution of our data. Furthermore, rankit analysis was used as a graphical method to delineate a useful clinical range, which includes the mean and meaningful 95% confidence limits for estradiol, progesterone, and 17OH-progesterone in early normal pregnancies.


Occupational cancer in men exposed to dust and other environmental hazards. Data using a series of approximately 14,000 patients admitted to Roswell Park Memorial Institute for Cancer Research between 1956 and 1965 have been analyzed for occupations cancer risks. A detailed epidemiological schedule involving occupational history, smoking, drinking, and various other etiological factors was taken prior to interview. A mass screening of these data for about 20 different sites of cancer and 50 suspect occupations was conducted, using age-adjusted relative risks. A number of relationships was found between particular occupations and cancers. This report gives a survey of these relationships for men in a subset of the occupations screened, i.e., those occupations where exposure to dust would be suspected. Unlike most previous occupational studies, this one has a broad focus on a set of occupations and cancer sites rather than a narrow focus on one specific occupation or cancer site. This broader survey provides useful insights into the role of occupational hazards in the overall public health problem of cancer and is not a substitute for intensive investigation of specific occupation-site relationships (which cannot be done here). It can, however, provide guidance on which relationships are likely to be of public health significance, and what directions the deeper investigations might take. This kind of perspective is provided for the 22 occupation-cancer-site combinations where the age-adjusted relative risk is significant at the 5% probability level.


Experience with the split-thickness graft technique in congenital absence of the vagina. Between 1961 and 1977 vaginoplasty was performed in 24 patients at the Zurich University Hospital, Department of Gynecology, using the split-thickness graft technique; in 22 cases the result was functionally satisfactory. Based on their experience and previous reports the authors describe the surgical technique and the follow-up measures designed to ensure a functionally and anatomically optimal result.


Smoking patterns by occupation, industry, sex, and race. Patterns of prevalence, amount, and cessation of smoking are computed for occupations by socioeconomic class, sex, and race, based on a probability sample of 39,011 households collected by the 1970 Health Interview Survey. Smoking is most prevalent in blue-collar occupations, while a high proportion of professionals and managers who smoke, stop smoking. Within industries, substantially higher percentages of individuals smoke in lower prestige paying jobs, while more smokers quit in the higher prestige paying jobs. Smoking is most prevalent among women managers and professionals, and least among those employed in traditional work. One surprising and possibly very important finding is that white smokers smoke about 20% more cigarettes per day than black smokers. Not only would it seem unreasonable to ascribe the larger rate of lung disease among blacks than whites (especially cancer), to smoking when blacks smoke significantly fewer cigarettes than whites, but this same negative relationship points to occupational exposure as the possible major cause for lung cancer.


Morphological changes in the amniotic epithelium in relation to placental weight and fetal maturity. A series of 52 placentas from the 36th week of gestation up to post-maturity was studied. The amniotic epithelium was studied with special regard to the morphological signs of maturation known to occur during this period. The results of the dating were compared with the presumed clinical age of the pregnancy and with the placental weight. A good correlation was found in 42.3% of the cases; the clinical age was overscored in 17.3% and underestimated in 40.4% of the subjects. No clear correlation was found between placental weight and histologic dating of the amniotic epithelium. The significance of the lipid laden amnios cells is discussed.


Nitrogen dioxide inhalation and human blood biochemistry. Blood from ten young adult male humans, exposed to 1 ppm or 2 ppm nitrogen dioxide (NO2) for 2.5--3.0 hr, was examined for evidence of biochemical changes. The experiments lasted three days. The subjects entered an environmental chamber, performed mild exercise, and completed a series of measurements of pulmonary physiology while breathing filtered air. Blood samples were then taken and analyzed. This regimen was repeated on the second and third day, except that the chamber atmosphere now contained 1 ppm or 2 ppm NO2. Paired group analyses were performed on the data. A statistically significant decrease was observed in the activity of the erythrocyte membrane enzyme acetylcholinesterase at both NO2 levels. Levels of peroxidized red blood cell lipids showed statistically significant elevations after inhalation of 2 ppm NO2 but not 1 ppm. Glucose-6-phosphate dehydrogenase was significantly elevated only after the second 2-ppm NO2 exposure. Small but statistically significant decreases were observed in both hemoglobin and hematocrit values after exposure to both NO2 levels. The experiment was repeated with NO2, (i.e., three days of filtered air) to detect possible effects of the experimental procedure. Decreases were again seen in hemoglobin and hematocrit, and acetyecholinesterase, although of smaller magnitude than when NO2 was inhaled. Other data showed random variations that were not additive over the three-day sham exposure period. It was concluded that significant blood biochemical changes resulted from NO2 inhalation, although the three-day experimental regimen independently produced changes that account for some of the apparent response.


Effect of stress stimuli on glycogen level in the rat uterus. Effect of prolonged exercise, acute cold exposure, and 24-h fasting on the glycogen level in the uterus of rats spayed and than treated with peanut oil or estradiol was investigated. It has been found that exercise increases significantly though transitorily the glycogen level in the uterus of the oil-treated group. Cold exposure resulted in significant reduction of the uterine glycogen level only in the oil-treated group. Fasting did not change the glycogen level in the uterus in the both groups. Five hours of swimming and fasting decreased significantly the blood glucose level.


Mortality experience of arsenic-exposed workers. The mortality experience of all pensioners from a copper smelter who were aged 65 or over between 1949 and 1973 has been studied. An index of arsenic exposure was developed for all operations in the plant for 1973. This was applied to all individuals studied so that a comparative measure could be made of each individual's working-life exposure to arsenic. The overall mortality of this cohort was 12.2% higher than for males living in the same area, of the same ages, and in the same time periods. The excess mortality was due chiefly to respiratory cancer where mortality was three times the expected. Because other contaminants were present in the atmosphere, it is not certain that arsenic was entirely responsible for the respiratory cancer observed, yet a close association with arsenic seems highly likely.


[Erythrocyte alteration in long standing labor inhibition with a beta-sympathicomimetic drug (Partusisten) (author's transl)]. The relative flow rate of the red blood cells in a hematocrit of 10% was measured with a 5 mu nuclepore filter system. The influence of Partusisten was determined by the alteration of the red blood cells. The in vitro concentration of 0.1 ng Partusisten/ml blood resulted in a relative improvement of the flow rate, which we also found in normal pregnancies. However, in a vivo concentration of 4 microgram intravenous Partusisten/min for 48 h, the red cell alteration properties decreased. After a greater time interval, the red blood cells alteration was about the same as in the pre-drug level. The uteroplacental perfusion changed in dependence to the concentration of the beta-mimetic drug (Partusisten). The presence of rigid red blood cells can be first seen in the microcirculation impairment. Depending on the concentration of Partusisten, a protective effect on the flow properties of the red blood cells could be achieved, which altered during pregnancy. However, in late gestosis, a lower dosage should be administered than in labor inhibition.


[On the origin of islands and septa of the human placenta (author's transl)]. The maternal or foetal origin of septa and islands of the human placenta was examined by counting the sex chromatin in their nuclei (Barr bodies); the origin of the septa was, in addition, determined by counts of the Y-chromatin previously stained with quinacrine fluorescence. Histological investigations were made on preparations stained after Masson-Goldner (trichrom). The results showed that in most cases the upper parts of the septa are exclusively composed of trophoblastic cells, whereas the lower third is preponderantly composed of decidual elements. Purely trophoblastic septa are rare. Islands are trophoblastic. Islands in which both cell types are present, or decidual islands appear to be very rare.


Health of workers exposed to 1, 1, 1,-trichloroethane: a matched-pair study. An epidemiologic study of 151 matched pairs of employees was conducted in two adjacent textile plants, one of which used inhibited 1,1,1-trichloroethane as a general cleaning solvent. Employees in the study population had exposures to the solvent for 6 yrs or less at varying concentrations which were measured by breathing zone sampling and personal monitoring. While cardiovascular and hepatic observations were of primary interest, other health parameters were also studied. Application of sensitive statistical techniques and careful examination of all data did not reveal any clinically pertinent findings that were associated with exposure to 1,1,1-trichloroethane. The statistically significant associations that were observed between health measures and nonexposure factors emphasize the need to consider age, sex, race, and other variables in designing epidemiologic studies.


