Relationship of metal metabolism to vascular disease mortality rates in Texas. The annual mortality rates for 1968 of six types of cardiovascular diseases among those persons over 45 years of age in 24 Texas communities were compared with respective community drinking water and urine metal levels of calcium, magnesium, potassium, lithium, strontium, and silicon. Numerous inverse correlations were found between mortality rates and the levels of various metals in both drinking water and urine. Positive correlations were also observed between several of the mortality rates and the ratio of the concentration of sodium to that of the other metals in both water and urine. Mean community urinary levels of lithium, magnesium, strontium, and silicon showed a direct correlation to the levels of exposure via the drinking water. The results of this study suggest that calcium, magnesium, lithium strontium, and silicon may protect against cardiovascular mortality; possibly, by competing with sodium and potassium for transport in the intestinal lumen, increasing excretion of sodium, or other mechanism.


Absorption of stable isotopes of iron, copper, and zinc during oral contraceptives use. The absorption of iron, copper, and zinc was determined in 22 women 19 to 25 years of age from the difference between intake and fecal output of the stable isotopes 58Fe, 65Cu, and 70Zn, as measured by neutron activation analysis. Of the 22 women, 14 were using oral contraceptive agents, and the other eight were not. Absorption in the group using oral contraceptive agents did not differ significantly from the group not using oral contraceptive agents. The overall iron absorption averaged 14%, copper 57%, and zinc 38%.


Nutritional success in a semi-arid land: examination of Tswana agro-pastoralists of the eastern Kalahari, Botswana. The cultural and environmental factors affecting the food quest and nutritional status of the Moshaweng Tlokwa, a Tswana agro-pastoral society occupying the semi-arid eastern Kalahari Desert of Botswana, are examined. Data are presented on methods of food procurement, storage, preparation, and preservation. Tlokwa diet is based on agriculture horticulture and animal husbandry but a surprising number of wild species are regularly used as food. This pattern is nutritionally protective and viewed by the author as a principal reason for Tlokwa dietary success in their semi-arid environment. Data are presented on food habits, dietary prohibitions, and characteristic diets of infants, children, adolescents, and adults. Many Tlokwa foods are encouraged or prohibited on the basis of the consumers age, sex, and social development. Such patterns reduce competition for dietary resources, assure a more equitable distribution of food, and sustain the nutritional quality of diet. During 1973 to 1975 the Tlokwa appeared healthy and well fed; heavy rain-fall had just broken a 7-year drought. Kwashiorkormarasmus, avitaminosis, or other classical signs of malnutrition were not observed. A trend towards bottle feeding was noted. Children and adolescents are rapidly losing their ability to identify edible wild food resources. The author concludes that the Tlokwa heretofore have coped satisfactorily with drought in their semi-arid territory and recommends continued diversification of their food quest. Diversity is viewed as essential if the Tlokwa are to maintain their nutritional well-being in coming decades.


Dietary studies of older Americans.

Dietary studies of older Americans. Dietary surveys assessing the nutrient intake of older Americans have been briefly summarized to make information readily available to researchers, nutrition educators, and other interested persons. Calories and eight nutrients are discussed in terms of studies reporting means below the standards used, or at least one-third of the subjects with inadequate intakes. Food energy and calcium were the nutrients most frequently found to be below standards. The mean caloric intake was below the standards used in all large national surveys and a number of the smaller studies. Calcium was deficient in many of the studies, with more women likely to have an inadequate intake than men. Protein and niacin were the nutrients most often found to be sufficient. The mean intake of protein was adequate in all reviewed studies, with the exception of the Ten-State Survey, regardless of standard or dietary methodology used to estimate protein consumption. Nevertheless, several studies reported that at least one-third of their subjects fell below the standard used. The mean intake of niacin was inadequate in the Missouri Congregate Meals Program Survey and in two small studies. The Ten-State Nutrition Survey reported at least one-half the females and one-third the males with intakes less than 6.6 mg/1000 kcal.


Dietary intake and the risk of coronary heart disease in Japanese men living in Hawaii. The relationship of dietary intakes to subsequent development of coronary heart disease (CHD) during a 6-year follow-up period was investigated in 7705 men of Japanese ancestry, ages 45 to 68 and living in Hawaii. Data on the intakes of calories and nutrients were obtained by 24-hr diet recall interviews at the base-line examination. An index for ingestion of traditional Japanese diet (Japanese diet score) was also calculated for each man. The men who subsequently developed myocardial infarction or died of CHD generally ate less than those who remained free of CHD, with statistically significant differences for total calories, total carbohydrate, complex carbohydrate or starch, simple carbohydrate other than sucrose, vegetable protein, alcohol, and Japanese diet score. However, when other major risk factors for CHD were taken into account, the negative association with CHD remained statistically significant only for alcohol and, to a lesser extent, total carbohydrate intakes. The lower total caloric intakes in CHD cases, largely due to decreased alcohol and carbohydrate intakes, could not be accounted for by either under-reporting of food consumption among obese men or diminished physical activity in CHD cases.


Quantitative and qualitative evaluations of protein intake in a geriatric subpopulations from a southern Swedish community. The daily intake of protein and the amino acid content of food samples collected in association with a dietary survey of male and female Swedish pensioners, were determined. Duplicate portions of 1-day, mixed food samples were collected. The samples were homogenized and the fat was extracted before lyophilization. Protein content was determined by a modified Kjeldahl method. Cysteine and methionine were determined by ion-exchange chromatography after performic acid oxidation follow by acid hydrolysis, whereas tryptophan was determined by a spectrofluorometric method. All other amino acids were analyzed by gas-liquid chromatography. Median protein intake was 0.69 g per person per kilograms of body weight per day for the male pensioners and 0.67 g per person per kilograms of body weight per day for the female pensioners and 0.67 g per person per kilograms of body weight per day for the female pensioners. The quality of protein consumed by the participants, determined by amino acid analysis, showed that lysine, threonine, and tryptophan were the limiting amino acids. The chemical score, when compared with the FAO reference protein, varied between 35 and 100 (mean = 77).


Pelvic actinomycosis and the intrauterine contraceptive device. A cyto-histomorphologic study. In 350 pancervico-vaginal (Fast) smears obtained from women using intrauterine contraceptive devices, organisms consistent with Actinomycetes have been found. Actinomycetes, representing cervicitis, endometritis, and pelvic abscesses clinically, have been observed histologically in some of these cases. Special stains, immunofluorescence, and anaerobic cultures have confirmed these organisms to be Actinomyces israelii. Actinomyces in the Fast smear occur in isolated clumps, revealing branching, filamentous organisms, and sulfur granules. They can be detected and diagnosed in a Papanicolaou-stained routine pancervico-vaginal smear. This diagnosis in Fast smears can identify users of intrauterine contraceptive devices who may have Actinomyces infection in the genital tract and who are at risk of developing clinical disease related to this infection.


Blood group substances as tumor antigens in the distal colon. Adenocarcinomas of the sigmoid colon and rectum were studied for the presence of blood group substances of the A, B, H system using the method of specific erythrocytic adherence. Of 17 adenocarcinomas studied, eight were found to have reactivity for blood group substances. All eight tumours showing reactivity for blood group substances were from patients of the blood group type A, whereas no blood group substances reactivity could be found in any of the adenocarcinomas from patients of the B blood group type. The epithelial cells of the entire colon contain blood group substances in the fetal period; however, shortly after parturition the epithelial cells of the distal colon and rectum rapidly lose the substances. The reappearance of the substances in adenocarcinomas of the distal colon suggests that these neoplastic cells are expressing certain characteristics of fetal colonic epithelial cells.


A modified ion-selective electrode method for measurement of chloride in sweat. A modified method of analysis of sweat chloride concentration with an ion-selective electrode is presented. The original method of sweat chloride analysis proposed by the Orion Research Corporation (Cambridge, Massachusetts 02139) is inadequate because it produces erratic and misleading results. The modified method was compared with the reference quantitative method of Gibson and Cooke. In the modified method, individual electrode pads are cut and placed in the electrodes rather than using the pads supplied by the company; pilocarpine nitrate (2,000 mg/l) is used in place of pilocarpine HCl (640 mg/l); sodium bicarbonate as the weak electrolyte is used instead of K2SO4. A 10-minute period for sweat accumulation is employed rather than a zero-time collection as in the original Orion method. The modification has been studied for reproducibility in individuals, reproducibility between right and left arm in individuals; it has been compared extensively with the quantitative method of Gibson and Cooke, both in normal individuals and in patients with cystic fibrosis. There is excellent agreement between the modified method and the quantitative reference method. There appears to be a slight bias toward higher concentrations of chloride from the right arm compared with the left arm, but this difference is not medically significant.


Hepatic tumors of long duration with eventual metastases. Two cases of leiomyosarcomatosis possibly arising from hamartomas of liver. The cases of two patients who had hepatic tumors of long duration interpreted as hamartomas in whom, after many years, widespread metastases of malignant smooth muscle cells developed in a pattern of "carcinomatous lymphangitis" in the lungs are described. In one of the cases calcification of the hepatic nodules was prominent. The smooth muscle origin of the malignant cells was established only on electron microscopic examination. These cases appear similar to others variously reported as mixed tumors, hepatic cell carcinomas, and mesotheliomas.


Mixed teratoid tumors of the liver and neck in trisomy 13. A fetus with trisomy 13 syndrome and teratomas of liver and neck is described. The relationship of aneuploidy and chromosomal instability to neoplasia is discussed. Teratomas of the liver are reviewed.


Malacoplakia of the endometrium, a probable cause of postmenopausal bleeding. A 60-year-old woman, 20 years post-menopausal, who had deforming rheumatoid arthritis of 7 years' duration and Sjögren's syndrome of 1 year's duration, had had postmenopausal bleeding for a month prior to admission to the hospital. A diagnosis dilatation and curettage was interpreted as showing acute suppurative endometritis. The patient was discharged, only to have recurrent vaginal bleeding. She was readmitted five weeks later, at which time results of another dilatation and curettage were interpreted as showing xanthromatous endometritis. Total hysterectomy with bilateral salpingo-oophorectomy was done. Examination of Epon-embedded endometrium 1 micrometer thick by light microscopy and subsequently by electron microscopy disclosed intracellular bacilliform organisms within phagolysosomes of atypical histiocytes, lamellar bodies, and various developing stages of calcospherites, Michaelis-Gutmann bodies. The curettings were then received and classic Michaelis-Gutmann bodies were identified in periodic acid--Schiff-stained sections.


