[Significance of lead immission for pregnant women and neonates in the Ruhr area]. Systematic measurements of blood lead levels in samples from 176 mature and premature neonates and 59 mothers in the western Ruhr-Rhine area demonstrated that at least 30% of statistical variance in blood lead levels depended on lead immission at the mother's place of residence. The close correlation between neonatal and maternal blood lead levels was confirmed. Identical and non-identical twins had almost the same blood lead levels. Using a biological system for determining lead immission, blood lead levels in areas not covered by the present study can be prognosticated.


[Diagnosis and operative treatment of coelic-artery compression]. Stenosis of the coeliac artery by compression occurs predominantly in youngish patients and three times more frequently in women than men. It gives rise to abdominal symptoms, due to chronic disturbance of intestinal arterial supply. In eight patients, operated on for this condition, the characteristic symptoms were of abdominal pain, epigastric vascular sounds, loss of weight, nausea and vomiting. Diagnosis could only be made by angiography of the coeliac and (or) mesenteric arteries, and lateral aortography. Analysis of 240 cases reported in the literature indicates that the condition is caused by compression of the coeliac artery by the medial arcuate ligament of the diaphragm, and only in a few instances by nerve tissue of the mesenteric ganglion of the coeliac plexus. Operative treatment (decompression of the artery) removes symptoms in 83% of cases.


[Antigenicity of serum albumin in allergy against cat or dog epithelium (significance of the radioallergosorbens test in the diagnosis of allergies)]. Intracutaneous, nasal provocation (NPT) and radioallergosorbens (Phadebas RAST) tests were performed on 49 subjects hypersensitive to cats and (or)dogs using serum albumin and epithelium extracts from cats and dogs. Serum albumin elicited intracutaneous reactions in most of the subjects, but gave positive NPT und RAST results in only a few and was, therfore, of limited clinical importance. The intracutaneous tests with epithelium extracts were positive in some subjects in whom other tests had been negative. It is possible that these false-positive skin tests were caused by serum albumin present in the extracts, while in others non-specific skin reactions were apparently caused by epithelial components. On the other hand, the results suggest that the few patients allergic to dogs were incorrectly diagnosed with the RAST. But the described in-vitro method increases the chances of diagnosing allergies against animal epithelia. It is furthermore useful in the interpretation of equivocal skin tests.


[Contribution to the aetiology of "reversible hepatic dysfunction" (Stauffer's syndrome) associated with renal tumours]. Biochemical changes, especially isolated rise in alkaline phosphatase and increased thromboplastin time, which have been described as "reversible hepatic dysfunction" (Stauffer's syndrome) were found in a 47-year-old patient with hypernephroma and hepatomegaly without liver metastases at post-mortem examination. The alkaline phosphatase could not be distinguished from the placental isoenzyme (Regan's enzyme). Increased thromboplastin time was due to circulating fibrinogen degradation products.


[Chemotherapy of metastasizing breast cancers. Indications and results]. Combined treatment with three or five chemotherapeutic drugs was given to 115 women with metastasizing breast cancer. These were unselected cases. Three drugs (cyclophosphamide, methotrexate and prednisone) were given to 49 patients, with remissions occurring in 28, arrest in a further five. Five drugs (additional to the three mentioned ones: vincristine and 5-fluorouracil) were given to 66, with remission in 45 and arrest of the disease in another eight. There was no certain difference between the response to the two forms of treatment. Mean survival time for both forms was 13 months in the remission group and six months in the failure group.


[Is there a risk of transmitting hepatitis by gastroduodenoscopy?]. Among 211 patients undergoing gastroduodenoscopy five had been carriers of Australia antigen. The same instrument had been used on all, and follow-up examination was carried out two and four months after the gastroscopy. Twelve patients died during the follow-up period of their original disease. Two additional patients became Australia-antigen positive. One of these had liver cirrhosis. In the other, surgery with multiple infusions of albumin had been carried out after gastroscopy and could have been the cause of the Australia-antigen transmission. No proven case of hepatitis transmission occurred in this group of patients.


[Experimental and theoretical studies on the in-vivo production of a partially synchronous proliferating cell population with vincristine]. The problem of whether vincristine can be used to synchronize partially cells in vivo was investigated. After injection of 0,0045 mug vincristine/g body-weight into mice practically all L1210-ascites tumour cells entering mitosis were arrested in metaphase up to the fourth hour. However, no second peak of the mitotic index was observed within 48 hours. Calculation of the theoretical mitotic index to be expected under the present experimental conditions also shows no second peak. The reason for this lack of synchrony is the long releasing time of the arrested cells.


[Fibromuscular dysplasia of the internal carotid and intracerebral arteries (author's transl)]. Fibromuscular dysplasia was found in six patients (four women over 50 years, a 20-year-old man and a five-year-old girl). Angiography (in five cases performed because of a cerebrovascular accident) gave the typical appearance of "knotted string" changes in the large and medium sized arteries. With marked localized arterial narrowing treatment is surgical. Conservative treatment remains sympotomatic because the cause of the disease is still unknown. Even surgical treatment brings only sympotomatic relief and, because of the slowly progressive nature, is indicated only when there are neurological signs.


[Combined traumatic rupture of the rotator cuff and nerve lesions (author's transl)]. Traumatic damage to the rotator cuff was diagnosed in 13 patients by clinical, electromyographic and arthrographic studies. The main features were failure to rotate, elevate or abduct the affected shoulder joint. Eight patients also had peripheral nerve lesions: axillary nerve lesion was present in five, partial brachial plexus lesion in three.


[Gastric polyps: prognosis and treatment]. 49 patients, previously treated for epithelial gastric polyps by resection or excision, were re-examined up to 22 years later. Except for those who had died of other diseases, in five histologically confirmed and in one a probable (radiologically) gastric carcinoma had been found. Three cases of gastric carcinoma without symptoms were discovered in the course of endoscopic follow-up examination. Two of these patients underwent radical operation (early carcinoma), while the third one proved to be inoperable. It is concluded that gastric polyps must be removed endoscopically or operatively and examined histologically: simple observation must be rejected. If the polyp is hyperplastic, local removal is sufficient. If there is a pure adenoma, two-third resection is essential. This is also true of hyperplasiogenic polyps if they are present in large numbers, while polypectomy is sufficient if solitary. Polyposis usually requires subtotal or total resection. Each patient with such polyps is exposed to a higher risk of gastric carcinoma. For this reason annual endoscopic control is necessary even if there are no symptoms.


[Digestive and endocrine functions after partial duodeno-pancreatectomy]. Pancreatico-duodenectomy was performed in 11 patients for malignant or inflammatory tumours of the head of the pancreas or the region of the papilla. Digestive and endocrine functions were determined after the operation. In all cases faecal fat values were abnormal, indicating a 90% loss of pancreas. 14C-exhalation measurement, chymotrypsin determination in stool, and amylose tolerance test were also performed. Oral glucose-tolerance tests with plasma-insulin measurement indicated asymptomatic diabetes mellitus in the majority of patients. Two patients whose diabetes was controlled by tablets before the operation required insulin treatment afterwards. A decreased serum-gastrin level proved the existence of gastric and extragastric sources of gastrin.


[Passive immunization against rubella: studies on the effectiveness of rubella-immunoglobulin after intranasal infection with rubella vaccination virus]. The effectiveness of high-titre rubella immunoglobulin was tested on rubella-susceptible female juveniles or young adults after intranasal immunization with rubella strain RA 27/3, 20 ml of rubella immunoglobulin having been administered intramuscularly to 56 subjects at different times (1, 3 and 5 days) after the immunization. The effect was demonstrated by seroconversion and virus isolation from the throat. In the control subjects (26) the secroconversion was 96% and in 42% of subjects virus was demonstrated in the throat. Early administration of rubella immunoglobulin (up to three days after immunization) depressed the seroconversion rate to 55% and virus isolation rate to 17.5%. Later administration (five days after immunization) increased the conversion rate to 81%, the isolation rate to 31%. There were no serious side effects of the immunization and the injection of the immunoglobulin. The results indicate that on early administration of an adequate amount of high-titre rubella immunoglobulin a protective effect can be expected, although this favourable effect-obtained in the conditions of this study-cannot be unreservedly transposed to the situation in wild virus infections.


[Moving-picture corss-sectional echocardiography in normal children]. Using a parallel-scan B-mode ultrasonic system (Vidoson, Siemens) 200 children with clinically normal hearts were examined. Using a cross-section parallel to the left sternal border, rapid and easily reporducible multi-frame echocardiograms were obtained with simultaneous presentation of the aortic, pulmonary and mitral valves. Interpretation of this cross-section, with echos from the three valves, the aortic route, pulmonary artery, right and left ventricles and left atrium, was checked against post-mortem studies and in-vivo contrast studies with ultrasonic contrast medium (indocyanine-green). As the described method is not ECG-triggered, only important morphological changes are demonstrable.


[Primary calcification in Hodgkin's disease]. A chance radiological observation of a calcified mediastinal tumour in 23-year-old woman led to its operative removal. Histologically it proved to be a Hodgkin's sarcoma in a nodular sclerosing form of Hodgkin's disease. There was no other clinical evidence of Hodgkin's foci and, after radiotherapy, the patient has been without recurrence for over one year.


[Focal lipodystrophy in the bone marrow]. Small areas of slowly progressive disseminated osteolytic disease of unknown clinical, radiological and biochemical aertiology developed over three years in a 59-year-old man with exercise-induced pain in the left leg as the only symptom. Several bone biopsies merely revealed circumscribed primary dystrophy of the univacuolar medullary fat tissue with destruction and new formation of bone. The process, which is restricted to fat tissue of the bone marrow, has been termed "focal liposystrophy". It was also found in a briefly described second case. The pathogenesis is largely identical with comparable changes in extra-osseous fatty tissue which are also of unknown aetiology and usually termed "idiopathic".


[A new rapid test for diagnosing micro-haematuria, compared with results of microscopic examination]. Micro-haematuria may be difficult to diagnose because the usual sediment methods may be inadequate and test strips may in practice not be sensitive enough. The demarcation between normal and pathological RBC excretion is, therefore, not always clearly established. A new test strip (Sangur-Test) has its lower limit of positive results at 1 000 RBC/ml urine and physiological ranges of RBC excretion could be distinguished from micro-haematuria with satisfactory accuracy. Comparative tests of 637 freshly voided urine specimens in routine diagnosis produced no false-negative results and in only a small percentage of cases recorded a higher RBC concentration than the ten-field sediment method.


