Chronic progressive renal disease: rate of change of serum creatinine concentration. The rate of change of the serum creatinine concentrations in 63 patients with chronic progressive renal disease of varied etiology was examined by linear regression analysis using the logarithm or the reciprocal of the serum creatinine concentration versus time. A single straight line was described by one or the other of these relationships in 53 patients. Six patients had an accelerated rate of nephron destruction terminally (two slopes) regardless of the mathematical analysis. The remaining four patients had course changes either due to apparent spontaneous remissions or temporally related to therapy. These data suggest that (functional) nephron loss in chronic progress disease is orderly and mathematically definable. The theoretical implications are that functional nephron loss is either exponential (log Cr) or constant (1/Cr).


Micropuncture studies of the filtration and absorption of albumin by nephrotic rats. The proximal tubular fluid albumin concentration of rats with immunologically induced nephrotic syndrome rose from 0.60 +/- 0.11 (SEM) mg/100 ml to 7.42 to 0.87 mg/100 ml. The glomerular filtration rate (GFR) was slightly depressed (P less than 0.001) and fractional water absorption unchanged (P greater than 0.45). Urinary albumin excretion rose from 0.18 +/- 0.03 (SEM) mg/100 g of body wt/24 hr to 78.5 +/- 39.5 mg/100 g/100 g of body wt/24 hr (P less than 0.001). The concentration of albumin in glomerular filtrate, calculated as the product of proximal tubular albumin concentration and fractional water absorption (4.53 +/- 0.60 mg [SEM]/100 ml), equalled that calculated from urine albumin concentration and whole kidney water absorption (4.14 +/- 0.84 mg/100 ml, P greater than 0.30). The data are interpreted to reflect a significant increase in filtered albumin and only a modest (if any) tubular albumin absorption in this study. Thus, the concept that tubular absorption plays a major role in the catabolism of albumin and the genesis of hypoalbuminemia in the nephrotic syndrome could not be confirmed.


Evaluation of hypercoagulability in users of oral contraceptives. Soluble fibrin monomer complexes (SFMC) were determined in users of different oral contraceptives. Quantitative gel filtration of beta-alanin precipitated plasma samples yielded the relative (per cent of total fibrinogen content) and absolute (mg per 100 ml plasma) amount of SFMC. Increased levels of SFMC were observed in users of oral contraceptives, when compared to age, parity and socioeconomic background matched control groups. This increase was more pronounced in users of Neogynon (0.05 mg ethinyl estradiol, 0.25 mg norgestrel) than in the one using Microgynon (0.03 mg ethinyl estradiol, 0.15 mg norgestrel). Users of Ovulen (0.1 mg mestranol, 1 mg ethynodiol diacetate) in addition to the rise of SFMC levels exhibited elevated fibrinogen levels in plasma. The data presented indicate a limited state of hypercoagulability in users of oral contraceptives.


[Microzone electrophoresis of non concentrated CSF (author's transl)]. This paper reports on a method which allows the separation of proteins of non concentrated CSF by means of the microzone technic. Pherograms of high quality were possible when the CSF contained more than 10 mg/dl total protein. Protein separation is completed in 16 min when one cellulose acetate strip with 150 V and 2 mA or when 150 V and 4 mA with two strips are used. Proteins were stained with nigrosine. The theoretical basis, technical details and error range of this method of protein separation are discussed.


[Effect of space flight on rat skeletal bones (an optical light and electron microscopic study)]. By light and electron microscopy long tubular bones of white Wistar rats were examined after a 22-day space flight and ground-based synhcroneous experiment. Approximately half of the flight rats showed loosened spongiose of metaphyses which was normally combined with a reduced area of the primary spongiose near the cartilaginous growth plate. This was suggestive of inhibited growth of bones in-flight. The light and electron microscopic examination of bones of flight rats revealed wide osteocyte cavities (lacunae) that could be associated with perilacunar osteolysis. The study of synchroneous animals demonstrated a less expressed spongiose of metaphyses found only in one third of the rats which was not usually combined with a reduced area of the primary spongiose near the cartilaginous growth plate. The histological examination of bones of flight rats on the 27th postflight day indicated that that period of time was insufficient for the normalization of all the changes.


[Effect of space flight factors on rat skeletal musculature]. Morphological and histochemical examinations of skeletal muscles of flight rats demonstrated atrophic and dystrophic developments in M. soleus which were followed by metabolic disorders in the muscular tissue. The changes were reversible, although they did not disappear entirely on the 27th postflight day. Early signs of atrophic developments were found in M. gastrocnemius, M. quadriceps, M. extensor digitorum longus and M. biceps brachii on the 2nd postflight day. The comparative study of the data obtained from flight and ground-based synchroneous rats showed that muscular pathologies developed as a result of hypodynamics and were enhanced by weightlessness-effects.


[Calcium and phosphorus content and the 45Ca incorporation into the bones and teeth of rats after a 22-day orbital space flight on board the "Cosmos-605" satellite ship]. Examinations of 37 rats flow for 22 days onboard the biosatellite Cosmos-605 revealed no changes in the mineralization coefficient or the Ca and P content in humerus and teeth of the animals on the 2nd and 26th postflight days. Radioisotope studies showed changes in the specific activity of Ca45 incorporation in humerus and incisors. In flight rats the parameter decreased by 37-44%, in synchroneous animals it increased by 102% in bones and by 20% in incisors as compared with the vivarium controls on the 2nd postflight day. The specific activity of Ca45 incorporation was 92.7% in humerus and 44.2% in incisors of flight rats and 72.9% in humerus and 94.7% in incisors of synchroneous rats as compared with the vivarium controls on the 26th postflight day.


