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In order to further investigate the metabolic alterations in the liver of cholesterol-fed rats, the following parameters were determined: (a) the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, citrate cleavage enzyme, acetyl CoC carboxylase, and fatty acid synthetase; (b) the rate of hepatic fatty acids synthesis in vivo or in vitro; and (c) the concentration of immunoreactive insulin, free fatty acids, and glucose in the plasma. The experimental diets usually contained 1.5% cholesterol and 0.5% cholic acid. Cholesterol feeding resulted in a three- to fourfold decrease in the activities of hepatic glucose-6-phosphate dehydrogenase, NADP-malate dehydrogenase, and citrate cleavage enzyme and up to a two-fold decrease in the activities of acetyl CoA carboxylase and fatty acid synthetase. The rate of fatty acid synthesis was not sifnigicantly decreased when rats were fed the cholesterol-supplemented diets for only 2 to 4 weeks, despite marked decreases in the activities of the lipogenic enzymes. But when cholesterol feeding was continued for periods longer than 5 weeks, there was a significant decrease in the rate of fatty acid synthesis in the liver. Cholesterol feeding decreased the levels of circulating insulin and elevated plasma free fatty acid levels. Plasma glucose levels were not significantly changed. Cholesterol feeding can result in a wide range of metabolic alterations. These metabolic alterations may have some impact on the development of hypercholesterolemic-related metabolic disorders.

The absorption kinetics of some 14-C-labeled simple sugards in adults of Schistosoma mansoni are described. The influx of fructose and 3-0-methylglucose was by diffusion alone, while glucose, 2-deoxyglucose (2DOG), galactose, glucosamine, and mannose were absorbed by mediated transport as well as by diffusion. Although absorbed glucose was rapidly metabolized, uptake rates of radio-glucose in 2-min incubations corresponded with the amount of glucose (determined chemically) removed from the incubation medium. In 30-min incubations 2DOG was slowly metabolized and accumulated against an apparent concentration difference. The mediated transport of glucose and 2DOG was inhibited in Na+-free media, and by the presence of ouabain, phlorizin, phloretin, and other sugars. Accordingly, influxes of glucose of 2DOG and 22-Na+ were coupled. On a per mg protein basis, female worms transported more 2DOG and glucose, but less glycine, than did males. However, the rate of glucose metabolism by male and female worms incubated together was greater than that of either males or females incubated separately. The nature of sugar transport in schistosomes and other flatworms is similar to that in vertebrates.

Diets of rats infected with Hymenolepis diminuta (CESTODA: Cyclophyllidea) were altered with respect to carbohydrate content and to roughage, and the effects on worm growth and development were studied. Compared to worms from rats fed a 56% glucose diet, those on a 56% starch diet were heavier at 10 and 15 days and had more immature proglottids at 5 days, mature prglottids at 10 days, and mature and gravid proglottids at 15 days postinfection. In addition, worms from rats fed the starch diet contained a higher carbohydrate concentration and a lower lipid concentration from those fed the glucose diet. Worms from rats fed diets with combinations of carbohydrates such as 51% starch-5% sucrose and 51% starch-5% lactose were not different from those fed the 56% starch diet. If rats were fed a pellet diet (Purina Laboratory Chow), the worms grew substantially larger than those from rats fed the 56% starch or combination diets. The differences could be overcome if a 6% roughage component were included in the 56% starch diet. Therefore, the starch-roughage diet here presented is recommended as the optimal defined diet for studies of the development of H. diminuta in the definitive host.

Henneguya sebasta sp. n. was found on the bulbus and truncus arteriosus and in the heart chambers of 7 species of marine rockfish, Sebastes, from central and southern California. The incidence of this parasite may be of economic interest to the sport and commercial fisheries because of its possible pathogenicity.

The survival of infective larvae of Ancylostoma caninum on outdoor grass plots was studied in 40 experiments over 1 year. Weather data were collected over the period. Mean larval survival from August to early November was 24 days (range 1 to 49), from December through February was 0 days, and from March to mid-August was 6.6 days (range 0 to 21). Moderate to high temperatures and substantial rainfall favored larval survival; low temperatures and rainfall favored larval destruction.

The ultrastruct of the adult subperiodic Brugia malayi (Brug, 1927) within pulmonary arteries of male jirds (Meriones unguiculatus) was studied by transmission electron microscopy. The cuticle consists of 10 sublayers (2 of which are prominently banded) and a typical outer unit membrane. Evidence is presented showing that the subcuticular region of the lateral chords comprises a functional complex of basal infoldings, multivesicular bodies, and associated mitochondria, which is probably engaged in the exchange of solutes across a permeable cuticle. Microbodies with paired, prominent cores, intracisternal A-particle viruslike bodies, nonstaining glycogen patches, and other structures are also present in the lateral chords. The platymyarian somatic musculature shares some coelomyarian characteristics, e.g., apparent neuromuscular connections and prominent glycogen deposits surrounded by mitochondria and other organelles. The alimentary tract has features typical of many nematodes. The luminal segments of the male and female reproductive tracts and their germinal products, excluding microfilariae, are described. Affinities with related species are discussed.

In both spring and fall, 12 Duroc, 12 Hampshire, and 12 Duroc times Hampshire F1 weanling pigs all reared under the same management were fed in pens of 3 to slaughter weights. Three Duroc and 4 Hampshire boars, essentially unrelated within breed, were used in sampling the breeds. Swine herd management allowed pig infection with Strongyloides ransomi and Ascaris suum, but neither clinical nor subclinical parasitism was evident in the herd. Pigs were percutaneously exposed by pens within breed and season, half to none (control) and half to 3,000,000 (exposed) S. ransomi infective larvae, Breed, treatment, and seasons were prominent sources of variation in pig response. Breeds failed to respond alike to parasitism in respect to experimental periods and exposure levels. This interaction response (P smaller than 0.01) showed that S. ransomi egg production increased rapidly for all breed groups but decreased quicker and greater in Durocs, slowest and least in Hampshires, with cross breds intermediate in these respects. The 2.0830 for mean of log A. suum EPG from exposed Durocs was near double that of control Durocs but the mean for exposed Hampshires was less than half that for controls; crossbreds tended to be intermediate in this respect. Daily gains of 0.70 and 0.73 for Durocs and crossbreds were similar (P greater than 0.10) but averaged 11.7% more (P smaller than 0.05) than the 0.64 kg for Hampshires and gains by control pigs were 20.6% above (P greater than 0.01) that of exposed pigs. Exposed pigs required more feed per kg of gain (P greater than 0.05) than control pigs (3.60 vs. 3.33 kg). Comparison of relative gains and feed efficiences of control and exposed pigs among and within breed groups supported the position that a superimposed exposure of 3,000,000 S. ransomi larvae was more severe for Hampshires, intermediate for crossbreds, and least severe for Durocs.

1. In decerebrate cats neurones in the region of the paramedian reticular nucleus were identified by responses to stimulation of implanted cerebellar electrodes. Approximately one half were antidromically activated and one half orthodromically. 2. Somatic stimulation and electrical stimulation of both hind limb and cranial nerves activated many of these cells. There was no correlation between the effects of these stimuli on cell firing and on blood pressure. 3. A number of rhythms in spontaneous firing were observed. One fifth of cells fired with the rhythm of efferent activity in the recurrent laryngeal nerve. In animals showing cycles of stability and instability in blood pressure corresponding phases of activity and inactivity in the firing of paramedian reticular neurones were observed. 4. Most paramedian reticular cells showed bursts of firing preceding abrupt rises in blood pressure but this was also observed with cells lateral to this area. 5. One third of cells studied showed changes in firing rate correlated with the changes in blood pressure which followed I.V. acetylcholine and noradrenaline. 6. Bilateral carotid artery occlusion, which always produced a rise in blood pressure, had little effect on cell firing.

1. Projections to the superior colliculus from fore and hind limb muscle nerves have been examined. 2. Hind leg nerve stimulation at strengths sufficient to excite Group II and III fibres elicited unit discharge in all layers of the superior colliculus and underlying tegmentum. 3. Forelimb nerve stimulation excited units in all layers of the superior colliculus and underlying tegmentum. Twenty per cent were activated by stimulation below Group II threshold, the remainder by stimulation above Group II threshold. 4. Most units activated by limb afferent nerve stimulation were also activated by visual stimuli. There was considerable convergence from both flexor and extensor nerves and most units were excited by stimulation of nerves in more than one limb. 5. Units fired either with a short or long latency or with a paired discharge. Short latency units were most common in deep collicular layers and the tegmentum, long latency units were most common in superficial layers. 6. The spinal pathway of the afferents is mainly in the dorsolateral quadrant contralateral to the recording site. The anatomical characteristics of the pathway are similar to the lateral funiculus climbing fibrespinocerebellar pathway.