Origin of the calvaria and its sutures.

Origin of the calvaria and its sutures. Studies indicate that the dura is the guiding tissue in the morphogenesis of the calvaria and its major sutures, which develop from ten to 16 weeks of fetal life. Overlying the central zones between the dural reflections ossification takes place, whereas none occurs over the reflections of dura, these being the suture sites. Strong evidence for the role of the dural reflections in determining the suture sites was obtained from the evaluation of instances of major brain malformations that must have antedated calvarial morphogenesis. These included holoprosencephaly, craniopagus, and dicephaly. The altered dural reflections, which related to the aberrant form of the brain, coincided with the position of the unusual sutures. Furthermore, a lack of a dural reflection was accompanied by a lack of development of a suture at that site.


The Coffin-Siris syndrome: five new cases including two siblings. Five new cases and one previously reported case of the Coffin-Siris syndrome are described. These cases plus the remaining four already published bring to ten the number of cases available for scrutiny. Constant features (100% frequency) include variable degrees of mental retardation, nail hypoplasia or absence with predominantly fifth digit involvement, hypotonia, infancy feeding problems, and retarded bone age. Frequent features (75% to 90%) include postnatal growth deficiency, microcephaly, wide nasal tip and mouth, prominent lips, eyebrow/eyelash hypertrichosis, and scalp hair hypotrichosis. Significant but less frequent findings include short philtrum (50%, scoliosis (40%), decreased fetal activity (40%), smallness for gestational age (30%), and congenital heart defects (30%). We found the craniofacial phenotype to be mild in the young infant, but progressively more characteristic with age. Autosomal recessive inheritance is suspected on the basis of our brother-and-sister pair.


Mycobacterial lymphadenitis in childhood. A total of 42 cases of childhood mycobacterial adenitis have been studied to define the optimal steps that lead to the correct diagnosis of this disease. Antigens from the atypical mycobacteria are not currently available, so the usefulness of tuberculin skin testing as a diagnostic tool was examined. Skin testing differentiates mycobacterial adenitis from infection caused by pyogenic bacteria. In addition, repetitive skin testing with tuberculin over a three- to six-month period is also useful in differentiating adenitis caused by atypical mycobacteria from that due to Mycobacterium tuberculosis. Children with atypical mycobacterial adenitis have a decreasing tuberculin response to repeated testing, while children with tuberculous adenitis have a stable response. Other factors that assist in the differentiation of adenitides include a history of recent exposure to tuberculosis and evidence of extralymphatic tuberculosis. Needle aspiration or partial excision in mycobacterial adenitis may lead to drainage and sinus tract information. A PPD skin test should be done prior to surgical manipulation of enlarged nodes. Children with reactive skin tests should undergo complete excision.


Recurrent mumps parotitis following natural infection and immunization. Mumps is presumed to confer permanent immunity. Three patients previously known to possess mumps serum antibodies subsequently developed clinical parotitis and showed a diagnostic fourfold rise in mumps V antibody. A review of the literature disclosed several cases of parotitis, either recurrent or postimmunization, but the preparotitis immune status of the patient was unknown or the cause of the mumps was not verified. Case reports of parotitis due to parainfluenza 3 and coxsackie viruses A and the heterotypic serological responses among the myxoviruses are reviewed. Parotitis, especially after prior immunization, requires definitive diagnosis by viral isolation and/or serology before it can be attributed to mumps virus.


Modification of recurrent otitis media by short-term sulfonamide therapy. Alternating cases of upper respiratory infection (URI) occurring within two months of an episode of otitis media were treated with either sulfonamides or decongestants. One hundred three cases of uncomplicated URI were treated with sulfonamide and 98 with decongestant. When adjusted for possible recrudescence rather than recurrence the rate was 4/71 (5.6%) and 15/76 (20%) in the treated and control groups, respectively. This difference is significant (P less than .001) and suggests that intermittent prophylactic treatment can modify the recurrence rate of otitis media in children.


Sudden infant death syndrome and prolongation of the QT interval. A standard lead II ECG was recorded during either the first or the fourth week of life or at both ages from 30 neonates whose sibling had died of the sudden infant death syndrome (SIDS). Electrocardiographic recordings also were obtained from 75 control neonates and from 52 adults who had had an infant who died of SIDS. The neonatal data revealed that the QT interval, corrected for heart rate (QTC), was longest during NREM (vs rapid eye movement [REM]) sleep. Furthermore, the QTC interval was longer within the fourth week than in the first week of life. However, the QTC interval of siblings of SIDS victims did not differ from that of the control infants, nor did the QT interval of parents of SIDS victims differ from published normal values. One neonate who subsequently died of SIDS did not have an abnormally long QTC interval. These data do not support the hypothesis that genetically determined prolongation of the QT interval plays a major role in SIDS.


Dermatoglyphic alterations associated with acute rheumatic fever in children. The dermatoglyphic configurations of 78 children with acute rheumatic fever were compared with those of 46 first-degree relatives and 1,310 normal subjects. Of the children with acute rheumatic fever, 75% had an ulnar deviation of the axial triradius. In about 40% of this group, the ulnar deviation was associated with a concomitant distal displacement, which resulted in a significantly higher mean maximal angle atd (P less than .001) and significantly lower mean ab and td ridge counts (P less than .001) relative to normal control values. The palmar dermatoglyphics of patients with acute rheumatic fever were more closely related to the configurations of first-degree relatives than to normal controls. The dermatoglyphic profiles of six patients were nearly identical to those of their first-degree relatives, all of whom had a history of acute rheumatic fever. Presence of abnormal dermatoglyphic profiles in a large proportion of children with acute rheumatic fever supports the hypothesis that certain individuals have a genetic predisposition to this disease.


Myocardial infarct in a child with systemic lupus erythematosus. An unusual case of systemic lupus erythematosus (SLE) in a young child is reported with sudden death from myocardial infarction. The diagnosis of lupus erythematosus in this patient was made by renal biopsy at the age of 3 years. Atherosclerosis of the coronary arteries and aorta was found at autopsy with occlusion of the anterior descending branch of the left coronary artery. It is suggested that  the vascular changes in this case were related to hypertriglyceridemia and prolonged prednisone therapy superimposed on a hypersensitivity vasculitis related to SLE.


Heterotopic gastric mucosa in the epiglottis and rectum. A case of gastric heteropia of the glossoepiglottic region in a 13-day-old girl is described. In addition to fundic-type mucosa, all main parts of the gastric wall were present. An additional case of gastric heteropia in the rectum was found in a 14-year-old boy. The mucosa was lined with a muscularis mucosae. Adjacent to this ectopia was a large peptic ulcer. Previoisly reported cases of gastric heterotopias are reviewed.


Effect of histamine H1- and H2-receptor blockade on canine gastric acid secretion. In dogs with gastric fistulae and Heidenhain pouches, inhibition of histamine-stimulated gastric acid secretion by the histamine H2-receptor antagonist metiamide is not increased by the addition of a histamine H1-receptor antagonist (mepyramine maleate). Under the conditions of this study there is no evidence for the presence of histamine H1-receptor sites on the gastric parietal cell.


Characteristic motor activity of the gastrointestinal tract in fasted conscious dogs measured by implanted force transducers. Gastrointestinal contractile actiivity from the gastric body to the terminal ileum in conscious dogs was continuously recorded for several weeks by means of chronically implanted strain-gage force transducers. It was found that the 24-hr changes in the gastrointestinal contractile activity consisted of the two different major patterns, the digestive and interdigestive patterns. In the interdigestive state, a cyclic, recurring, caudad-moving band of strong contractions starting in the stomach and the duodenum and traversing the entire length of the small intestine was observed. When one band of strong contractions reached the distal ileum, another developed in the stomach and the duodenum again and propagated in a caudad direction. Such recycling episodes interrupted by long-lasting quiescence repeatedly occurred until the next meal. These characteristic contractile activities observed in our dogs are identical with the interdigestive myoelectric complex of the stomach and the small bowel recently reported by Code and Marlett (5). Four sequential phases (I-IV) of the migrating myoelectric complex, defined in terms of action potential activity, seem to correspond to the resting (quiescence), preceding irregular contractions, strong contractions, and subsiding contractions observed in the present study, respectively. Function and control mechanism of the interdigestive contractile activity were discussed.


Phlegmonous enterocolitis.

Phlegmonous enterocolitis. Eight cases of phlegmonous enterocolitis which involved the small intestine exclusively in 5 patients, colon exclusively in 2, and both small intestine and colon in one are reported. Seven of the cases were studied at autopsy. The intestinal lesion was clearly the cause of death in 3 patients and was probably a secondary finding in 4 others. In one case, the cecum was involved and this segment was surgically resected. Five of the patients gave a history of alcoholism. The livers of the 7 patients studied at autopsy were all abnormal; cirrhosis was present in 4, severe fatty metamorphosis in 2, and moderate fatty metamorphosis in 1. The clinical, morphological, and bacteriological aspects of phlegmonous gastritis and phlegmonous enterocolitis are similar, and these two conditions are thought to represent the same infectious disease involving different levels of the gastrointestinal tract. In most patients the factor(s) predisposing to infection of the gastric and intestinal wall are unknown. In some patients mucosal injury of varied type and septicemia appear to have been the forerunners of the phlegmonous lesion. The possible relationships of ischemic bowel injury, alcoholism, and liver disease to phlegmonous inflammation of the gastrointestinal tract are discussed.


Motor effect of dopamine on human sigmoid colon. Evidence for specific receptors. The effect of dopamine on human sigmoid motility has been studied in 26 subjects. To record mechanical activity of the sigmoid colon, two small, air-filled balloons mounted on a probe introduced through a sigmoidoscope were used. The recordings were made at a distance of 25 and 15 cm from the anal edge. Dopamine was infused for 10 min after a 30-min control infusion of physiologic solution. Mean amplitude, mean duration, mean frequency, percentage of motor activity, and motility index of the pressure waves were determined. The motor response to dopamine was characterized by an increased baseline pressure with phasic waves superimposed. Dopamine produced a significant response at the dose of 5 microgram/kg/min. Alpha and beta antagonizing agents failed to oppose the effect of dopamine, while anticholinergic drugs enhanced its motor action. These studies suggest that dopamine may stimulate the motor function of human large bowel through specific receptors.