[Effect of accelerations, additional weight load and hypokinesia on protein catabolism in the Japanese quail (Coturnix coturnix japonica)]. Activities of glutamate and xanthine dehydrogenases were measured in four groups of quails (coturnix coturnix japonica): 1) hypodynamic birds which were kept in an area which made 1/4 of the control, 2) birds exposed to an increased weight load, 3) birds exposed to 3g. and 4) control birds. The experimental birds were exposed to the above treatment for 1 to 6 hours a day during 8 days. The birds were fed on a forced basis to eliminate differences in food intake. The activity of glutamate dehydrogenase was measured in the liver and that of xanthine dehydrogenase was assayed in the liver, kidneys and femoral muscle. It was found that increased gravity, weight load and hypodynamics affected the first and last stages in protein catabolism.


[Water metabolism changes during prolonged hypokinesia with an antiorthostatic posture of the body]. Variations in the total content of body fluid and intravascular fluid were measured during a 49-day bed rest experiment and a 25-day recovery period. During the experiment the test subjects were kept in the head-down position at an angle of -4 degrees. The diminished motor activity led to a decrease of the absolute and, to a greater extent, of the relative content of water in the body which was associated with intravascular losses. The major changes in fluid balance occurred during the first two weeks of the bed rest experiment; this may be attributed to the head-down position of the test subjects.


[Phosphocreatine metabolic indices during increased and decreased energy expenditures in man]. Changes in phosphocreatine metabolism (creatinine excretion in the urine and arginine content in plasma--one of the amino acids that are involved in creatine synthesis) were studied in 40 male test subjects who performed increased or decreased work and consumed standard protein food. It was shown that there was a correlation between creatinine excretion in the urine and the content of arginine in plasma, on the one hand, and the amount of nitrogen consumed, on the other. It was also found that at increased or decreased energy expenditures creatinine excretion and arginine content elevated. These data are indicative of changes in phosphocreatine metabolism in response to the environmental effects.


[Hemodynamics of healthy persons under various regimens of negative pressure around the lower half of the body]. Thirty male athletes kept in recumbency served as test subjects in 90 LBNP experiments. In the experiments the negative pressure level varied from 40 to 80 mm Hg. During LBNP application the heart rate, arterial pressure, cardiac output, vascular tone and other parameters of circulation were measured. Cardiac output stabilized whereas other cardiovascular parameters changed significantly. Mechanisms of compensatory reaction during LBNP application and indications of its tolerance are discussed.


[Motor activity of mice in a magnetic field of varying intensity]. Mice were exposed to a constant magnetic field of 250-4,000 oersted and alternative magnetic field of 100 oersted and a frequency of 100 Hz. The animals showed changes in the motor activity whose level and pattern depended on the field intensity. An exposure to a constant magnetic field of 1000 oersted inhibited significantly motor activity of mice. The motor activity was slightly activated during an exposure to a constant magnetic field of 500 oersted and immediately after an exposure to a constant magnetic field of 4000 oersted and to an alternative magnetic field of 100 oersted and a frequency of 100 Hz.


[Prevention of altitude decompression sickness during short flights in a depressurized cabin at high altitudes]. Forty altitude chamber experiments were carried out in which 18 test subjects participated. The purpose of the experiments was to prevent decompression sickness in a pilot using an altitude compensatory suit and oxygen mask. It was demonstrated that oxygen breathing on the ground and at an altitude of 8 km for 20 and 50-60 min eliminated severe symptoms and lowered the frequency of occurrence of mild symptoms of decompression sickness during the subsequent 10-20 and 60-120 min exposures to altitudes of 40,000 and 11,000 m respectively. An increase in the absolute pressure to 240-290 mm Hg in the altitude garment prevented decompression sickness of altitudes of 11,000-15,000 m and eliminated it if it occurred at lower barometric pressure.


Ganglioneuroma-containing tumours of the adrenal medulla in Alderly-Park rats. The histopathology of 7 adrenal tumours, consisting partially or entirely of ganglioneuroma, is described and their origin discussed.


[State of hematopoiesis during irradiation simulating radiation exposure in prolonged space flight]. The paper presents the results of studies of the peripheral blood and bone marrow of 36 male dogs exposed to a chronic 3 year gamma-irradiation (from the Co60 source) at a dose rate of 0.17 rad per day which was combined with acute irradiations. The animals received two doses -360 and 564 rad in total. The leukoblastic system showed inhibition and decreased reactivity in case of irradiation with a higher dose. The red blood cell balance remained stable for a long period of time due to activated erythropoiesis.


The transmission of Theileria annulata to a rabbit by the larvae of the tick Hyalomma rufipes. A New Zealand White rabbit on which larvae of Hyalomma rufipes were fed died of theileriosis due to Theileria annulata 22 days after the larvae had fed. The larvae were direct progeny of an enorged female collected from trade cattle in the veterinary control post at Ibadan. The danger attending the feeding on rabbits of first progeny of ticks collected from cattle in countries where some tick-borne diseases are endemic is highlighted. The possibility of transovarial transmission of Theileria is discussed.


[Nitrogen, carbohydrate and lipid metabolic indices in man during a prolonged stay under hyperbaric conditions]. Some parameters of the protein, fat and carbohydrate metabolism were examined in men who worked in a nitrogenoxygen atmosphere at 5 ata. Three series of 15-18 day experiments were carried out on two test subjects in each. The test subjects were kept on a well balanced diet. In the first experimental series no additional vitamins were given. In the second and third experimental series the test subjects were given an Undevit vitamin complex. Test subjects of the first group showed changes in nitrogen metabolism and an increased content of sugars in blood. Test subjects of the second and third groups displayed minor, if any, changes of that kind. After the experiments the parameters returned to the normal within different periods of time.


[Dependence of the species makeup of a mixed culture of microscopic algae on the illumination and on the rate of nutritional element intake]. The existence of microalgal polycultures in a continuous culture is discussed. This depends on both physiological characteristics of algae and the rate with which nutrient elements are supplied. The routes of control of the species structure of the polyculture are discussed.


Fibrosarcomas induced by cobalt chloride (CoCl2) in rats. Hyperlipaemia persisted for more than 12 months in rats treated with cobalt chloride, 9 of 20 treated rats and 1 control rat died within the first year, and 8 of the surviving animals developed fibrosarcomas--in 4 of these the tumour was far removed from the injection sites. The results are discussed with reference to the use of cobalt chloride treatment for anaemia in patients with chronic renal failure.