[Lipid islands in the gastric mucosa].

[Lipid islands in the gastric mucosa]. Circumscribed lipoid deposition in the gastric mucosa ("lipid island") can macroscopically be mistaken for "early cancer" of the stomach. The aetiology of the lipid islands is not quite clear. Precise diagnosis is possible only with selective biopsy and special staining. Such lipid islands were found in five patients among 1 200 gastrocopies.


[Congenital hypoplasia of the right ventricular myocardium (Uhl's anomaly)]. Partial aplasia of the right ventricular myocardium (Uhl's anomaly) was found at post-mortem examination of a 71-year-old woman. Most of the cases of this anomaly end fatally, in infancy or childhood, with treatment-resistant right heart failure, the diagnosis being only rarely made in life.


[Differential diagnosis of benign liver tumours (two cases of focal nodular hyperplasia)]. Two patients (33-year-old man and 24-year-old woman) with focal nodular hyperplasia of the liver were treated by surgery in 1973. This is a rare neoplasm of the liver which, according to past experience, is a benign one. The clinical signs and symptoms in the two patients were uncharacteristic, but on angiography there was marked tumour vascularization. Histologically the tumour is closely related to a hamartoma but its classification is diffucult because of the confused nomenclature.


[Conservative treatment of phytobezoars of the stomach with cellulase]. In a female patient anaemia due to chronic blood loss occurred after gastrectomy and subsequent vagotomy. Gastroscopy showed a phytobezoar to be the cause. In a second patient who had not had gastric surgery a phytobezoar was found as well as a prepyloric ulcer during investigations for upper abdominal symptoms. In both cases the phytobezoars could be removed completely within a short time after dissolution by an oral cellulase containing enzyme preparation and gastroscopic breaking-up.


[Pre-renal failure due to villous adenoma of the colon]. A 68-year-old man with known villous adenoma of the rectum had recurrent severe episodes of dehydration and electrolyte loss, misinterpreted as being due to "chronic pyelonephritic". The dehydration proved, in fact, to be due to the adenoma and ceased after removal of the tumour.


[Pancytopenia in diabetes mellitus treatment with tolbutamide?]. Pancytopenia developed in a 72-year-old woman after three years of tolbutamide treatment. When tolbutamide was discontinued and the usual treatment of pancytopenia undertaken, the anaemia persisted while the leukopenia and thrombocytopenia were reversed. Pancytopenia during tolbutamide treatment is extremely rare. But the blood picture and platelet count should be regularly checked in all patients receiving sulphonylurea drugs, ten days after starting treatment, every three months for the first year and then once yearly.


Direct effect of testosterone and its 5alpha-reduced metabolites on pituitary LH and FSH release in vitro: change in pituitary responsiveness to hypothalamic extract. A continuous flow incubation (perifusion) system was used to examine the effect of testosterone (T) and three of its 5alpha-reduced metabolites, dihydrotestosterone (DHT), 5alpha-androstane-3alpha, 17beta-diol (3alpha-Adiol) and its 3beta-epimer (3beta-Adiol) on LH and FSH release, induced by hypothalamic extract (HE). In the absence of steroids, successive identical pulses of HE, of 10 min duration each, administered at hourly intervals over a 8-hr period, caused highly reproducible release of LH and FSH. In experimental perifusions, the amounts of LH and FSH released in response to standard 10-min pulses of HE administered at hourly intervals during the continuous infusion of steroid for 4-6 hr were compared with the responses of the same pituitaries to the standard test pulses of HE given before the start of the steroid infusion and after its cessation. All the androgens tested altered pituitary responsiveness. At the 0.1 and 1.0 mug/ml dose level there were differences between the steroids in the way they influenced the responsiveness of the pituitary overtime. Their effects at these two doses fell into three categories depending on whether there was initially: 1) an augmentation of HE induced LH release (T and 3beta-Adiol), 2) augmentation of both FSH and LH release (DHT), OR 3) NO AUGMENTATION IN THE RELEASE OF EITHer gonadotrophin (3alpha-Adiol). All the androgens ultimately suppressed pituitary responsiveness to HE and all were associated with changes in the ratios of LH and FSH released. When the dose of T and 3 beta-Adiol was raised to 10 mug/ml or that of DHT lowered to 0.01 mug/ml the initial stimulatory phase was not seen. Epitestosterone, the biologically inactive epimer of T, did not alter the responsiveness of the pituitary of HE.


Studies on the heterogeneity of labeled iodoprotein from iodine-replete and iodine-deficient rats as determined by susceptibility to proteolysis. Thyroid iodoprotein from rats fed a high-iodine diet (HID) or a low-iodine diet (LID) were labeled with radioiodine in vivo for periods ranging from 4 hr to several days. Standardized aliquots of thyroid homogenate from rats with various treatments were digested for 4 hr with 1% pancreatin or with 0.003% pancreatin after 30 min pretreatment with beta-mercaptoethanol (ME-P). Four-hr labeled iodoprotein from both LID and HID rats was equally susceptible to digestion with 1% pancreatin; however, such iodoprotein from LID rats was more susceptible to digestion with ME-P than that from HID rats. With increasing intervals up to 7 days between administering radioiodine and removing the thyroids, there was a progressive rise in the resistance to digestion in iodoprotein from LID rats, but only a slight increase in resistance in iodoprotein from HID rats. If propylthiouracil was added to the diet beginning 24 hr after radioiodine administration, there was a marked increase in the rate of development of resistance of iodoprotein to digestion. Radioautographs showed that the radioiodine was localized primarily in the peripheral follicles after 2 days PTU. Similar differences in susceptibility to digestion were found in purified thyrogobulin prepared from HID and LID rats. No change in susceptibility to digestion of thyroid iodoprotein with time after labeling was seen in hypophysectomized LID rats in which thyroid secretion and thyroglobulin turnover is known to proceed at an extremely slow rate. The data indicate that there are at least two types of iodinated thyroglobulin in the rat thyroid. One is readily susceptible to digestion and has a rapid turnover in the thyroid. The other is more resistant to digestion, has a slow rate of turnover and is located primarily in the peripheral follicles.


Precocious puberty: the effect of adrenalectomy on PMS-induced ovulation and progesterone secretion. Female Sprague-Dawley derived rats were received at 21 days of age and either sham-operated or adrenalectomized on that day. Half of the animals received either 25 IU pregnant mare's serum gonadotrophin (PMS) or 0.9 saline at 9 AM on the next day; the other half were injected at 26 days of age. On the day of expected ovulation (days 24-25 and days 28-29) the rats were killed at 4-hr intervals and the incidence of ovulation determined. Serum progesterone and corticosterone were measured with the intent of comparing the pattern of these steroids with the timing and incidence of ovulation. Twenty-two-day-old rats given PMS ovulated later (at 0400 on day 25) than did the 26-day-old rats (at 2400 on day 28). Adrenalectomized ADRX rats ovulated later than intact controls at both ages (ovulation complete at 1600 on days 25 and 29, respectively). There was a reduced ovarian weight response to PMS in ADRX rats but uterine weights were not consistently different from intact PMS-treated rats. Associated with the different timing of ovulation and organ weight response in the ADRX rats there was a lower serum progesterone response on days 24-25. In intact PMS-treated rats, the rhythm of the serum corticosterone was different in the two age groups. It is concluded that adrenalectomy alters the normal response to PMS resulting in a delay in the time of ovulation. It is possible that the adrenal normally participates in the induction of ovulation after PMS, possibly by acting as an internal priming agent to facilitate gonadotrophin release in the young rat.


Vitamin D, dietary calcium and parathyroid hormone interactions in chicks. The effect of dietary vitamin D levels on the response to iv injected parathyroid hormone (PTH) was studies in chicks fed one of three diets: D-deficient, Control-D (1.4IU cholecalciferol/g diet), or High-D (70 IU cholecalciferol/g diet) during the first 4 weeks post-hatching. Compared to chicks on Control-D diet, chicks on the D-deficient diet had significantly decreased plasma Ca levels at 2 and 4 weeks and increased plasma P levels at 17 and 21 days. The plasma Ca response to a low dose of PTH (15 USP U/100 g body wt) 1 hr postinjection was normal at 1 week, reduced at 2 weeks and absent at 4 weeks in D-deficient chicks. However, a 4-16-fold higher dose of PTH did elicit a significant, though subnormal, response in this group at 3 and 4 weeks. Chicks fed the D-deficient diet with 2.8% Ca, compared to 1.4% Ca, showed a near normal plasma Ca level and bone ash content and only a small increase in plasma P at 17 and 21 days. However, the plasma Ca response to 15 U PTH/100 g body wt in this group was significantly increased only at 17 days and not at 21 days. In contrast, the hyperphosphatemic response to PTH was not markedly diminished in the D-deficient group, and it was restored to Control-D levels in the D-deficienyt High Ca group. These data suggest that different mechanisms may be involved in the Ca and P responses.


Placental steroidogenesis in the rat: progesterone production by tissue of the basal zone. Previous reports suggested that the rat placenta had a rather limited capacity for steroidogenesis, particularly with respect to progesterone production. We found that the basal zone in the rat placenta, which contains the steroidogenic giant cells, can be isolated by simple surgical separation, and using them for in vitro incubations, significant conversion of pregnenolone-7 alpha-3H to progesterone-1H could be demonstrated. The 5alpha-reduced metabolites of progesterone, as well as compounds of the delta4 pathway, including 17alpha-hydroxyprogesterone, androstenedione and testosterone were also isolated and characterized. When progesterone-7alpha-3H was added as precursor, most of it remained unmetabolized, but qualitatively identical products were isolated as were found when pregnenolong-7alpha-3H was used as precursor. Incubations of the whole placenta and of labyrinth tissue yielded relatively much lower progesterone-3H from pregnenolone-7alpha-3H. Our results have thus established that the rat placenta is a steroidogenic organ, just as in many other species. Past difficulties in isolating progesterone from in vitro studies may possibly be due to the intense activity of the enzyme 5alpha-reductase when the whole placenta was used.