Effects of cocaine on rat pancreatic enzyme secretion and protein synthesis. The effects of cocaine on amylase secretion and total protein synthesis was studied by use of vitro rat pancreatic tissue. In vitro, cocaine (2 or 10 mM) did not modify basal release of amylase; at a concentration of 2 mM, it reduced the secretory response to pancreozymin by 32% and that to urecholine by 68%. Incorporation of amino acids into total proteins was decreased by 15% by cocaine 2 mM and by 49.5% at 10 mM. Administered in vivo at a dose of 15 mg/kg intraperitoneally, cocaine was associated with decreased in protein synthesis 30, 90, and 180 min after its injection. These results indicate that cocaine can affect basic functions of the exocrine pancreas and reduce its response to secretagogues.


Transpyloric extension of gastric carcinoma. Transpyloric extension of gastric carcinoma occurred in 17 (20%) of 88 patients with gastric carcinoma. In the majority of cases, this was a microscopic phenomenon, but in 7 patients with gastric carcinoma there were gross changes in the duodenum which were reflected in the upper-gastrointestinal series. Contrary to general opinion, transpyloric extension of gastric carcinoma is not a rare finding.


The risk of hepatitis B to hospital personnel. A prospective study among personnel exposed to patients without isolation precaution. During a two-week period 54 ward personnel were exposed to two patients with severe type B hepatitis. No specific isolation precautions were used other than separate collection of hypodermic needles. During a 22-week follow-up period, there was no evidence of either overt or subclinical hepatitis in development of hepatitis B surface antigen or antibody to the surface antigen that could be attributed to exposure to the patients. This data does not support requirements for cumbersome and complicated isolation procedures during the care of patients with type B hepatitis.


Serum lysozyme, serum proteins, and immunoglobulin determinations in nonspecific inflammatory bowel disease. The serum levels of lysozyme, serum electrophoresis, and serum immunoglobulins were determined prospectively in 101 patients with ulcerative colitis, ulcerative proctitis, Crohn's disease, or nonclassifiable nonspecific inflammatory bowel disease. Although the mean serum lysozyme concentration of patients with Crohn's disease (10.5 +/- 6.8 microgram/ml) and ulcerative colitis (9.6 +/- 4.1 microgram/ml) performed by a standardized lysoplate method was significantly greater than normal controls (6.0 +/- 1.5 microgram/ml), the results did not correlate with the diagnosis nor with the degree of disease activity. Individually separated protein fractions and serum immunoglobulins also did not correlate with the serum lysozyme levels. This study indicates that measurement of the level of serum lysozyme in individual patients is not helpful in determining the cause or degree of activity of nonspecific inflammatory bowel disease.


Transvenous (transjugular) liver biopsy. An experience based on 100 biopsies. Transvenous (transjugular) liver biopsy consists in taking a liver specimen through a needle introduced into the liver parenchyma from the lumen of a hepatic vein. This procedure was attempted 104 times in 98 patients in whom percutaneous needle liver biopsy was contraindicated because of massive ascites and/or bleeding tendency. A liver specimen was obtained in 100 out of these 104 attempts; the tissue specimens were unfragmented and large enough to allow correct evaluation of liver architecture in 57 biopsies. The procedure was followed by no or only minor complications in all out patients except one who suffered a fatal intraperitoneal hemorrhage in relation to perforation of liver capsule; perforation was due to an excessive front rotation applied to the needle, a maneuver which therefore must be avoided. It is concluded that transvenous liver biopsy is a workable, efficient, and acceptably safe procedure for obtaining liver specimens in patients with massive ascites and/or bleeding tendency.


[3H]thymidine-labeled colonic epithelial cells and mucosa in mice and man. Since normal epithelial cell proliferation occurs chiefly in the lower two thirds of colonic crypts, the presence of aberrant DNA-synthesizing cells (tritiated thymidine labeled) at the mouth and on the surface of colonic crypts is being assessed as a predictive indicator of the development of neoplasia in patients at high risk. These would include patients with previous polyps or colon cancer or family history of either or both. Surface cells are obtained by pulsatile saline lavage of the lower bowel and incubated with tritiated thymidine ([3H]TdR) for autoradiographic observation. Findings in each high-risk category are presented and compared with [3H]TdR labeling data from a biopsy taken at the close of the procedure. The lavage technique has also been carried out on mice injected with the colon carcinogen 1,2-dimethylhydrazine (DMH). Mice were demonstrated to have [3H]TdR-labeled cells and cellular atypic while being hemoccult negative and asymptomatic for overt disease. Evaluation of human material preliminarily demonstrated the presence of surface-labeled epithelial cells in a high percentage of patients at risk for colon cancer.


Effect of diester and diether phosphatidylcholine on intestinal absorption of neutral and acidic sterols. The effects of nondigestible diether phosphatidylcholine on intestinal absorption of cholesterol and dihydroxy and trihydroxy conjugated bile salts were studied in bile fistula rats using radioactive substrates. No inhibition of absorption of either dihydroxy or trihydroxy bile salts was observed. Nondigestible phospholipid did, however, significantly inhibit cholesterol absorption. Under control conditions with natural phosphatidylcholine in the intestinal perfusate, absorption of cholesterol was significantly greater when infused with taurocholate (TC) as compared to results obtained after infusion with taurochenodeoxycholate (TCD). Studies were repeated using radioactive rat liver phosphatidylcholine to determine whether the observed decrease in cholesterol absorption could be correlated with a decrease in digestion and absorption of rat liver phosphatidylcholine. No evidence was found for decreased absorption of this phospholipid when given with TCD. It is concluded that less cholesterol is absorbed in the presence of TCD as compared to TC, but the mechanism for this remains unexplained.


Enteropeptidase levels in duodenal juice of normal subjects and patients with gastrointestinal disease. Enteropeptidase, trypsin, and chymotrypsin activity in basal and secretin-stimulated duodenal juice of 20 normal adult volunteers and 15 patients with gastrotestinal disease were determined. All enzyme concentrations showed skew distributions, but fluctuations in the secretin-stimulated juices were less pronouced than in the basal secretions. Secretin administration had no influence on the release of enteropeptidase from human duodenal mucosa, but resulted in a very small increase in secretion of pancreatic enzymes. Six out of seven patients with chronic alcoholic pancreatitis or cancer of the pancreas exhibited highly significant elevations of enteropeptidase in their basal as well as secretin-stimulated duodenal juice. It is suggested that raised luminal enteropeptidase activity may be the result of pancreatic insufficiency or elevated blood glucagon concentrations.


Skin test reactivity in inflammatory bowel disease in the United States and Czechoslovakia. Inflammatory bowel disease (IBD) patients in the United States of America (USA) and Czechoslovakia (CSSR) were categorized by clinical, pathological, and radiological criteria as having Crohn's disease (CD) or ulcerative colitis (UC) and were tested with five skin test antigens [Candida, mumps, purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), and trichophytin] at two different dilutions in an attempt to elicit some evidence of anergy. No significant differences were encountered between the USA and CSSR populations or between any patient group and its controls.


Control of lower-esophageal-sphincter contractile activity by motilin in conscious dogs. The effect of synthetic motilin on contractile activity in the lower esophageal sphincter (LES) and the stomach has been studied in 5 healthy dogs by means of chronically implanted strain gage force transducers. Motilin produced strong contractions in the LES and the stomach simultaneously after intravenous doses ranging from 0.3 to 2.7 microgram/kg hr, which were similar to the naturally occurring interdigestive contractions in the LES and the stomach. However, these contractions could be induced only in the interdigestive state; infusion of motilin into dogs in the digestive state brought about no significant effect on either the LES or the stomach.  Motilin-induced contractions in the LES and the stomach were instantly abolished by ingestion of food. It is considered that the contractions induced by motilin are identical with the naturally occurring interdigestive contractions in the LES and these contractions are the most orad component of the interdigestive cyclic recurring caudad-moving bands of strong contractions in the dogs.


Gastric polyposis due to multiple hyperplastic adenomatous polyps. Four cases of gastric polyposis in which the multiple polyps were hyperplastic adenomatous polyps are presented with endoscopic and histologic description. The multiple hyperplastic adenomatous polyps in our cases showed more diffuse involvement of specific regions of the stomach than is usual with papillary adenomatous polyps. Hyperplastic adenomatous polyps have a low potential for malignancy, and it is suggested that they may be followed by periodic observation rather than fulguration or removal.


Stimulation of mucus and nonparietal cell secretion by the E2 prostaglandins. The effects of prostaglandin E2 (PGE2), 15-methyl prostaglandin E2 (15M), and 16,16-dimethyl prostaglandin E2 (16DM) on gastric mucus and nonparietal cell secretion in rats were measured. Alcian blue binding was used as a measure of gastric mucus. Applied topically, all three agents stimulated nonparietal cell secretion, and PGE2 and 16DM stimulated the secretion of mucus, increasing the fraction in the gastric contents but not that adherent to the mucosa. Topical 15M did not stimulate the production of mucus. Given intranveously, all three agents increased the amount of mucus in the gastric contents without altering the amount of mucus bound to the mucosa. The prostaglandins had no effect on nonparietal cell secretion when given intravenously. These effects could be relevant to the ability of the E2 prostaglandins to protect the gastric mucosa from damage.


Intraluminal pressure profiles and mucosal movements in the stomach and duodenum. Records of a possible relationship between intraluminal pressure profiles and movements of the mucosal layer are not obtainable. A prospective study was initiated to investigate this aspect in the pyloric region of the stomach and in the duodenum. The results indicate that simultaneously with certain contraction waves of the walls, all mucosal folds within the confines of the contraction change in direction to become longitudinal, thus forming longitudinal intraluminal mucosal troughs. (It is presumed that these will enhance linear flow of semiliquid intestinal contents.) The phenomenon occurs regularly and is an inherent component of various contraction waves, including peristalsis. The definition of peristalsis should probably be expanded to include reference to this mucosal component. These normal findings may serve as a base line for the investigation of mucosal motility patterns in pathological situations, e.g. peptic ulcer.