1. Of paramedian reticular neurones a significantly higher proportion of those antidromically activated from the cerebellum than of those orthodromically activated from this source were excited by acetylcholine. 2. Receptors for acetylcholine were of the muscarinic type. 3. No differences were found in the proportions of cholinoceptive and non-cholinoceptive cells responding to stimulation of cranial and limb nerves or to changes in blood pressure either spontaneous or induced. 4. Either a cholinergic pathway to paramedian reticular cells projecting to the cerebellum was not activated in these experiments or the receptors for acetylcholine are not located at synapses. An association between muscarinic receptors and acetylcholinesterase may be present with cells of this area.

1. The volume of distribution of [14-C]carboxyl inulin has been studied in slices of outer and inner medulla from rat kidney incubated in Krebs phosphate-bicarbonate Ringer, modified to render it iso-osmolal with the tissue fluids in these zones, under three conditions, (a) aerobically at 37 degrees C (control), (b) anoxically at 37 degrees C, and (c) aerobically at 0 degrees C. 2. Under control conditions near steady-state volumes of approximately 24 and 42 mul./100 mg wet weight slice were obtained for outer and inner medulla respectively during the period 10-30 min from the start of incubation. In the outer medulla the volumes of distribution in anoxic and hypothermic slices exceeded that in control slices during this time, but control values increased from 30 to 100 min so that after 100 min the distribution volumes were approximately 30 mul./100 mg under each set of conditions. 3. In the inner medulla control and anoxic slices had inulin distribution volumes of approximately 42 mul./100 mg during 10-30 min, rising to over 50 mul./u99 mg by 100 min. Slices incubated hypothermically reached a steady-state value of approximately 40 mul./100 mg by 30 min, which did not increase further for up to 100 min. 4. All slices lost about 10% of their initial weight during the first 3 min of incubation. Thereafter control slices maintained weight constancy for at least 30 min (outer medulla) or 100 min (inner medulla); slices incubated anoxically or hypothermically gained weight, the gains being greatest in anoxic outer and hypothermic inner medulla. 5. The K concentration within control slices (both zones), hypothermic outer and anoxic inner medulla attained equilibrium when slice [K] was approximately 8 times medium [K] (5-9 mM). In anoxic outer and hypothermic inner medullary slices [K] fell to a significantly greater extent, but interpretation of these findings in terms of slice K loss is subject to modification in respect of the increases in slice weight (water content) accompanying the [K] decreases. 6. There was a transient (1-3 min) rise in [Na] in all slices. This was followed by a [Na] decrease, which was most apparent in control slices, and finally a gradual increase towards medium [Na] (141 and 180 mM for outer and inner medulla respectively).

1. The changes in the volumes of cells in slices (thickness 0-3-0-4 mm) of rat renal outer and inner medulla have been investigated during aerobic incubation for 20 min at 37 degrees C in Krebs phosphate-bicarbonate Ringer modified by the addition of urea or sucrose in order to produce a range of media hypo- and hyperosmolal with respect to the calculated tissue fluid osmolalities in these regions. 2. On the assumption that under these conditions the measured inulin space approximates to the true extracellular space (ECS), it was found that osmotic swelling or shrinkage of cells was not accompanied by any significant variation in the absolute size of the ECS. 3. Calculated cell volume changes in both regions were minimal when slices were incubated in urea-containing media iso-osmolal with tissue fluids in that region. In sucrose-containing media minimal cell volume changes occurred when media were hypo-osmolal in relation to tissue fluids by a factor of approximately 0-68. 4. In all except the most hypo-osmolal media studied, calculated cell volume changes (as percentage of initial volume) were linearly related to the reciprocal of the incubation media osmolalities. The points of interception of the regression lines on the cell volume axis were dependent upon both the region studied and the composition of the incubation medium (urea or sucrose). 5. These changes were accompanied by variations in slice solute concentrations. Slice [Na] was greatest, and slice [K] least, following incubation in those media producing the greatest percentage changes in cell volume. 6. The volume of distribution [14-C]sucrose within the inner medulla was 61-7 plus or minus 2-5 mul./100 mg wet weight of tissue (mean plus or minus S.E., n equals 6) after 10 min incubation. The increase to 70-8 plus or minus 4-2 mul./100 mg (n equals 6) after 100 min was not significant (0-1 greater than P greater than 0-05). The volume of distribution within the outer medulla rose markedly during this period, from 38-1 to 58-2 mul./100 mg.

"Affirmative action" programs call for special activities to ensure that women and minorities participate in employment and educational opportunities in the numbers in which qualified members of these groups are represented in the nation or community. Six kinds of activities should receive priority in establishing a medical school affirmative action program: (a) review of salaries for equity, (b) establishing goals for hiring in both faculty and nonfaculty jobs, (c) review of admissions criteria to assure that women and minorities are not required to meet a higher standard than white males to include accurate predictors of the success of applicants from these groups, (d) survey of physical facilities to assure that lounges and facilities for women are equivalent to quality and convenience to those available to men, (e) examination of employment and instructional policies to identify any which have a "disparate effect" on the success of women and minorities and modification of such policies wherever alternatives are possible, (f) review of staff, student, and administrative attitudes to assure that the institutional atmosphere conveys support of equal opportunity. Success in accomplishing each of these priorities will build a basis for success in other aspects of the equal opportunity program.

The clinics of a single university hospital center were observed to determine a practical rationale for and impediments to implementing a medical care evaluation program. A quality assurance mechanism is especially important in the ambulatory care setting because of problems with patient compliance, lack of policy continuity, lack of intercommunication among care providers, no counterpart for most inpatient quality-oriented activities, structural defects in many clinics, and general emphasis on the inpatient medicine. Impediments to implementing quality assurance programs include the condition of clinic records and individual charts, lack of established criteria for care, problems of care provider intercommunication during the evaluation process, manpower availability, choice of evaluation method, and method of implementing resulting plans for corrective action.

In the longitudinal study reported here a comparison was made of changes in basic professional orientations of students during the first three years of professional socialization four health fields in Israel: medicine, dentistry, pharmacy, and nursing. Data are analyzed from the same groups at three points: prior to entry, at the end of year one, and at the end of year three. The image of the "competent" professional is analyzed in terms of a set of underlying traits which in all four populations are shown to group themselves empirically into three dominant components: People, Science, and Status. The priorities accorded to these components are quite similar in all four professions, suggesting a common basic orientation among them. The analysis also points to different levels of absolute emphasis on the components and to changes in patterns of emphasis during the early stages of socilization.

The advantages of a formal grading system in assessing a student's capability to practice medicine remain controversial. Students prefer the pass/fail method, while faculty lean toward the traditional approach. The efficacy of a modified pass/fail grading system in detecting superior academic achievement, as well as in predicting house staff performance, was evaluated. Mean scores on the examinations of the National Board of Medical Examiners of students selected fo Alpha Omega Alpha were significantly higher than those of other students, although the faculty was unaware of these results when selecting candidates. Chairmen in institutions where 125 students had served their first graduate year of training felt that 85 percent of the dean's letters summarizing the student's academic performance over a three-year period accurately indicated subsequent performance on the house staff. These results suggest that a modified pass/fail grading system can detect superior students as well as provide relevant information with respect to subsequent performance as a physician.

Factor analysis of medical student ratings of basic science instruction yielded three dimensions of student perception of instruction: faculty-student rapport, outside work, and aspects of student comprehension. While these factors are similar to those identified in other studies, they differ in respects probably reflecting differences between medical students and other students and differences in questionnaire design.

A judgment of the relevance of nine basic sciences courses was tested by the pair comparison method. The test groups consisted of first-, second-, third-, and fourth-year medical students; interns and residents; basic sciences faculty; and clinical faculty. The data obtained from all groups proved to be consistent. Three strata of relevance were detected. Physiology, pathology, and pharmacology comprised the stratum of maximum relevance. The anatomy sciences (gross anatomy, histology, cell biology, and embryology) formed a stratum of lowest relevancy. The comparative relevancy of biochemisty and microbiology fell between the two extremes. Two approaches for making the anatomy disciplines more relevant are discussed.

This is a report on a national study of minority group applicants and entrants to the 1970, 1971, and 1972 entering classes of U.S. medical colleges. The aim of the investigation was to further understanding of the factors involved in attempting to increase minority representation in education for the practice of medicine. Data from the Association of American Medical Colleges are used to examine characteristics of successful and unsuccessful minority applicants to medical school. Socieconomic, personal, institutiona, and geographical factors that relate to the recruitment and progress of minority students in medicine are analyzed and evaluated. Differences between Caucasian and minority group students affecting admissions, retention, and promotion are documented. The investigators also compare the projections of a 1970 AAMC task force report with actual occurrences in the national effort to expand educational opportunities in medicine for blacks and other underrepresented minority students (that is, American Indians, Mexican Americans, and mainland Puerto Ricans). This comparison shows substantial progress toward the projected figures but a need for renewed commitment if they are to be reached. Suggestions are offered for improving the recruitment and progress of minority medical school entrants by such means as the AAMC Simulated Minority Admissions Exercises and by ongoing programs at individual medical schools. The study also yielded such pertinent findings as the following: 1. Confirmation that the racial characterizations self-reported by medical school applicants have a high degree of accuracy and an increasing degree of completeness. 2. An encouraging increase in the number of black premedical students who will potentially apply for the medical school classes entering in 1976 and 1977. 3. Growth in the enrollment of low-income medical students, most of it explained by the increase in the numbers of minority group members who have been admitted in recent years. 4. More mobility among blacks than Caucasians with regard to attending medical schools in other than their region of legal residence. 5. A higher proportion of women, of older, and of married students among minority medical school matriculants than among Caucasian matriculants. 6. A slightly higher medical school retention rate for Caucasians than for students from underrepresented minority groups, possibly explained in part by the greater diversity in the socioeconomic and educational backgrounds of the latter. 7. A positive relationship for blacks between the size of undergraduate college attended and successful completion of the first year of medical school.