[Some personality characteristics of cadets with varying levels of flight proficiency]. The paper gives assessment of personality characteristics of pilot-cadets and discusses their influence on the marks in flying disciplines. The study uses a discrimination analysis and presents a statistically optimal generalized criterion that can be applied to quantitative prediction of the success of flight training.


Naturally occurring superfoetation in the rat. A case of superfoetation in the rat is described and an estimate of the incidence of naturally occurring cases in a colony of Porton strain Wistar (LAC:P) rats rats is made (0-09-0-27% of litters born).


Differences in production of solid Landhscütz tumours in BALB/c and ICR mice. Landschütz tumour cells in the ascitic form injected subcutaneously into BALB/c or ICR mice produce solid tumours which grow progressively in most ICR mice but regress in nearly all BALB/c mice. Solid tumours in the peritoneal wall (produced by intraperitoneal inoculation of ascitic cells and treatment with normal serum) grew in both strains, but were more invasive in ICR mice. Surgical interference in BALB/c mice with these tumours, allowing adhesion of tumour to skin or subcutaneous fascia, resulted in cessation of tumour growth or regression.


Vaginal impedance measurement used for mating in the rat. An apparatus consisting of 2 silver ring electrodes attached to a plastic rod and connected to a transistor indicator was used to measure electrical impedance changes in the vagina of rats. A statistically significant increase in electrical impedance occurred at proestrus. By determining when this peak occurs, the optimal time for pairing can be established. In paired animals the absence of the peak provides a reliable means of diagnosing pregnancy.


Vaginal impedance measurement used for mating in the guinea-pig. A method for determining the phase of the oestrous cycle by measuring the electrical impedance of the vaginal mucous membrane was examined in the guinea-pig. The apparatus consisted of silver ring electrodes attached to a plastic rod and connected to a transistor indicator. A cyclic increase in impedance was found, and significantly higher values were recorded during the phase of increase (proestrus) than at other times of the cycle. By determining this peak the right time for pairing can be chosen. Conversely, the disappearance of this cyclic culmination in impedance pointed to early pregnancy with a high degree of reliability.


Formation of renal medullary lysosomes during potassium depletion nephropathy. The biochemical correlates of droplet formation in renal inner medullary cells of potassium-deficient rats were studied. An increase in the activities of five hydrolytic enzymes typical of lysosomes was associated with an increase in the number and size of droplets observed during progressive potassium depletion. Acid phosphatase activity increased 7-fold whereas beta-glucuronidase, beta-galactosidase, cathepsin, and acid DNase increased 2- to 4-fold in medullary homogenates at 25 days of depletion. Following potassium repletion the activities returned to normal at a rate dependent upon the duration of potassium depletion. The decreases in enzyme activities were associated with a concomitant rapid disappearance of the droplets from medullary cells. Protein synthesis for new droplet enzyme formation was studied by measuring the rate of [14C]leucine incorporation into protein in medullary slices. The rate increased at 1 day of depletion and reached a maximum which was 139 per cent higher than control after 7 days of depletion. In droplets isolated from medullary tissue during progressive potassium depletion the rate of protein labeling with [14C]leucine and acid phosphatase specific activity increased in parallel. When droplet proteins were separated by gel electrophoresis, acid phosphatase activity was detected in a protein band which had been labeled with [14C]leucine, thereby suggesting new enzyme protein formation. The increase in enzyme and protein synthesis and a previously demonstrated increase in phospholipid synthesis and membrane formation indicate that potassium depletion induces specific alterations in renal inner medullary cell metabolism which result in increased lysosome formation.


Lipid accumulation in the stationary phase of strain L cells in suspension culture. Strain L (Earle) cells in suspension tissue culture exhibit a logarithmic growth period followed by a stationary or plateau phase. Lipid to cell and lipid to protein ratios were found to be at minimal levels during logarithmic growth and increased 13 per cent and 42 per cent, respectively, in cultures in the stationary phase. The lipid accumulation was due to elevated cellular levels of phospholipid and cholesterol, which each increased in nearly the same ratio. Cellular triglyceride and free fatty acid content was not significantly altered. There was a loss of cellular protein in the older cultures that largely accounted for the greater increase in the lipid to protein ratio. Electron microscopic examination of cells from the stationary phase revealed numerous autophagic vacuoles and dense bodies, many of which contained membranous debris and other cytoplasmic components in different stages of autodigestion. These varied and complex membrane-bound structures localized acid phosphatase activity on cytochemical examination, establishing them as autophagic lysosomes. The present correlative biochemical and morphologic studies indicate that the observed elevation of phospholipid and cholesterol in stationary phase cells occurred as a result of autophagocytosis and demonstrate the role of cell injury in the accumulation of lipid of this type.


Interaction of crocidolite asbestos with hamster respiratory mucosa in organ culture. Organ cultures of hamster trachea were used to study the effects of crocidolite asbestos on the respiratroy epithelium and the uptake of asbestos by cells of the mucosa. International Union Against Cancer (U.I.C.C.) crocidolite was suspended in medium over a range of concentrations and precipitated on the epithelial surface for 1 hour. At intervals during the ensuing 4 weeks, morphologic changes were documented by light, scanning electron, and transmission electron microscopy. Cytotoxic alterations in differentiated mucosal cells appeared to relate to the amount of crocidolite added to the cultures. Necrosis and desquamation of surface cells were accompanied by basal cell hyperplasia. These proliferating cells phagocytosed the dust and incorporated it into lysosomes. Crocidolite was also found interposed between cells of the hyperplastic basal cell layer. Transport of asbestos particles to the submucosa and uptake by mesenchymal cells was apparent after 1 week.