Human exocrine pancreatic response with different types of secretin. Influence of sex, age, and previous intraduodenal sorbitol infusion. A comparative analysis of the exocrine pancreatic secretion response with three different kinds of impure secretin was performed. Two series, carried out in Buenos Aires (Vitrum and Boots secretin), were compared with the Dreiling series (Lilly secretin) done in New York. All tests were performed with a single I.V. submaximal (1 U./kg.) dose of the hormone and with the same Dreiling technic. The evaluation showed: 1. The absence of significant differences in men among the three series. 2. Contrary to the results with the Lilly product, with both the Boots and Vitrum secretin the hydrelatic but not the ecbolic values are significantly greater in men than in women. This seems to reflect a sex-linked different sensitivity to secretin of the "pancreon" units. 3. Either in men or women the pancreatic secretion is not influenced by the age of the individual. 4. The Boots secretin results are not modified by the previous sorbitol intraduodenal infusion.


The pancreas: a correlation of function and structure. Fifty-two patients with or without pancreatic disease were studied with both secretin test and endoscopic retrograde pancreatography. Pancreatic histopathology was obtained by exploratory laparotomy in half of these patients. The following conclusions were reached: 1. Secretory tests are the most sensitive indicators of chronic pancreatitis, although not all cases of chronic pancreatitis will be discovered by this test. 2. When secretory tests show low volume output, pancreatography is crucial in differentiating between malignant ductal obstruction or pancreatic replacement by fibrosis or atrophy. 3. Histologic correlation with ductular structure and/or secretin function is frequently discordant. 4. The secretin test and pancreatogram measure different parameters and the use of both these complementary studies will lead to increased diagnostic accuracy and better understanding of pancreatic pathophysiology.


Intrasplenic pancreatic pseudocyst complicating severe acute pancreatitis. Since 13 cases of intrasplenic pancreatic pseudocysts have been previously described in the world literature, an additional case is reported. The mechanisms for the development of this lesion are: 1. direct extension of the pancreatic cyst into the splenic hilum; 2. digestive effects of pancreatic enzymes on splenic vasculature and parenchyma; 3. pancreatitis occurring in ectopic intrasplenic pancreatic tissue and 4. liquefaction of splenic infarcts secondary to thrombosis of the splenic vessels. Criteria for diagnosis and current available diagnostic methods are discussed. Early surgical intervention with splenectomy and possibly caudal pancreatectomy, is advocated.


Chronic active hepatitis and ulcerative colitis associated with eosinophilia, nonthrombocytopenic hypergammaglobulinemic purpura and serologic abnormalities. A patient with chronic active hepatitis (CAH) and ulcerative colitis (UC) associated with eosinophilia, nonthrombocytopenic hypergammaglobulinemic purpura and serologic abnormalities is presented. Abnormal liver function, gastrointestinal and systemic symptoms as well as the associated epiphenomena responded dramatically to oral corticosteroid therapy. The remission was maintained during an eight month follow-up period with low dose prednisone therapy.


Cancer of the colon as a late sequel of pelvic irradiation. A patient, who developed carcinoma of the rectum nine years following therapeutic radiation for pelvic malignancy is presented. The relationship of radiation to carcinoma of the colon is reviewed. This relationship makes rigorous follow-up of patients with radiation induced chronic proctocolitis essential.


Mucinous carcinoid and endometriosis in an inside-out appendix. This is the first report of the simultaneous occurrence of mucinous carcinoid and endometriosis in an inside-out appendix. The literature concerning carcinoids, endometriosis and intussusception of the appendix is reviewed. The mucinous, or goblet cell carcinoid was positive for mucin, argentaffin and argyrophil stains. Paneth cells were present. Two and one-half years with no tumor recurrence suggest good prognosis as previously reported.


Immunoglobulins in submassive hepatic necrosis. The presence of submassive hepatic necrosis in acute liver injury of viral or toxic etiology in liver biopsy specimens is of great diagnostic and prognostic significance. Liver biopsy, however, cannot be performed in some of these patients due to an abnormal coagulation profile. Hence, other noninvasive methods for diagnosis of submassive hepatic necrosis would be helpful. We compared the serum immunoglobulin-G levels in 15 patients with typical acute viral hepatitis and 19 patients with severe acute viral hepatitis with submassive hepatic necrosis. The difference of the Ig-G levels in both groups was statistically significant. By using discriminant analysis we found that it was possible to make the correct diagnosis of submassive hepatic necrosis in 89.5% of patients with acute viral hepatitis when only Ig-G levels were utilized.


The value of emergency angiography in the diagnosis and prognosis of acute mesenteric arterial insufficiency. Selective angiography is the technic which provides a higher accuracy in diagnosing an acute mesenteric arterial insufficiency. If carried out at an early stage it surpasses any other technic. It permits not only obtaining topographic data to locate the occlusion but also the detection of aspects of the collateral circulation in the loops of the bowel, thus enabling us to determine the therapeutic procedure to follow. We have done selective angiography of the superior mesenteric artery in nine patients in all of whom we identified the embolic disease. In five of these patients the embolus was in the main trunk and in four it was in the distal branches. The mortality rate varied depending on the site of the embolus and the time elapsed in the process. In three of the patients with distal localization and in one with trunk localization and sufficient arterial permeation, a conservative therapy was used with good results in all of them.


Meconium ileus equivalent.

Meconium ileus equivalent. A case of meconium ileus equivalent in a 30-year old man is presented. The pathology and therapy for the condition are discussed.


Granuloma (sarcoid?) of the pancreas. A case report. Clinically apparent pancreatic disease due to sarcoidosis has not been described in typical sarcoid patients. A few cases have been described at exploratory laparotomy and pancreatic involvement in autopsied cases is more common than generally appreciated. We report a patient not previously known to have sarcoidosis whose presentation with pruritus, eosinophilia and cholestatic serum chemistry suggested a reaction to phenothiazines. The correct diagnosis was made during surgery for an asymptomatic gallstone. No other evidence of pancreatic disease has become apparent during follow-ups of two years.


Congenital duodenal stenosis. The duodenal cervix sign. A case of congenital duodenal stenosis is reported complicated by recurrent pancreatitis. The diagnosis was not initially entertained because of the pancreatitis. The radiographic appearance on gastrointestinal series was unusual for pancreatitis. The finding of an anomalous celiac axis on arteriography suggested the possibility of other congenital anomalies. The diagnosis of congenital duodenal stenosis was confirmed at laparotomy. The obstruction was relieved with a duodenojejunostomy. Two year follow-up reveals the patient to be asymptomatic without recurrence of pancreatitis. This is the first endoscopic report of this lesion and the presence of the duodenal cervix sign should suggest the diagnosis of congenital duodenal stenosis.


Mid esophageal stricture.

Mid esophageal stricture. A patient presented with a mid esophageal stricture. Clinical, radiological and histological studies led to a diagnosis of columnar-lined (Barrett) esophagus.


The relationship of psychosocial factors to coronary heart disease in the Framingham study. I. Methods and risk factors. Questionnaires administered to 1822 members of the Framingham Heart Study from 1965 to 1967 provided measures of personality type, sociocultural mobility, situational stress and somatic strain. Clusters of questions selected by a panel of experts, and verified by item and factor analysis, formed scales of Type A behavior and other psychosocial states. The Framingham Type A behavior scale was significantly correlated with daily stress (.47), emotional lability (.43), tension (.42), anger symptoms (.34), and ambitiousness (.31). Women were less likely than men to be ambitious and to exhibit the Framingham Type A behavior, and were more likely than men to be emotionally labile, tense, and to suppress hostility. Few consistent associations were found between psychosocial stress measures and levels of blood pressure or cholesterol. Social status and marital conflicts were significantly associated with patterns of smoking. The Framingham Type A behavior pattern and other psychosocial measures were not related to the level of CHD risk, as determined by the Framingham logistic equations.


The relationship of psychosocial factors to coronary heart disease in the Framingham study. II. Prevalence of coronary heart disease. In a cross-sectional study of 1822 persons aged 45 to 77 years of age, the association of 20 psychosocial scales with coronary heart disease (CHD) prevalence was assessed. Women (aged 45 to 64 years) with coronary disease scored significantly higher on the Framingham Type A behavior, emotional lability, aging worries, tension, and anger symptoms scales than women free of CHD. The prevalence of CHD was significantly higher among working women and housewives classified as Type A than as Type B behavior. Among men under 65 years, Framingham Type A behavior, aging worries, daily stress, and tension were associated with the prevalence of myocardial infarction (MI). For men and women over 65 years, marital dissatisfactions or disagreements were significantly related to the prevalence of CHD. In a multivariate analysis, the above associations were controlled for age, blood pressure, cholesterol, smoking, and other psychosocial scales. Among women under 65 years of age, Framingham Type A behavior and emotional lability remained significant discriminators of CHD prevalence. Aging worries significantly differentiated men under 65 with and without MI. Issues related to the interpretation of results from cross-sectional studies are discussed, and four hypotheses are suggested for future prospective work in this area.


Blood pressure of children, ages 2 1/2-5 1/2 years, in a total community--the Bogalusa heart study. Eighty per cent of all identified children 2 1/2-5 1/2 years old in a total geographic community in Bogalusa, Louisiana, were examined for cardiovascular disease risk factor variables, including blood pressure (BP), anthropometric measurements, and blood lipids. Blood pressure was measured by three instrument types, each with three readings, according to a rigid, randomized design. Results from the three instruments were compared, and potential biases for each instrument are listed. All observations on the children were analyzed by multiple regression with BP as the dependent variable. After controlling for the mood of the child, the authors found that some index of body size was positively related to BP, whereas age, race, and serum lipids were not consistently related. The regressions of blood pressure on height as well as on log weight fit straight lines. These results conform with the findings for the 5- to 14-year-olds in this community. The basal or fundamental reference blood pressure is likely to rise gradually from birth to the age of incipient adult stature, and to be linearly related to height and to log weight. Changes observed over time are needed to relate BP levels in childhood to the early natural history of essential hypertension.