Process and outcome analyses were carried out on a group of patients who had uncomplicated cholecystectomy. The postoperative length of stay and patient satisfaction were also measured. A random sample of 80 charts was selected from 222 eligible records for process analysis. Outcome was evaluated in 218 of the 222 eligible patients against explicit criteria. More patients were in the symptomatic and back-to-work group than expected. The peer consensus was that these results were not related to the surgical procedure or specifically related to gallbladder disease. Ninety-five per cent of the patients assessed care as good or excellent, and 90 per cent felt the length of postoperative stay was satisfactory. When the patients were divided according to surgeon, significant differences in the length of postoperative stay were found in the 154 patients without common bile duct exploration. After the findings were presented to the surgeons through an educational program, changes occurred which resulted in a decrease of nearly one day in the postoperative hospitalization.

Numerous methodologies have been devised to measure various aspects of the quality of health care. Revised bibliographies of articles of articles reporting these methodologies are made available periodically. This paper is an attempt to devise a use ful framework for cataloguing these methods in order that health care planners and administrators can readily assess the means available to quantify aspects of health care under their scrutiny. A decision tree is presented for the decision maker to follow through according to his requirements, and a discussion presents a brief summary of the methods in each particular category. Gaps indicating the need for further research are identified.

Conditions for using single measures or combinations of measures of physician performance are discussed. Studies reporting combination indices of proficiency are reviewed for their use of equally or differentially weighted components and for the use of these with many or with single diagnoses, Comparisons of diagnostic-specific measures are made using differential and equal item weights. Under the general conditions of this research, few psychometric differences existed. The use and acceptability of differential item weights in this research are also discussed.

Human growth hormone (hGH) was administered to a group of osteoporotic patients at two dosage levels for a period of 6 mo each. The first dose employed was 2 units subcutaneously daily, and the second dose was 0.2W-3/4 units (where W is body weight expressed in kg) daily. There was no significant change in serum-cholesterol or triglyceride concentration despite the production of hyperglycemia and soft-tissue swelling on the higher dosage regimen. A number of factors may account for the conflict between our findings and a previous report in which hGH administration had a lypocholesterolemic, hyperglyceridemic effect. These factors include differences in sex, age, dosage, and duration of treatment. Nonetheless, it is clear that from a therapeutic vantage, even if hGH were readily available, it would not be a useful hypocholesterolemic agent.

Turnover rates and metabolism in the leg region and the splanchnic region, of free arachidonic and oleic acid have been examined in five healthy subjects at rest and during bicycle exercise. A continuous intravenous infusion of tritiated arachidonic acid and 14-C-labeled oleic acid was given. The rate constant for arachidonic acid turnover at rest was 0.44 plus or minus 0.004/min as compared to 0.29 plus or minus 0.02 for oleic acid. Significant correlations between turnover rate and arterial concentrations were observed for both acids in the resting state. The turnover of arachidonic acid was not significantly altered during exercise which caused an eight- to ninefold rise in pulmonary oxygen uptake. In contrast, the turnover of oleic acid rose markedly with exercise; its rate constant increased by approximately 90% to 0.57 plus or minus 0.05/min. The fractional uptakes of the two acids in the leg region were similar in the resting state. The splanchnic fractional uptake for arachidonic acid significantly exceeded that for oleic acid at rest. There was a net uptake of arachidonic acid in the splanchnic region in all subjects studied. In vitro incubations of whole blood deomonstrated a significant exchange of arachidonic as well as oleic acid between plasma and blood cells. We conclude that the metabolism of plasma free arachidonic acid differs from that of oleic acid in that (1) its fractional turnover at rest is about 50% higher, (2) its splanchnic fractional uptake is about 60% higher, and (3) its turnover rate is unaffected by physical exercise. It is further suggested that the high turnover rate of arachidonic acid, and to a less extent that of oleic acid, could be due in part to an exchange of fatty acids between plasma and endothelial cells.

A dose-response study of the effect of somatostatin on plasma growth hormone (GH) and immunoreactive insulin (IRI) levels was performed in normal subjects and acromegalic patients. In normal subjects 150 mug of somatostatin completly suppressed GH and IRI responses to arginine, while with 75 and 37.5 mug only a partial suppression was usually observed. Basal levels of plasma IRI were significantly lowered within 15 min from the start of somatostatin injection at each of the three dose levels. In three acromegalics the doses of 150 and 75 mug of somatostatin were effective in lowering both GH and IRI levels; the dose of 37.5 mug was still effective in lowering plasma IRI levels, while GH levels were not significantly modified. A dose of somatostatin inhibiting GH secretion without affecting insulin secretion has not been found either in acromegalics and in normals. It was concluded that the effects of somatostatin on GH and IRI secretion cannot be easily dissociated.

Serum cholesterol and triglyceride concentrations were determined in 46 patients with active acromegaly but with otherwise intact pituitary function. The mean serum-cholesterol level of the patients was lower and the mean serum-triglyceride higher than in the basic population of comparable age. The incidence of hypercholesterolemia was similar to that in general population, whereas the incidence of type IV hypertriglyceridemia was almost three times higher than in control population. The serum triglyceride level was not related to relative body weight, basal serum growth hormone, or insulin concentrations, nor did it correlate with glucose tolerance or with plasma-insulin response to oral glucose. However, the patients with highest plasma-insulin response had significantly higher serum triglyceride than the rest of the acromegalic group. The endogenous serum-triglyceride turnover rate showed no consistent changes, but increased serum triglyceride was associated with increased production rate. Upon successful surgical treatment of the acromegaly, serum-triglyceride level decreased in most of the cases who initially had hypertriglyceridemia. It is concluded that acromeagaly can give rise to moderate secondary hypertriglyceridemia.

The effects of exogenous parathyroid hormone, administered for 3 days, were compared in six hyperthyroid and six hypothyroid subjects. Maximum increments were much greater in hyperthyroid than in hypothyroid subjects for serum calcium (3.5 mg/100 ml versus 1.6 mg/100 ml), urine calcium (476 mg versus 79 mg), urine hydroxyproline (56 mg versus 11 mg), and urine phosphorus (671 mg versus 192 mg). Maximum decrease in serum phosphorus (minus0.9 mg/100 ml versus minus 0.1 mg/100 ml) was also greater in hyperthyroid subjects. Serum parathyroid hormone immunoreactivity was significantly higher in hypothyroid subjects (0.48 ng/ml) that either normals (0.21 ng/ml) or hyperthyroid subjects (0.19 ng/ml). The data support the concept that excess thyroid hormone sensitizes and deficient thyroid hormone blunts the responsiveness of bone to parathyroid hormone. This may lead to a state of hypoparathyroidism in hyperthyroidism and hyperparathyroidism in hypothyroidism.

From earlier studies, it appeared that postmenopausal women with osteoporosis may not be so responsive to therapeutic calcium infusions as younger men. A study of seven women with postmenopausal osteoporosis revealed that only one had a good therapeutic response as judged by sustained decrease in bone pain and improvement in calcium balance. It is concluded that a series of calcium infusions is unlikely to be therapeutically useful in postmenopausal osteoporosis.

This study was designed to observe the effects of hemmorrhage on the mobilization of free fatty acids from adipose tissue under a variety of experimental conditions. Experiments were conducted in fasting rabbits and dogs. A significant fall in arterial plasma free fatty acids was observed in rabbits following hemorrhage of 4 ml every 2 min and after inducing acute hemmorrhaged to a mean arterial blood pressure of 40 mm mercury. Adipose-tissue free fatty acids and arterial-plasma free fatty acids were simulatneously measured before and after hemorrhagic hypotension until death. Afterial free fatty acids fell significantly following hemorrhage, while the concentration of adipose-tissue free fatty acids rose significantly. In the next series of experiiments, dogs were pretreated with an alpha-receptor blocking agent phenoxybenzamine and acutely hemorrhaged. The results showed a significant rise in arterial free fatty acids concentration and an insignificant increase in adipose-tissue free fatty acids. These results suggest that hypoperfusion of adipose tissue plays an important role in the decreased supply of a major body fuel following hemorrhagic hypotension. The results are compatible with the view that metabolic fuel failure may be an important factor in the development of the complications of acute hemorrhage and suggest the concept that adipose tissue may be an important target organ in hemorrhagic shock.