[The adenocarcinoma of the cervix: study of 81 cases (author's transl)]. The present study deals with 81 primary adenocarcinomas of the uterine cervix diagnosed and treated in the departement of gynecology and obstetrics of the University of Zürich from 1950 through 1977. Clinical and morphological data such as patients age, character and duration of symptoms, clinical and anatomical stage, histological differentiation of the tumor and therapy were recorded and analysed in relation to patients survival. Of all these factors the stage of the tumor at time of diagnosis proved to have the highest prognostic significance.


Hematological studies in induction of abortion by extra-amniotic administration of sulproston. The prostaglandin E2 derivative, Sulproston, was administered extra-amniotically for the induction of abortion in an average dosage of 200 microgram, in ten patients. With a success rate of 50%, the subjective side effects were very slight. Temperature, pulse rate, blood pressure and frequently of breathing did not change markedly. The ADP- and collagen-induced platelet aggregation showed a tendency to increase but disaggregation remained the same. Spontaneous platelet aggregation according to Breddin did not change. The parameters examined of the coagulation and fibrinolytic system showed only a slight increase in fibrinolytic activity during and after induction of abortion. The remaining hematological parameters showed no changes.


Effects of oral contraceptives on zinc and copper levels in human plasma and endometrium during the menstrual cycle. Effects of Ovulen-21, Demulen, Enovid-E and Ovral on zinc and copper levels in human plasma and endometrium during the menstrual cycle have been studied. Both plasma and endometrium copper levels were significantly elevated above the control values (P less than 0.001) in women taking oral contraceptives while the zinc levels remained reasonable constant.


[Specific glucocorticoid receptor activity in the lungs and concentration of corticosteroids in the plasma of newborn rabbits during the first hours of life (author's transl)]. Nine pure-bred albino New Zealand white rabbits were delivered on the 30th day of gestation (term 31 days) by Caesarean section. The concentration of dexamethasone binding receptors in the cytosol and nucleus of the lungs as well as the total plasma corticosteroid levels were measured in the newborns before the first breath, after 30 min, 1, 2, 4, 6 and 24 h after birth. The level of plasma corticosteroids increased after birth while the concentration of the receptors in the cytosol and nucleus decreased but was still present after 24 h as well as in the lungs of adult animals. A temporary increase in the concentration of the nuclear receptors after 1 and 2 h is explained by the translocation and binding of the abundantly produced steroid-receptor-complex to the nucleus. The stress of hypo- and hyperthermia on the newborns showed variable behaviour with respect to receptor activity. However, the relationship between the corticosteroid levels in the plasma and the concentrations of the receptors in the cytosol and the nucleus of the lungs was similar as in fetuses kept under "physiological" conditions. It may be concluded from these results that in the rabbit the specific glucocorticoid receptor activity in the lungs decreases after birth but is present throughout life.


[Cell mediated immunity in cervical cancer patients: evaluation by in vitro leukocyte-migration-inhibition-assay (author's transl)]. Cellular mediated immune reactions (CMI) against tumour associated antigens are the demonstration of an interrelationship between tumour and tumour host. They are related to the stage and prognosis of the disease. 41 patients with cervical cancer were tested by leukocyte-migration-inhibition test. Cryostat sections of 10 micron of the tumour-tissue, gained by excision or curettage and histologically defined, were taken as tumour antigens. The test was performed in Sykes-Moore-Chamber as so-called one-way-test with the lymphocytes/leukocytes and macrophagen of the tumour patient. Reactions against autologous and homologous tumour tissue and against recall antigens (tuberculin and varidase) were tested. There was no overall diminution of cellular mediated immune reactions. CMI was demonstrated in 69.7% (inhibition in 30.3%, stimulation in 39.4%) in the autologous and in 51.3% in the homologous system (21.6% inhibition, 29.7% stimulation).


[The so-called recanalisation of cotyledonary vessels with endangitis obliterans of placenta vessels (author's transl)]. With a graphic reconstruction on serial sections, performed with placentas which altogether showed so-called recanalisation, it is possible to work out the fact, that the recanalisation is an effect of the paravascular capillary network and with it to clarify the problem of the so-called recanalisation. It is proved, that the paravascular capillaries undertake compensatory hemodynamic functions and this undertaking of function prevents a complete occlusion of the cotyledonary vessels, so that you have to speak of restlumen and restflow but not of recanalisation. The endangitis obliterans of cotyledonary vessels is again unequivocally pointed out by this phenomenon as a intravital process.


[Comparative high rising dose study of oral 17-alpha-ethinylestradiol (EE2), estriol (E3), and parenteral 16-alpha-17-beta-estrioldihemisuccinate (E3-suc) in their effects on serum levels of glutamate transaminase (GOT), pyruvate transaminase (GPT), leucine amino peptidase (LAP), alkaline phosphatase (AP), and bilirubin in 30 hysterectomized and ovarectomized women (author's transl)]. 30 hysterectomized and ovarectomized women were treated with three different estrogens: EE2 orally, E3 orally, and E3-suc intramuscularly. Each patient received one substance over 5 days doubling the dose every consecutive day, and switching to another estrogen after a treatment free interval of 2 days, rising the dosage of the second preparation twofold every consecutive day over another 5 days. Thus, each patient served as her own control with respect to 2 of the 3 tested estrogens. Six groups were required to test all sequences possible. The patients were allocated by random. GOT, GPT, LAP, AP and bilirubin were estimated daily over 2 weeks. The starting dose of EE2 was 0.25 mg, of E3 2 mg, and of E3-suc 2.5 mg. There were marked elevations of all serum enzymes during the week of EE2 treatment. If EE2 was given in the first week, and either E3 or E3-suc in the second one there was a prompt fall of all enzyme levels in spite of the approximately tenfold higher dose of the latter two estrogens. There were only minor elevations of the enzymes after oral E3 and parenteral E3-suc in some subjects and no differences of response between these two estrogens. Bilirubin reacted with an overall rise in the majority of patients irrespective of the type of estrogen.


[Hormonal status of women after hysterectomy compared with controls (author's transl)]. Plasma-FSH, -LH, -Estradiol-17beta, and -Progesterone were determined weekly in women aged between 28 and 43 years who had been hysterectomized 5-10 years before. The endocrine parameters were compared with those of women with a normal cycle and two groups of premenopausal women, the one showing a fixed hypergonadotropic state, the other slightly elevated but still cyclic fluctuations of FSH and normal LH values. After hysterectomy, normal ovulatory cycles were found in all women of up to 40 years, in 75% of those between 41 and 45 years and in 50% of those beyond 46 years. The average age of women with fluctuating or fixed hypergonadotropism was 2 years less in the hysterectomiced group. Thus, a certain acceleration of ovarian insufficiency caused by hysterectomy cannot be denied.


Clinical correlates of resectability and survival in gastric carcinoma. The course of 201 patients with carcinoma of the stomach treated from 1962 through 1966 was followed with 97% determinacy for 10 years. The actual five year survival rate was 11%; the ten year rate was 7%. The mean duration of survival was 5.8 +/- 2.7 (S.D.) months. These results were similar to those reported for the period 1922-1926. Survival was strongly correlated with the surgeon's assessment after exploration. All patients alive after five years had operations thought to be curative, usually partial gastrectomies; the survival rate of this group was 24%. Gastroenterostomy was ineffectual palliation. Better results will require nonsurgical adjuncts, since the correlates of survival are those of minimally invasive cancer.


Management and survival of carcinoma of the colon: results of a national survey by the American College of Surgeons. Survey results of long- and short-term outcome audits of colon cancer in participating hospitals with cancer programs conducted during 1976-7 by the American College of Surgeons are presented. In the long-term audit of 38,621 cases reported by 327 hospitals in 46 states, the overall percentage of cases in localized stage (29.3%) is significantly lower than in the recent series from the National Cancer Institute. The observed survival was substantially lower than the survival rates published in recent smaller series; however, survival approaches the end results for the period 1967-1973. In the short-term audit, the analysis of 11,655 cases diagnosed in 1976 and reported by 491 hospitals from fifty states showed that while 41% of patients had symptoms for less than a month, only 29.5% were diagnosed in the localized stage. Surgery was the predominant treatment modality with an overall resectable rate of 83%. No difference was observed in the stage at diagnosis when the short-term audit (1976) was compared with that found in the long-term audit (1971). The results suggest that the early diagnosis of symptomatic patients may not always substantially improve the cure and survival rate. The screening of asymptomatic patients is suggested as the more promising approach to the substantial improvement of presently less than ideal end results.