Cerebral cortical changes in acute experimental hypertension: An ultrastructural study. Multiple focal cortical areas of increased vascular permeability to tracer substances occur in experimental hypertensive encephalopathy. In this study, rats with angiotensin-induced acute hypertension were used to determine whether increased permeability was associated with focal cerebral edema and if so, the tissue component involved. In addition, the mechanism of increased permeability and the types of vessels involved were investigated using horseradish peroxidase as a tracer. Quantitative morphometric studies 8 minutes after the onset of hypertension demonstrated significant perivascular glial swelling around arterioles, venules, and capillaries; the swelling was confirmed to the permeable areas and absent in the nonpermeable areas of the same animals. Ninety seconds after the onset of hypertension, horseradish peroxidase reaction product was present in focal superficial segments of the walls of penetrating arterioles but rarely in venular and capillary walls. At this time period endothelial cells showed prominent pinocytotic uptake of tracer. Eight minutes after the onset of hypertension, reaction product was again found in arteriolar walls and had extravasated into the surrounding extracellular space of the neuropil as well. Extravasation also occurred through capillary and venular walls but was less frequent. At this time interval endothelial pinocytotic activity was still prominent. There was no mechanical damage of vessel walls in the form of endothelial discontinuities or disruption of interendothelial spaces. Tracer was not found in interendothelial jundtions in continuity from lumen to base. The principle mechanism of increased permeability was enhanced pinocytosis, which occurred rapidly, being demonstrable 90 seconds after the onset of hypertension; it was observed principally in permeable arteriolar segments.


Reversal of hypertension by transplants and lipid extracts of cultured renomedullary interstitial cells. Transplants and lipid extracts of the same monolayer tissue culture of renomedullary interstitial cells from murine renal medulla exerted a similar antihypertensive action in rats having hypertension of the sodium-volume-dependent-type. The antihypertensive action resembled that caused by lipid extracts of rabbit renal medulla and extracts of lapine renomedullary interstitial cells grown in tissue culture. The recession of the arterial pressure of the hypertensive animals usually occurred slowly and steadily to a maximum within 6 to 12 hours. On occasions, a substantial acute depressor effect preceded the slow and steady decline of the pressure. As the pressure was lowered, there was either minimal or no change in the pulse rate. The lowering of the hypertensive pressure before there was vascularization of the transplant appears to support the view that the transplanted cells secreted and/or liberated an antihypertensive substance(s) that seeped out and was absorbed by nearby capillaries and/or lymphatics and circulated and acted in the manner of a hormone. The extracted and purified lipid from the same cells as used for transplantation is proposed as a candidate for such hormonal action. Evidence is presented that minimizes the possibility of the classic renomedullary prostaglandins as this antihypertensive lipid. The findings add support to the concept that the kidney exerts a hormonal antihypertensive action that opposes the well known hormonal prohypertensive renal actions.


A scanning and transmission electron microscopic comparison of puromycin aminonucleoside-induced nephrosis to hyperalbuminemia-induced proteinuria with emphasis on kidney podocyte pedicel loss. Ultrastructural changes in the visceral epithelium and proximal tubules of rats were studied by scanning and transmission electron microscopy during the onset and progression of puromycin aminonucleoside nephrosis (PAN)-induced proteinuria. These changes were compared with those that occur during a similar degree of proteinuria induced by intraperitoneal injections of albumin. With the onset of proteinuria and oliguria, PAN rats exhibit loss of podocyte pedicels and podocyte major processes, an increase in pinocytotic activity, and an accumulation of cytoplasmic vacuoles and granules of variable size, shape, and electron density. Loss of podocyte pedicels involves a gradual decrease in pedicel height beginning at the pedicel tip and progressing down the pedicel arm, formation of nublike protrusions and interpedicel microbridges (35 to 45 nm. in width and 40 to 60 nm. in length) along the pedicel's base, the merging of microbridges to form more extensive regions of interpedicel contact, and a gradual broadening and retraction of pedicels. In response to hyperalbuminemia-induced proteinuria, kidney podocytes exhibit reactions during PAN, however, the podocyte pedicels, slit pores, and major processes of rats with hyperalbuminemia-induced proteinuria remain discrete. The loss of pedicels and major processes during PAN, therefore, apparently results from the effects of puromycin aminonucleoside per se rather than from the proteinuria associated with this disease. The proximal tubules of rats with hyperalbuminemia-induced proteinurea exhibit the same characteristic changes as PAN rat proximal tubules (i.e., loss of brush border, dilated lumina, abnormally thin walls, and accumulation of periodic acid-Schiff positive electron-dense luminal casts and cytoplasmic protein absorption droplets). The significance of these ultrastructural findings during PAN and hyperalbuminemia-induced proteinurea are discussed in terms of the etiology of PAN.


Secretory and ultrastructural responses of hyperfunctioning human parathyroid tissues to varying calcium concentration and vinblastine. Parathyroid hormone (PTH) secretion from abnormal hyperfunctioning human parathyroid tissues was studied in vitro to determine whether abnormal tissues were responsive to changes in calcium concentration and what role their subcellular organelles played in secretion. Hyperfunctioning tissues from one patient with secondary parathyroid hyperplasia, four patients with parathyroid adenomas, and one patient with parathyroid carcinoma were incubated in media containing low calcium (0.75 mM), normal calcium (1.5 mM), high calcium (3.0 mM), or vinblastine (0.01 mM), a microtubular disrupter. Also, in order to correlate ultrastructural responses with PTH secretion, after incubation tissues of one adenoma were objectively quantitated by stereologic techniques. Low calcium consistently stimulated mean PTH secretion from hyperplastic and adenomatous tissue, but only during the 1st hour of secretion. Low calcium inconsistently stimulated carcinomatous tissue. High calcium suppressed mean PTH release from all tissues. Vinblastine did not consistently inhibit secretion from adenomatous or hyperplastic tissue. Ultrastructural analysis of adenomatous tissue showed a sparsity of granules (0.87 per cent of cellular volume) compared to previously studied bovine tissues. Low calcium significantly increased the volume fraction of pinocytotic vesicles to 300 per cent (p less than 0.01) and reduced the surface area of straight (inactive) membrane to 60 per cent (p less than 0.01) of the normal calcium control. Secretion granules, when present, were adjacent to submembrane vesicles. The number and structure of microtubules were not changed by low or high calcium or vinblastine. Our findings indicate that parathyroid adenomas and hyperplastic tissues can respond acutely to low calcium stimulation and high calcium suppression. However, the acute response to low calcium stimulation may not be sustained in some cases because of limited storage of hormone. The increase in pinocytosis in low calcium-stimulated tissue suggests a coupling of exocytosis with membrane endocytosis, possibly related to membrane recycling. Our findings with vinblastine suggest that microtubular integrity is not a prerequisite for basal PTH secretion in adenomatous tissue.