A nationwide study of all 2330 patients hospitalized for a first definite acute myocardial infarction in Israel during a one-year period revealed a significantly lower 21-day mortality rate of patients treated by anticoagulants: 8.3 versus 27.3 per cent in those not receiving such therapy (p less than 0.0001). Out of the 22 hospitals studied, the effect was present in 18, absent in two, and not assessable in two. There was a highly significant inverse correlation between the proportion of patients receiving anticoagulant therapy in each hospital and the total 21-day mortality from infarction in that institution (r equals 0.57; less than 0.01). The superior survival of patients on anticoagulant therapy did not seem related to differences in age, sex, disease severity, site of infarction, diagnostic criteria or type of hospital. Despite the obvious limitations of retrospective studies the data justify a re-evaluation of the approach to the problem by further investigative effort.

During a state-wide retrospective study of myocardial infarction discharges from Maryland hospitals from July, 1966, through June, 1967, the relation of in-hospital case fatality rates to use of anticoagulants was examined in 1,156 patients. In patients who did not receive anticoagulants, the rate was 2.5 times that of those who did (p less than 0.0001). A large difference in case fatality rates between the anticoagulant and no-anticoagulant groups persisted when the data were analyzed by demographic and medical-care variables. When patients were classified according to clinical characteristics relating to prognosis, including arrhythmia, congestive heart failure and shock, the difference between the groups were also demonstrated. Although such a retrospective study cannot demonstrate conclusively the value of anticoagulant therapy, the data are sufficiently suggestive of a beneficial effect to warrant reopening the anticoagulant question.

In an attempt to confirm three reports suggesting a causal link between rauwolfia antihypertensive drugs and female breast carcinoma, all cases of such cancer appearing among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Most residents use a single care facility, and patterns of hypertension diagnosis, rauwolfia and other drug use, and medical-care-system patronage were abstracted from medical records. The prevalence of recorded rauwolfia use among the controls were 20 per cent, and that of other drug use was correspondingly high. The risk ratio for rauwolfia use was estimated to be 1.2 (95 per cent confidence interval, 0.7 to 2.2). Risk ratios between 1.0 and 2.0 were also found for other drug use and for measures of care-system patronage. These results do not support the hypothesis that reserpine causes breast cancer.

Medical liability insurance is in a state of emergency brough on by escalating premiums or withdrawal of insurance companies from the market. Solutions, supported by legislation, must be sought for the sake of both patient and physician. As a temporary method of correction joint underwriting associations appear to be the most practical suggestion. Long-range changes should include the establishment of powerful malpractice arbitration boards whose conclusions and evidence would be submitted in case of further appeal, the delegation of more power to the medical profession to enforce standards, shortening of the period specified in the statutes of limitation, limitations on contingency fees, and elimination of the applicability of such legal doctrines as ad damnum clauses and res ipsa loquitur.

We examined the causes of death in patients previously resuscitated from out-of-hospital ventricular fibrillation. In 51 months, 234 patients were sucessfully resuscitated, hospitalized and discharged home. During follow-up observation, 89 episodes of recurrent ventricular fibrillation or death (or both) occurred, 64 of which (72 per cent) were unexpected, out-of-hospital circulatory arrests. Ventricular fibrillation occurred in 77 per cent of the 44 episodes in which the electrocardiogram was observed. Ten patients survived one or more episodes of recurrent ventricular fibrillation. Median time to recurrent ciruclatory arrest was 20 weeks after the preceding episode. Prodromal symptoms were infrequent, and activity levels were generally low at the time of cardiac arrest. Recurrent ventricular fibrillation of sudden death (or both) occurred predominantly when the initial episode was not associated with acute myocardial infarction. Patients resuscitated from ventricular fibrillation are susceptible to early recurrence, probably reflecting continuing myocardial electrical instability.

To evaluate the efficacy of transbronchial lung biopsy in the diagnosis of sarcoidosis, 26 consecutive patients with clinical features of sarcoidosis underwent this procedure during fiberoptic bronchoscopy. In 21, the biopsy revealed noncaseating granuloma and, in the remaining five, normal lung parenchyma. Subsequently, two of these five patients were found to have tuberculosis, one was confirmed as having sarcoidosis, and the fifth has not had further evaluation. Transbronchial lung biopsy was therefore successful in the histologic confirmation of sarcoidosis in 21 of 23 patients. The only complication was one 20 per cent pneumothorax, which resolved spontaneously. Because of its low morbidity rate, high diagnostic yield and specificity transbronchial lung biopsy is recommended as one of the initial procedures for obtaining histologic confirmation in patients with suspected sarcoidosis.

Hemorrhagic cystitis is a common side effect of cyclophosphamide therapy not observed with other alkylating agents. In five patients receiving cyclophosphamide by mouth for prolonged periods with large cumulative dosage urinary-bladder tumors fatal to four and requiring cystectomy in the lone survivor developed. These observations strongly suggest chemical carcinogenicity of this drug in the production of these tumors. Increasingly, cyclophosphamide is being used for non-neoplastic disease. These circumstances suggest careful follow-up observation of patients in whom hemorrhagic cystitis from this drug develops for evidence of bladder cancer, as well as restraint in use of cyclophosphamide for non-neoplastic diseases if alternative therapy is available.

The use of line-shape decomposition techniques permitted the small 5-bond (5-J51') and 4-bond (4-J61') proton-proton coupling constants of a series of uracil nucleosides and nucleotides to be determined accurately. From an analysis of these coupling constants we have determined that the uracil base is in a predominantly anti conformation in aqueous solution and the mean position is not substantially altered by phosphate substitution at the 2', 3', or 5' positions, by changing the furanose stereochemistry from a ribose to a deoxyribose or an arabinose, or by an increase in temperature of 43 degree C.

Ethidium bromide intercalation strongly effects the circular dichroism spectrum of DNA in the region of 230-300 mu, in a complex manner. In this report we present a study that quantitizes the relationships of the circular dichroism spectrum in the region of 230-300 mu and the ethidium bromide induced optical activity centered around 308 mu. We present evidence of two hidden cooperative bands that are probably the negative counterparts of the 308 mu band and 330 mu shoulder positive cooperative bands. The hidden band is quantitatively characterized. We confirm that the direct effect of ethidium bromide on the DNA spectrum is simply linearly proportional to the amount of intercalated dye. We also observe that the ethidium bromide enters freely when there is a molecule intercalated for every 3 sites, but that the intercalation is more difficult when the molecule intercalates at every second site.

We describe here a new method for the electron microscopic mapping of sequence homology in nucleic acids. Specific segments of the T7 chromosome have been isolated following digestion with the restriction endonuclease from Hemophilus aegyptious (Haey). Denatured segments are annealed to the l-strand of T7 DNA; treatment of the hybrid with glyoxal allows only guanosine residues in the single-chain region to the reacted, producing an adduct which will no longer hydrogen bond with its complement on the r-strand. When the segment is displaced and the glyoxalated l-strand allowed to renature with the r-strand, "H" shaped structures are produced in which the duplex region corresponds to the position of sequence homology with the segment. The conditions employed for glyoxalation do not detectably disrupt duplex regions as small as 400 base pairs. This procedure should be generally useful for observing sequence homology in more complex DNA molecules containing duplex regions which can be specifically enriched for and their arrangement determined by electron microscopy.

Using a radioimmunoassay (RIA) based on the Farr technique with radioactively labeled 3-H-DNA for quantitative measurements of anti-DNA antibodies in sera of patients with systemic lupus erythematosus (SLE), the influence of molecular weight of DNA (ranging from 0.1 times 10-6 to 22.0 times 10-6 daltons) on binding and precipitation in this system has been investigated. Comparing our results with mathematical models it follows that one antibody molecule is fixed on the average to a statistical DNA segment of 2 times 10-6 to 4 times 10-6 daltons. Furthermore binding capacity of the DNA was found to be independent of the molecular weight, as demonstrated in a double label experiment using 14-C and 3-H-labeled DNA of different size. However, the amount of radioactivity precipitated was found to depend on the molecular weight of the labeled DNA following a non-linear function. It was calculated that a minimal ratio of fixed antibody molecules per a certain size of DNA was necessary for precipitation. The mathematical treatment of the observed non-linear precipitation dependence will be discussed using various statistical models. Our results indicate that the quantitative measurements of anti-DNA antibodies with the Farr technique e.g. for diagnosis and control of SLE in clinical immunology is highly dependent on the molecular weight of the labeled DNA used in the assay system and reliable results are only obtained with DNA of a sufficiently high molecular weight.