The surgical management of acute occlusion of the superior mesenteric artery. A study of 103 cases of acute occlusion of the superior mesenteric artery is presented. The relation of site of occlusion to etiology, extent of infarction, and survival following resection and revascularization is described. Included is an analysis of the technical factors contributing to successful revascularization, the specific complications of revascularization, and the application of elective second look operations and angiographic techniques. The persistant high mortality (85% in this series) can probably be reduced but only by advances in these areas along with progress in the more general aspects of management of elderly patients with multiple system problems and failure.


A multifactorial analysis of melanoma: prognostic histopathological features comparing Clark's and Breslow's staging methods. A multifactorial analysis was used to identify the dominant prognostic variables affecting survival from a computerized data base of 339 melanoma patients treated at this institution during the past 17 years. Five of the 13 parameters examined simultaneously were found to independently influence five year survival rates: 1) pathological stage (I vs II, p = 0.0014), 2) lesion ulceration (present vs absent, p = 0.006), 3) surgical treatment (wide excision vs wide excision plus lymphadenectomy, p = 0.024), 4) melanoma thickness (p = 0.032), and 5) location (upper extremity vs lower extremity vs trunk vs head and neck, p = 0.038). Additional factors considered that had either indirect or no influence on survival rates were clinical stage of disease, age, sex, level of invasion, pigmentation, lymphocyte infiltration, growth pattern, and regression. Most of these latter variables derived their prognostic value from correlation with melanoma thickness, except sex which correlated with location (extremity lesions were more frequent on females, trunk lesions on males). This statistical analysis enabled us to derive a mathematical equation for predicting an individual patient's probability of five year survival. Three categories of risk were delineated by measuring tumor thickness (Breslow microstaging) in Stage I patients: 1) thin melanomas (<0.76 mm) were associated with localized disease and a 100% cure rate: 2) intermediate thickness melanomas (0.76-4.00 mm) had an increasing risk (up to 80%) of harboring regional and/or distant metastases and 3) thick melanomas (>/=4.00 mm) had a 80% risk of occult distant metastases at the time of initial presentation. The level of invasion (Clark's microstaging) correlated with survival, but was less predictive than measuring tumor thickness. Within each of Clark's Level II, III and IV groups, there were gradations of thickness with statistically different survival rates. Both microstaging methods (Breslow and Clark) were less predictive factors in patients with lymph node or distant metastases. Clinical trials evaluating alternative surgical treatments or adjunctive therapy modalities for melanoma patients should incorporate these parameters into their assessment, especially in Stage I (localized) disease where tumor thickness and the anatomical site of the primary melanoma are dominant prognostic factors.


Carotid endarterectomy: a follow-up study of the contralateral non-operated carotid artery. In a study of 103 patients surviving carotid endarterectomy, follow-up information was obtained from all patients over a period of time extending to four years. This was done so that better decisions could be made regarding recommendations for contralateral carotid surgery. In this follow-up study, only three patients had contralateral surgery. Three additional patients had events clearly in the territory supplied by the contralateral carotid artery, and no patient suffered a contralateral stroke. There were an additional four patients who suffered stroke in territory not supplied by the contralateral carotid artery. In addition, four patients experienced classical transient ischemic episodes referrable to the operated carotid artery and ten patients experienced nonclassical cerebral ischemia. Seven of the 103 patients died at times remote from the carotid surgery of nonstroke cause.


A new nonpenetrating ballistic injury.

A new nonpenetrating ballistic injury. A new, nonpenetrating ballistic injury mechanism involving individuals protected by soft body armor is described. Experimental studies using laboratory animals have demonstrated that despite stopping missile penetration, the heart, liver, spleen, and spinal cord are vulnerable to injury. The rapid jolting force of an impacting bullet is contrasted with the usually encountered mechanisms producing blunt trauma injury. The experimental methodology used to assess a 20% increase in survival probability and an 80% decrease in the need for surgical intervention with a new soft body armor is reviewed. Five cases of ballistic assaults on law enforcement personnel protected by soft body armor are presented. Four emphasize the potentially lifesaving qualities of the armor, while the fifth indicates the need for torso encircling design. Hospitalization should follow all assaults, regardless of the innocuous appearance of the skin lesion and the apparent well being on the assaulted individual. Therapeutic guidelines for patient management are suggested.


Postoperative pneumoperitoneum: an unusual etiology. Although postoperative pneumoperitoneum is a common finding, it is particularly disturbing when there is an increase in the amount of postoperative pneumoperitoneum or when the radiographic finding of pneumoperitoneum is accompanied by such physical findings as increased abdominal tenderness, peritoneal signs or paralytic ileus. Four patients operated upon at the Mount Sinai Hospital are presented. All patients underwent abdominal surgery for treatment of some form of inflammatory bowel disease and all were receiving systemic corticosteroids in the postoperative period. Abdominal findings of tenderness, ileus and peritoneal irritation developed shortly after the removal of Penrose drains in the postoperative period. Pneumoperitoneum was confirmed by abdominal roentgenographs. The first patient in this group underwent a laparotomy with essentially negative findings other than a freely open drain tract. The subsequent three patients were managed by close observation and frequent abdominal radiographs. These three patients had contrast roentgenographic studies of the upper gastrointestinal tract to rule out perforation of a peptic ulcer, and in the patient upon whom reservoir ileostomy had been performed, a contrast study of the reservoir was performed. All patients recovered fully with this management and there were no sequelae. The mechanism for the appearance of pneumoperitoneum after removal of drains, particularly when the patient is receiving systemic corticosteroids, is discussed. Emphasis is placed on the need to consider and rule out perforation of a hollow viscus in this situation before accepting drain removal as the sole cause of post-operative pneumoperitoneum.


Postmastectomy reconstruction.

Postmastectomy reconstruction. Reconstructive surgery following mastectomy has had an increased acceptability with improved techniques and prostheses. Plastic reconstructive procedures following prophylactic mastectomy were performed in 104 patients and following mastectomy for cancer in 88 patients. Capsular contractions have not occurred with the use of a subpectoral pocket and detection of recurrent cancer is not hampered by the materials now used.


Muscle blood flow following thermal injury. Peripheral circulation is markedly increased during the hyperdynamic-hypermetabolic phase of thermal injury and appears to be directed primarily to the burn wound. To determine whether any portion of this extra blood flow reaches another major peripheral vascular bed, blood flow in the tibialis anterior muscle of the lower leg was measured by 133Xe clearance in ten hemodynamically stable, nonseptic burn patients (mean burn size = 42.5% total body surface) and five control subjects. Muscle blood flow was 3.52 +/- 0.26 ml/100 g.min (mean +/- S.E.M.) in these patients and 3.29 +/- 0.24 in controls, indicating that resting muscle perfusion was unaffected by the extent of total body surface injury, size of leg burn, or elevated rectal temperature (38.2 +/- 0.2 degrees C) of the patients. These results confirm the interpretations of previous studies suggesting that most of the increased peripheral blood flow following thermal injury is directed to the surface wound. Local and systemic factors responsible for the maintenance of muscle perfusion in the face of alterations in muscle metabolism following thermal injury are discussed.


Muscle and plasma amino acids after injury: the role of inactivity. The amino acid pattern following total hip replacement is characterized by increases in muscle of the branched chain amino acids (leucine, isoleucine and valine), the aromatics (phenylalanine and tyrosine) as well as methionine. The nonessential amino acids in muscle tend to decline, glutamine having the most marked change. Plasma levels of the essential amino acids increase while the nonessentials tend to decrease. This pattern differs from that observed in other catabolic states (uremia, starvation, untreated diabetes) and is significantly different from the effects of inactivity and starvation combined. This suggests that injury can be characterized by a unique pattern of muscle and plasma amino acids.