The role of LH in the luteotrophic process of lactating rats. The role of LH in the leuteotrophic process was examined by evaluating progesterone secretion in pregnant, lactating, and pregnant lactating rats, and the response of these rats to antisera against LH (LHAS) was observed. Ovarian venous progesterone concentration in lactating rats was elevated as litter size increased. Treatment with LHAS on day 8 postpartum of rats nursing 12 pups significantly decreased peripheral progesterone levels within 24 hr. Treatment with LHAS on days 8 and 9 of pregnancy terminated gestation in all normal pregnant animals by in similarly treated pregnant lactating rats gestation was maintained until day 14 in 4 of 10 rats. If the litter was removed from pregnant lactating dams at the time of initiation of LHAS treatment, pregnancy was interrupted in all 12 animals. Ovarian venous progesterone concentration was reduced by greater than 90% 24 hr after LHAS treatment on day 8 of normal pregnant rats and 20alpha-OH-P increased such that the concentration of total progestins remained constant. Ovarian venous progesterone concentration 24 hr after LHAS treatment of pregnant lactating rats was reduced by 50% in animals receiving daily estradiol treatment by LHAS had little effect in pregnant lactating animals which received a single injection of estradiol on day 4 postpartum. The level of 20alpha-OH-P in pregnant lactating animals was not affected by LHAS. The results of these studies demonstrate that in lactating rats nursing a large litter (12 pups) LH is part of the luteotrophic complex, and the data obtained from studies in pregnant lactating rats suggest that when pregnancy and lactation are superimposed the role of LH in the luteotrophic process on day 8 of gestation is diminished.


Transformation of 3H-dopamine during transport from CSF to hypophysial portal blood. The capacity of the hypothalamus to transport dopamine from brain tissue into hypophysial portal blood was investigated. One hour after injection 10 muCi of 3H-dopamine into a lateral ventricle of male rats, radioactivity was present in the brain, in the anterior pituitary gland, and in systemic plasma. The highest concentration of radioactivity was found in the hypothalamus, whereas the lowest was found in systemic plasma. The cerebrum and systemic plasma contained over 50% of the dose injected, whereas the anterior pituitary gland contained no more than 0.2%. Three doses of 3H-dopamine (0.1, 1, 1nd 10 muCi) were injected into a lateral ventricle, and hypophysial portal and arterial blood were collected at 7 mu1/min for two hours. Ten min after injection, radioactivity was detected in hypophysial portal blood, reached a peak within 15-20 min, and then declined gradually to attain a concentration similar to that in arterial blood. Portal and arterial plasma and tissue extracts from rats injected intraventricularly with 3H-dopamine were subjected to gel filtration on a Sephadex G-10 comumn and to paper electrophoresis. The hypothalamus as well as the cerebrum contained several radiolabeled substances one of which appeared to behave like 3H-dopamine. However, no free 3H-dopamine was evident at this time either in blood or in the anterior pituitary gland. The results of chromatography and electrophoresis of dialyzed portal plasma indicate that much of the radioactivity was bound to macromolecules (probably plasma proteins) larger than 10,000-12,000 molecular weight. When the radioactive compound was dissociated from the macromolecule with perchloric acid, the dissociated compound did not behave as free 3H-dopamine as judged by gel filtration and electrophoresis. It is concluded that a transformation of 3H-dopamine occurred during passage from the CSF to blood and that no 3H-dopamine was present in portal blood. A large portion of the radioactivity was bound to plasma macromolecules.


Acute inhibition of mineralization and stimulation of bone resorption mediated by hypophosphatemia. Using rats previously labeled with 45Ca, the effects of a severely phosphate deficient diet on calcium mobilization from bone into serum were examined in both intact and thyroparathyroidectomized (TPTX) RATS. With the TPTX animals, increased calcium mobilization from bone was evident 12 hr after the rats had been placed on the low phosphorus diet. At that time period, both TPTX and intact rats had become severely hypophosphatemic. However, in intact rats, calcium mobilization was not observed until 48 hr had elapsed. Both intact and TPTX hypophosphatemic rats developed hypercalcemia. To determine if inhibition of calcium deposition into bone contributed to this change, the course of 45Ca movement from blood into bone was followed in an experiment where rats received a single injection of the isotope at the time the low phosphorus diet was given. The animals on the low phosphorus diet showed a significantly lower bone specific activity and a higher serum specific activity compared to the control group, indicating calcium deposition into bone was inhibited. We conclude that the acute response to hypophosphatemia, resulting from the low phosphorus dietary regimen, was an increase in bone resorption and an inhibition of bone mineralization. The increase in bone resorption occurred more rapidly in TPTX rats than in the intact animals.


Electrophoretic patterns of serum albumins collected from hereditary obese and diabetic mice. Sera collected at different post-feeding times from C57BL/6J, C57BL/6J-ob/ob, C57BL/KsJ and C57BL/Ksj-db/db mice were electrophoresed in urea-containing gels. According to variation in susceptibility of albumin molecules to urea denaturation, several ligand-binding albumins migrated as different bands. Sera collected at different post-feeding times from C57BL/6J mice showed different electrophoretic patterns; serum collected after a 20-hr starvation period consisted mainly of fatty acid-bound albumin (Band 1); serum collected after refeeding lacked fatty acid-bound albumin but contained slower migrating bands (Bands 3-7, the nature of which are obscure and show a resemblance to normal human sera. Sera collected during and after feeding from C57BL/6J-ob/ob mice showed an albumin pattern resembling that collected during and after feeding from C57BL/6J normal mice, but that collected during the fasting state from ob/ob mice contains Bands 3-7, which were not observed in the fasting state in normal mice. On the contrary, sera collected from C57BL/KsJ-db/db mice showed quite different patterns; Bands 3-4 did not appear in the sera collected during and after feeding, although the albumin pattern in the fasting state showed a normal pattern. Administration of insulin or anti-diabetic agents to fasted mice induced Bands 3-7, suggesting a relationship of Bands 3-7 to glucose metabolism of insulin action. To study the nature of the albumin-ligand complex, in vitro experiments were conducted and are reported herein.


Steroid production by the isolated rabbit ovarian follicle. III. Actinomycin D-insensitive stimulation of steroidogenesis by LH. The action of LH on steroidogenesis by isolated rabbit ovarian follicles has been examined. Follicles were incubated in culture medium at 37 C with medium being changed every 15 min. Media were analyzed for progestin, androgen and estrogen using established radioimmunoassay procedures. 'progestin and androgen secretion declined rapidly within 1.5 hr of incubation. Addition of LH (NIH-LH-S16), 5 mug/ml, for as little as 1 sec caused a dramatic increase in synthesis and secretion of androgen (greater than 100%) with lesser increases in secretion of progestin and estrogen. When puromycin and cycloheximide were added separately with LH there was inhibition of steroidogenesis for as long as either inhibitor was present in the medium. Addition of puromycin or cycloheximide after a mixture of LH and puromycin or cycloheximide delayed steroidogenesis until all of either inhibitor was removed. Actinomycin D in the medium failed to inhibit LH-induced steroidogenesis. These data suggest that the action of LH on steroidogenesis by the rabbit ovarian follicle probably occurs at the translational level and the binding of LH to the follicular ce-ls is a very rapid process.


Modification of stress-induced prolactin release by dexamethasone or adrenalectomy. A study was conducted to determine the influence of conditions known to alter ACTH secretion on prolactin release by the pituitary. Dexamethasone or 0.9% NaCl was injected subcutaneously into intact male rats 4 hr before a 2-min ether stress. Other rats were submitted to the ether stress 2 weeks following adrenalectomy. Five min following exposure to the ether stress, the rats were decapitated and trunk blood was collected. Dexamethasone (31, 125 or 500 mug/kg) blocked the stress-induced prolactin release in a dosage dependent manner with the highest dose decreasing plasma prolactin to levels similar to those observed in rats not exposed to the ether stress. Conversely, adrenalectomy was found to potentiate prolactin release due to ether stress. The results indicate that the adrenal may play a regulatory role in stress-induced prolactin release. The are also consistent with the suggestion that a common pathway or mechanism may be involved in pituitary release.


Formation and secretion of 5alpha-androstan-17beta-ol-3-one, 5alpha-androstan-3alpha,17beta-diol and 5alpha-androstan-3beta,17beta-diol by the perfused rabbit testis epididymis. Rabbit testes epididymides were perfused in vitro at 36.5 C with an artificial medium containing bovine red blooc cells. Three major testosterone metabolites were formed and subsequently elaborated into the venous effluent of testes epididymibdes when testosterone-1,2,6,7-3-H was infused into the artery of the perfused organ. In contrast, testosterone-1,2,6,7-1-H remained unchanged when incubated in the artificial medium under similar conditions. Elution volume from a Sephadex LH-20 column, development in three ascending paper chromatographic (APC) systems, acetylation and development in a fourth APC system followed by gas liquid chromatography (GLC) of the acetylated products tentatively identified the radioactive-metabolites as 5alpha-androstan-17beta-ol-3-one (DHT), 5alpha-androstan-3alpha,17beta-diol (3alphaol) and 5alpha-androstan-3beta,17beta-diol (3beta-ol). The identity of these 5alpha-reduced testosterone metabolites was confirmed by crystallization to constant specific activity in the presence of authentic carrier steroid. These results suggest that DHT and androstanediols formed by perfused rabbit testes epididymides subsequently escape into the venous effluent.


Partial masculinization of rat liver enzyme activities following treatment with FSH. The metabolism of 4-(4014C)androstene-3,17-dione and 5alpha-(4-14C)androstene-3alpha, 17beta-diol was studies in the microsomal fraction and that of 4-(4-14C) androstene-3,17-dione in the 105,000 times g supernatant fraction of livers from castrated male and female rats treated with LH and FSH. Administration of LH led to significant decreases in 17-hydroxysteroid reduction and 7alpha-hydroxylation of 4-androstene-3,17-dione in both male and female rats and in 6beta-hydroxylation of 4-androstene-3,17-dione in female rats. FSH on the other hand specifically stimulated (masculinized) the following sex-dependent hydroxylations: 16alpha-hydroxylation of 4-androstene-3,17-dione in female rats and 2alpha-, and 2beta- and 18-hydroxylation of 5alpha-androstane-3alpha,17beta-diol in male rats. The metabolism of 4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol was also studied in castrated male and female rats given testosterone propionate and in castrated female rats given testosterone propionate in combination with LH or FSH. It was shown that neither LH nor FSH could compensate for the relative androgen-unresponsiveness exhibited by female as compared to male rats. It is concluded that FSH but not LH may participate in the regulation of sex-dependent hydroxylase systems in rat liver.?2,Author


Male-induced precocial puberty in female mice: confirmation of the role of estrogen. Previous work has shown that exposure of prepubertal female mice to an adult male results in an immediate, sequential release of LH and estrogen. An ovulating release of LH follows in a predictable 3-day period, providing that male-exposure occurs at a particular body weight. Using this three day system, the present objective was to determine how effectively exogenous estrogen would substitute for the male's presence. Control experiments established that neither social isolation nor exposure to a castrated male would yield ovulatory puberty within the 3-day experimental period. Immature females were then subjected to a variety of sequences of three daily treatments including male-exposure and/or steroid injection. Two days of male exposure and no treatment on the third day was as effective in eliciting ovulation on the third night as 3 full days of cohabitation. Furthermore, either or both of the first two days of male-exposure could be mimicked by single injections of estrogen if followed by male-exposure for the remainder of the experimental period. A single injection of estrogen on the first day was ineffective in eliciting ovulation unless followed by male-exposure for 2 days, by a second injection of estrogen on day 2, or by an injection of progesterone on the third day. It was concluded that, as far as the induction of puberty is concerned, the important action of the male's presence is to elicit estrogen secretion (via a subovulating release of LH), and that this process must continue for 2 days, even in immediately prepubertal females, if the pubertal ovulation is to occur during the third night.