One hundred cervical and thoracic myelographies were performed with the non-ionic, water-soluble contrast medium metrizamide. Good myelograms were obtained in almost all cases, adverse effects were minor, no serious complications occurred, and no convulsions were seen. Metrizamide is better than gas or isophendylate for demonstrating intraspinal expansive lesions of affections of the root sleeves.

Multiple primary tumors are a common mode of presentation in familial neuroblastoma but must be differentiated from metastatic disease. The cases of 2 siblings with multiple neuroblastomas are presented and 44 additional cases of neuroblastoma reviewed. It was found that primary tumors localize to the posterior mediastinum, the adrenals, and the paravertebral ganglia whereas metastatic disease is found in the anterior and middle mediastinum, bones and para-aortic nodes. Based on these observations, the diagnosis of multiple primary tumors can be made and should lead to early consideration of familial neuroblastoma.

The ratio of patellar length to width was analyzed in comparison with subjective examination using radiographs of the affected knees in patients with hemophilia, juvenile rheumatoid arthritis (JRA), and controls to determine the usefulness of this measurement in differentiating the two diseases. A statistically significant difference was found between the proportion of JRA patients, controls, and patients with hemophiliac arthritis involving the knee. It was difficult to distinguish hemophilia from JRA by subjective analysis of the appearance of the knee using standard criteria. The patellar ratio is a more objective criterion which should be helpful in the radiological differentiation of JRA from hemophilia affecting the knee.

A review of the records of 23 patients with squamous cell carcinoma of the oral tongue and floor of mouth treated with irradiation after excisional biopsy has shown that: (a) Radiotherapy, primarily using interstitial radium implants, results in excellent local control of the primary area (100%) with preservation of function. (b) The frequency and severity of soft-tissue and bone necrosis may be reduced by not exceeding 5,500-6,000 rads from radium implants when only subclinical aggregates of cancer cells are probably present. (c) Theincidence of subsequent neck disease is low-8.7% (2 of 23 patients), and does not warrant routine elective irradiation of the cervical lymphatics.

Optimized 60-Co dose distributions for the moving-strip technique were calculated for 3 patients using a PC-12 minicomputer program which corrects for field obliquity and changes in patient thickness. Beam profiles were measured using an ionization chamber in a water phantom. A Masonite phantom was constructed to simulate a patient and used to measure optimized and unoptimized midplane dose distributions by thermoluminescent dosimetry. Measured midplane doses agreed with computer-calculated doses within experimental error. The computer optimization technique improved dose uniformity, reducing the midplane dose variation from plus or minus 12-13% to plus or minus 3-4%.

Lamellar keratectomy was performed in dogs to induce capillary endothelial proliferation at the limbus of the eye and the radiation response of endothelial cells was evaluated in terms of the dose required to prevent neovascularization in 50% of irradiated eyes (NVD50).Single- and split-dose experiments were carried out before and after induction of proliferation to determine the response of slowly and rapidly proliferating endothelial cells. the NVD-50-S prior to induction were about 400 rads greater than those following induction,indicating increased resistance of slowly proliferating cells. Split-dose studies indicatedthat the radiation repair capability was about 350 rads, either before or after induction.

Cultured human kidney T-1 cells were irradiated in flasks or on coverslips at different depths in a water phantom using the Los Alamos Meson Physics Facility Biomedical negative pion beam. Postirradiation colony formation and cell multiplication were assayed. Maximum cell inactivation occurred in the vicinity of maximum pion dose. Comparison of dose-survival curves with those found following x irradiation indicated RBE = 1.4 plus or minus 0.3 for colony formation and approximately 1.5 for growth delay. Delivery of 400 pion rads in four fractions resulted in higher survival than did delivery of 400 rads in a single fraction.

Radiographic features of the Swan-Ganz catheter and the complications associated with its use are described. Pulmonary infarcts develop subsequent to wedging of the catheter in a peripheral position, failure to deflate the balloon after use, and maintenance for morethan 72 hours. The radiology of the infarct is usually classical in appearance, i.e., pleural-based density which resolves in 14-21 days. The frequency of pulmonary ischemia may BE related to compromise of the venous and collateral arterial circulation in intensive care unit patients in whom the catheter is used.

Preliminary measurements of the biological effects of negative pions on cells in culture are reported. Cell survival as a function of depth was obtained by using gelatin to suspend the cells. The results indicate that the effects are more pronounced at the peak portion of negative pions. Cell-survival curves were also obtained under oxygenated and hypoxic conditions. The biological effectiveness at the peak was found to be a factor of 2.0 higher than at the plateau. The oxygen enhancement ratio was 1.5 at the peak. No significant differences in biological effects were observed above 14 mm in the peak region.

To determine if contrast agents after the blood-brain barrier by opening tight junctions between endothelial cells and by increasing pinocytosis, the distribution of horseradish peroxidase (HRP) was evaluated after intracarotid injections of contrast media. HRP did not cross the endothelium of cerebral blood vessels. Tight junctions remained closed. There was increased endothelial cell pinocytosis and swelling of astrocyte end-feet.

A new small intestinal biopsy technique was developed and evaluated: it involves the rapid replacement of a simple duodenal tube using a controllable spring guide and fluoroscopy. A suction biopsy catheter was then passed coaxially through the tube as often as needed for sampling, after which other diagnostic studies were done with the same intubation. In clinical trials totaling 31 biopsies in 15 adult patients, the method proved safe and effective. Currently, the time required to intubate the ligament of Treitz and obtain two biopsies is usually less than 15 minutes.

Videodensitometry of the margins of the fluoroscopic image of the left ventricle (LV) was used to evaluate LV wall motion. Differentiation of the wall motion signal reflected the velocity of LV contraction (dv/dt) during various inotropic interventions in 6 anesthetized dogs. Alterations in dv/dt were similar to changes in simultaneously measured LV peak dP/dt and the quotient of dP/dt and developed LV pressure, two widely accepted parameters of LV contractile state.

The effects of increasing single selective doses of prostaglandin E1 (PGE1) on superior mesenteric arterial flow and portal and systemic blood pressures were studied in dogs to assess its value as a vasodilatory agent for pharmacoangiography. PGE1 consistently increased blood flow, with an average increase of 187%, but had minimal effect on portal and systemic blood pressure. 25 mug of PGE1 gave an ideal flow curve for pharmacoangiography, with a maximum effect 30 seconds after injection.

Experimental venous thrombi were created in 19 dogs, using either thrombin or sodium morrhuate. Eighteen thrombi (95%) were identified by radionuclide venography; however, an 85% false-positive rate was found when nonoperated limbs were studied. The models employed were considered unsuitable for studying the accuracy of labeled particles in diagnosing deep venous thrombosis for the reasons discussed in the text.

Charged-particle bombardment of thick beryllium targets produces a neutron yield varying with angle, and an isotropic gamma component. Differences in detector response in such a field are due to neutrons alone. With accurate neutron spectral distributions and measurements of detector response, a computer code can be used to determine the neutron sensitivity of the detector as a function of energy.

Inclined lateral projections prove useful in defining aneurysms situated about the circle of Willis. For these projections, the x-ray tube and film changer are positioned as for a true lateral projection. The MCA lateral projection (patient's head inclined away from the side of injection) is valuable in investigating aneurysms of the internal carotid artery, posterior communicating artery and middle cerebral artery trifurcation. The ACA lateral projection (head inclined toward the side of injection) may be used to define aneurysms in the region of the anterior communicating artery.

Thirty minutes after reconstitution, radiochemical purity determinations of the lung-scanning agent Macrotec (99m-Tc-MAA) indicated 95-100% technetium labeling: 76% of the particles had a mean diameter of 10-50 mu. Rat tissue distribution studies indicated lung uptake of 98% at 15 minutes. The biological half-life in the lung was 8.3 hours. In 12 patients requiring emergency lung scans, 9 scans were rated excellent. No liver, spleen or thyroid uptake or adverse reactions were noted.

The Inter-Society Commission for Heart Disease Resources report concerning optimal resource guidelines for radioactive tracer studies of the heart and circulation is described. This report is an overview of the status of cardiovascular radionuclide diagnostic studies as well as a guideline to the hospital resources (physical and human) required for a high-quality nuclear medicine laboratory dealing with this area of study. These guidelines are directed to physicians and hospital administrators who are currently responsible for planning and organizing nuclear medicine programs or who anticipate a future need for such services in their community.

The diagnostic quality of roentgenographic images transmitted by interactive television was evaluated. A series of 100 kidney, ureter and bladder, chest, and bone radiographs were read individually by five radiologists, both on direct viewing and on viewing a monitor image of the television signal. The latter was transmitted by microwave a distance of 28 miles, including four transmission legs. Analysis in terms of receiver operating characteristic curves and critical tables indicated that the television interpretations were of acceptable accuracy, in view of the participants' inexperience with teleradiology.