Gastroesophageal reflux in duodenal ulcer patients before and after vagotomy. Gastroesophageal reflux was investigated in 80 patients with duodenal ulcer by analysis of symptomatology and the acid reflux test. Resting gastroesophageal sphincter pressure (GESP) and postvagotomy reduction in basal and pentagastrin stimulated gastric acid secretion were also studied. Reflux symptoms were present in 40% of the patients, and this incidence was significantly reduced two months after vagotomy. In patients studied late after operation reflux symptoms were still less frequent than before operation, but not significant. After vagotomy, no significant changes in the fasting GESP or in gastroesophageal reflux as determined by the pH glass electrode were demonstrated. Thus, the decrease in reflux symptoms may be explained by the significant reduction in gastric acid secretion. Denervation of the cardia and the lower esophagus does not influence GESP or gastroesophageal reflux.


A sequential, prospective analysis of immunologic abnormalities and infection following severe thermal injury. A sequential, prospective analysis of humoral and cellular immune function was performed on 20 burn patients with injuries involving >/=45% total body surface area. Infected patients had significantly worse neutrophil bactericidal activity against Staphylococcus aureus 502A than did noninfected patients. Chemotaxis of neutrophils correlated poorly with infection although chemotaxis was frequently abnormal. The opsonic index of serum was depressed early after the burn but returned to nearly normal values by the fourth to the fourteenth postburn day. There was no difference between infected and noninfected patients. Serum levels of IgG, properdin and C3, while initially low, remained within the normal range after the ninth postburn day in both groups. Factor B levels rose rapidly during the first three weeks after injury to more than double normal levels in many patients. Suggestive evidence for consumption of opsonic protein occurred with five of 19 episodes of bacteremia. The responsiveness of isolated lymphocytes to PHA was normal. However, patients' sera were shown to significantly inhibit the responsiveness of normal lymphocytes to PHA. Analysis of immunologic profiles for individual patients indicates that abnormalities of neutrophil function are the most important acquired defect predisposing patients to the development of bacteremia following major thermal injury; abnormalities of opsonic action play a secondary but important role.


Cancer risk in extensive ulcerative colitis. Two hundred thirty-four patients with extensive ulcerative colitis from the city of Göteborg, Sweden have been followed up and the cumulative risk of development of cancer of the large bowel was estimated. These patients constitute all persons in this region who developed an extensive ulcerative colitis between 1951 and 1974. All patients were followed up until December 1975. The mean observation time was 8.5 years, median value six years. Fifteen patients developed carcinoma of the large bowel. Five of the 15 patients were still alive in December 1975. The expected number of colorectal carcinomas in a matched reference group was 0.49. The cumulative incidence of carcinoma 25 years after the onset of colitis for the whole group of patients was 34% and for those who developed the disease before 25 years of age it was 43%.


A serological survey for Babesia in cattle in Scotland. III. The rates of acquisition and loss of antibody to Babesia and their effects on observed levels of antibody incidence. Data for age and the incidence of antibody to Babesia divergens in cattle from areas of high and low endemicity have been analysed using three simple epidemiological models to estimate the rates of gain and loss of antibody. The models adequately described the observations but did not allow for an increased recovery rate attributable to acquired immunity in older animals. The rate of loss of babesial antibody in the absence of challenge was estimated directly from data for age and the incidence of antibody in Irish bred cattle located in nonendemic areas of Scotland. These data suggested an antibody loss rate of 0.25 per annum but did not provide firm evidence for the form of the antibody loss curve. Measurements of the titre of babesial antibody supported the conclusions drawn from studies of antibody incidence. In Irish bred cattle from non-endemic areas titres declined gradually over eight to ten years, whereas in cattle from an area of high endemicity, titres did not change appreciably with age. Cattle tested within one to three months of infection exhibited high titres.


The biochemical and serological taxonomy of Leishmania from the Aethiopian zoogeographical region of Africa. The electrophoretic variation of the enzymes MDH, GPI, G6PGH, 6PGDH were determined for 68 strains of Leishmania isolated in the Aethiopian zoogeographical region. Other characters determined were the DNA buoyant density of nuclear and kinetoplast DNA and the excreted factor serotype. The strains could be readily identified on the basis of these characters thus assisting in the elucidation of epidemiological problems. On the basis of these characters the strains could be divided into six groups. Three of the groups corresponded to L. donovani s.l., L. major and L. aethiopica. The three other groups identified at present have no specific name associated with them.


The exsheathment and migration of Brugia pahangi microfilariae in mosquitoes of the Aedes scutellaris species complex. Studies on the Aedes scutellaris complex of mosquitoes showed that refractory and susceptible species can be distinguished by reference to the proportion of Brugia pahangi microfilariae which reach the thorax within three hours of a feed. Migration ceased approximately 1 1/2 hours after feeding in refractory species, in which only 50% of the ingested worms reached the thorax, In susceptible species over 95% of the ingested microfilariae reached the thorax, and migration lasted for three hours after a feed. Differentiation could be achieved by studying the levels of exsheathment, but it is suggested that analysis of migration levels forms a reliable, accurate and quick method of distinguishing refractory from susceptible species.


Species differences in contractility of seminiferous tubules and tunica albuginea as related to sperm transport through the testis. Frequency and depth of contractions and tonus--i.e., diameter of the tubule or shift of the baseline for the capsule--of both the seminiferous tubules and the tunica albuginea were quantified for rat, mouse, rabbit, hamster and ground squirrel tests. In the ground squirrel, contractility was measured prior to, during and after breeding. The rat testes had the strongest tubular contractions; those of the mouse, squirrel and rabbit exhibited intermediate values, and the hamster tests had the weakest tubular contractions. The rabbit tests exhibited the strongest, most well-developed rhythmical capsular contractions while the rat, mouse, hamster and squirrel tests showed no definite rhythmical contractions. Hamster tests apparently depend primarily upon fluid secretion by the seminiferous tubules for sperm transport through the tests to the epididymis, while the squirrel, rat and mouse tests utilize both fluid secretion and some tubular contractions. The rat apparently utilizes tubular contractions more so than the other rodents studied for sperm transport.


Hyaluronidase release from guinea pig spermatozoa as affected by reproductive tract secretions and metabolic inhibitors. Cauda epididymal sperm of mature guinea pigs were incubated (37 degrees, 5% CO2 in air). 10% of the total enzyme activity was released into the medium in 4 hr, 30% in 24 hr. Addition of lysolecithin resulted in rapid release of hyaluronidase. Vitamin C (0.54 mM), sodium fluoride (0.02 M), and cholesterol increased the rate of release whereas citrate (20 mM) diminished it. No effect upon hyaluronidase release was noted upon addition of KCN (10(-2)M), progesterone (250 microgram/ml), testosterone (500 microgram/ml), spermine (1.15 mg/ml), inositol (5.6 mM), or chloroquine phosphate (0.54 mM).


Effects of pipecolinomethylhydroxyindane on testicular and adrenocortical function in rats. Mature and young adult rats were treated with a single dose of 115 mg and 50 mg of pipecolinomethylhydroxyindane (PMHI) maleate per kg of body weight. Large intraperitoneal doses were toxic in mature rats and the growth of younger animals were retarded by the lower subcutaneous dose. In both instances, PMHI caused a rapid reduction in testis weight with arrested spermatogenesis. Atrophic changes to the ventral prostrate and the lowering of blood testosterone levels suggests that the actions of PMHI are not strictly confined to the seminiferous tubules. This was further substantiated by the demonstration of direct inhibition by PMHI of testicular androgenesis in vitro. The actions of PMHI on steroidogenesis may be readily reversible and, compared to tubular actions, are of a minor nature. There were no clear-cut adrenocortical responses to PMHI administration but there was some depression of adrenal gland weight, plasma corticosterone, and aldosterone.


Ultrastructure of acrosomal malformations in men with obstructive azoospermia. Testicular biopsies from ten infertile men with obstructive azoospermia were evaluated by light and electron microscopy. Light microscopic analysis revealed normal testicular pattern with active spermatogenesis and many spermatozoa. At ultrastructural level the majority of early spermatids presented acrosomal abnormalities that become evident during the approach of the acrosomal vesicle to the anterior pole of the nucleus, and in subsequent maturational stages; these spermatids continue their development until mature spermatozoa with malformed acrosomes. The type of malformation was very similar in all cases observed and was associated with the same type of seminiferous tubule pattern in patients with the same type of azoospermia. The abnormalities at acrosomal level were related to an abnormal differentiation rather than to degenerative changes. Acrosomal disturbance did not influence nucleus morphology or chromatin condensation.