Reversal of orotic acid-induced fatty liver in rats by clofibrate. The addition of 1 per cent orotic acid to a sucrose-enriched semipurified diet results in markedly fatty liver when fed to rats for 7 to 22 days. Light microscopy reveals lipid droplets, mostly small, distributed throughout the cytoplasm of all hepatocytes. Electron microscopy shows that all the endoplasmic reticulum (ER) is broken into vesicles. Within the interior (cisterna) of each vesicle one or more lipid droplets are present. Morphologic signs of normal lipid transport (ER to Golgi apparatus to space of Disse) disappear: the Golgi elements are flattened and lack very low density lipoproteins particles; the Golgi-derived secretory vacuoles are not present. Biochemical analyses show an increase in hepatic triacylglycerol levels, to approximately 8 times the levels of sucrose-fed controls by the 7th day, 18 times by the 15th day, and 25 times by the 22nd day. Hepatic cholesterol levels increase, 2- to 4-fold. Serum triacylglycerol levels fall markedly; serum cholesterol levels are reduced. Immunoelectrophoretic determinations show that the apoprotein B component of plasma lipoproteins is practically absent at 7 days and increases slightly at 22 days. Reversal of an orotic acid-induced fatty liver is achieved by adding ethyl chlorophenoxyisobutyrate (clofibrate or CPIB) to the diet. By 8 to 16 days the ER of the hepatocytes returns to its usual parallel configuration and lipid droplets are not seen within its cisternae. Morphologic features of normal lipid transport reappear. GERL becomes prominent, distended with small particles, interpreted as lipid undergoing degradation. Lipid-containing residual bodies are common. Peroxisomes are more numerous than in hepatocytes of control rats. Liver triacylglycerol levels approach sucrose-fed control levels, and serum triacylglycerol levels return to chow-fed control levels. Hepatic cholesterol levels are similar to those of sucrose-fed and chow-fed controls, whereas serum cholesterol levels are lower. Serum apoprotein B levels return to chow-fed control levels. A sequence of events terminating in the removal of lipid from the hepatocytes is suggested by observation of morphologic changes following chlorophenoxyisobutyrate administration. This appears to involve transport of lipid into the cytosol where it accumulates as large spheres. Extensive accumulations of smooth ER appear. The cytosol lipid then disappears as the rough ER develops. Peroxisomes and mitochondria are prominent during the reversal process.


C-cell hyperplasia. An ultrastructural analysis. The C-cell is the source of the hypocalcemic polypeptide hormone, calcitonin. Sequential increments in calcitonin response to provocative calcium and pentagastrin infusions have been used to identify family members at high risk for the development of medullary thyroid carcinoma, a neoplasm of C-cell origin. Correlative light microscopic and immunohistochemical studies have permitted the identification of a spectrum of C-cell proliferative abnormalities ranging from C-cell hyperplasia (CCH) to invasive medullary thyroid carcinoma. Ultrastructurally, both normal and hyperplastic C-cells occupied an intrafolliculat localization, being separated from the interstitium by the follicular basal lamina and from the luminal colloid by extensions of the follicular cell cytoplasm. These relationships were maintained in areas of advanced hyperplasia where C-cells often completely encircled and displaced the follicular epithelium. Nodular CCH was characterized by the complete obliteration of the follicular space by C-cells. In these areas, prominent reduplications as well as occasional defects in the basal lamina were noted. Some of the solid C-cell nodules adjacent to areas of medullary thyroid carcinoma appeared to form by gradual replacement of follicles by C-cells and did not represent sites of intrathyroidal vascular or lymphatic extension. Two major cell types were noted in cases of CCH. One cell type which was filled with secretory granules measureing 280 nm. in diameter (type I) predominated in areas of diffuse CCH and was also found in control thyroid glands. The larger number of secretory granules in this cell type together with the relative lack of development of granular endoplasmic reticulum and Golgi regions suggested that these cells were in the storage phase of their secretory cycle. The second cell type had fewer secretory granules, which measured 130 nm. in diameter (type II), and was characteristically located in areas of nodular CCH. Type II granules were found in cells with cytologic evidence of active protein synthesis and secretion. Variations in granule morphology and cell ultrastructure may be correlated with functional variations in C-cell populations.