Diarrhea and school toilet hygiene in Cali, Colombia. In a 4-week period in early 1976 in a poor, working class area of Cali, Colombia, the prevalences of diarrhea, vomiting, common cold, and head lice in schoolchildren were measured in relation to classroom size and to the condition of the school toilets. The study found that unhygienic toilet conditions were related to diarrhea, and it was estimated that if all schools could reach the modest level of hygiene of the two schools with the relatively best facilities, diarrhea would be reduced by 44% and vomiting by 34%. Toilet hygiene was found to be unrelated to colds or head lice, which have similar social class distributions to diarrhea and vomiting. Crowding was found to be related to a small percentage of the prevalences of vomiting, head lice and colds.


Airborne spread of measles in a suburban elementary school. A measles epidemic in a modern suburban elementary school in upstate New York in spring, 1974, is analyzed in terms of a model which provides a basis for apportioning the chance of infection from classmates sharing the same home room, from airborne organisms recirculated by the ventilating system, and from exposure in school buses. The epidemic was notable because of its explosive nature and its occurrence in a school where 97% of the children had been vaccinated. Many had been vaccinated at less than one year of age. The index case was a girl in second grade who produced 28 secondary cases in 14 different classrooms. Organisms recirculated by the ventilating system were strongly implicated. After two subsequent generations, 60 children had been infected, and the epidemic subsided. From estimates of major physical and biologic factors, it was possible to calculate that the index case produced approximately 93 units of airborne infection (quanta) per minute. The epidemic pattern suggested that the secondaries were less infectious by an order of magnitude. The exceptional infectiousness of the index case, inadequate immunization of many of the children, and the high percentage of air recirculated throughout the school, are believed to account for the extent and sharpness of the outbreak.


Emergence of a new arbovirus disease in Brazil. I. Isolation and characterization of the etiologic agent, Rocio virus. In April, 1975, an epidemic of human encephalitis was detected in several counties in the State of São Paulo, Brazil; the epidemic continued into 1976. A virus was isolated from central nervous system (CNS) tissues of a 39-year-old male who died on December 8, 1975; the virus was found to be a new flavivirus for which the name Rocio virus is proposed. Nine further isolations of Rocio virus were obtained from CNS tissues of 17 patients who died with clinical symptoms of encephalitis. Isolations of virus and serologic evidence of Rocio virus infection in a significant proportion of the encephalitis patients suggested that Rocio virus was the etiologic agent of the epidemic. Rocio virus was isolated only from patients who died within 5 days of onset of illness. The virus was isolated from two sentinel mice exposed in the epidemic zone and from a rufous collared sparrow (Zonotrichia capensis) collected in the area.


Coronary risk and estrogen use in postmenopausal women. Of some 15,500 women resident in a retirement community during an 11 year interval, 220 suffered a cardiologically ascertained first myocardial infarction. A case-control study demonstrated no association between estrogen use and myocardial infarction. The observed lack of association may be explained by an already high coronary risk in this age group, by the low daily estrogen dose, and by the short duration of estrogen use. The well-known association between hypertension and myocardial infarction was confirmed.


A comparison of dietary methods in epidemiologic studies. Three methods of estimating group and individual dietary consumption have been developed and assessed in a case-control study of diet and breast cancer. The methods comprised a 24-hour recall, a detailed quantitative diet history directed to the most recent two-month period and the two-month period six months before, and a four-day diet diary. There is a high degree of correlation between the estimates of food consumption for the controls using each of the methods. The highest estimate was obtained from the diet history, with a slightly higher estimate in the period six months before than the current period, while the lowest is found in the 24-hour recall. The latter corresponds with the same method in a Nutrition Canada Survey. It is concluded that all methods ara applicable to case-control studies, but the diet history is preferred when current food intake may be influenced by a disease.


A study of diet and breast cancer.

A study of diet and breast cancer. A case-control study has been conducted in four areas in Canada in which 400 cases of breast cancer matched by age and marital status with neighborhood controls were administered a medical and dietary history questionnaire, a 24-hour recall for dietary information and a four-day diet record. The Study has produced evidence of an association between an increased intake of nutrients, especially total fat, in both pre-menopausal and post-menopausal women with breast cancer. Reasons why a weak association might have been anticipated are discussed, and it is concluded that in reality the association is stronger. Furthermore, its consistency with other evidence, both experimental and international, suggests that it is causal.


An epidemiologic study of breast cancer. A case-control study has been conducted in four areas of Canada in which 400 cases of breast cancer matched by age and marital status with neighborhood controls were administered medical and dietary questionnaires. The study is suggestive of an increased risk of breast cancer in post-menopausal women with younger age at menarche and an increased risk with delay of age at natural menopause. No protective effect of early age at first pregnancy was demonstrated in either pre- or post-menopausal women. An increased frequency of pregnancies of four months duration or less was found in cases compared to controls and a greater frequency in pre-menopausal cases compared to controls of a history of irregular menstrual periods. In pre-menopausal women no association has been found between increased height and weight as risk factors for breast cancer. For post-menopausal women, however, a weak association with increased height has been found, while a strong association with increased weight both at the time of menopause and the 12 months preceding diagnosis has ben confirmed.


Childhood sibling aggregation of coronary artery disease risk factor variables in a biracial community. To analyze aggregation of risk factors for coronary artery disease (CAD), the authors studied 4538 children from the biracial community of Bogalusa, Louisiana. Of these children ranging in age from two to 18 years, 2535 had at least one sibling, permitting the calculation of F-ratios and intraclass correlation coefficients. Those calculations revealed statistically signigicant F-ratios for all anthropometric, blood pressure and lipid variables studied. Of the lipoprotein variables studied only alpha-lipoprotein showed no statistically significant aggregation (for black children). The analysis failed to reveal any significant differences in intraclass correlations between black and white children.


Leptospirosis: a common-source outbreak due to leptospires of the grippotyphosa serogroup. In the period August 1-10, 1975, seven cases of leptospirosis occurred in residents of Stewart County, Tennessee. Based on serologic evidence, the infection was caused by leptospires of the Grippotyphosa serogroup. Epidemiologic study showed that the patients apparently acquired their infection while swimming in Cub Creek, a small local stream. Stagnation of the stream resulting from subnormal rainfall may have contributed to the timing of the outbreak. The source of leptospiral contamination for the stream could not be determined.


The reappearance of a classical epidemic of infectious hepatitis in Worcester, Massachusetts. Worcester, MA, experienced an outbreak of hepatitis during 1969-1970, an expected event which had occurred previously at eight-year intervals since reporting of the disease began in 1950. Other Massachusetts communities of similar character and the nation did not experience an epidemic during that same period. An extensive epidemiologic study of the disease illustrated that the epidemic followed the classical pattern in which individuals 5-14 years old were most affected irrespective of sex. During the interepidemic years from 1968-1972 in Worcester, and in all years (1968-1972) in both New Bedford and Springfield, MA, those primarily affected were young adults 15-30 years old, with male cases predominating. Sociodemographic statistical analyses also indicated the classical pattern of the less affluent, less educated, and sometimes the more crowded populations being at greater risk of contracting the disease. This outbreak of hepatitis was comparable to another in Greenland two years later in which immunologic methods differentiated between type A and type B viral infections. The data from both studies support the conclusion that the type B virus, often associated with parenteral drug use, is the predominate infectious agent during the interepidemic (endemic) periods. The type A virus is most likely responsible for the periodic epidemics.


Compatibility and stability of diazepam injection following dilution with intravenous fluids. The compatibility and stability of diazepam injection were studied following dilution to 10 different concentrations in dextrose 5% in water, normal saline, Ringer's injection and lactated Ringer's injection. Prepared solutions were examined for clarity and pH throughout a 24-hour period. Clear solutions were filtered and then assayed 24 hours after preparation using UV spectrophotometry. Solutions which formed visible precipitates before 24 hours or which did not demonstrate acceptable potency (greater than or equal to 90%) were assayed after shorter time periods. Dilutions lower than 1:20 (5 mg in 20 ml) resulted in immediate visible precipitates in all four diluents. The 1:20 dilution was compatible with all four diluents and maintained acceptable potency for four hours, whereas at 1:40 dilution (5 mg in 40 ml) diazepam was stable for at least 6-8 hours in the same diluents. At higher dilutions of 1:50, 1:75 and 1:100 (5 mg in 50, 75 and 100 ml, respectively) the injection was compatible with and stable in all four diluents for 24 hours. Further studies are required before the use of diazepam injection as an infusion can be recommended. However, if in some circumstances it is necessary to administer diazepam as an infusion, it is recommended that it be diluted in dextrose 5% in water, normal saline, Ringer's injection or lactated Ringer's injection to a dilution of at least 1:40 and used within 6 hours or to a dilution of 1:50 and used within 24 hours.


Hospital pharmacy in Australia.

Hospital pharmacy in Australia. Hospital pharmacy practice in Australia is reviewed. Topics covered include pharmaceutical education, drug distribution, purchasing of pharmaceuticals, and hospital pharmacy staffing and services. Australia has a national health insurance system which directly affects both community and hospital pharmacy practice. While traditionally Australian hospital pharmacy practice has followed the British system of drug delivery, practitioners have tried to introduce innovations such as intravenous admixture services, unit dose drug distribution systems and drug information services. The limitations imposed by restricted governmental funds have inhibited the introduction of innovations. The Society of Hospital Pharmacists of Australia offers a continuing education correspondence course which leads to the granting of a Fellowship in Hospital Pharmacy.


Recommended procedures for in-use testing of large volume parenterals suspected of contamination or of producing a reaction in a patient. National Coordinating Committee on Large Volume Parenterals. Guidelines for hospital detection of possible microbial contaminants of large volume parenterals are presented. Operational definitions are given, and the guidelines are divided into procedures or steps (1) to be taken in the patient care area by its personnel and that are practical for application in the hospital microbiological laboratory with limited facilities, and (2) those for the expert microbiological laboratory of health departments, teaching hospitals, large community hospitals or specialized research laboratories with experience and responsibility for handling more detailed procedures.