Fine structure and development of Sertoli junctions in human testis. Complicated interdigitation-like junctions between the immature Sertoli cells were frequently observed in prepubertal testis (3--8-year-old). Tight or gap junctions could not be found. Subsurface cisternae appear in the testes of 7 and 8-year-old boys. In pubertal testis (11 to 13 years old), junctional specializations between Sertoli cells are composed of membrane fusions, bundles of microfilaments and associated cisternae. These tight junctions block the deep penetration of lanthanum into the seminiferous tubules. The lanthanum-filled Sertoli junctions show characteristic features of membrane fusions. In the seminiferous tubules spermatocytes were not present at 11 years of age but complete spermatogenesis was noted at 12-13 years of age. It is suggested that the human blood-testis barrier is estabilished shortly before or after the spermatogonia proliferate to give rise to primary spermatocytes.


Serum LH and FSH following passive immunization against circulating testosterone in the intact male rat and in orchidectomized rats bearing subcutaneous silastic implants of testosterone. Subcutaneous Silastic implants were designed to release quantities of testosterone approximating that produced by the rat testis and appropriate testosterone treatment was found to produce a physiologic inhibition of both LH and FSH secretion in orchidectomized rats. In rats bearing such testosterone implants, intravenous injection of an ovine anti-testosterone serum (0.3 cc) was sufficient to completely abolish the inhibitory effects of the testosterone implant for a period of 3 days as judged by the development of typical post-castration increases in serum LH and FSH. When this dose of antiserum was administered to intact adult male rats, the increases in serum LH on days 1, 2, and 3 post-injection were approximately 19%, 15%, and 11% of those observed in untreated castrates. Increases in serum FSH in antiserum injected rats followed a pattern similar to that for serum LH but the response was slightly greater (19%, 23%, and 22% of the castrate response) and there was no indication of a decreasing effect during the three days following injection. In these experiments, passive immunization against testosterone in intact male rats produced a clearcut stimulation of both LH and FSH release, but produced no data to support the suggestion that the intact testis can secrete nonsteroidal compounds capable of producing a differential inhibition of FSH secretion.


N-acetyl-beta-D-hexosaminidase in the epididymis after vasectomy. The activity of the lysosomal hydrolytic enzyme, N-acetyl-beta-D-hexosaminidase, was determined in the epididymis of control and vasectomized rats. Vasectomy did not cause changes in enzyme levels suggesting normal metabolic function in the epididymis.


Testicular biopsy of secretory azoospermia: electron and light microscopic analysis. The histological and ultrastructural features of testicular cells were examined in testes with secretory azoospermia in seven patients with germinal cell arrest, two with Sertoli-cell-only; and one with tubular hyalinization. Germinal cell arrest was characterized by the presence of spermatogonia AD, AP, B, and some primary spermatocytes: these cells had similar ultrastructural features typical of the adult normal testis. Sertoli cells contained large number of various lipid inclusions and lipofuscin bodies. The multilayered peritubular wall presented increased collagen fibers. The cytoplasm of Leydig cells was filled with dilated vesicles of smooth endoplasmic reticulum and precursors of Reinke crystalloids. A blockage in the seminiferous tubules occurred after puberty, when tubular components, peritubular wall and Leydig cells had reached maturity.


Fine structure and cytochemistry of the morphogenesis of round-headed human sperm. Ejaculates and testicular biopsies of two infertile men were examined at ultrastructural and cytochemical levels. The two patients presented spermiograms in which all the spermatozoa had globular heads. Wide Golgi areas and large masses of annulatae lamellae were evident during spermatogenesis. Abnormal acrosomal vesicles were evident during early spermatid stage. Among the late spermatids, there was a small group characterized by a fibrous sheath showing considerable malformation, and "spindle shaped body." In Sertoli cells, detached acrosomes undergoing degeneration were noted. Low TPPase activity was found in Golgi complex and in abnormal acrosomal vesicles of early spermatids. As regards acid phosphatase, was localized in spermatocytes and in early spermatids, but not in late spermatids and mature spermatozoa. Leydig cells had high phosphatase activity.


Carnitine-binding related supressed oxygen uptake by spermatozoa. L-carnitine (25 mM) reduced oxygen uptake immediately by 40% in ejaculated bovine spermatozoa, but not in ejaculated human spermatozoa or in spermatozoa from bovine and rat epididymis. [3H]-L-carnitine was bound five times as much to ejaculated bovine spermatozoa as to bovine spermatozoa from the cauda epididymis and to human ejaculated spermatozoa. This indicates the presence of a factor in the accessory male sex organs which, through changes in the membrane and/or intracellulary, increases the [3H]-L-carnitine binding sites and makes the spermatozoa susceptible to carnitine inhibition.


Metabolic changes induced in human spermatozoa by subagglutinating concentrations of specific antibodies. The effects on sperm metabolism of subagglutinating concentrations of infertile female sera, containing antisperm antibody, were studied. Sera were selected by their differential agglutinating or immobilizing properties and by high titers of activity. Only the immobilizing antibodies were able to decrease sperm viability. Basal and succinate depending oxygen uptake, thus as progressive motility was decreased by sera producing mixed agglutination and more drastically by that producing immobilization independent of the presence of complement. The sera with head-to-head agglutination properties induced an increase in the above mentioned physiologic parameters. Tip of tail-to-tip of tail agglutinating sera having no effect on oxygen uptake were able to induce a significant increase in progressive motility. Conversion of 14C-Glucose to 14CO2 was decreased by sera that induced tip of tail-to-tip of tail agglutination and complement-independent immobilization. The sera which induced head-to=head agglutination and immobilization on the presence of complement, were without effect. None of the tested sera showed any acitivity over the conversion of 14C-Glucose to 14C-Lactate.


Endocrinological and physiological features after steroid treatment of male rats. The effects of medroxyprogesterone acetate (Provera), testosterone propionate (TP), ethinyl estradiol (EE), and ethynodiol diacetate (ED) treatments on sperm population in different segments of the male rat reproductive tract, reproductive organ weights, circulating androgens and fertility were studied. Ten microgram TP given for five days reduced the sperm population and organ weights. A marked reduction in the number of sperm and reproductive organ weights was observed in males orally treated with estrogens. Only long-term (20 days) treatment with Provera (1 mg/day) significantly reduced sperm population and reproductive organ weights. Combination of TP and Provera resulted in a more pronounced reduction in sperm counts and organ weights. Among steroids studied, estrogen was the only compound which suppressed fertility and circulating steroid levels.


Hemodynamic mechanism of erection in the human penis. Six infertile patients and one patient with ureteral calculus were studied to elucidate the intrapenial hemodynamics of erection. Xe-133 was infused into the corpus cavernosum and visual sexual stimulation (V.S.S.) provided to induce erection. Xe-133 clearance curves declined at a uniform rate in the nonerect penis without V.S.S. Xe-133 clearance curves for five patients with complete erection at V.S.S. indicated a sudden drop upon erection. Unlike previous reports, it was noted that penial erection can occur independently of a venous-return blocking mechanism.


Immunoglobulin deposits and testis tubular membrane pathology in human sterility. Immunoglobulin deposits were detected by IF technique on tubular membranes of sterile patients' testicular biopsies (40%). Positive staining was correlated with high-grade tubular membrane damages (15 over 23 M3, M4, M5 sections were positive, against 0 over 5 M0 sections).


A new orchidometer.

A new orchidometer. A new orchidometer has been designed consisting of a plastic plate perforated with elliptical holes in which the testicle is fitted. The relationship between the longitudinal and the transversal diameters of the testis can be evaluated for all states of testicular growth.


Sperm head surface area as an individual characteristic of a donor's sperm. The mean surface area of the head of fixed and stained spermatozoa from 12 healthy, young donors was measured on 3 occasions separated by 8-day intervals. The mean area varied appreciably between individuals, and considerably less between samples from the same donor.


Arginine evaluation to verify sperm maturation in man. A modified version of Sakaguchi's histochemical reaction is proposed for the evaluation of arginine content in spermatozoa as an index of sperm maturation. Results obtained with this procedure, compared with DNA and basic nuclear proteins determinations in the sperm cells from normal subjects and from patients with oligospermia, appear to confirm the usefulness of this technique.