The angiographic appearance in a patient with multiple bile-duct hamartomas of the liver is described. The lesions showed abnormal vascularity, consisting of grapelike clusters of small rings, which could be confused with other benign and malignant conditions demonstrable by angiography; however, it may ultimately prove to be characteristic of this uncommon lesion. The angiographic differential diagnosis is discussed.

Analysis of radiographic and physical findings in 114 patients with trauma to an extremity demonstrated that when other physical findings are normal, arteriography is unnecessary. If any physical sign of peripheral vascular injury exists, such as weak or absent pulse, neurologic deficit, bruit, or expanding hematoma, arteriography is essential to define the anatomy and determine the need for surgery.

C-terminal octapeptide of cholecystokinin was administered at six dose levels, 4-128 ng/kg, by 184 intravenous injections to three mongrel dogs under several pressure conditions of the biliary system. Gallbladder contraction was monitored radiographically. A good, dose-dependent contraction response resulted with intraductal pressures of 0 and 10 cm water. At 20 cm water, a markedly reduced and dose-independent response occurred. No contraction response was found with an intraductal pressure of 30 cm water. This animal experimental work suggests that in man, a contraction response of 30% or more may rule out significant common bile duct obstruction.

A CGR mammographic unit was modified to provide a more accurate method of measuring skin thickness. Evaluation of 418 normal patients indicated that skin thickness is greater in men than women, is less in older individuals, and, to a less extent, is greater in more obese patients. Height and race do not have a statistically significant bearing on skin thickness values. These "normal" values may prove useful as a screening criterion in evaluation of patients with possible acromegaly or Cushing's syndrome. Other potential applications are being investigated.

Three cases demonstrating avulsion of the coracoid process from the scapula associated with acromioclavicular separation are presented. Two patients were adolescents and one a young adult, suggesting that the coracoid base epiphyseal plate in this age group may be weaker than the coracoclavicular ligaments. A cranially-angled view of the shoulder was diagnostic in two cases. Recognition of this condition is mandatory if the orthopedist is planning fixation of the clavicle to the coracoid to remedy an acromioclavicular separation.

Rupture of the corpus luteum in a young woman can cause massive hemoperitoneum, seen as free fluid in the flanks and pelvis on abdominal films. Radiographic examination alone cannot distinguish hemorrhage due to a ruptured corpus luteum or ectopic pregnancy from pus due to a ruptured appendix or a tubo-ovarian abscess; however, the presence of nonclotting blood on culdocentesis excludes abdominal sepsis. If these symptoms and findings occur during the latter half of the menstrual cycle in a young woman of low parity who has a normal menstrual history and a negative pregnancy test, a ruptured corpus luteum is a more likely diagnosis than ectopic pregnancy.

Seminars covering the use of radiographic studies in the emergency room were given to the house staff. Greater efficiency in ordering indicated studies was achieved, and fewer repeat studies and unnecessary radiographic examinations were ordered. In addition, the radiologist and his staff became more aware of clinical problems in the emergency room. The authors feel that a series of seminars of this type can have a beneficial effect on general patient care.

An anomalous branch of the cavernous carotid artery, not reported previously, is described. Its appearance and distribution were unlike those of any known cavernous branch, originating at the level where the trigeminal artery is usually found but having no communication with the basilar artery. Its distribution approximated that of the anterior inferior cerebellar artery. The author believes that this is an unusual form of persistent embryonic communication between the carotid artery and the vessels of the posterior fossa.

Several non-steroidal anti-inflammatory agents (NSAIA) are shown to inhibit the net production of prostaglandin (PG)- like activity from arachidonic acid by a cell-free preparation of guinea-pig lung. Moreover, these agents also antagonize PGE-1-induced contractions of the isolated gerbil colon. The anti-spasmogenic effects are reversible and specific. At high concentrations, indomethacin and mefenamic acid interfere with the binding of PGE-1 to a broken cell preparation of rat epididymal adipocytes. Taken together the data indicate that NSAIA interact with prostaglandins at multiple sites and are consistent with the suggestions reported previously that NSAIA may have multiple in vivo actions.

Intravenous injection of SC-19220 (3-9 mg/kg) caused dose-related hypothermic responses in cats. Repeated administration of SC-19220 resulted in tolerance to its hypothermic action. During SC-19220-induced hypothermia, the hyperthermic activity of both prostaglandin E-1 and leukocytic pyrogen was reduced or abolished. Neither prostaglandin E-1 nor leukocytic pyrogen was antagonized when given shortly after recovery from SC-19220-induced hypothermia or by doses of SC-19220 which did not cause hypothermia. Although these results may indicate a role of prostaglandins in normal physiological thermoregulation, it is also possible that production of hypothermia by SC-19220 is unrelated to prostaglandin antagonism.

Intramuscular injection of the 15-methyl analogue of prostaglandin F-2alpha (15-ME-PGF-2alpha) is being used to initiate second trimester abortion. The natural prostaglandin F-2alpha (PGF-2alpha) is a known pulmonary pressor agent but there is little information about the cardiovascular effects of the analogue. Consequently, we compared the hemodynamic responses to the two forms in twenty-three anesthetized dogs. Given I.M. or I.V. 15-me-PGF-2alpha produced a greater and more sustained rise in pulmonary arterial pressure than PGF-2alpha. Intramuscular 15-me-PGF-2alpha also elicited a more prolonged increase in pulmonary vascular resistance than prostaglandin F-2alpha given I.M. or I.V. The methyl analogue (I.M. or I.V.) causes a greater initial fall in systemic arterial oxygen tension and cardiac output, and a greater increase in systemic resistance than I.M. PGF-2alpha. Breathlessness seen during abortion induced by prostaglandin F-2alpha or its methyl analogue may be caused by acute pulmonary hypertension in addition to bronchoconstriction.

A high concentration of indomethacin (40mu-g/ml) substantially reduced contractions of guinea-pig isolated ileum in Krebs solution to nerve stimulation with electrical pulses or nicotine. Responses to acetylcholine and histamine were also inhibited, but to a smaller extent. Low concentrations of prostaglandin E-2 (2 or 4ng/ml) mainly restored all the excitatory responses. Using a modified bathing solution (lacking in phosphate and with some other changes) indomethacin 0.36mu-g/ml selectively inhibited nerve-mediated contractions. The results explain differences in various reports, and support the possibility that prostaglandins modulate the response to cholinergic nerve activity.

In order to determine whether the venoconstrictor response to BK was dependent on prostaglandin (PG) synthesis, effects of indomethacin (INDO) on responses to bradykinin (BK) and norepinephrine (NE) were studied in canine lateral saphenous vein. Cumlative dose-response curves (10-9-10-6M BK or NE) were done in the presence and absence of INDO (10-6M). In the presence of INDO, responses to BK were markedly enhanced while responses to NE were unchanged. After prolonged periods in the bath, responses to BK were enhanced in control strips while responses of strips which had been treated with INDO were depressed. These results suggest that BK does not normally cause venoconstriction by stimulating synthesis of a venoconstrictor PG and that the increase in response to BK after prolonged periods in the bath may be related to changes in PG synthesis.

Prostaglandin analogues in which the alkyl chain attached to C-15 in the natural compounds is replaced by an alkyoxyalkyl group have been synthesised. Compounds of the 17-oxa series are particularly potent luteolytic agents and are selective in the sense that they are less effective than PGE-2alpha in causing isotonic contractions of isolated uterus muscle.

A method for the evaluation of PGF-2alpha and PGE-2 biosynthesis in rat cerebral cortex is described. Tissue slices were incubated without any added precursor for different lengths of time. The analytical procedure involves prostaglandin extraction, purification and quantitative determination by mass fragmentography. Significant amounts of both prostaglandins were synthesized. The biosynthesis reached a plateau after 30 minutes and the ratio of PGF-2alpha to PGE-2 was approximately 3.

Prostaglandin F-2alpha (PGF-2alpha) was administered via a Foley catheter over a 12 hour period to 8 healthy volunteers awaiting laparoscopic sterilisation. The amount of PGF-2alpha infused varied between 500 mu-g and 2000 mu-g every 2 hours for 6 doses. Plasma progestins and oestradiol 17beta, and urinary estrogens and pregnanediol were assayed throughout the study period. There was no evidence of luteolysis in any patient although vaginal bleeding of varying duration occurred in all women within 36 hours of administration of PGF-2alpha.

A group of five patients awaiting laparoscopic tubal diathermy were followed by daily assay of luteinising hormone (LH) and progesterone. Between five and eight days after the LH peak, prostaglandin F-2ALPHA (PGF-2ALPHA) was injected into either the corpus luteum or the ovarian stroma. Doses of 100 mu-g into the corpus tuteum, 1000 mu-g into the adjacent stroma and 500 mu-g into an indeterminate ovarian structure had no effect on peripheral plasma progesterone levels or uterine bleeding. An injection of 500 mu-g or 1000 mu-g given unequivocally into the corpus luteum produced a rapid and profound fall in plasma progesterone levels, the nadir coinciding with the onset of uterine bleeding which commenced 24 hours after the injection and persisted for more than seven days. Injection of 100 mu-g in the same volume of saline had no such effect. Despite continued bleeding plasma progesterone levels returned to normal luteal levels for three days and then fell again.