Subcellular pathology of rat liver in cholestasis and choleresis induced by bile salts. 1. Effects of lithocholic, 3beta-hydroxy-5-cholenoic, cholic, and dehydrocholic acids. Cholestasis or choleresis was induced in the rat by intravenous infusion (0.05 to 0.2 mumole per minute per 100 grams of body weight) of sodium taurolithocholate, 3beta-hydroxy-5-cholenoate, taurocholate, and dehydrocholate either singly or in combination after or without cannulation of the common bile duct. Bile flow was monitored and ultrastructural changes were examined by scanning and transmission electron microscopy up to 3 hours after bile salt administration. Taurolithocholate induced acute cholestasis and ultrastructural alterations consisting primarily of dilation of bile canaliculi, loss of canalicular microvilli, and lamellar transformation of the canalicular membrane. Occasionally, crystalline precipitates were present within the canalicular lumen and in the pericanalicular region of hepatocytes. 3beta-Hydroxy-5-cholenoate caused similar but less severe ultrastructural changes than those induced by taurolithocholate. Dehydrocholate had a greater choleretic effect than taurocholate, but neither induced noteworthy ultrastructural change. When infused simultaneously with taurolithocholate, taurocholate reversed cholestasis and largely prevented development of the ultrastructural changes induced by taurolithocholate. In contrast, simultaneous infusion of dehydrocholate prevented neither cholestasis nor development of the ultrastructural changes induced by taurolithocholate, which were more striking than those caused by taurolithocholate or 3beta-hydroxy-5-cholenoate alone. In addition, structural changes associated with cholestasis induced by these bile salts either singly or in combination were more pronounced and frequent in the periportal zone than elsewhere in the hepatic lobule. These results suggest that both taurolithocholate and 3beta-hydroxy-5-cholenoate induce cholestasis by affecting the structural and functional integrity of the bile canalicular membrane and also, in part, by forming untransportable precipitates. The contrasting effects of taurocholate and dehydrocholate on taurolithocholate-induced changes suggest that taurocholate overcomes the effect of taurolithocholate by solubilizing it into mixed micelles, but dehydrocholate and its metabolites have little or no such effect. The intralobular variation in severity of ultrastructural changes probably reflects the accumulation of bile salts in greater concentrations in hepatocytes near the portal triads.


Chronic human schistosomiasis mansoni. Pathology of the Disse's space. In chronic human schistosomiasis mansoni, the entire hepatic lobule is involved. The hepatovascular barrier is modified and shows hepatic sinusoids with hypertrophy and stratification of endothelium, basement membrane-like deposits, perisinusoidal fibrosis, diminution of hepatocellular microvilli and hepatocellular clasmatosis into the sinusoidal circulation. This transformation of an open circulation to a partly closed one may decrease the blood hepatocyte exchanges in schistosomiasis mansoni.


Potassium permanganate reaction in amyloidosis. A histologic method to assist in differentiating forms of this disease. A simple and reproducible histochemical method for distinguishing different chemical types of amyloid is described. The method is based on the affinity of amyloid for Congo red dye after exposure to potassium permangenate and dilute sulfuric acid. The permanganate method represents a modification of the Romhanyi trypsin technique. It yields comparable results while obviating some of the technical difficulties associated with the latter method. The permanganate reaction was applied to a series of amyloid samples of known amino acid composition, to amyloid samples fixed in a variety of different preservatives, and to tissues obtained at autopsy from 67 amyloidosis patients whose disease had been previously subclassified on the basis of clinical presentation and autopsy observations. This method distinguished amyloid protein AA from other varieties of amyloid and proved effective when applied to amyloid samples preserved in any of several commonly used fixatives. This simple histochemical method proved useful in subclassifying amyloid type in the patient series particularly when used in conjunction with the available clinical history and the organ distribution of amyloid accumulation.


Regeneration and differentiation of minced anterior tibial muscle explants from mice with MED myopathy. Rapid regeneration of mouse anterior tibial muscle occurs when minced muscle is explanted into the leg of a recipient previously prepared by excision of the corresponding anterior tibial muscle. This technique was used to study regeneration of muscle from mice with a delayed, recessive myopathy, motor endplate disease (MED). There was rapid regeneration of the explanted muscle and functional restoration after 15 weeks without signs of MED disease or evidence of the myofiber degeneration which normally occurs after 14 days in homozygous animals. Therefore, MED disease is not intrinsic in the affected muscles but appears to be dependent on the general humoral or possibly neural, environment present in mice with MED disease.


The functional capacity of guinea pig megakaryocytes. I. Uptake of 3H-serotonin by megakaryocytes and their physiologic and morphologic response to stimuli for the platelet release reaction. The functional capacity of guinea pig megakaryocytes was tested by studying their ability to concentrate serotonin and their response to agents which trigger the platelet release reaction. Megakaryocytes can concentrate 3H-serotonin as demonstrated by autoradiography after exposure to 0.5 muM 3H-serotonin and by quantitative measurement of isotope incorporation within 60 minutes. Uptake of isotope is rapid and linear within the first 30 minutes and tapers off between 30 and 60 minutes. Incorporation of isotope is diminished during exposure to cold, 2 muM reserpine, and 20 muM imiprimine. The following triggering agents: 10(-5) to 10(-3) M ADP, 1 to 100 units of thrombin, 10(-5) to 10(-3)M epinephrine, and 1 to 12 muM ionophore A23187 all produce significant release of stored 3H-serotonin. In the presence of ADP, albumin and serum completely inhibit the release of serotonin. Scanning microscopic studies show that coincident with serotonin release the triggering agents produce marked changes in cell shape. Transmission electron microscopy on these cells shows that there is the appearance of a prominent contraction zone, which is composed of microfilaments, and also variable diminution of cytoplasmic granules. The specifically induced serotonin release from megakaryocytes coupled with shape change and evidence of cell contraction produced by certain agents demonstrate one aspect of the functional similarly between megakaryocytes and platelets.


Right-hemisphere language dominance in a case of left-hemisphere arteriovenous malformation. This paper reports a case of surgical removal of a left-hemisphere arteriovenous malformation (AVM) in a left-handed adult without subsequent speech or language deficit. Preoperative intracarotid amobarbital testing indicated right-hemisphere language dominance. Our patient demonstrated no language involvement prior to or following surgery. We speculate the congenital nature of a left-hemisphere AVM may dictate right-hemisphere language dominance, thereby explaining the lack of residuals following removal of AVMs in left-hemisphere speech and motor areas.


Stimulus picture identification in articulation testing. The present study was designed to compare the percent of correct initial identification of stimulus pictures on the Goldman-Fristoe Test of Articulation with the percent correct identification on the Arizona Articulation Proficiency Scale. This study was undertaken in an effort to clarify the results of a previous study in which the Goldman-Fristoe, a test designed to reduce time of administration, took significantly longer administration time than the Arizona, a traditional type of articulation test. Twenty normal-speaking and 20 articulation-defective children served as subjects for the study. Each subject was administered those portions of the articulation tests which included stimulus pictures used to elicit production of the consonants and consonant blends. Each child's initial identification of the stimulus picture was recorded. Results indicated that the Arizona test elicits significantly (p less than 0.001) more correct initial stimulus picture identifications thandoes the Goldman-Fristoe test.