Pharmacological effects of a combination of butorphanol and acetaminophen. Isobolographic analysis was used to study in mice the combined oral analgetic action of butorphanol, a new centrally acting analgetic, and acetaminophen, an antipyretic analgetic. Combinations of butorphanol-acetaminophen exhibited analgetic effects which were greater than were expected from just an additive analgetic action of each drug. Consequently, a significant synergistic effect occurred after the simultaneous oral administration of butorphanol and acetaminophen. Furthermore, oral administration of butorphanol-acetaminophen mixture to conscious dogs at approximately 20 times the recommended human dose resulted in little or no effect on aortic blood pressure and arterial blood pH,pCO2 and pO2. Heart rate was slightly reduced and this resulted in a small increase in the PR interval and a prolongation of the QT interval of the lead II surface electrocardiogram.


Pharmacology of budralazine, a new antihypertensive drug. Antihypertensive and pharmacological properties of budralazine were examined in comparison with other antihypertensive drugs. Budralazine was orally effective against various types of hypertension in rats and it, like reserpine but unlike hydralazine, produced a much greater pressure reduction in hypertensive than in normotensive rats. The drug was similar to reserpine and alpha-methyldopa but not to hydralazine in showing a gradually progressive action. At equihypotensive oral doses, budralazine was less potent than hydralazine in producing tachycardia in unrestrained SHR. After long-term therapy, it effectively prevented the development of hypertension in SHR to almost the same extent as did hydralazine. Budralazine failed to produce diuresis in SHR at antihypertensive doses but antagonized isolated rabbit aortic contractions induced by vasoconstrictors and decreased femoral arterial resistance in dogs. Thus, the antihypertensive budralazine is characterized by the ability to produce vasodilator, non-diuretic and weak cardiac stimulant effects.


Subcutaneous administration of somatostatin analogs as a major factor in the enhancement of the duration of action. Somatostatin and Des(Ala1Gly2)desaminol[Cys3]descarboxy-]Cys14[-]D-Trp8[dicarba3,14-somatostatin (Ia) are more potent inhibitors of glucagon, insulin and growth hormone release than the L-Trp8 analog (Ib). However when infused intravenously, these three compounds are equipotent but short-acting inhibitors of pentagastrin evoked gastric secretion in the dog. The duration of inhibition of equieffective antisecretory doses is significantly increased following subcutaneous administration 30 min prior to a food stimulus. The longest duration of antisecretory action is seen with the D-Trp8 analog (Ia) after subcutaneous administration.


Study of in vitro effects of hydralazine metabolites--comparative evaluation of products of hydroxylation, hydrolysis and conjugation. K+ contractures were induced in paired strips of rabbit aortic smooth muscle. The relationship between relaxant effects and the bath concentration of hydralazine acetone hydrazone (HA), 4-OH-hydralazine (HH) and phthalazine (P) was studied over the concentration range 10(-5)-10(-3)M. All compounds were active, HA = HH greater than P (p less than 0.05; n = 6) at concentrations in the range 10(-4)-10(-3M, HA greater than HH at a concentration of 10(-3M (pgreater than 0.01). The activity of HA did not depend on significant reconversion to hydralazine (H) in the bath ( less than 0.5%). A range of H derivatives may contribute to the hypotensive effects of administered H.


Effect of in vivo treatment by dexamethasone and indometacin on DNA synthesis in rat macrophages in culture stimulated by inflammatory exudate. The acute inflammatory exudate obtained 4 hr after intrapleural injection of dextran in rats is able to induce DNA synthesis and division of normal rat macrophages in culture. The influence on this phenomenon of two types of pretreatment of rats with dexamethasone or indometacin has been investigated. Exudates of rats treated with dexamethasone decreased the DNA synthesis in control macrophages. On the contrary, exudates of rats treated with indometacin had no effect on this DNA synthesis. These results could be explained by the different actions of the two anti-inflammatory agents on cellular migration in pleural exudates. In macrophages harvested from rats treated with dexamethasone or indometacin the DNA synthesis induced by inflammatory exudates was decreased. This identical response elicited by these two agents could be related to their direct antimitotic activity on macrophages.


The effect of indoprofen on phenylquinone-writhing and prostaglandin synthesis. The ability of indoprofen or sodium indoprofen to inhibit phenylquinone-writhing and renal prostaglandin synthesis was determined in mice following a single oral dose of either drug. Male mice (4/group) were treated with 1.5 mg/kg indoprofen or sodium indoprofen. Inhibition of phenylquinone-writhing was determined at 2, 4, 8, 16 and 32 hr post treatment. Animals were sacrificed and blood collected for determination of plasma indoprofen concentration. Kidneys were removed and prepared for determination of renal prostaglandin synthesis by an in vitro technique. Phenylquinone-writhing was significantly depressed by both preparations at 2 and 4 hr post treatment. Sodium indoprofen also significantly depressed writhing at 8 hr post treatment. Renal prostaglandin synthesis, like phenylquinone-writhing, was significantly depressed at 2 and 4 hr after drug treatment. Plasma indoprofen concentration was correlated with both inhibition of phenylquinone-wrighing and inhibition of renal prostaglandin synthesis. When writhes were plotted versus prostaglandin synthesis, a positive correlation was observed suggesting a temporal relationship between inhibition of phenylquinone-writhing and inhibition of renal prostaglandin synthesis.


Pharmacological analysis of the effects of substituted benzamides on the isolated guinea-pig ileum. Study of metoclopramide, sulpiride, bromopride, tiapride and sultopride. The effects of metoclopramide (Mcp), sulpiride (Sp) and some of their derivatives: bromopride (Br), tiapride (Ti) and sultopride (Stp) have been compared on the guinea-pig isolated ileum. 1. Br and Ti have, like Mcp, and indirect cholinergic stimulating effect on the intestinal smooth muscle. Sp and Stp are devoid of such an effect. 2. At high doses, all the benzamides have a direct inhibitory effect on the ileum. 3. Mcp, Br and Ti (10(-5)M) potentiate the responses of the ileum to acetylcholine (ACh). At high doses (10(-4)M) the effects of all benzamides on the responses to ACh as well as to histamine (H) are mostly inhibitory. 4. Mcp and Br (10(-5)M) inhibit the responses of the ileum to serotonin (5HT) while Ti, Sp and Stp potentiate them. 5. Neural pathways and calcium mechanisms are involved in the potentiations of ACh and 5HT responses since the enhancements observed are abolished in the presence of tetrodotoxin or in the absence of Ca++.


Properties of two derivatives of gamma-aminobutyric acid (GABA) capable of abolishing Cardiazol- and bicuculline-induced convulsions in the rat. The gamma-NH2 function of GABA was blocked with either benzoyl group (BG1) or a pivaloyl (timethylacetyl) group (PG2). The two derivatives of GABA obtained by the synthetic procedure were chemically pure and fully characterized. Both 14C-BG1 and 14C-PG2, unlike 14-C-GABA, are able to penetrate the blood-brain barrier in rats after subcutaneous injection. BG1 reached its highest concentration in brain 5 min after injection and PG2 after 30 min. This difference appears to be related to the different hydrophobic character of the two compounds, measured after experiments of partition in a water ethylacetate system, and to the different rate of diffusion following subcutaneous administration. BG1 abolished pentetrazole- and bicuculine-induced convulsions in rat when injected 5 min before the administration of the convulsants and PG2 had similar effects when injected 30 min before convulsants. BG1 and PG2 had a slight inhibitory effect on GAD and both BG1 and PG2 acted as substrates for the action of proteolytic enzymes that convert the two compounds back to GABA. Toxicity of both BG1 and PG2 was practically undetectable in rat following administration of the compounds up to 1 g/kg. Glutamate oxidation by rat brain mitochondria was not affected by either BG1 or PG2.


Yohimbine-induced stimulus control in the rat. Rats were first trained in a 2-lever operant test chamber using a fixed ratio 10 schedule of water reinforcement. Discrimination training was then begun. In sessions following the injection (i.p.) of yohimbine . HC1 (3 mg/kg), responses on 1 of the 2 levers were reinforced. In sessions following the injection of saline, responses on the remaining lever were reinforced. The distribution of responses between the 2 levers prior to reinforcement provided an index of discrimination. The criterion for stimulus control was set at 80% correct responses in each of five consecutive sessions. In a group of six rats, criterion performance was begun after a mean of 33 sessions. Cross tests were conducted in yohimbine-trained subjects with d-amphetamine, harmaline, and LSD. Each test drug yielded intermediate results, i.e., response distribution was significantly different from both the yohimbine and the saline training conditions. No significant antagonism of yohimbine-induced stimulus control was achieved with BC-105, phentolamine, or butaclamol, purported antagonists at serotonergic, alpha-adrenergic, and dopaminergic receptor sites, respectively.