Evolution of adrenal-regeneration hypertension in blinded rats. The influence of blinding upon the blood pressure and adrenal regeneration of monoephrectomized but otherwise normal and mononephrectomized adrenal-enucleate rats on a high Na intake was evaluated. Blinding had no effect on control blood pressure, or upon the incidence, course and severity of adrenal-regeneration hypertension. Similarly there was no discernible effect on the regeneration of enucleate adrenal glands. The adrenal glandsands of otherwise normal blinded rats showed some enlargement in proportion to body weight, a finding which is probably attributable to loss of body weight in several animals.


The androgen status of vasectomized rats. Several factors related to androgen status were examined in vasectomized and sham-operated rats during and at the end of the 7th postoperative month. Average serum testosterone levels during the 7th month were based on three biweekly bleedings of 12 rats in each group, with determined values of 1.84 plus or minus 0.61 ng/ml (X plus or minus SD) for vasectomized rats and 2.38 plus or minus 0.78 ng/ml for sham-operated rats. Although average serum testosterone levels were 23% lower in vasectomized rats as compared to sham-operated controls, high coefficients of variation (33% and 32% in the two groups, respectively) rendered the difference insignificant. Within 1 hr of hCG administration, serum testosterone rose to 5.07 plus 1.94 ng/ml and 5.73 plus or minus 3.21 ng/ml in vasectomized and sham-operated rats. Eighteen hr after castration, testosterone had fallen below 0.25 ng/ml in both groups. Weights of testes and accessory sex organs were similar in both groups. Significant differences were not detected in the abundance, volume, or ultrastructure of Leydig cells. Each category of data collected in this study failed to reveal statistically significant differences were not detected in the abundance, volume, or ultrastructure of Leydig cells. Each category of data collected in this study failed to reveal statistically significant differences between the two groups, thereby supporting the essential normalcy of vasectomized rats with respect to androgen status.


Prostaglandin levels in tissues of the male reproductive system in six strains of mice. Prostaglandin E and F were measured in the testis, epididymis and vas deferens of six strains of inbred mice (A/J, AKR/J, C57BL/6J, DBA/2J, BALB/J and CE/J. The concentration of PGE and PGF was significantly higher in the vas deferens than in either the testis or the epididymis. Furthermore, the cauda epididymis contained a higher level of PGs than the caput portion. The relative preponderance of PGF to E varied between the tissues. The levels of PGs in the studies tissues indicated that they might be directly associated with the biological process of sperm maturation. The significant differences among strains of mice suggested that the observed variation might be, to a large extent, genetic.


On the quaternary structure of high-molecular-weight proteins from the bovine eye lens. Electron micrographs of high (40-S) and very-high-molecular-weight (240S) alpha-crystallin preparations show large aggregates with a random arrangement of individual low-molecular-weight alpha-crystallin molecules. The electron microscopic data are completed with viscosimetric and light-scattering experiments. All data obtained with higher-molecular-weight alpha-crystallins point to aggregates with non-spherical structures.


Studies on messenger and ribosomal RNA synthesis in plant tissue cultures induced to undergo synchronus cell division. Messenger and ribosomal RNA metabolism was tudied in a plant tissue culture system: cells from the quiescent tubers of Helianthus tuberosus (Jerusalem artichoke) were induced to divide synchronously and dedeifferentiate by excision and culture of explants in nutrient medium. Large accumulations of ribosomal RNA and protein started early in the 20-h lag-period preceding the first division. In pulse-labelling experiments, two types of polydisperse messenger-like RNAs were detected one with and one without a poly(adenylic acid) sequence. In the first 2 h of culture the two polydisperse RNA fractions were the predominant types of RNA synthesised. Ribosomal RNA synthesis was very low during the first 2 h, but acclerated later. Low concentrations of actinomycin-D strongly inhibited ribosomal RNA synthesis, but had little effect on the synthesis of transfer RNA or either type of polydisperse messenger-like RNA. In explants cultured with low concentrations of actinomycin-D ribosomal RNA accumulation was completely inhibited, but cell division and protein accumulation occurred, though at a reduced rate. It is concluded that the synthesis and accumulation of new ribosomal RNA which normally occur during culture are not required for the induction of cell division or for protein accumulation, i.e. the ribosomal RNA existing in the quiescent tuver cells can support protein accumulation and cell division induced by excision and culture. The quiescent tuber tissue is also shown to contain significant amounts of messenger-like RNA.


Determination of mRNA half-life in HeLa cultures by a poly(A)-independent direct analysis of specific radioactivity of mRNA. mRNA specific radioactivity in HeLa cultures exposed to (3H)uridine (10 muM) was determined directly by a highly selective poly(A)-independent method which we have described previously. Neither uridine in mRNA nor UTP approached the specific radioactivity of the exogenous (3H)uridine, but attained steady-state specific radioactivities which remained a third below the value of the added precursor. Using the labeling data for the evaluation of mRNA turnover, previously described by Greenberg, mRNA half-life in exponentially growing HeLa cultures was found to be 0.87 times the cell doubling time. Decay curves of mRNA in prelabeled cultures were in accordance with these values (half-life equals 0.79 times the cell doubling time) when corrected for growth and also for "reutilization" which was accomplished by relating uridine labeling in mRNA to UTP specific radioactivity. The experiments showed that an exact evaluation of mRNA turnover is possible only when the following points are taken into account. a) A constant supply of exogenous labeled uridine must be provided to guarantee a constant specific radioactivity of UTP. b) Labeling of CTP and of cytidine in RNA are delayed when compared with UTP and uridine in RNA. Corrections for cytidine labeling in RNA are therefore required. c) As rRNA approached a definitely lower steady-state specific radioactivity than mRNA, mRNA specific radioactivities must be determined directly (i.e. by radioactivity and absorbance at 260 nm in isolated mRNA fractions) in order to evaluate true turnover of this RNA species.


Molecular forms of yeast invertase.

Molecular forms of yeast invertase. The molecular forms of yeast invertase have been studied. It is shown that by gel filtration on Sephadex G-200 it is possible to demonstrate the presence not only of a light, carbohydrate-free, invertase, and a heavy invertase containing 50% carbohydrate, but also of a continuous spectrum of molecular forms that probably represent the sequential addition of mannose to the light form during the secretion process, which culminates in the formation on the heavy enzyme that is found outside the cytoplasmic membrane. The elution volume-void volume ratio in Sephadex G-200 varies from 1.75 of the light to 1.05 of the heavy invertase. The separation of invertase has also been achieved by ion-exchange chromatography and by isoelectric focusing and is facilitated by removal of the heavy form by ammonium sulphate precipitation. During the protoplasting process the removal of the cell wall is accompanied by the loss of most of the heavy form. Thintermediate forms are exclusively detected inside the protoplast, together with the light invertase and a small amount of heavy invertase. The effect of 2-deoxy-D-glucose and cycloheximide on the biosynthesis and distribution of molecular forms of yeast invertase has also been studied. In the presence of 10 mM glucose Saccharomyces 303-67 repressed cells readily synthesize invertase during the two-hour incubation period. Upon the addition of 2-deoxy-D-glucose, at a concentration of 75 mu g/ml, the observed inhibition in the cells is 60%, but if the activity is measured after breaking the cells, only a 31% inhibition is found, revealing an accumulation of invertase inside the protoplast. 2-Deoxy-D-glucose originates a pile-up of the light and intermediate forms at the expense of the formation of the heavy enzyme, showing that the inhibition of the glycosilation and, therefore, the secretion process, has taken place. In the absence of de novo invertase synthesis originated by cycloheximide, the glycosilation process still takes place as indicated by the accumulation of the heavy form at the expense of the light, carbohydrate-free, enzyme.


Electrophoretic characterization of membrane proteins during chloroplast development in barley. Membranes of plastids isolated from greening 15-cm (6 days) barley seedling were analysed electrophoretically using acid-soaked polyacrylamide gels. During greening five new major classes of membrane-bound proteins appeared having apparent molecular weights of 100 000, 63 000, 41 000, 39 000, and 34 000, respectively. As greening progressed these proteins became the prominent feature of the electrophoretic pattern. Chloramphenicol and cycloheximide each had different inhibitory effects on the appearance of the new protein bands. Mutants of barley (xantha-f, g, h) blocked at an early stage in chloroplast development lacked the light-induced bands. Conversely, mutants xantha-b-12 and b-18 with lamellar systems organized into giant grana lacked some, but not all, of the light-induced bands. At the early stages of greening the newly formed membrane proteins and chlorophyll were inserted into existing membranes. At later stages, all membrane components appeared to be synthesized. Evidence is discussed that certain membrane proteins are specific for grana, while others are associated with stroma lamellae.


Black-white differentials in infant mortality in the South, 1940-1970. This paper examines the trends and variations in the black-white differentials in infant mortality in ten selected Southern states during the 1940-1970 period. The patterns observed from the Southern states are compared with those observed from seven selected Northern states and the country as a whole. The ratios of black to white infant mortality rates and Fein's "time-lag" statistics are used as measures of the extent of black-white differentials. The gaps between blacks and whites in both neonatal and postneonatal mortality rates have widened in the Southern states between 1940 and 1970. No significant differences between the Southern states and the Northern states in the extent of black-whites differentials in infant mortality were observed. A positive association between variations among the Southern states in postneonatal mortality differentials and income differentials was found, while neonatal mortality differentials had a weak inverse relationship with income inequality. A series of general explanations of the observed trends and variations have been presented. Also, a detailed methodological consideration of the possible influence of artifacts of the data upon the trends and variations had been made.