PGE-1(50 mu-g/animal) and PGF-2ALPHA (250 mu-g/animal) caused a transient increase in serum LH at 5 min after injection. PGE-1(250 mu-g/animal) had a biphasic effect on serum LH. A small peak was obtained at 5 min, and a second, larger peak at 60 min after injection. It is suggested that the first peak is a result of the stress associated with injection of the PGs, whereas the second peak represents a physiological effect of PGE. Subcutaneous injection of PGE-1(1 mg in arachis oil b.i.d.) for 10 days did not effect the concentration of LH in serum, the function of the accessory sexual glands or the sexual activity. PGF-2ALPHA, given at the same dose and in the same manner, increased the sexual activity but left all other variables unaffected. The pituitary responsiveness to LH-RH was unaltered by the treatment with PGE-1 and PGF-2ALPHA.

Prostaglandin F-2ALPHA (PGF-2ALPHA) was measured by immunoassay in plasma and milk of four cows (six experiments). After 30 mg PGF-2ALPHA im, plasma PGF-2ALPHA peaked at 15 minutes (2.4 plus or minus 0.7 ng/ml) and declined toward basal values by 3 hours; maxiumum milk PGF-2ALPHA (0.91 plus or minus 0.12 ng/ml) occurred at 1 hour. The average excretion rate in milk was 2.9 mu-g/day 0.9 mu-g (0.003%) of which was due to the 30 mg PGF-2ALPHA injected. In six nonpregnant control cows, daily changes of milk PGF-2ALPHA and progesterone were not consistently related.

The response of the non-pregnant human uterus to intravenous (i.v.) injections and intra-uterine instillation of various doses of prostaglandin E-2 (PGE-2) was evaluated at the different phases of the menstrual cycle in 13 fertile regularly menstruating women who were neither lactating nor using any hormonal therapy. Uterine contractility was recorded by the microballoon technique in at least three sessions(proliferative, mid-cycle and secretory) in a single cycle with endometrial biopsy performed immediately following the last session to ascertain that the particular cycle was an ovulatory one. Single i.v. injections of PGE-I had a consistent stimulatory effect on the contractility throughout the cycle with a tendency towards a decreased uterine response at mid-cycle and luteal phase as compared to the proliferative part of the cycle. Intra-uterine instillation of the compound induced a peculiar and interesting type of response. In the proliferative and secretory phases of the cycle the response was one of stimulation; being more pronounced in the former period. However, around ovulation time, the local administration induced an evident uterine relaxation in most cases without any instance of stimulation. The possible implication of this triphasic response behaviour on the non-pregnant uterus within certain physiological events and pathological conditions is discussed.

Termination of second trimester pregnancy with intra-amniotic administration of 15 (S) 15 methyl prostaglandin F-alpha (15 me F-alpha) was attempted in fifty patients. One group (26 patients) was given 1 mg of the analogue and the other group received 2.5 mg. The abortifacient efficacy of 15 me F-2alpha was similar in both groups; over 90% of the patients aborted with a single dose. There was a higher incidence of vomiting, diarrhoea and incomplete abortions in the group treated with 2.5 mg 15 me F-2alpha. Although the mean injection-abortion interval in the 2.5 mg group was shorter, it is concluded that intra-amniotic administration of 1 mg 15 me F-2alpha provides a better regime, giving high efficacy with a single dose, a low incidence of side effects and greater safety in case of inadvertent entry of the intra-amniotic dose into systemic circulation.

Placental progesterone contents were studied in 10 patients therapeutically aborted at midtrimester by intraamniotic infusions of hypertonic saline, and from 14 patients (12-20 weeks) aborted by intraamniotic instillation of prostaglandin F-2alpha. The mean S.E. of the progesterone was 1.99 plus or minus 0.07 ug/g. placental tissue in the first group, while with prostaglandin abortion the placental progesterone was 1.45 plus or minus 0.08 ug/g. tissue, which is significantly lower than the results in the first group (P equals 0.001). The possible mechanism of action of prostaglandin as an effective abortifacient is discussed.

Periodic collections of uterine venous blood were obtained from three nonmated, three pregnant and two mated but nonpregnant ewes in which uterine veins were cannulated with polyvinyl tubing on day 11 postestrus. Frequent sampling was achieved in three of these ewes with additional cannulae in the ovarian veins. Blood samples were collected at 3-hr intervals from 0600 on day 12 to 1800 on day 13 and then 6-hr intervals through day 15. On day 13, three additional samples at 30-min intervals were collected between 1400 and 1530. Prostaglandins F (PGF) in plasma were quantified by radioimmunoassay. On day 12, one ewe in each group had at least one measurement which suggested an increased rate of release of PGF into the uterine vein. Seven of eight ewes on day 13 appeared to have increased rates of release of PGF from the uterus between 0900 and 1500. The highest level measured in each ewe during this period ranged from 2.7 to 11 ng per milliliter. Concentrations of PGF in ovarian venous plasma in two of three ewes were positively correlated (P less than .05) with concentrations of PGF in uterine venous plasma (r equals .64 in each ewe). No evidence was obtained that pregnant and nonpregnant ewes differ in rate or pattern of release of PGF from the uterus into the uterine vein on days 12 and 13. Comparisons could not be made with confidence concerning PGF either in uterine veins on days 14 and 15 or in ovarian veins on all days due to limited number of observations.

The absorption of radioactive labeled protein from the pericaridal cavity and from the parietal and visceral membranes of the pericardium was investigated in 49 dogs. The absorption of 1 ml/kg injected diluted dog serum is slow (T1/2 About 24 hrs). The rate of protein absorption, particularly of the lymphatic transport, is lower from the parietal pericardium than from the epicardium. About 35 to 50% of the protein absorbed from the pericardium is removed by the blood capillaries, the rest by the lymphatic system. The major part, about 60%, of the protein absorbed by the lymphatics is transported by the cardiac lymph vessel, the remainder by lymphatics joining the great veins on the right side of the neck. The thoracic duct plays only an insignificant part in the transport of protein from the pericardial cavity.

Investigations have been performed on the metabolism and organ distribution of 5,6-trans-25(OD)D-3, which represents an analog of vitamin D-3 being active in uremia. This analog is rapidly metabolized into at least two more metabolites. The main storage organ for this compound seems to be fat, whereas liver and intestinal mucosa showed at 24 hrs the highest concentration of polar metabolites. In contrast to 25(OH)D-3 5,6-trans-25(OH)D-3 is much less absorbed from the intestinal tract, which should be considered if this compound is applied for treatment of uremic bone diseases.

A regional epidemiological investigation comprising one-tenth of the Danish population showed the annual incidence of new gastric ulcers during the period 1963-68 to be 0.44 per 1000 inhabitants aged 15 years and over. The corresponding incidence of solitary ulcers among former 'non-ulcer' patients was 0.31 per 1000. Similar incidence rates have been registered in comparable investigations from other Northern European countries within the last decades. The disease appears, however, to be relatively more frequent in Danish women than in women elsewhere, excluding in Australia. The annual incidence varied, but no indications of a systematic trend was registered. In solitary ulcers the ratio male: female was 1.1:1, while it was 2.2:1 in the cases in which a duodenal ulcer had been demonstrated, earlier or simultaneously with the gastric ulcer. The age incidence was identical for the two categories of patients. In both groups a considerable rise in the incidence was registered only in age groups above 40 years. In men the incidence was maximal for the 60-64 year age groups, while in women it increased with increasing age. The age-specific incidence rates of diagnostication as well as of symptomatic debut did not vary significantly according to the localization of the lesion.

Duodenal bile acid concentration following a standard meal, glycine/taurine (G/T) ratio, vitamin B12 absorption, and faecal fat were determined in 79 patients with Crohn's disease. Intestinal resection had been made in 50 patients before the study, and no evidence of recurrence was present at the time of the study. Among 46 patients subjected to ileal resection of 10-180 cm, a reduced duodenal bile acid concentration and vitamin B12 malabsorption was almost invariably present when 50 cm or more of ileum had been removed. Patients with smaller resections and unoperated patients did not show a consistent pattern. Vitamin B12 absorption and duodenal bile acids were of equal value as indicators of ileal dysfunction with the exception that, in 10 ileostomy patients, duodenal bile acids were decreased in every case, but vitamin B12 absorption only when 80 cm of ileum or more had been resected. G/T-ratio was related to the extent of ileal resection-being elevated after large resections (80 cm or more)-but not to the presence of an abnormal flora. Faecal fat was much more elevated in ileostomy patients with large ileal resection (80 cm or more) than in unoperated patients and patients without an ileostomy.