Revision and reorganization of a hospital pharmacy policy and procedure manual. The development of a hospital pharmacy policy and procedure manual which can provide employees with an immediate source of current and reliable operating information is discussed. Flexibility and the capability to be readily revised were key factors in the design of the manual. A table of contents, a referencing system and physical specifications for the manual were determined. Policies and procedures on format, writing style, distribution, responsibility, revisions and additions, and review were established. Sample policies and procedures are presented. The concept of a procedure specialist to coordinate all activities regarding the manual was examined. It is recommended that all staff members participate in the development and revision of policies and procedures.


Pharmacist's impact on chronic psychiatric outpatients in community mental health. The impact of a specially trained pharmacist upon the treatment of chronic psychiatric outpatients being maintained within their communities was studied. The quantity and costs of the services provided were assessed as well as patient satisfaction and well-being. Three years of management information data from eight mental health centers were used to compare the medication monitoring services provided by pharmacists and psychiatrists. In a separate study of chronic psychiatric outpatients, patients treated exclusively by the pharmacist were compared with patients treated by other mental health professionals on measures of community adjustment and satisfaction with treatment. The pharmacist monitored the medications of about 200 chronic psychiatric patients each month. The cost of a pharmacist providing medication monitoring services was 40% of the cost of providing that service by a psychiatrist. The pharmacist's patients were found to be functioning in the community as well as or better than other patients and their reported satisfaction with treatment was at least that of other chronic psychiatric patients sampled. The psychiatric pharmacist in this study successfully monitored stabilized psychiatric patients within their communities.


Pharmacist involvement in a tuberculosis outpatient clinic. The role of a pharmacist in a rural tuberculosis outpatient clinic is described. The clinic functions primarily in a follow-up capacity, necessitating complete records of each patient's medical progress, including a summary of prior drug therapy and observed response. The pharmacist is responsible for maintenance of patient records, patient consultation, onsite drug preparation and dispensing, and teaching responsibilities. The pharmacist-physician interaction in this setting is discussed. This program was devised to help improve patient compliance with antituberculosis drug therapy.


Computer system for unit dose drug distribution. A computerized unit dose drug distribution system, part of an online hospital information system, is described. Differences between manual and computerized pharmacy distribution, and the advantages and deficiencies of the automated system are discussed. The system seems to improve pharmacy's efficiency, accuracy, control of drugs and capabilities for patient monitoring and drug use review. If mechanical failure occurs, back-up procedures keep the distribution system operational. The computer system is believed to decrease the time spent by pharmacists on routine distribution tasks, leaving time for other necessary pharmacy functions.


Correlation of predicted versus measured creatinine clearance values in burn patients. Four methods for predicting creatinine clearance (Ccr) from serum creatinine concentration (Scr) were evaluated in 19 male burn patients with burn wound sepsis. Measured Ccr values were calculated from 24-hour urinary catheter collections. Steady state Scr values were obtained during the same collection interval. Predicted Ccr values were derived from Scr using the methods of Cockcroft and Gault (Method II), Siersbaek-Nielsen, Kampmann and others (Method III) and Jeliffe (Methods I and IV). Wide differences between measured and predicted values were observed but were statistically significant (p less than 0.05) for Method I only. The smallest mean difference (+/-0.02 ml/min/1.73 m2) occurred with Method II measured-predicted data pairs. Method III predicted Ccr values which correlated best with measured values (r=0.770) and showed the least variability (+/-7.6 ml/min/1.73 m2). All methods appeared to overestimate when measured Ccr was less than 60 ml/min/1.73 m2. Use of estimated lean body weights did not improve correlations between predicted and measured Ccr values. While Methods II and III may provide useful initial approximations of Ccr in burn patients, reliance upon predicted Ccr values for dosage modification in burn patients may result in an insufficient reduction in dosage. Whenever possible, dosage regimens for drugs with narrow therapeutic margins should be developed or adjusted using pharmacokinetic values determined in the individual patient.


Anticholinergic psychosis.

Anticholinergic psychosis. A case of anticholinergic psychossis in a 17-year-old male following suspected ingestion of an unknown amount of benztropine mesylate is discussed. The borderline mentally retarded patient exhibited acute psychosis and physical signs common to anticholinergic and amphetamine intoxications such as mydriasis, tachycardia and hypertension. Intramuscular chlorpromazine hydrochloride and oral haloperidol were administered to sedate the patient. The differential diagnosis of anticholinergic intoxication was based on the patient's physical and mental symptoms, the short duration of the psychosis and a negative urine assay for amphetamine. The neuropsychiatric signs of and treatment for anticholinergic psychosis are discussed. Physostigmine salicylate is the drug of choice for reversing the signs and symptoms of anticholinergic poisoning. Benzodiazepines may be used if sedation is indicated, but use of phenothiazines for this purpose should be avoided.


Drug Regulation Reform Act of 1978.

Drug Regulation Reform Act of 1978. Provisions of the Drug Regulation Reform Act of 1978 are discussed. Included in the discussion are drug monographs and product licenses, investigations and approvals of drugs, drug information, labeling, promotion and education, penalties, and the National Center for Clinical Pharmacology. The Act eliminates the individual NDA approach to regulation and replaces it with a system of monographs on "drug entities" and "drug product" licenses. It amplifies and redefines the investigational process to facilitate and promote research while protecting patients' rights. It also divides the commercial investigation process into two phases: drug innovation investigations and drug development investigations.


Moisture permeation of newer unit dose repackaging materials. Moisture permeation of some unit dose repackaging materials currently available was tested and compared with the results of an earlier study. Seventeen unit dose containers marketed for hospital pharmacy repackaging were tested. Most of the samples were prepared in a laboratory under optimal physical and mechanical conditions. The methodology involved packaging a desiccant pellet, storage at 75 +/- 3% relative humidity and 20 +/- 2 C, and weighing at various time intervals. Each container was placed into one of four classes depending upon the amount of weight gain. In general, moisture permeation values for all types of materials were much lower than in the previous study. The results show that improved moisture protection can be achieved through modifications in typical repackaging systems.


Furosemide-induced adverse reactions during hospitalization. The frequency and types of adverse reactions (ARs) occurring in hospitalized patients receiving furosemide were surveyed prospectively in a four-year study at the José Joaquin Aquirre Hospital in Santiago, Chile. A team of clinical pharmacists and clinical pharmacologists monitored 533 patients receiving furosemide and recorded patient characteristics, laboratory test results, drugs administered, and suspected ARs. Definite or probably furosemide-induced ARs were detected in 220 (39.8%) patients. No ARs were fatal but 7.6% of patients, all having cirrhosis of the liver, had severe ARs. Of the ARs recorded, 95.2% were dose-related. The most common ARs were electrolyte disturbances (23.5% of patients), extracellular volume depletion (9.0% of patients) and hepatic comma (3.6% of patients). Total and daily furosemide doses, lengthened hospitalization and hepatic disease were significantly associated with the frequency of ARs (p less than 0.001). The dosage of furosemide did not account for the increased frequency of ARs in patients with hepatic disease. The frequency of hypokalemia was not reduced significantly when furosemide was administered with potassium chloride or potassium-sparing diuretics (p less than 0.05). The frequency of severe furosemide-induced ARs is low, but ARs are more common in patients with cirrhosis of the liver. These patients should be closely monitored for furosemide-induced ARs.


Comprehensive self-medication program for epileptic patients. The establishment and operation of a comprehensive self-medication program for hospitalized epileptic patients are described. The patients in the program are required to meet established behavioral criteria during each of four stages of self-medication before progressing to the next stage. The patient has increasing responsibility in each successive phase of the program. The areas of patient involvement for the pharmacist are: (1) obtaining a medication history, (2) teaching patients about seizure medications, (3) conducting patient consultations during the self-medication program and (4) counseling the patient at discharge.


Characteristics of hospital pharmacy practice in Indiana. Hospital pharmacy practice in Indiana was surveyed to determine drug distribution services, additional services, staffing and salaries. Questionnaires were mailed to the directors of the 113 licensed hospital pharmacies in the state; 63% responded. Unit dose drug distribution systems were used by 19% of the hospitals for all beds; by 16% for some of their beds. Intravenous admixture services were provided by 43% of the respondents. Drug use review, patient education and inservice education were all provided by more than 10 of the respondents; in general, clinical services were not well developed. Salaries for directors were related more to hospital bed size than to years of experience as a pharmacist. Howeever, salaries for staff pharmacists were related more to years of experience than to hospital bed size. It appeared that staff pharmacists who want to earn more income must consider an administrative position.


Model for a formal, prospective antibiotic use review program. A model for conducting prospective review of antibiotic orders is proposed. Before the drug is dispensed, a screening procedure is set up in which the incoming antibiotic drug order and the patient's drug profile are reviewed against previously established criteria. Noncompliance with any of the criteria is followed up as soon as possible with the prescriber who must either justify the noncompliance or authorize the changes necessary to achieve compliance. The drug is then dispensed. A prospective antibiotic review program combined with selective retrospective audits would be effective in assuring rational antibiotic use.


Rapidly progressive renal failure as the primary manifestation of Wegener's granulomatosis. A 43-year-old woman was treated for a rapidly progressive glomerulonephritis with periodic renal dialysis for a period of over one year before the development of a pulmonary lesion which enabled a diagnosis of Wegener's granulomatosis to be made. The lung lesion cleared rapidly with azathioprine and steroid therapy; severe renal failure, however, persisted, necessitating continued hemodialysis. An early and predominant manifestation of a rapidly progressive glomerulonephritis in the presence of minimal, if any, upper respiratory disease, albeit rare, should be considered as a possible presentation of Wegener's granulomatosis.


Clinical experience with a simple screening test for Cushing's syndrome combining the determination of plasma cortisol circadian rhythm with the overnight dexamethasone suppression test. In 17 normal subjects and 126 patients with various endocrine disorders, including 13 patients with Cushing's syndrome, plasma levels of fluorogenic corticosteroid were measured at 9 AM and midnight, and again at 9 AM the following morning, after the patient had received 1 mg of dexamethasone by mouth immediately after the midnight sampling. Basal morning levels of plasma corticosteroids were of little diagnostic value in differentiating between Cushing's syndrome and non-Cushing's states because of the wide overlap of values observed. At midnight the overlap almost completely disappeared. After overnight suppression, only one patient with a mild form of Cushing's disease had normal (false-negative) results in two of four instances. There were virtually no false-positive results, except for two patients with anorexia nervosa showing minor abnormalities of the test. The results were in general agreement with those of the classic Liddle test. However, one patient with Cushing's disease had repeatedly abnormal responses to overnight suppression and normal responses to the Liddle test. When the inhibitory tests gave equivocal results in the differential diagnosis between exogenous obesity and Cushing's disease due to adrenal hyperplasia, the response of plasma corticosteroids to hypoglycemia, normal in obesity and absent in Cushing's disease, proved to be an excellent ancillary test in differentiating between the two conditions.