Female professional work opportunities: a cross-national study. While economic development has been associated with increased participation of females in the labor force, it remains problematic whether sexual equality within the labor force has also increased. This study examines the differentiation of structural variables, specifically economic and demographic variables, on female participation and sexual equality within a specific sector of the labor force: the professions. The units of analysis are primarily European countries with the inclusion of the United States, Canada, Australia and New Zealand. The findings indicate that those economic development factors (female higher education enrollment rate and professional demand) significantly related to the female professional participation rate are distinct from those structural factors (economic growth rate, working age male deficiency) affecting sexual equality within the professional sector.


Stouffer's model of migration: a comparison of interstate and metropolitan flows. The objectives of this paper are (1) to evaluate the accuracy of the intervening opportunities-competing migrants hypothesis (Stouffer, 1960) in estimating 1955-1960 interstate migration streams in the United States and (2) to compare the results with those obtained by Galle and Taeuber (1966) for metropolitan migration. Our results strongly confirm Stouffer's hypothesis and yield parameter estimates highly comparable to those obtained  for metropolitan migration, except that competing migrants exert a stronger influence than intervening opportunities in interstate migration. Our study is based on 2,256 interstate migration flows in the continental United States, whereas Stouffer's intercity study and Galle and Taeuber's metropolitan study were each based on 116 migration flows. Our results indicate that Stouffer's theory holds for different levels of aggregation with remarkable consistency. Several theoretical models of the migration process are more compatible with Stouffer's original 1940 formulation of intervening opportunities than his 1960 reformulation. Estimates for interstate data indicate that the 1940 definition provides slightly better results. For both these reasons, it would seem that the 1940 formulation should be given serious consideration in future tests of Stouffer's hypothesis.


Competition between spontaneous and induced abortion. Because of their similar timing in pregnancy, spontaneous and induced abortions can be viewed as competing outcomes. Some intended abortion operations are anticipated by earlier miscarriages while some potential miscarriages are forestalled by earlier deliberate interruptions of pregnancy. Previous treatments of this competition are reviewed, and a new analysis is made on the basis of New York data. A simple rule for approximating the reduction in apparent incidence of spontaneous abortion in the presence of induced abortion is presented. The effects of nonreporting and misreporting of pregnancy outcomes upon this rule are examined by means of the Perrin-Sheps renewal process. Two expectations are tested on Taiwanese data.


Conceptive delay, nonsusceptible period, and cohort fertility patterns. A model of cohort fertility pattern by duration of marriage is built on the parameters of conceptive risk, its decline along parity, and the length of the nonsusceptible period. The model is found to fit satisfactorily a variety of cohort fertility patterns. Birth intervals by parity are then inferred from the estimated parameters. The present model is developed for comparative analyses of fertility trends and for fertility projections which take into account ongoing changes in birth intervals and completed family-size distributions which may be observed in current sample surveys.


Levels and patterns of infant and child mortality in Ghana. This paper attempts to measure infant and child mortality levels and also to determine their structure by utilizing the results of the 1968-1069 National Demographic Sample Survey which was conducted under the directorship of the author. Among the major problems encountered in the exercise are the adjustment of the current raw mortality data and the estimation of infant and child mortality from independent source material. The estimated infant mortality rates range from 56 per 1,000 live births in the Accra Capital District to 192 in the Upper Region during the late 1960's. The urban rate is lower than the rural rate, 98, as against 161 per 1,000 live births. A large proportion of the deaths among children aged 0-4 occur in the second year of life, and deaths in this age group account for the bulk of the deaths within the age group 1-4 years.


On a method for studying family size preferences. The concept of desired family size is widely accepted, and numerous studies have been undertaken to measure its level in certain population groups. The determination of desired family size has generally followed the direct question procedure through which the respondent states some whole number as representing her family size wishes at some specified period in her life. Limitations of this method have been recognized, and some research has been conducted toward the development of other techniques of measuring desired family size. The purpose of this paper is to discuss a method of estimating desired family size based on the concept of paired comparison, where the response is restricted in order to reduce respondent bias. Emphasis is on estimation of parameters and test statistics appropriate for evaluating the applicability of the underlying model.


Sons, daughters or both?: an analysis of family sex composition preferences in the Philippines. An analysis of family sex composition preferences as well as the relationship between actual family sex composition and desire for no additional children among a national sample of Filipino women is presented. An emphasis on balance or son-daughter equivalence is strongest in Metropolitan Manila. Son preference is highest in rural Mindanao and Sulu, primarily due to the concentration of Muslims in this section of the country and secondarily to its pioneer environment and the presumed utility of sons in such a milieu. The importance of eliciting sex composition preferences from both husbands and wives as well as distinguishing the "striking for a balance" from sex-linked preferences in future research is discussed.


Measuring change in sex composition.

Measuring change in sex composition. The present paper deals with changes over time in the sex composition of a given population. Such changes are generated by the components of population change: natality, mortality, immigration and emigration. The objective of this paper is to propose a model which provides a quantitative statement concerning the effect of each such component on the change in the sex composition of the population. It is shown that the model is applicable to the measurement of sex composition by either the masculinity proportion of the sex ratio. To demonstrate the application of the proposed model, an example based on Canadian data is given.


The welfare effect of an additional child cannot be stated simply and unequivocally. There is no single calculable welfare effect of an additional person. Rather, there are many different judgments, which may be negative or positive. The welfare effect depends upon the particular economic situation the child will be born into, which point in his life-cycle one refers to, whether he is expected to have a positive effect upon his particular sort of economy and society during and after his lifetime, and most of all, on the kind of welfare criterion used. Furthermore, no matter which welfare criterion is used, the welfare effect of an added individual summarized over time is especially sensitive to the particular assumptions made.


A genetic study of lactose digestion in Nigerian families. The ability to digest orally administered lactose was determined in individuals representing a number of Nigerian ethnic groups. The data are mainly presented as family pedigrees. In those families where both parents were unable to digest lactose, all of the progeny were lactose nondigestors. If one parent, usually of Northern garopena origin or of the Fulani tribe, could digest lactose, then the progeny contained some or all individuals who were capable of digesting the disaccharide. There was no difference in the results when either the mother or the father was the lactose digestor. Ten families were studied where one parent was of Europena or Yoruba-European origin (lactose digestor) while the other was proper Yoruba 0lactose nondigestor). From these matings, there were 18 lactose digestors and 11 lactose nondigestors. We have concluded that the ability to digest lactose is transmitted as an autosomal dominant and represents the mutated gene or a polymorphism.


Plasma adrenaline and serum gastrin: studies in insulin-induced hypoglycemia and after adrenaline infusions. Serum gastrin, plasma adrenaline, and blood glucose concentration were measured in 12 patients during insulin-induced hypoglycemia. Six patients had a duodenal ulcer, and 6 patients, 2 to 3 months earlier, had undergone a selective gastric vagotomy due to a duodenal ulcer. The lowest blood glucose concentration was obtained 30 min after the injection of insulin. The rise in plasma adrenaline showed a significant correlation with the degree of hypoglycemia attained. Serum gastrin was approximately doubled in both groups of subjects during the test. There was a strong correlation between rise in serum gastrin expressed in percentage of the basal value and the plasma adrenaline during hypoglycemia. In other experiments, adrenaline was infused intravenously in normal subjects in amounts (6 mug per min for 20 min) resulting in plasma concentrations comparable to those seen during the infusion. It is concluded that adrenaline is a hitherto little recognized factor influencing the gastrin response to hypoglycemia.


Lack of dietary regulation of jejunal glycolytic enzymes and disaccharidases in obesity: the role of insulin. Dietary regulation of jejunal glycolytic regulatory enzymes and disaccharidases were studied in 9 obese subjects, aged 9 to 18 years. These subjects were divided into two groups on the basis of altered carbohydrate metabolism as measured by circadian insulin levels and flux of glucose, inorganic phosphorus, and insulin measured during a 5-hr oral glucose tolerance test. Those patients with nocturnal hyperinsulinemia and abnormal carbohydrate flux showed no adaptation of jejunal enzymes. These data suggest that both glycolytic regulatory enzymes and disaccharidases are susceptible to insulin regulation.


Plasma catecholamines and postoperative gastric emptying and small intestinal propulsion in the rat. The role of adrenal medullary discharge of catecholamines on inhibition of gastric emptying and small intestinal propulsion after laparotomy was examined in rats. The rate of movement of a 51Cr-labeled liquid test meal, which had been introduced by gastric intubation, out of the stomach and through the small intestine, was retarded 12 hr after laparotomy. Adrenal demedullation produced a striking decrease in plasma catecholamines and abolished surgically induced elevation of the catecholamines, but had no significant effect on gastric emptying or intestinal propulsion in rats subjected to laparotomy or in the unoperated control animals. Thus circulating catecholamines play little if any role in controlling normal gastroinestinal motility or in the postoperative decrease in rate of gastric emptying and small intestinal motility.


Stimulation of proteolytic digestion by intestinal goblet cell mucus. Intestinal goblet cell mucus (GCM) was added to incubations of casein and trypsin (or chymotrypsin) to discover whether mucus could inhibit proteolysis. Contrary to expectation, GCM stimulated casein hydrolysis, reaching a maximum effect at a GCM to casein ratio (w/w) of 0.083. GCM did not contain proteolytic enzymes or proenzymes as contaminants, nor did GCM serve as a substrate for trypsin. Stimulation was not reduced by removing 85% of the sialic acid from GCM. Harsh physical treatment (boiling and freezing) of casein decreased (50%) the GCM effect, as did partial predigestion of casein by trypsin, and elevation of trypsin concentration beyond 3 mug per ml. Thus the undegraded structure of casein appeared to be important for the stimulation of proteolysis by GCM. GCM also enhanced the hydrolysis by trypsin of intestinal brush border membrane protein, but had no effect on the hydrolysis of hemoglobin, albumin, or benzoyl arginine ethyl ester. These results suggest that GCM reacts with specific substrates, in a fashion which promotes their digestion by trypsin or chymotrypsin.