The diagnosis of chronic persistent hepatitis is based on a combination of clinical and morphological data. During a 7-year period 26 cases were diagnosed in 3 medical departments in Copenhagen. In 22 patients the disease was considered to be a sequela to acute viral hepatitis, and 12 had Australia antigen in serum. Only few patients had circulating auto-antibodies. The clinical and biochemical activity at the time of diagnosis was usually slight. A morphological and clinical follow-up study revealed that the course of the disease was generally benign. However, in 3 patients the last repeat biopsy showed progression to cirrhosis, severe portal fibrosis, and chronic aggressive hepatitis. Such exceptions may represent a sampling error in the interpretation of the first needle biopsy, or the correct diagnosis may have been chronic aggressive (active) hepatitis at a stage with slight activity. Clinical and biochemical observation is recommended in chronic persistent hepatitis, and in some patients serial needle biopsies are necessary to reveal the few exceptional cases which progress to an active chronic liver disease.

Electrical spike potentials and intrauminal pressure variations were recorded from the human duodenum and distal ileum before and after i.v. administration of 80 log Ivy units of cholecystokinin. In the duodenum, quantitative calculations of motility gave identical values before and after drug administration, and results were identical in patients before and after cholecystectomy as well as in hernia patients without upper gastrointestinal disease. A decrease in amplitude of the spike potentials was observed in the duodenum during the first few minutes after drug administration in all groups. Recordings from the distal ileum in ileostomy patients showed a significant increase in motility after CCK administration whereas the spike potential amplitude was unchanged.

120 Danish patients with ulcerative colitis, admitted consecutively to a Department of Gastroenterology, were investigated for lactose malabsorption. The prevalence was 9.2 percent, which is not significantly higher than that in a mixed Danish gastroenterological material, There was no difference in distribution according to age and sex, and the incidence was not correlated to the severity of the ulcerative colitis. The possible reasons for the wide variation in the incidence of lactose malabsorption in materials of patients with ulcerative colitis are discussed, and it is concluded that the main cause must be that the materials with the highest incidence include patients of races and ethnic groups in which lactose malabsorption is a common finding.

Dogs were provided with oesophageal fistulae, fully innervated pouches of the fundic stomach and the duodenal bulb, and a gastric cannula. Gastric secretion was stimulated by sham feeding for 10 min. The bulbar pouches were perfused either with 0.9 per cent NaCl or with 0.1 N HCl. Plasma gastrin concentrations were determined by radioimmunoassay. Bulbar acidification effectively inhibited gastric acid secretion. Plasma gastrin responses were not suppressed. Instead, plasma gastrin concentrations were higher than in controls. The results show that the bulbar mechanism does not inhibit gastric acid secretion by reducing gastrin release.

Dogs were provided with innervated pouches of the fundic stomach and the duodenal bulb. One dog also had an isolated pouch of the distal duodenum. Acid secretion was stimulated by intravenous infusion of a low dose of pentagastrin (ICI 50 123). Bulbar pouches were perfused with solutions of 0.9% Na C1, 0.1 N HC1, 40% glucose, 40% NaC1, and 40% peptone or with 0.1% solutions of acetylcholine chloride. Acidification of the bulbar pouches profoundly inhibited the acid output from the gastric ppoches. Perfusion with acetylcholine produced a transient inhibition of acid secretion. When hypertonic solutions were perfused through the bulbar pouches or the pouch of distal duodenum, no inhibition occurred. It is concluded that hypertonic solutions are not activators of the bulbar inhibitory mechanism that has been shown to respond to reduction of the intrabulbar pH. Inhibition following bulbar perfusion with acetylcholine may mean that liberation of the hypothetical humoral agent, bulbogastrone, to some extent is under cholinergic control.

The effect of 140 mug of 16,16-dimethyl PGE2 on gastric emptying and intestinal transit of a barium-food mixture has been studied in 8 healthy male volunteers. The propagation of the test meal was followed from the stomach to the colon by fluoroscopy wit repeated photograph ic recording. It was found that this analog significantly enhanced the rate of gastric emptying in most subjects, and the food-contrast medium also appeared sooner in the colon following the prostaglandin analog. In addition, the duodenum and the first part of the jejunum had a flaccid and dilated appearance on several occasions after administration of prostaglandin. The more rapid emptying of the stomach after administration of the prostaglandin analog is probably explained by a decreased duodenal resistance towards the gastric outflow; the earlier appearance of contrast in the colon could partly be due to the more rapid gastric emptying following administration of the prostaglandin analog.

The hepatic microsomal metabolism of antipyrine, as measured by its metabolic clearance, was investigated in 18 patients either before, during, or after hepatic encephalopathy. The antipyrine clearance measured in 13 patients during hepatic encephalopathy (4.6 ml/min. S.D. 14) was significantly lower than that of 5 patients investigated 4 weeks before or after hepatic encephalopathy (9.6 ml/min. S.D. 1.9). The clearance of antipyrine as a measure of a quantitative liver function is substantiated by the present observations, and its use as a prognostic indicator of acute liver failure is suggested.

Bile acid kinetics were characterized in 8 patients with portal liver cirrhosis with the aid of 24-14C-cholic acid and randomly 3H-labelled chenodeozycholic acid. Although not significant on a statistical basis, pool size, synthesis, and fractional turnover of cholic acid in the cirrhotic patients tended to be smaller than in normolipidaemic controls without evidence of liver disease. The most significant findings in the present patients were the subnormal cholic acid: chenodeoxycholic acid ratio of both bile acid pool size and synthesis and the low concentrations of deozycholic acid in duodenal bile specimens. Possible explanations for these findings are discussed.

Following preincubation of intrinsic factor- (IF-) bound 57CoB12 with the jejunal sediments of 6 patients with the blind-loop syndrome, the mean uptake by the sediments of IF-57CoB12 (28.1 percent plus or minus 4.2 percent S,E.M.) was significantly higher than the mean uptake by jejunal sediments from 5 control patients (5.8 per cent plus or minus 3.5 percent) (p smaller than 0.01). The uptake by the sediments significantly decreased when the incubations were carried out in the presence of lincomycin and neomycin. The jejunal sediments from the patients with the blind-loop syndrome inhibited the uptake of IF-57CoB12 by perfused rat intestinal segments (p smaller than 0.01), whereas the sediments from the control patients had no such inhibitory effect (p smaller than 0.5).

Inspired by the hypothesis that vitamin C controls the transformation of cholesterol into bile acids, the biliary lipid composition was examined in 10 healthy persons before and after 7 to 15 days' treatment with alrge doses of ascorbic acid. No significant difference between the values before and after treatment were found. It is stressed that the study does not allow evaluation of the hypothesis, but it may be concluded that vitamin C most likely has no place in the medical treatment of cholesterol gallstones.

We have shown the presence of lactoferrin in the pancreatic juice of patients with chronic calcifying pancreatitis (CCP) and its absence in controls. In this work, lactoferrin has been found in saliva, but neither in gastric juice nor in bile. Therefore, a technique for collecting the human duodenal juice with a rubber tube and preventing its contamination with saliva is described. In the duodenal juice of 15 patients with CCP, 52 controls without evident pancreatic diseases, and 9 cases of pancreatic diseases other than CCP, lactoferrin has been searched for by immunological methods before and after an intravenous injection of CCK-PZ (3 U CHR) + secretin ( C U). The lactoferrin test in positive in 5, inconclusive in 6, and negative in 41 cases, and in the 9 cases of non-CCP pancreatic diseases it is negative. The use of this test in the diagnosis of CCP is proposed.

Some factors influencing the comfort of old people (mean age 73 years) in a modern home for the aged were studied. Most (76 percent) of the old persons were satisfied with their living conditions. Only one-fourth (24 percent) of the inmates were dissatisfied. The most important factors causing dissatisfaction were discomfort due to illnesses, and disagreement with other residents. On the whole, the old people were more satisfied with their life at home for the aged than is ofter supposed.

The results of a combined dermatological and surgical treatment of varicose ulcers was studied in 100 patients. This chronic disease, often persisting for decades, was halted in 90 percent of leg operated upon. Even when the general outcome of the treatment was favourable, it was found that, for 5 out of the 12 ulcers which were the same or larger in size at follow-up than before operation, the patient assessed the result as good or even excellent. This finding deserves further study. It indicates that patients and physicians sometimes use different standards by which to measure therapeutic success.

The mental health center movement represents a new mode of care for the mentally ill. People are treated on an out-patient basis rather than in institutions. The therapeutic work is mainly carried out by so-called paraprofessionals who seem to be well qualified for the job. However, when organizing such a treatment system there appear to be several important factors which need to be taken into account: (1) the therapist's need to work individually and independently, (2) the therapist's need for personal training, (3) the therapist's need to be heard when they channel information from the community to the service system, (4) the need for open and direct communication in the system to ensure that the therapists work within the frame of accepted therapeutic procedures, (5) the importance of the therapists' being represented at the highest decision-making level in the system in order to ensure that their needs are met. The author stresses this as an inevitable necessitiy in order to give the therapists the appropriate working-background.