1-desamino-8-D-arginine vasopressin (DDAVP) concentration test. Classical dehydration and vasopressin tests for estimation of renal concentrating capacity are inconvenient and sometimes hazardous. We attempted to use the new potent long-lasting synthetic vasopressin analogue (DDAVP) which has no side effects for testing renal concentrating capacity in adults. Four groups of persons were investigated: in Groups 1 and 3, 11 and another 11 healthy subjects; in Group 2, seven convalescent older patients; and in Group 4, 11 patients with pituitary diabetes insipidus (DI). Groups 1 and 2 were investigated during 15 hours' dehydration; DDAVP was given at the end of the 12th hour intravenously (4 microgram) or intransally (80 micron). DDAVP failed to influence strikingly the normal increase in renal concentration induced by lengthening the dehydration from 12 hours to 15 hours. On the other hand, in patients with DI under prolonged treatment as well as in healthy individuals (Group 3), a dose of 20 to 40 microgram of DDAVP administered intranasally induced (at least) as high peak urine osmolality during ad libitum fluid intake as was induced in normal subjects (Group 1) by 12 hours' dehydration alone. In patients with DI the maximal effect of DDAVP obtained during ad libitum fluid intake could be further enhanced by added dehydration. Urine sampling for osmolality three hours after a single intranasal dose of 40 microgram DDAVP during ad libitum fluid intake is a new safe, simple and convenient test for rapid estimation of concentrating ability.


Control of cholesterol embolization by discontinuation of anticoagulant therapy. A 64-year-old man developed multisystem disease including renal failure while receiving anticoagulants. Renal biopsy showed cholesterol embolization. Discontinuation of anticoagulants resulted in prompt cessation of symptoms and dramatic improvement in renal function.


Serum concentrations and urinary excretions of zinc in cirrhosis, nephrotic syndrome and renal insufficiency. Serum zinc conentrations are decreased in patients with a variety of clinical disorders including cirrhosis, nephrotic syndrome and renal insufficiency. Urinary zinc excretions are increased in the first two disease states. Symptoms of acute zinc deficiency (anorexia, dysfunction of smell and taste and mental and cerebellar disturbances) and chronic zinc deficiency (growth retardation, anemia, testicular atrophy and impaired wound healing) are common in these patients. It remains unresolved whether these low serum zinc concentrations in these disease states are indicative of true symptomatic or asymptomatic zinc deficiency, or merely reflect a decrease in available zinc-binding proteins, as well over 90% of serum zinc is bound to protein in normal subjects. The correlation between serum zinc and albumin concentrations, reportedly the major zinc-binding protein, is unimpressive. Studies of serum and urine binding of added radiozinc65 using Sephadex G-200 gel column chromatography and polyacrylamide gel electrophoresis suggest most of the radiozinc is bound to a protein with a molecular weight near albumin (68,000). Polyacrylamide gel electrophoresis suggests this might be a prealbumin. The low serum zinc concentration in the patient with nephrotic syndrome does not appear to be due to loss of zinc bound to urinary protein.


Adult respiratory distress syndrome following mammary augmentation. Sudden death after subcutaneous injection of silicone has been described. However, there are no cases in the literature of clinically diagnosed noncardiogenic pulmonary edema. In the patient reported here, progressive hypoxemia and diffuse pulmonary infiltrates occurred following intramammary injection of a material presumed to be silicone. The presence of birefringent particles in the alveolar macrophages implies entrance of this material into the vascular compartment, its embolization to the lung and migration across the damaged alveolar-capillary membrane. Large volume subcutaneous injections of silicone should be added to the differential diagnosis of the etiology of the adult respiratory distress syndrome.


Myeloid metaplasia of the central nervous system in patients with myelofibrosis and agnogenic myeloid metaplasia. Report of 3 cases and review of the literature. Foci of meningeal myeloid metaplasia were found in 3 of 11 consecutive autopsied patients with myelofibrosis and agnogenic myeloid metaplasia. The  clinical and pathological findings in an additional seven published patients with agnogenic myeloid metaplasia who developed neurological manifestations due to pressue of hemopoietic tumors in the central nervous system are reviewed.


The prevalence of antibody-coated bacteria in urine. The prevalence of urinary antibody-coated bacteria (ACB), suggesting renal bacteriuria, was studied in three groups of patients: inpatients whose physicians suspected urinary tract infections, asymptomatic outpatients with neurogenic bladders but without urethral catheters, and asymptomatic inpatients with indwelling urethral catheters. The prevalence of ACB was 67% of inpatients with positive cultures without catheters, 94% of patients with neurogenic bladders, and 36% of patients with urethral catheters. These results suggest a high prevalence of upper urinary tract involvement in patients with positive urine cultures, even if asymptomatic.


Myeloma and pernicious anemia.

Myeloma and pernicious anemia. Four cases of pernicious anemia developing in association with multiple myeloma are described. The description now of 14 cases demonstrating the association of these two disorders suggest a causative relationship. These observations, in addition to the previously well-documented increased coincidence of pernicious anemia and benign monoclonal gammopathy and pernicious anemia and hypoglobulinemia, suggest that screening for vitamine B12 deficiency in patients with gammopathies and for protein abnormalities in patients with pernicious anemia is indicated.


The effect of hypoxia on posthyperventilation breathing. The breathing patterns after voluntary hyperventilation were determined in 14 healthy young subjects under four different conditions: (1) normoxia, (2) hyperoxia, (3) hypoxia, and (4) sudden administration of oxygen against a background of hypoxia to evaluate the effect of hypoxia on the pattern of the posthyperventilation breathing. Under hypoxia the ventilation in the immediate posthyperventilation period was depressed although no decreased ventilation was observed under hyperoxia or normoxia in this period. Sudden administration of oxygen depressed further the decreased ventilation in the posthyperventilation period.


A syndrome of severe midface retraction, multiple skull anomalies, clubfeet, and cardiac and renal malformations in sibs. A brother and sister presented with an uncommon malformation syndrome consisting of severe midface hypoplasia, congenital heart defect, hydronephrosis, clubfeet, hypertrichosis, hypoplasia of dermal ridges, and radiographic skeletal anomalies in the skull, hands and feet. The boy died shortly after birth; the girl lived for 16 months and exhibited severe failure to thrive, epilepsy, diminished growth, and profound motor and intellectual retardation. Additional observations include postaxial hexadactyly in the girl, and mesomelic brachymelia and peculiar, narrow fingernails in the boy. The occurrence of the syndrome in two sibs of different sex suggests autosomal-recessive inheritance.


Calcitonin in thyroidectomized patients. Hypothyroid patients with total or near-total thyroidectomy were found to have detectable immunoreactive calcitonin in the serum and urine. These findings suggest that human calcitonin may be secreted by extrathyroidal tissues.


5alpha-reductase activity of genital and nongenital skin fibroblasts from patients with 5alpha-reductase deficiency, androgen insensitivity, or unknown forms of male pseudohermaphroditism. Serially subcultured fibroblast strains from genital (foreskin, labium majus) skin, as a group, have considerably more steroid (testosterone) 5alpha-reductase activity than those form nongenital skin. Foreskin strains varied 40-fold and labial strains even more. Labial strains overlapped nongenital strains of either sex more frequently than did prepuce strains. The activity of foreskin strains from two siblings with proven 5alpha-reductase deficiency was clearly lower than that of any of 18 control stains. The comparative behavior of the various strain types indicates that labial and nongenital strains should not be used to support a clinical suspicion of male pseudohermaphroditism due to 5alpha-reductase deficiency. The activities of labial strains from patients with complete androgen insensitivity (testicular feminization) - five with the receptor-negative variety and two with the receptor-positive type - were as variable as those of control labial strains. The decreased 5alpha-reductase activity observed in fresh skin slices of some patients is probably and expression of their functional estrogen/androgen imbalance in vivo.


Acute respiratory failure: a rare complication of perfusion photoscintigraphy in a patient with bullous emphysema. Acute cardiorespiratory failure occurred in a patient with advanced bullous emphysema following perfusion photoscintigraphy with radiolabeled macroaggregated albumin. Complications of perfusion photoscintography are rare. However, in patients with advanced pulmonary vascular disease, special precautions may decrease the minimal hazard associated with perfusion photoscintigraphy.


The frequency and financial burden of genetic disease in a pediatric hospital. Medical charts from 1973 were reviewed from a general pediatric hospital whose admissions comprise 55% of those in the surrounding metropolitan area. The study population (4,115) was selected by using charts from January, March, May, July, September, and November of that year. The patients were categorized by diagnosis as to I) clearly genetic disorders, II) multifactorial disorders, III) developmental anomalies, IV) familial conditions, or V) nongenetic conditions. Of all admissions, 4.5% had genetic disorders (0.6% chromosmal, 1.2% autosomal dominant, 2.2% autosomal recessive, 0.5% X-linked recessive); 22.1% had multifactorial/polygenic conditions; 13.6% developmental anomalies; 13.2% familial disorders, and 46.6% nongenetic disorders. Patients with clearly genetic disorders (category I) were found to have had an average of 5.3 admissions as compared to 1.6 for patients with nongenetic conditions (category V). Of genetic patients (category I) 12.8% had more than 20 admissions as compared to only 1.2% for all patients studied (categories I-V). The length of hospitalization for genetic patients was 3.4 days as compared to 3.0 for all patients and 2.5 for nongenetic patients. Although the cost per day for genetic patients, exclusive of physicians' fees, was lower than for all patients, the total cost of hospitalization was the same (($450.98 as compared to $446.99 for all patients). Of all patients, 60.2% studied had third-party coverage, whereas only 43.8% of genetic patients did. Of all patients, 15.6% paid "out of their pockets" whereas 30.5% of genetic patients did. This study suggests that genetic patients have many more admissions which are slightly more expensive; that they stay longer in hospital; that they travel farther, and that their families end up paying the bill more often. No unusual differences in religion, race, age, or parents' marital status or occupation were found. It was remarkable that only one quarter of patients with genetic illness had received genetic counseling.