The Budd-Chiari syndrome: correlation between hepatic scintigraphy and the clinical, radiological, and pathological findings in nineteen cases of hepatic venous outflow obstruction. From 1965 to 1972, 19 patients with the Budd-Chiari syndrome were investigated. An underlying diagnosis was made in 10 cases, polycythemia rubra vera being the commonest etiology. Percutaneous liver biopsy confirmed the diagnosis in 18 patients, and in 14 the site of hepatic vein obstruction was defined or its presence suggested by hepatic venography. Hepatic scintiscanning showed predominant central localization of radiocolloid in 7 patients. In another 8 patients this appearance was present in association with other less specific features. These findings were correlated with inferior vena cavography in 13 patients in whom a characteristic narrowing and distortion of the vein throughout its intrahepatic course was noted. In 3 other patients, the vein was found to be occluded. Autopsy evidence in 6 patients suggests that the central concentration of radiocolloid on scintiscanning and the narrowing and distortion of the inferior vena cava were due to disproportionate enlargement of the caudate lobe. Additional studies indicated that the separate venous drainage of the caudate lobe may be preserved when the main hepatic veins are occluded and that hypertrophy of the caudate lobe occurs because of its relatively more efficient perfusion. Demonstration of the enlarged caudate lobe by scintiscanning and inferior vena cavography provides valuable diagnostic support for the Budd-Chiari syndrome.


Prognostic significance of subacute hepatic necrosis in acute hepatitis. A retrospective analysis has been made of 57 patients with subacute hepatic necrosis demonstrated on a liver biopsy obtained during the course of an episode of acute hepatitis. Fourteen patients have been lost to follow-up. One patient died acutely with massive hepatic necrosis, while 8 have developed chronic active liver disease. Two of nine biopsies subsequently performed on patients who had shown complete clinical and biochemical resolution revealed an inactive postnecrotic cirrhosis. The incidence of these complications developing in patients with subacute hepatic necrosis was approximately 30%. These findings add qualitative  support to the position that liver biopsy findings bear important prognostic value in patients with acute hepatitis.


Serum ferritin in patients with iron overload and with acute and chronic liver diseases. An immunoradiometric assay was used to determine serum ferritin in patients with iron overload disorders and in patients with liver disease. In patients with iron overload, serum ferritin was closely correlated in an exponential manner with quantitative measurements of storage iron; however, a different relationship applied when storage iron levels were within normal range, suggesting that circulating ferritin is in equilibrium with two functionally distinct tissue ferritin pools. High ferritin levels were common in patients both with acute and chronic liver disease, normal values being virtually confined to women and to subjects with a history of recent hemorrhage. In liver disease generally, serum ferritin varied both with the serum transaminase level and with liver iron concentration, but correlated well with neither factor separately. There was no correlation with the serum iron or total iron-binding capacity. An extremely close correlation was found between serum ferritin and an empirical index derived from the product of the serum transaminase times liver iron concentration, implying that the circulating level depended on both the degree of hepatocellular injury and liver iron store. There was a close linear correlation between the serum ferritin-transaminase ratio and liver iron concentration in all disorders studied, and this index may prove to be the most useful value for diagnostic purposes.


Sulfation and renal excretion of bile salts in patients with cirrhosis of the liver. Renal excretion of bile salts was studied in 17 patients with cirrhosis of the liver. The average quantity of bile salts in urine was 10.2 plus or minus 8.3 mg per 24 hr, 56% of which were sulfated. Of the individual urinary bile salts, 24% oithocholate were sulfated. In contrast, neither sulfated nor nonsulfated bile salts could be detected in urine from 2 normal subjects. Kinetics of bile salt metabolism was measured in 2 of the cirrhotic patients after oral administration of [14C] cholate and [3H] chenodeoxycholate. Approximately 3 to 12% of bile salts synthesized in liver were excreted in urine. Most urinary bile salts (76 to 80%) were sulfated, whereas only 4 to 5% of serum bile salts and 7 to 10% of biliary bile salts were sulfated. Renal clearance of cholate was more than 3 times greater than the clearance of chenodeosycholate or deoxycholate. Renal clearance of sulfated bile salts was 20 to 200 times greaterthan the clearance of the corresponding nonsulfated bile salts.


Sulfated and nonsulfated bile acids in urine, serum, and bile of patients with hepatobiliary diseases. Large amounts of bile acid sulfate were found in the urine of patients with hepatobiliary diseases. In patients with acute hepatitis, daily excretion of bile acid into urine was 68.24 plus or minus 51.80 mumoles per day, and the percentage of sulfated bile acid was 83.4 plus or minus 16.7%. In patients with chronic hepatitis and cirrhosis, a slight increase of urinary bile acid was observed (2.89 plus or minus 2.69 and 5.27 plus or minus 4.28 mumoles per day, respectively), and the percentage of sulfated bile acid was 73.9 plus or minus 28.6 and 44.6 plus or minus 30.4%, respectively. In patients with obstructive jaundice, a moderate increase of urinary bile acid was found (32.62 plus or minus 18.35 mumoles per day), and the percentage of sulfated bile acid was 58.3 plus or minus 22.6%. In patients with hepatobiliary diseases, the elevation of both levels of sulfated and nonsulfated bile acids in serum was observed. The percentage of sulfated bile acid was 9% in normal serum, and varied from zero to 82.8% in pathological sera. A remarkable increase of sulfated bile acid was found in patients with obstructive juandice and acute hepatitis, while a slight elevation was found in patients with chronic hepatitis and cirrhosis. Sulfated bile acid in bile was nonexistent or below 0.5% of total bile acid. According to these findings, the increased bile acid in serum of patients with hepatobiliary diseases might be more easily excreted into the urine as sulfated bile acid.


Biliary excretion of iodipamide.

Biliary excretion of iodipamide. Conflicting data have been reported concerning the optimum dose and rate of administration of iodipamide required to obtain maximum radiographic opacification of the biliary tree during intravenous cholangiography. Experiments were performed in dogs to determine the effect of plasma concentration on the excretion and concentration of iodipamide in the bile and urine during a steady state of infusion and excretion. The data indicate that a hyperbolic relation exists between the plasma concentration and both the biliary concentration and the total biliary excretion. A mathematical expression of these relations is presented. At low plasma concentrations, iodipamide was not excreted in the urine. However, at high plasma concentrations, urinary excretion increased sharply. It appears that a biliary concentration of iodipamide sufficient to achieve adequate radiographic visualization of the biliary tree can be obtained without significant renal excretion by constant infusion of iodipamide at an appropriate rate in dogs. Stepwise increase in the infusion rate until adequate radiographic visualization is obtained may be the best method for performing intravenous cholangiography to obtain visualization with the least amount of iodipamide in order to minimize toxicity.


Preoperative cytological diagnosis of gastric leiomyosarcoma. A report of three cases. Gastric leiomyosarcoma has rarely been diagnosed prior to operation. Three cases are presented in which a cytological diagnosis compatible with leiomyosarcoma could be made preoperatively by exfoliative cytology using a brushing technique under direct vision. Data which favor the diagnosis of leiomyosarcoma are: (1) spindle-shaped cells with malignant looking nuclei; (2) cells with extremely long, fiber-like cytoplasms and hyperchromatic nuclei; (3) large, anaplastic malignant cells. Smears from 3 patients showed a mixture of these different cell types. This cytological presentation is probably unique and diagnostic for leiomyosarcoma.


Effect of phenobarbital in a case of extrahepatic cholestasis. Phenobarbital was administered to a patient with extrahepatic biliary obstruction who was initially thought to have cholestatic hepatitis. On two occasions, administration of the drug was associated with a decrease of jaundice, pruritus, and serum bile acid levels. This strongly suggests that phenobarbital may be effective not only in intrahepatic cholestasis, as reported earlier, but also in extrahepatic obstruction, and therefore cannot be used for the differention of these two types of cholestasis.


In vitro studies of ulcerative ileojejunitis. A patient with ulcerative ileojejunitis was studied by determination of HL-A phenotype, by measurement of jejunal IgA synthesis using a labeled amino acid incorporation technique, and by in vitro organ culture. The patient carried the HL-A8 phenotype in common with 87.5% of patients with gluten-sensitive enteropathy. During a period of exposure to dietary gluten, jejunal tissue from the patient exhibited in high IgA synthetic rate. In organ culture of the jejunal biopsy specimen there was an increase in alkaline phosphatase activity in the absence, but not in the presence, of gluten peptides. The synthetic rate value and the organ culture behavior are similar to those observed in patients with gluten-sensitive enteropathy in exacerbation. During a period in which the patient was not exposed to dietary gluten, including prolonged period of intravenous alimentation, jejunal IgA synthesis and organ culture behavior were studied repeatedly. In contrast to patients with gluten-sensitive enteropathy in remission (i.e., on a gluten-free diet), jejunal IgA synthesis did not decline. However, in organ culture in the patients tissue now behaved like that of other patients with gluten-sensitive enteropathy in remission: alkaline phosphatase activity increased during culture in the presence and absence of gluten peptides. These studies support the concept that ulcerative ileojejunitis is a complication of gluten-sensitive enteropathy in which escape from control by gluten restriction has occurred. They suggest that ulcerative ileojejunitis due to a supervening pathological process which is, at least in part, immunological in nature.


Changes in the mitotic cycle induced by alpha-solanine. Low concentrations of alpha-solanine stimulated the growth of cultured human fibroblasts, while higher concentrations (greater 30 mug ml-1) had a markedly inhibitory effect. Autoradiographic studies indicated that the stimulation of cell growth was due to a shortening of the G1 phase. Feulgen microdensitometry of cells treated with high doses of alpha-solanine revealed an abnormal accumulation of cells in G2. The response of cultured human fibroblasts to low doses of alpha-solanine is comparable to that of sex hormones on target tissues. It is concluded that by virtue of either its stimulatory or its inhibitory effect on cell growth, alpha-solanine could act as a human teratogen.


Prevalence of Edwards' syndrome. Clustering and seasonal variation? The incidence of Edwards' syndrome was found to be 1 per 4857 newborn children of 34000 consecutively newborn children in two Danish counties. Six of the 7 cases were born during the months of February through April. The incidence was high compared with the expected incidence of Edwards' syndrome of approximately 1 per 10000. This might be due to clustering in the area studied during the period 1967 to 1973. The finding of variations in incidence of children with Edwards' syndrome in different parts of the world, as well as the finding of seasonal variation in birth of such children, indicates that some of the etiological factors of nondisjunction of chromosome 18 are of an environmental nature.