Effect of isoniazid on the metabolism of 14C-diphenylhydantoin in rats. The effect of isoniazid (INH, 0,5, 10 or 20 mg/kg; p.o.) on the metabolic disposition of 14C-diphenylhydantoin (DPH, 50 mg/kg; i.v.) was studied in rats for 5 hours. The disappearance rate of 14C from the blood was similar up to 2 hr, whereas at 3 hr the levels of 14C were significantly higher in 10 and 20 mg/kg INH-treated rats than the controls. While the urinary excretion remained virtually unaltered, the fecal excretion of 14C was significantly reduced in the presence of INH. Increasing doses of INH caused a corresponding increase in the concentration of 14C in the blood, plasma, liver, kidney, lung, brain, skeletal muscle, fat, heart, tests and spleen. At the end of 5 hr, about 74% of the radioactivity was present as unmetabolized DPH in the plasma of control animals; this was increased significantly in a dose-related manner by INH, reaching a concentration of 93% at the highest doses of INH administered. The results suggest that the INH-induced elevation of DPH-derived 14C in plasma and its marked accumulation in other tissues is due to inhibition of both the p-hydroxylation of DPH and the glucuronidation of its metabolites.


Effects of chlordiazepoxide-scopolamine combinations on shuttle-box avoidance performance of mice. Chlordiazepoxide and scopolamine, given separately, during training in the shuttle-box or in trained mice, improved avoidance responding. Avoidance facilitation was much more evident, especially in the initial phases of training, when the two drugs were combined.


A study of the mechanism of transport of delta9-tetrahydrocannabinol in the rat submaxillary gland in vitro. In vitro studies on rat submaxillary gland slices with 3H-delta9-THC (3.6 X 10(-6)M) showed that this drug was transported into and accumulated by salivary tissue. Approximately 50% of the delta9-THC was firmly bound in or on the tissue. The uptake of 3H-delta9-THC was unchanged from control conditions (pH 7.4, 37 degrees C, 100% oxygen, 3.2 X 10(-6)M) when the metabolic inhibitors, 2,4-dinitrophenol (10(-3)M) and cyanide (10(-3)M) were used or when oxygen was replaced by nitrogen. The efflux of 3H-delta9-THC from salivary gland slices increased following addition of an excess of unlabeled drug. These data suggest a passive transport process for the movement of delta9-THC into salivary tissue with a possible saturable binding site operating on or in the interior of the salivary cell.


Effect of phthalate esters on drug metabolizing enzyme activities in rat liver. Dibutyl-, di(2-ethylhexyl)-, di(3, 3, 5-trimethylhexyl)- and didecylphthalate (DBP, DEHP, TMHP, DDP) all caused an increase in the amount of hepatic cytochrome P=450, when administered intragastrically to rats. No statistically significant increase could be detected in the catalytic activities dependent on cytochrome P-450 (Benzo(a)pyrene hydroxylation, ethoxycoumarin deethylation). Dibutylphthalate inhibited these reactions, when added to the incubation in vitro. Phthalates caused an increase in the activities of epoxide hydratase, and glutathione-S-transferase. Conjugation of 0-aminophenol and 4-methylumbelliferone with glucuronic acid was increased after phthalate administration.


A selective tonic activation of gastrointestinal smooth muscle by substance P. Mechanical and electrical activity of smooth muscle preparations from fundus, corpus, and antrum of guinea-pig stomach and from distal ileum of guinea-pig were recorded, and the effects of Substance P were examined. Substance P activated selectively the tonic activity of corpus, fundus, and ileum of guinea-pig before and after blockade of phasic contractions. The tonic activation of Substance P is accompanied by increasing of number and amplitude of spike discharges and by decreasing of amplitude of slow potentials in corpus. The tonic activation of Substance P is potentiated parallel with reduction of Ca++ up to 0.6 mmol.


A modulating role of prostaglandins in responses of guinea-pig isolated ileum to various agonists. Small doses of prostaglandin E2 (0.3, 0.6 and 0.9 ng/ml) and prostaglandin F2alpha (0.25, 0.5 and 0.75 ng/ml) significantly potentiated the responses of the guinea-pig isolated ileum to cholinergic substances, i.e. acetylcholine, methacholine, carbachol and pilocarpine. All substances were applied from the serosal surface of the guinea-pig isolated ileum. The greatest potentiation of carbachol effect was obtained, and the smallest was the potentiation of pilocarpine effect. The same small doses or prostaglandins E2 and F2alpha did not influence the response of the guinea-pig isolated ileum to histamine and nicotine.


Reversal of adenine-induced depression of mouse locomotor activity by amphetamine. Adenine (200 mg/kg) was found to depress locomotor activity in mice. Dl-, and d-amphetamine reversed the depression of locomotor activity produced by adenine while l-amphetamine was found to be incapable of reversing the adenine-induced depression. The stimulation of mouse locomotor activity caused by dl- and d-amphetamine in mice treated with adenine was less than that caused by equal dosage of these agents in mice not treated with adenine. Mice treated with adenine showed marked depletion of brain norepinephrine, dopamine and serotonin, irrespective of whether or not they had been treated with d- or l-amphetamine, and whether or not these agents were capable of reversing adenine-induced depression of locomotor activity.


The influence of anti-inflammatory compounds on some effects of BCG in the rat. In the rat, intravenous injection of BCG induced an increase in complement activity, oxidative activity towards paraphenylenediamine and serum haptoglobin level. A strong correlation was shown between oxidative activity and haptoglobin level. These increases were inhibited by glucocorticoids (cortisone, dexamethasone, methylprednisolone) but not by two non-steroidal anti-inflammatory drugs (indometacin, phenylbutazone). It is suggested that these BCG effects are related to the release of macrophage constituents and that this is inhibited by glucocorticoids.


Acute cocaine intoxication in the conscious dog: pathophysiologic profile of acute lethality. Cocaine HCl was infused intravenously to conscious mongrel dogs until death (0.5 mg/kg/min; 0.82 ml/min). All animals convulsed (mean convulsive dose: 12 +/- 1 mg/kg) and died approximately 42 min after the beginning of cocaine infusion (mean lethal dose: 21 +/- 2 mg/kg). All animals exhibited significant increases in arterial systolic and diastolic pressures, left ventricular pressure, cardiac output, heart rate, respiratory rate, minute volume, tidal volume, oxygen uptake, plasma glucose, blood lactate and body temperature. Statistically significant reductions from pre-drug control levels were observed in total peripheral resistance, arterial pH, and arterial pO2.


Influence of short-term administration of clofibrate on insulin and glucagon response to protein ingestion in man. Nine normal and two mildly hypertriglyceridemic subjects were treated with 2 g of clofibrate per day for 8 days. A significant fall in serum triglyceride and cholesterol concentration was observed from the second day onwards whereas free fatty acid levels were minimally affected. Insulin and glucagon responses to the ingestion of 200 g of meat were tested before and at the end of clofibrate treatment. Insulin response was significantly depressed (-28 +/- 12%) by the drug whereas glucagon response was enhanced but not to a significant degree. The ratio between insulin response and glucagon response was decreased by 38 +/- 11% (p less than 0.01) after treatment. A positive correlation was observed between the effects of clofibrate on basal triglyceride concentration on one hand and the effects of the drug on insulin and insulin/glucagon response to the protein meal on the other hand. Since insulin and glucagon are known to influence triglyceride metabolism, our data are compatible with the concept that the hypotriglyceridemic effect of clofibrate is--at least partly--related to the observed changes in insulin and glucagon reactivity.


Effect of specific growth limitations on cell wall composition of Staphylococcus aureus H. Conditions are described for the continuous culture of a derivative of Staphylococcus aureus H in a fully defined minimal medium in which cysteine is the sole amino acid. The effects of growth under various nutrient limitations on the composition and properties of the cell wall have been studied. The proportion of ribitol teichoic acid present in the wall, and the extent to which it is substituted with N-acetylglucosamine, varies in bacteria grown under different conditions as does the composition and extent of cross-linking of the peptidoglycan. Neither the derivative nor the original strain H produced teichuronic acid when grown under phosphate limitation.