Replication patterns of three isodicentric X chromosomes and an X isochromosome in human lymphocytes. Chromosomes from four patients with variants of the Turner syndrome were investigated by G- and C-bandind and DNA replication techniques. Their karyotypes were: 1) 46,X,idic(X)(q28), 2) 45,X/46,X,idic(X)(q24), 3) 45,X/46,X,idic(X)(p11), and 4) 46,X,i(Xq). In patients 1, 2, and 3, the abnormal X was isodicentric, with different break-and-fusion points in each case. In each, the G-band pattern on one side of the breakpoint was a mirror image of that on the other side. Each had two distinct C-bands, only one of which was associated with a primary constriction. The fourth patient had an isochromosome of the long arm of an X in which only one C-band could be discerned. Replication studies were done on lymphocyte cultures by incorporating a thymidine analogue and staining with acridine orange. In addition, replication patterns of normal early- and late-replicating X chromosomes were studied in two normal females. In the four patients, all the normal X chromosomes had normal early-replication patterns. The two idic(X) chromosomes with break-and-fusion points on their long arms almost always had symmetric replication patterns, which demonstrates that the corresponding bands replicated synchronously. In contrast, many of the idic(X)(p11) and i(Xq) chromosomes showed asymmetric or asynchronous replication. In each, the replication pattern of the abnormal X was similar to the equivalent portions of a normal late-replicating X.


The effect of supine and lateral positions on intra-arterial pressure in hypertensive pregnancies. The effect of posture of blood pressure remains controversial, perhaps due to the subjective nature of indirect blood pressure measurements and the disturbing influence of environmental impulses at the time of measurement. In this study intra-arterial blood pressure was recorded directly in seven toxemic gravid women in an environment with a low impulse level. There were short-term fluctuations of up to 25 mm. systolic and 15 mm. diastolic. The effect of changes in position on blood pressure was not constant and the differences were small. The effect on blood pressure of changing the environment by talking to the subject was impressive and the difference was more than twice the largest posture-induced difference.


Isolated diagonal artery disease.

Isolated diagonal artery disease. The clinical, electrocardiographic, angiographic, and hemodynamic features of seven patients with isolated, severe (greater than 75% of diameter) narrowing of a diagonal branch of the left anterior descending artery are presented. The incidence of this entity was 0.5% among patients with arteriosclerotic heart disease undergoing coronary angiography. Angina was severe in two patients, moderate in four, and mild in one. One patient had unstable angina. Stress tests were abnormal in two of three patients. Six patients had normal left ventricular angiograms, and one had a mildly decreased ejection fraction. All patients survived a mean follow-up of 18 months (range 6 to 32). No patient suffered a myocardial infarction. Five became asymptomatic on medical therapy; one patient with mild and another with moderate angina were unimproved. This rare anatomic subset of patients with coronary artery disease has a favorable short-term prognosis.


Comparison of the ventilation response to CO2 rebreathing in healthy smokers and nonsmokers and subjects with bronchitis. A comparison of ventilatory tests and the response to carbon dioxide rebreathing was made in healthy smokers, nonsmokers, and in subjects with bronchitis. The response to carbon dioxide (CO2) rebreathing was the same in the healthy population but diminished in the bronchitic group. Effects of smoking on maximal expiratory flow rates did not correlate with the results of carbon dioxide rebreathing. A consistent pattern of relationship of ventilation response to carbon dioxide and age of the subject was apparent.


Management of male hyperprolactinemic hypogonadism. A 30-year-old man with a prolactin secreting pituitary adenoma and hypogonadism was studied. Except for hyperprolactinemia, the results of his pituitary function tests were perfectly normal. Although the mechanism is uncertain, hyperprolactinemia alone may interfere with male reproductive function. The patient's impotence and infertility were successful managed with injections of human menopausal gonadotropins (HMG). Adverse interaction between gonadotropins and prolactin along the hypothalamic-pituitary-testis axis may be corrected by HMG injections in certain cases.


Oral propranolol in hypercalcemia associated with apathetic thyrotoxicosis. A 68-year-old man with a history of organic heart disease and marked weight loss was found to have apathetic thyrotoxicosis and hypercalcemia. Oral propranolol, 20.0 mg four times a day, provoked a gradual fall in serum calcium and alkaline phosphatase. It is concluded that relatively small doses of oral propranolol may be effective in the management of hypercalcemia accompanying thyrotoxicosis and that beta-blocking agents may not only inhibit the enhanced bone resorption caused by thyroid hormones but also block the stimulated osteoblastic activity.


Prolactin levels in nursing mothers.

Prolactin levels in nursing mothers. Plasma prolactin (hPRL) concentration was measured in four nursing mothers during 24 hour periods. Blood was collected via indwelling catheters and sleep and nursing periods were recorded. Elevated hRPL levels and amenorrhea were seen for as long as 13 months post partum in mothers whose infants nursed frequently. One mother, whose infant nursed less frequently, menstruated and had lower prolactin levels but continued to lactate. Plasma hPRL rose after nursing periods in nine of 18 instances at two months post partum, but in only five of 27 instances at six months post partum. Nighttime release hPRL was higher (five of six) in nursing mothers, just as in normal subjects (five of seven). Therefore it was concluded that prolactin levels in nursing mothers may remain elevated for over one year post partum if frequent nursing continues. Lactation may continue in spite of normal hPRL levels. A consistent rise in hPRL is not seen with nursing episodes occurring after two months post partum. Nursing mothers, like normal women, tend to have higher nighttime release of hPRL.


Influence of imidazole carboxamide on platelet functions and coagulation in vitro. Influence of imidazole carboxamide (DTIC, NSC-45388) on some platelet functions, plasma coagulation, and fibrinolysis in vitro was investigated, using different concentrations of the drug (80 and 160 microgram/ml). The lower concentration, which corresponds to that obtained in plasma after administration of therapeutic doses in man, did not significantly influence any of the important platelet functions. It is concluded that after current dosage of the drug, bleeding disorders caused by impairment of platelet functions are improbable. However, following the higher concentration of DTIC, a significant inhibition of the increase in light transmission of platelet-rich plasma provoked by standardized freezing and thawing procedure, was demonstrated. Furthermore, the same dose of the drug caused partial retardation of the retraction of reptilase clots. The authors assume that DTIC has a "stabilizing effect" on the cell membrane, particularly in higher concentrations.


Choriocarcinoma with cerebral metastases coexistent with a first pregnancy. A case is presented of choriocarcinoma with cerebral metastases which was unsuspected until a life-threatening life-threatening situation occurred. A viable infant was born and there was dramatic response to treatment with probable cure.


A direct radioimmunoassay for estriol-16alpha-glucosiduronate: its use in the determination of plasma and urine levels and renal clearance of this conjugate in pregnancy. A direct radioimmunoassay which does not require hydrolysis or chromatography has been developed for estriol-16alpha-glucosiduronate in pregnancy plasma and urine. The antigen used in the development of this antiserum was prepared by joining the carboxylic acid group of estriol-16alpha-glucosiduronate covalently to the epsilon-amino group of the lysine residues in bovine serum albumin. Results indicate that the direct radioimmunoassay yields levels of estriol-16alpha-glucosiduronate in late pregnancy urine that are comparable to those obtained by mroe elaborate procedures involving chromatographic separation of the estriol conjugates, followed by enzymic hydrolysis and measurement of the freed estriol. In addition, good correlation was found between the total estrogen values in urine obtained by currently used chemical procedures and urinary levels of estriol-16alpha-glucosiduronate. The renal clearance of estriol-16alpha-glucosiduronate was determined in eight normal women during the third trimester, and the mean value +/- S.D. was 404 +/- 81 ml. per minute (range, 248 to 494). This method is suitable for the evaluation of variations in the plasma and urine levels of estriol-16alpha-glucosiduronate in pregnancy and offers significant advantages over the presently used chemical methods for monitoring fetal well-being.


Twins: causes of perinatal death in 12 United States cities and one African city. The perinatal mortality rate in a large U. S. study was 139 per 1,000 births for twins and 33 per 1,000 for singletons. Sixteen per cent of the twin deaths were due to amniotic fluid infections, 11 per cent to premature rupture of the membranes, 8 per cent to the monovular twin transfusion syndrome, 8 per cent to large placental infarcts, 7 per cent to congenital anomalies, and the rest to over 20 other disorders. The perinatal mortality rate for monozygotic twins was 2.7 times that for dizygotic twins, mainly due to more amniotic fluid infections, congenital anomalies, and the twin transfusion syndrome in the monozygotic pairs. To study the role of poor maternal nutrition on twins, a similar study of perinatal mortality rates was undertaken in Addis Ababa, Ethiopia. Addis Ababa twins had 2.5 times the mortality rate of U. S. twins, mainly due to a higher frequency of amniotic fluid infections, abruptio placentae, cord accidents, obstructed labors, congenital syphillis, and the twin transfusion syndrome in the Ethiopians.


Intrauterine transfusion with the use of phased array ultrasonography: a new technique. Continuous ultrasonic observation of needle placement for aspiration, biopsy, or catheter placement is a novel and specific use of phased array imaging. In the case of IUTx, catheter placement into the fetal peritoneal space is accomplished rapidly, with reduced risk of fetal trauma, and without exposure to ionizing radiation. Experience with 27 transfusions in 11 patients is presented.


Fetal movements associated with fetal heart rate accelerations and decelerations. In normal pregnant women, the relationship between the FHR and fetal movements (FM) was evaluated during 1,541 consecutive observed FM of at least 1 second's duration. Two observed FHR changes were: (1) accelerations and (2) accelerations followed by decelerations. An acceleration in FHR was observed in association with 91.2 per cent of all FM of 1 to 3 seconds' duration and with 99.8 per cent of FM of longer than 3 seconds' duration. FM were associated with an acceleration followed by a deceleration 66.7 per cent of the time. FM lasting longer than 1 second and associated with neither accelerations nor decelerations were seen 1.8 per cent of the time.