Structural X-chromosome abnormality in a female with gonadal dysgenesis. A patient with gonadal dysgenesis and 46 chromosomes is described. In the inactive X chromosome there seems to be a deletion of the short arms and an insertion of heterochromatin in the long arms. The most probable mechanism to explain this structurally abnormal X is a pericentric inversion, with breakage and union having occurred in the centromeric heterochromatin of the short arm and in band q23 of the long arm. An amplification of the centromeric heterochromatin left in the short arm is also supposed.


Structural aberrations of chromosome 18. II. The 18q- syndrome. Report of three cases. 3 cases of the 18q- syndrome, 2 boys and 1 girl, are presented, and a comparison with data from the literature is given. The following features are typical of the syndrome: short stature, mental retardation, muscular hypotonia, a peculiar dysmorphia of the face and ears, cryptorchidism and small scrotum in males, proximally implanted thumbs, tapering fingers, excess of whorls on the fingertips, and dorsally implanted second toes. Midface hypoplasia with hypertelorism and cleft palate, as well as strabismus, were present in 2 of our patients, whereas all 3 showed nystagmus and prominence of anthelix and antitragus. In addition, 2 patients exhibited narrow ear canals and impaired  hearing. One patient had coloboma of the iris and choroid, pale optic discs, and cleft lip; another had umbilical and inguinal hernias. Two cases represented de novo deletions of the long arm of chromosomes 18, whereas the karyotype of the father of third case revealed a balanced translocation t(15;18)(q24;q21).


Red cell glutamic-pyruvic transaminase gene frequencies in the region of the Po Delta (Ferrara, northern Italy). The red cell glutamic-pyruvic transaminase phenotype has been determined in 294 individuals from the region of the Po delta (Ferrera, northern Italy). No correlation with past malarial morbidity has been detected. The gene frequencies found in this survey are similar to those reported for other Caucasian populations. One GPT3/GPT1 individual has been found.


A girl with karyotype 46,XX,del(7)(qter-p 15:). A girl with partial deletion of the short arms of one chromosome 7 is described. Among many other symptoms she has craniosynostoses. Early closure of cranio-sutures has previously been described in 2 of 3 patients with partial deletion 7. Investigation of a number of genetic marker systems shows that the HL-A, MN, AcP, and GPT loci are not located in the deleted segment.


Bovine veneral vibriosis: cure of genital infection in females by systemic immunization. Cure of female cattle with venereal vibriosis by systemic immunization with killed Campylobacter fetus cells in incomplete Freund adjuvant was investigated. Heifers infected in the cervicovaginal area with a cloned population of C. fetus venerealis were vaccinated subcutaneously 14 and 24 days thereafter with the infecting strain in incomplete Freund adjuvant. Six of eight vaccinated heifers were free of infection 25 to 48 days postinfection. One of the cured animals had an intercurrent infection which precluded interpretation of a vaccine effect. All controls remained infected 48 to 51 days postinfection, when the experiment was terminated. In vaccinated animals, agglutination titers against whole cells of the infecting strain reached peaks varying from 1,280 to 20,480 in serum and from 20 to 5,120 in cervicovaginal mucus (CVM) within days 24 to 32 postinfection. No consistent relationship was noted between levels of whole cell antibodies in serum and those in CVM. Evidence for the occurrence of antigenic variation in the organism after vaccination was sought by comparing the agglutinability of the infecting strain and CVM isolates in serum and CVM extracts. Serum samples of most cured heifers agglutinated whole cells prepared from isolates of the respective heifers to the same extent as cells of the infecting strain. In the corresponding comparisons, those from noncured animals agglutinated isolates to lower titers. CVM extracts from one cured animals agglutinated isolates derived from the same or closely spaced CVM samples to titers comparable with those obtained with the infecting strain. In the remaining animals, CVM extracts which agglutinated the infecting strain produced lower or undetectable reactions with corresponding isolates. It is proposed that the elimination of infection is dependent upon opposing responses of host and parasite, of which the degree of antigenic alteration in the infecting strain and the rate of mobilization and the concentration of specific antibodies in the genital secretions are key factors.


Effect of prednisolone on the leukocyte counts of ponies and on the reactivity of lymphocytes in vitro and in vivo. Treatment of ponies with a single dose of prednisolone markedly reduced the number of blood lymphocytes. A decrease of the number of eosinophils was also observed. In contrast, the number of neutrophils significantly increased. These profound changes were temporary and returned to the pretreatment level within 48 h. The number of monocytes did not show any of the significant changes post-prednisolone treatment. The reactivity of the blood lymphocytes of these ponies, in vitro, to stimulation with phytohemagglutinin (PHA) or streptokinase-strepto-dornase (SK-SD) was measured by incorporation of (3-H)thymidine by deoxyribonucleic acid of lymphocytes. The ponies' blood lymphocytes responded very well to PHA stimulation. The incorporation of (3-H)thymidine into deoxyribonucleic acid of the PHA-stimulated lymphocytes was 14 times greater than incorporation of the nonstimulated lymphocytes. SK-SD-stimulated lymphocytes incorporated only three times more (3-H)thymidine than nonstimulated lymphocytes. There was no significant difference in stimulation of lymphocytes with PHA or SK-SD before or after the prednisolone treatment. However, a significant decrease in the dermal response to the homologous antigen after this treatment in sensitive ponies was observed.


Detection of long-term cellular immunity to Coxiella burneti as assayed by lymphocyte transformation. Delayed hypersensitivity to the antigens of Coxiella burneti, Nine Mile strain, was demonstrated in human subjects with various past histories of exposure to the organism by using lymphocyte transformation assays. Individuals with histories indicating exposure to C. burneti up to 8 years before the study demonstrated marked lymphocyte transformation in vitro to whole-cell antigens consisting of formalin-killed C. burneti phase I and phase II. These individuals also demonstrated a marked lymphocyte response to the trichloracetic acid-soluable phase I antigen. One individual who acquired Q fever during the study and one individual who received an experimental Q fever vaccine 4 years earlier were also evaluated by the lymphocyte transformation assay. It was also found that phase I trichloroacetic acid-soluble material was capable of acting as an antigen in the assay, whereas the phase II trichloroacetic acid-soluble material did not contain any antigenic material capable of causing lymphocyte transformation. The complete phase I trichloroacetic acid-soluble antigen, which was found to consist of protein and carbohydrate, was chemically fractionated into monospecific fractions. The fraction treated to eliminate carbohydrate was the only fraction found to elicit an in vitro response.


Primary immunoglobulin response of herons to infection with Venezuelan encephalitis virus. Seven to nine days after inoculation with a replicating antigen, Venezuelan encephalitis virus, hemagglutination-inhibiting antibodies were present in plasma of 18 to 20 black-crowned night herons (BCNH), 14 of 15 great egrets (ge) , and 7 of 7 snowy egrets (SE). 19S (immunoglobulin M) precedes 7S (immunoglobulin G) antibodies in all but one bird of six GE, six SE, and six BCNH. 19S antibodies were detected for only 2 to 4 weeks post-inoculation. The induction period for both types of antibody was prolonged by 2 to 6 days as compared with earlier studies in gallinaceous birds using nonreplicating antigens. A marked delay in reaching peak titer of 7S antibodies was also observed. Hemagglutination inhibition tests were nearly as sensitive as neutralization tests for detecting 19S and early 7S antibodies. Size of virus inoculum did not measurably affect time of induction or titer of antibodies.


Characterization of endotoxin from Fusobacterium necrophorun. Endotoxic lipopolysachharide (LPS) was obtained from phenol-water extraction of cell walls prepared from mass-cultivated Fusobacterium necrophorum. The LPS was relatively free of nucleic acids and low in protein, and constituted about 4% of the cell walls. Upon acid hydrolysis, some of the components detected were hexosamines (7.0%), neutral and reducing sugars (50.5%), heptose (6.4%), 2-keto-3-deoxyoctonate (0.8%), lipid A (21.0%), and phosphorus (1.7%). Under electron microscopy the LPS appeared mainly as ribbon-like trilaminar structures, and upon chemical treatment it displayed a behavior resembling that reported in certain enterobacterial LPS. The LPS was lethal to mice, 11-day-old chicken embryos, and rabbits. Endotoxicity in mice was enhanced at least 1,380-fold by the addition of 12.5 mug of actinomycin D. Induced tolerance to lethal effect of the endotoxin and rapidly acquired resistance to infection by F. necrophrum viable cells were also demonstrated in mice. The endotoxin produced both localized and generalized Shwartzman reactions as well as biphasic pyrogenic responses in rabbits. These results firmly establish the presence of a classical endotoxin in F. necrophorum, thus providing strong support to our recent suggestion that cell wall-associated components may contribute significantly to the pathogenicity of F. necrophorum.


A new method of cone electroretinography: the rapid random flash response. A new procedure is described for cone electroretinography using a cross-correlation method of signal processing to give the response to flash stimuli which occur at randomly timed intervals. The output waveform is different than the usual repetitive flicker response, and can be presented on any desired time base. An unfamiliar aspect of this process is that most of the random time intervals between consecutive stimuli are shorter in duration than the output waveform. For the parameters described, the output waveform gives the response to approximately 1,640 stimuli in 65.5 sec., with a signal-to-noise ratio which is higher than that obtained when conventional averaging techniques are used over similar time periods. This allows more precise and statistically significant estimates to be made of the time and amplitude parameters of the cone response. Normal values are given for implicit (delay) time and amplitude, and examples are provided for comparison of the random flash response and conventional average electroretinograms (ERG's) in normal subjects and patients with retinal degeneration.


Experimental BUdR congenital cataracts.

Experimental BUdR congenital cataracts. Bilateral cataracts were produced in all 64 newborn rats from five pregnant rats treated on the sixteenth day of gestation with an intraperitoneal injection of bromodeoxyuridine (BUdR).


Optic nerve and retina after experimental circulatory arrest. The retinas and optic nerves of late juvenile and adult Rhesus monkeys that had survived transient, total arrest of systemic circulation were normal when examined with the light microscope. The period of circulatory arrest ranged from 12 to 30 minutes and the subsequent survivals ranged from four hours to one year. The optic nerve and retina thus seem to share with the rest of the brain a surprising degree of resistance to damage from circulatory arrest.