[Studies in fattening bulls on the regulation of phosphorus requirements by ad libitum intake]. Experimental studies into 21 fattening bulls have failed to support the assumption that phosphorus demand might be regulated by ad-libitum intake. A group feeding on lowphosphorus diet was compared to a normally fed control group. Both did not differ from one another regarding consumption of a high-phosphorus mineral mixture. Economically unjustifiable luxurious consumption rather must be expected, depending on taste, habit, and social eating behaviours.


[Behavior of various blood constituents (glucose, fructose, insulin, lactate, pyruvate, free fatty acids, inorganic phosphate) and half-life of monosaccharides in the plasma after i.v. infusion of glucose, fructose, galactose and invert sugar solutions in ruminants. 1. Studies in calves and heifers]. Studies into the half-life of monosaccharides as well as into the effects of intravenous infusion of sugar solutions (0.5 g/kg body weight of glucose, fructose, galactose, and invert sugar) on the concentration of various blood components were undertaken with six calves and five heads of young cattle. Half-life values of glucose and galactose were of nearly identical magnitude over the first weeks of age, whereas that of fructose was much longer on account of slower conversion. Infusion of invert sugar solution, therefore, cannot be recommended for calves during the first three weeks of age. Infusion of the above monosaccharides led to more or less strongly pronounced rise of insulin levels in the blood serum. More or less strongly marked pyruvate increase took place following infusion, if the pyruvate concentration in the blood plasma had been low before infusion. Lactate levels in the blood usually underwent little change, whereas the levels of free fatty acids and inorganic phosphate in the blood plasma usually were reduced.


[Behavior of various blood constituents (glucose, fructose, insulin, lactate, pyruvate, free fatty acids, inorganic phosphate) and half-life of monosaccharides in the plasma after i.v. infusion of glucose, fructose, galactose and invert sugar solutions in ruminants. 2. Studies in cattle]. Monosaccharides were intravenously injected to eight adult heads of cattle, between 380 kg and 670 kg in live weight, to study, in the context of stress endurance, the half-life values of the sugars as well as monosaccharide effects upon concentrations of various blood components. The fructose concentration in the blood plasma went up temporarily following the infusion of glucose solution. Fructose infusion usually caused only little rise of the glucose concentration in blood plasma, with hypoglycaemia occurring quite often towards the end of an experimental period. The half-life values of sugar in blood plasma were between twelve and 29 and those of fructose between ten and 17 minutes. The rate of fructose conversion was higher than that of glucose conversion, but values were identical in some cases. The pyruvate concentration in the blood and the insulin level in blood plasma went up in response to infusion of monosaccharide solutions. Urine excretion of monosaccharides following invert sugar infusion was less than half of that in response to glucose infusion.


[Behavior of various blood constituents (glucose, fructose, insulin, lactate, pyruvate, free fatty acids, inorganic phosphate) and the half-life of monosaccharides in plasma after i.v infusion of glucose, fructose, galactose and invert sugar solutions in ruminants. 3. Studies in sheep]. Monosaccharide half-life as well as the effects of intravenous infusion of 0.5 g/kg body weight glucose, fructose, and invert sugar solutions on insulin levels in blood plasma as well as on pyruvate and lactate concentrations in the blood were measured in two adult sheep weighing 72 kg and 65 kg. The half-life values for glucose were 16 minutes and 19 minutes and that for fructose 20 minutes. Glucose half-life, following infusion of invert sugar, was 35 minutes or 25 minutes, while that of fructose was 16 minutes in either case. Infusion of fructose solution was followed by a somewhat sizeable and prolonged rise of the glucose levels in blood plasma. Infusion of glucose solution resulted only in short-time increase of fructose concentrations in blood plasma. The highest insulin rise in blood plasma was found to have taken place in response to infusion of fructose solution. Pyruvate and lactate concentrations underwent merely minor changes. Reference is made to the potential benefit of using invertose solution in the treatment of ketosis (cf. second communication).


[Mineral content in the serum of young bulls in a bull rearing center]. Hygiene checks were applied to 97 young bulls of dairy breeds and 300 of beef breeds on a bull raising centre, between 1972 and 1975. Their normal blood serum levels of organic phosphorus, calcium, and magnesium were compared to the levels of the same minerals in feed rations. Blood serum values were compared also between animals with pathological changes in the supporting, locomotor, and genital systems as well as in sperma and pellet, on the one hand, and those without such changes, on the other. Also compared were sons of different fathers of the beef breed, with the view of elucidating certain peculiarities specific of blood lines.


[Radiochemical method for the determination of the activity of the gluconeogenetic key enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase in swine livers]. Described in this paper is a technique for the determination of pyruvate carboxylase and phosphoenolpyruvate carboxykinase, two key enzymes of gluconeogenesis in swine liver. The technique is based on measurement of radioactively labelled carbon incorporated in the common metabolite, oxalacetate. The optimum measuring conditions to establish the enzymes in liver homogenate and supernatant are reported and compared with data given by other authors. The found parameters of kinetic properties were in good agreement with the findings obtained from purified enzymes from swine liver.


[Experimental study on cattle anemia due to immune antibodies. 3. Effects of anemia on the liver]. A characterisation in greater detail was undertaken of haemolytic anaemia caused by immune antibody and its effects on the liver of young cattle. Bioptate follow-up tests were applied to two animals, while bromosulphalein half-life and SGOT activity were determined in seven. Centrolobular liver necrosis was not reproducible. Some moderate liver cell damage was histologically detected. Certain responses recorded from the reticulohistiocytary part of the liver were interpreted as a consequence of aggravated damage to erythrocytes. The above moderate liver cell damage failed to produce statistically secured rises in bromosulphalein half-life nor SGOT activity.


[Use of copper for the support of physiological reproductive processes. 1. Copper level in the serum of castrated male swine after various applications of copper and copper compounds]. Various copper compounds (CuSO4, Cu-glycinate, Cu-lactate, Cu-citrate) were applied subcutaneously, intramuscularly, and intravenously to 17 barrows, doses being up to 50 mg Cu, while doses between 0.5 g and 1.0 g CuSO4 were orally administered. Curves of copper levels in the serum then were checked at different times. In response to intravenous application, copper levels reached maximum values as early as after two minutes and dropped to the normal about 90 minutes from application. Subcutaneous and intramuscular applications had but little effect on serum copper levels, while oral administration actually had none at all.


[Determination of enzyme activities in the synovial fluid of farm animals]. Reported in this paper are methods for spectrophotometric determination of the activities of lactatedehydrogenase (LDH) and aspartate-aminotransferase (AspAT) and for colorimetric determination of the activity of N-acetyl-beta-glucosaminidase (NAG) in the synovial fluid of farm animals. Optimum conditions are suggested, as a result of these studies, for reactions of those enzymes in synovial fluid. The behaviours of these enzymes in synovial fluid were compared to those in the blood serum of domestic animals and man and exhibited close agreement. The test-kits at present commercially available for applications in human medicine and used in the determination of LDH and AspAT activities are suitable also for the determination of enzyme activities in synovial fluid. Enzymes in synovial fluid are highly responsive and, even smallest amounts of synovial fluid, therefore, are sufficient for positive findings in laboratory diagnosis.


[Use of invert sugar, fructose and sorbitol and on their effect on various plasma constituents after intravenous infusion in the dog]. Glucose and fructose half-lives following intravenous infusion of 1.0 or 0.5 g/body weight invertose solution (200 g/l) were established in six Beagle dogs. The average half-lives measured were 7.8 for glucose (variation between 6.0 and 13.5) and 7.5 for fructose (variation between 4.5 and 11.0), all values given in minutes. Administration of invertose instead of glucose for parenteral energy supply proved favourable in various respects. Infusion of invertose was temporarily followed by rises within physiological limits of lactate and pyruvate in the blood and of insulin concentrations in the blood plasma, whereas the levels of free fatty acids declined. A 25-per-cent fructose solution was infused (0.5 g/kg body weight) to three dogs, and the half-lives then measured were six, nine, and 13 minutes. The insulin concentration rose temporarily, while the free fatty acids went down. The same doses of sorbite gave half-lives of 15.5 or 17 minutes. Infusion was followed by temporary increase of fructose and insulin in the blood plasma.