Imitative and spontaneous articulatory assessment of three-year-old children. One hundred children (25 three-year-old girls, 25 three-year-old boys, 25 three-and-a-half-year-old girls, and 25 three-and-a-half-year-old boys) were administered an articulation test using the spontaneous method and then the imitative method of stimulus presentation. No significant differences were found between the methods of stimulus presentation on the subjects' total articulation scores. Articulatory performance was significantly influenced by age, sex, and the interaction of age and sex.


Bekesy comfortable loudness: supportive case studies. Two cases of radiographically or surgically confirmed acoustic neurinoma are presented. In each case a mild, unilateral sensorineural hearing loss was identified. Results of threshold Bekesy audiometry were negative while the Bekesy comfortable loudness (BCL) procedure indicated significant auditory adaptation in both patients.


Programming for articularion modification. Within the past decade, principles and techniques of programmed instruction have been applied to the procedures of articulation modification in a number of preconstructed programs. The analysis of nine of these programs reveals that the majority of them are characterized by precisely stated objectives, ordered sequences of materials and procedures, clearly established criteria and rigorously controlled methods of reinforcement and recording of responses. Evaluation of the preconstructed programs raises some questions about the appropriateness of certain aspects of the technology to the process of articulation modification.


Programmed instruction.

Programmed instruction. This report presents a description of the principles of programmed instruction and an explanation of all major components of a program. No attempt is made to review or critique all available speech and language programs, but certain programs are discussed in some detail in order to illustrate adequate application of programming principles.


An earmold for the geriatric patient.

An earmold for the geriatric patient. This article describes a rehabilitation innovation for the elderly hearing-impaired patient. To minimize the problem of lack of fine finger dexterity in the elderly, an earmold was designed with a small handle. A brief description of the design is provided. A case study describes the usefulness of this earmold.


A comparison of the Auditec of St. Louis cassette recordings of NU-6 and CID W-22 on a normal-hearing population. Articulation functions were generated on a normal-hearing population with the Auditec of St. Louis cassette recordings of the NU-6 and CID W-22 speech discrimination tests. Both tests were similar and yielded slopes of about 4.4%/dB. Each gave a speech discrimination score of approximately 95% at 32 dB SL. Speech reception thresholds were obtained with monitored live voice and yielded good test-retest consistency. Speech thresholds were about 9 dB better than the ANSI (1969) specifications.


Facilitating transfer and maintenance of fluency in stuttering therapy. The present state of stuttering therapy programs enables the clinician to render many stuttering virtually stutter-free in the clinic. A major clinical problem, however, is the transfer of fluency to nonclinical situations and its maintenance over time. Concepts and techniques extrapolated from the literature on behavior change are applied to assessment, treatment objectives, treatment techniques, and to a number of procedures designed to facilitate transfer and maintenance during therapy. When fluency has been established, self-control techniques based on speech practice, self-monitoring, and the deliberate use of self-administered and social contingencies are stressed. Guidelines for termination of therapy and follow-up are given. For many of these techniques, specific examples are offered from clinical work with stutterers. Other techniques are presented because of their potential relevance and their demonstrated effectiveness with a variety of clinical problems.


The performance of children with auditory perceptual disorders on a time-compressed speech discrimination measure. A time-compressed version of the PB-K 50 speech discrimination measure was administered to 20 children diagnosed as displaying auditory perceptual disorders. Results indicated that these children performed equally well at both 0 and 30% time compression. Performance decreased significantly at 60% time compression. Comparison of the results with normative data indicated that performance of the two groups of children was similar at the 30% time compression condition but that children with auditory perceptual disorders performed poorer at both 0 and 60% time compression. The results were discussed relative to short-term memory abilities.


The influence of nonspecific immunotherapy on the course of murine melanoma. BCG, Corynebacterium parvum, vitamin A, and levamisole were continuously administered to C57 BL/6 mice bearing B16 melanoma prior to, with following tumor implantation as well as before and coincident with surgical excision of the implanted tumor. Only the group given levamisole prophylactically for 8 weeks before tumor inplantation showed a significant difference from control mice but a tenfold increase in dosage in this drug did not exert a comparable effect.


Malignant teratoma of the nasal cavity.

Malignant teratoma of the nasal cavity. A case of malignant teratoma of the nasal cavity in an adult is presented. Histologically, the tumor consisted of mesenchymal malignant structures in addition to entodermal and ectodermal malignant elements. Whereas surgical treatment of the primary tumor has been generally considered preferred, this patient was given a full course of radiation therapy alone to the primary lesion. There is no clinical evidence of tumor 5 years following diagnosis. Three years following treatment of the primary tumor, neck lymph node metastasis appeared contralaterally. Management of this problem was with radical neck dissection followed by postoperative radiotherapy. Function of the eyes, nose, and paranasal sinuses remains normal. A review of the literature suggests that radiotherapy is of little value in the management of malignant teratomas. This case demonstrates an opposite point of view.


Autoantibodies to an altered IgG in human breast cancer. Recent studies have shown that antibody in the serum of patients with carcinoma of the breast reacts with two distinct antigens obtained from breast cancer tissue. Hence, there are two antibodies. The first antibody reacts against the Fc fragment of immunoglobulin and is also found in the sera of patients with benign breast disease and certain inflammatory lesions and, therefore, does not seem to have any significant meaning for the patient with carcinoma of the breast. The second antibody is directed against the Fab fragment of human immunoglobulin that is found in breast cancer tissue. Recent experiments have shown that in immunodiffusion tests, this autoantibody reacts not with normal IgG(Fab), but rather with heat-aggregated Ig(Fab). It is thought that tumor-associated antibodies react with antigens on the tumor cell surface. Intracellular enzymes then proceed to fragment the attached antibody, leaving the Fab fragments attached on the cell surface. With intact immunosurveillance, the host appreciates this altered immunoglobulin (Fab). It is suggested that the autoantibody then formed against this fragment reacts with the fragment attached to the tumor cell, thereby allowing the tumor cell to be destroyed. Clinical data supporting this hypothesis are derived from the fact that 9 patients having this autoantibody to the Fab fragment are alive at 1 year after their carcinoma of the breast.