Physical properties of experimental vitreous membranes. I. Tensile strength. The tensile strength of vitreous membranes, induced by silk sutures imbedded in the vitreous body and removed one to two weeks later, was investigated in rabbits. Three types of membranes were distinguished by their appearance under an operating microscope; dense, opaque, cylindrical membranes, (Type 1), broken with 2 to 16 Gm. of force and elongated from 127 to 200 per cent before breaking; thin, cylindrical membranes, (Type 2), broken with 200 mg. to 2 Gm. of force and elongated from 51 to 152 per cent before breaking; and thin film-like membranes imbedded in formed vitreous gel, (Type 3), broken with 200 mg. to 5.5 Gm. of force and elongated from 53 to 186 per cent before breaking. Vitreous membranes formed two to eight weeks after surgery resisted forces greater than those required to detach rabbit retina. The results of the experiment are relevant in the design of vitrectomy instruments.


Quantitation of pilocarpine flux enhancement across isolated rabbit cornea by hydrogel polymer lenses. The comparative effect on pilocarpine flux across rabbit cornea induced by two hydrogel polymer lenses containing equal doses was quantitated in a transport chamber. This closed system featured continuous flow of a tear analog but excluded variables of the internal eye influencing concentration. Flux induced by both lenses increased linearly with time. At 240 minutes total flux was a whole order greater than that induced by the same pilocarpine dose in free fluid. Analysis of pilocarpine in tear analog effluent showed the flux to be independent of the available dose retained in the hydrogel polymer lens, suggesting that corneal transport of pilocarpine to the aqueous may involve mediation by a carrier system.


Intact omentum for ocular vascularization. Twenty dogs had their intact omentum extensively lengthened by a series of surgical maneuvers. Transverse incisions were then made along the chest, shoulder, neck, and scalp which were undermined and connected to form a subcutaneous tunnel through which the omentum was brought up to the orbit. The lateral rectus muscle of the eye was divided and a scaleral flap developed along the lateral superior region of the eye which exposed the choroid upon which the omentum was secured. Subsequent studies demonstrated vascular connections between intraocular vessels and those of the omentum. Proof of the existence of these vascular connections was based upon fluorescent funduscopic, gross, and histologic evidence.


Blood flow measurements in the iliac arteries by an improved angiographic cinedensitometric technique. The blood flow of iliac arteries was measrued by means of an improved angiographic chindensitometric technique. This consists of cineradiographic recording of contrast injection into the iliac arteries, followed by optical analysis of the "washout" phase of the contrast material at selected sites. In 25 pateints without perpheral vascular disease, undergoing abdominal angiography for different reasons, the blood flow measruements in left iliac arteries were within the limits of 371-766 ml


Experimental arteriovenous fistula. Creation and percutaneous catherter obstruction with cyanoacrylate. Arteriovenous fistula models were created of plastic and in dogs, allowing exploration of the intraarterial use of tissue adhesive, isobutyl cyanoacrylate. A delivery system utilizing superselective coaxial catheterization was developed on the model. Carotid artery to external jugular vein shunts constructed in 19 dogs provided a suitable in vivo model. Using varied injection techniques, the shunts were occluded in 17 of 17 treated animals. Three dogs subsequently died because of embolization to the lungs and one carotid artery was occluded. Techniques to avoid these complications were devised. Refinement of the intraarterial use of these adhesives will offer us another mode of treatment of vascular abnormalities.


Selective arterial embolization for the control of traumatic splenic bleeding. Artificial splenic trauma was created and treated with embolic material injected selectively into the splenic artery in 10 dogs. The bleeding was controlled by the original or a repeat embolization within the first 3 hours in all dogs. Seven dogs survived for 2 months. On angiograms performed prior to sacrifice, the arteries supplying the infarcted section of the spleen were again patent. Although both the arterial branches and the amount of splenic parenchyma in the area of infarction were smaller, the area of artificial trauma could not otherwise be identified. The histologic examination of the area of injury indicated healing of the injury and resolution of the infarct. The results of the study would indicate that selective embolization is a feasible method of controlling bleeding from splenic injury. Although embolism would not replace splenectomy as the generally used method, it could be used in patients who were not otherwise candidates for operative splenectomy.


Urinary magnesium and oxalic acid excretion in patients with recurrent oxalate urolithiasis. Of patients with oxalate-containing calculi of the upper urinary tract who were surveyed for stone recurrences after an average of 4 years and 7 months, the relationship between the stone recurrence and the urinary excretion of stone components was studied. Seventy-one cases for urinary calcium and magnesium, 48 cases for phosphorus, 36 cases for oxalic acid, and 29 cases for uric acid were available for estimate. The urinary excretion of calcium, magnesium, phosphorus, and uric acid was the same for noncurrent patients as for recurrent patients. However, the ratio of magnesium to (calcium x oxalic acid) in the urine patients with oxalate stone recurrences was significantly lower than that in the urine of patients without recurrences.


Effect of film graininess and geometric unsharpness on image quality in fine-detail skeletal radiography. Three direct x-ray films and three geometric conditions were used to study the effect of noise and sharpness on high resolution radiography of the hand. The Wiener spectrum of film graininess and the MTF of geometric unsharpness were measured. Radiographs of a wire mesh and a hand phantom, together with the Wiener spectra and MTFs, led to the following conclusions regarding fine-detail skeletal radiography, as currently employed: 1) bone structure detectable in vivo does not show minute structural detail; 2) the technique is primarily noise-limited; 3) the use of better geometry or finer grain film for improving resolution or noise is of limited practical value, whereas the use of poorer geometry or more noisy film results in appreciable degradation of skeletal images; and 4) the present standard technique for in vivo radiography of the hand, therefore, may be very nearly optimal for clinical applications.


Biliary and urinary excretion of iopanoic acid in the dog. The urinary and biliary excretion of iopanonic acid was studied in anesthetized dogs infused with sodium iopanoate and trace amounts of 125I-iopanoic acid to provide a wide range of plasma concentrations. Samples of kidney and liver were also analyzed for total radioactivity. The sole excretory product in urine and bile was the glucuronide conjugate. The secretory biliary Tm for for iopanoic acid varied between experiments. Biliary concentration far exceeded that of plasma and liver/plasma ratios were all greater than unity. The fractional rate of urinary excretion varied 1-80% and was strongly correlated with hepatic function, e.g. the rate of bile flow. The data are interpreted to indicate that, depending on the rate of bile flow, the glucuronide formed in the liver is partioned between bile and blood, the latter for urinary excretion. This mechanism is discussed in relation to cholecystographic visualization and to the problem of nephrotoxicity.


Ureteral function. II. The ureteral catheter and the urometrogram. The relationship between the urometrogram and the indwelling ureteral catheter was studied on female dogs having surgically explanted bladders. A new monitoring technique was employed which allowed for simultaneous recording of urometrogram, spurt volume, wave speed, and wave geometry for each peristaltic wave. The  caliber of the catheter was shown to influence both contractile amplitude and basal pressure level of the ureter. In one case, an increase in catheter size from 3.6 Fr. to 5 Fr. resulted in a 5-mm Hg rise in basal pressure with a simultaneous increase of 35 mm Hg in peak pressure amplitude. In addition, it was also shown that in dog ureters, catheters as small as 3.6 Fr. may result in elevated pressure levels. Based on experimental observations and an understanding of the passive and contractile characteristics of ureteral smooth muscle, a new model ofthe urometrogram is presented which is based on a contact pressure between the ureteral wall and catheter.


The effect of geometric and recording system unsharpness in mammography. Modulation transfer functions (MTFs) and test object radiographs were used to study the effect of geometric and recording system unsharpness in mammography with the CGR Senographe x-ray unit. Results show that geometric unsharpness can be a significant factor in the detection of microcalcifications within the breast, depending on the size and shape of the focal spot, the focal spot-to-recording system distance, and the object-to-recording system distance (o.r.d.). A new recording system for mammography, the DuPont Lo-dose system, requires approximately 1/15th the exposure of a direct x-ray film, such as Kodak RP/M, to provide mammograms with comparable photographic density. With the Lo-dose system, geometric unsharpness can be reduced by use of a specially designed long cone with an increased focal spot-to-recording system distance. This cannot be accomplished with direct x-ray films because the x-ray unit is operating at near-maximum output conditions even when short cones are used. Although direct x-ray films have a higher resolution than the Lo-dose system, at certain o.r.d.s total resolution is found to be affected more significantly by geometric unsharpness than by the Lo-dose recording system. In several cases, clinical results show improved detection of microcalcifications at larger o.r.d.s by the Lo-dose system with a long one, combined with a reduction by a factor of 15 in patient exposure.


Cystoscopy of chemically induced bladder neoplasms in rabbits administered the carcinogen dibutylnitrosamine. Subcutaneous injection of the carcinogen dibutylnitrosamine into male rabbits led to bladder papillomas, hemangiomas, and carcinomas within 17 to 26 months. The progress of the developing bladder lesions was readily followed by cystoscopy.


Accuracy and its relationship to experience in the interpretation of chest radiographs. One hundred chest radiographs, randomly selected from a hospital population, were read by 8 radiologists at 4 different levels of training and experience. All statements in the 800 interpretations were analyzed for accuracy. The analysis was based on deviation from a "true" report. Approximately 26% of significant and potentially significant statements were errors. Eighty per cent of these were false negative, 20% false positive. While significant individual differences in interpretive accuracy were found, there was no consistent pattern related to the duration of training beyond the first year of residency. Once an individual's radiologic education has progressed beyond a fundamental level, individual reader characteristics overshadow experience in the accuracy of chest film interpretation.


Epithelialization after cystotomy.

Epithelialization after cystotomy. Cystotomies were performed on mature guinea pigs using aseptic technique, and one layer closure with polypropylene sutures. It was found that epithelialization over the suture material was completed by 3 days and that epithelialization of the bladder mucosa itself after a mucosa-mucosa approximation was completed within 4 days. The main significance of this investigation is that the normal bladder mucosa was completely healed within 4 days.


Microangiographic anatomy of the cat's eye. The microangiographic anatomy of the cat's eye is presented. The characteristic vascular pattern of each of the three distinct circulations, retinal choroidal, and ciliary is described and illustrated.


The value of a stent in primary ureteral repair. Serum creatinine determinations and intravenous urography studies were made preoperatively and postoperatively on 14 dogs. Each dog underwent bilateral midureteral transection, followed by immediate elliptical ureteral reanastomosis. An indwelling stent was employed for 10 days on one side only. The use of an intraureteral stent did not influence the degree of stricture formation after ureteral repair. Factors contributing to the development of postoperative ureteral strictures are discussed.