Responsiveness to endocrine manipulations in breast cancer after "prophylactic" castration. Two hundred and one cases of premenopausal women with breast cancer who underwent prophylactic castration with subsequent recurrence were review to ascertain the degree of responsiveness of these patients to subsequent endocrine manipulation. We show that the standard endocrine manipulations, particularly the major ablations, retain a fair degree of activity in this group. There is a suggestion that the longer the castration-recurrence interval, the higher the chance of a response, but the difference is significant only for osseous-dominant disease. As in other patient groups, responders to subsequent endocrine manipulations live longer than nonresponders.


The National Pancreatic Cancer Project: an update. Cancer of the pancreas is now the fourth most common cause of cancer-related death in the United States. The diagnosis of this disease is difficult and the therapeutic results are discouraging. Recognizing these factors, the National Cancer Institute has funded the National Pancreatic Cancer Project as of 1 January 1975, in an attempt to stimulate new and more active research in this field at both the basic and the clinical levels. Some of the work that has already been funded by the project is outlined as a means of familiarizing a larger number of people with the activities of this particular National Organ Site Program.


The anatomy of the arteries and veins of the breast. Textbook accounts of this subject are inadequate. This review considers the work of Cooper and Salmon and reproduces some of their figures. Applications in the diagnosis and treatment of cancer are discussed. The largest mammary arteries are the lateral (from the axillary) and the anterior medial and posterior medial (from the internal thoracis). The branches of these arteries do not follow the duct system, but instead form a plexus in the anterior fat layer. Normally there are no hypervascular or hypovascular areas. The contribution of the mammary branches of the posterior (aortic) intercostal arteries is minor. There are superficial and deep sets of veins, the latter associated with arteries. Mammary vessels of living women are demonstrated by infrared photography, thermography, and mammography. In the diagnostic use of these methods there is a tendency to rely upon the concept of normal vascular symmetry, but this is a fallacy.


Increased effect of a transmissible entity on the control of cancer in C3 H/St mice. Three hundred and seventy-one mice of the C3H/St inbreds bearing spontaneous tumors of mammary gland origin have been used in this experiment. All mice studied were lineal descendents of a tumor-bearing mouse which had been injected with a liver extract. In this descent there appears to be a transmissible entity presumably induced by the injection of the liver extract. Following 15 generations of inbreeding after the appearance of a transmissible entity, a second sudden reversal of effect on cancer growth in mice has been indicated. This change has progressively altered the growth of cancer from a very low effect to a maximal effect, i.e., to a complete regression of a high percentage of the tumor. The maximal effect of the transmissible entity is the complete suppression of the growth of cancer during, at least, through the 25th period of observation, thus producing negative values of tumor growth. All these effects of the growth and fate of spontaneous tumors of mammary gland origin in mice have been obtained in a single lineal descent of C3H/St inbreds without resorting to any outcross.


Open-heart surgical centers. Standards and monitoring. This article contains the essence of a report presented to the Council of The American Association for Thoracic Surgery (AATS) by an Ad Hoc Committee on Issues composed of the authors, on October 13, 1976. Because of urgent demand to have this information immediately available, early publication was desirable. However, to have official endorsement of the AATS would have necessitated waiting until April, 1977, the date of the next meeting of the Association. Since this would delay publication of this information for more than one year, it was considered reasonable by the Council that it be published as a free-standing statement of the authors.


Myocardial protection with cold, ischemic, potassium-induced cardioplegia. A total of 204 patients, ages 3 months to 84 years, underwent open-heart surgery with the aid of cardiopulmonary bypass with moderate hypothermia. For protection of the myocardium, cardioplegia was induced by washing out the coronary arteries with an iced, buffered, isoosmolar, potassium-based infusate. After aortic cross-clamping, the aortic root or individual coronary arteries were perfused with 500 to 2,000 c.c. of an aqueous solution (at zero to 4 degrees C.) containing 20 mEq. of potassium. Periods of ischemic arrest as long as 208 minutes have been well tolerated, with only two of the eleven hospital deaths considered heart related. Defibrillation occurred spontaneously in 41 per cent and after one shock in 47 per cent of patient, without apparent correlation between duration of ischemia and restoration of effective rhythm.


Extracorporeal membrane oxygenator support for cardiopulmonary failure. Experience in 28 cases. We have used extracorporeal membrane oxygenation (ECMO) for 28 patients (14 children and 14 adults) over a 5 year period. Nine patients improved on ECMO and 5 were long-term survivors. ECMO was used for pulmonary insufficiency in 24 patients. Initially, only moribund patients were treated, but recently the combination of open lung biopsy and pulmonary insufficiency index (PII) has been used to select patients. The best results have been obtained in newborn cases and the adult capillary leak syndromes; the major problem has been progression to fibrosis despite ECMO support. ECMO was used for cardiac failure in 4 patients. Children with postoperative cardiac failure did the best; profound shock was not reversed with venoarterial bypass. ECMO support is lifesaving in selected cases of pulmonary insufficiency. Initial trials in cardiac failure and the infant age group in this series suggest that ECMO will have an even greater role in those applications.


Heparinless femoral venoarterial bypass without an oxygenator for surgery on the descending thoracic aorta. Heparinless femoral venoarterial bypass without an oxygenator has been used for surgery in 11 patients with aortic lesions requiring cross-clamping of the descending thoracic aorta. Mixed venous blood circulates in the lower half of the body and proximal hypertension is controlled. Surgical time is not rushed, and the bleeding of heparinization is avoided. All patients are well.


A clinicopathological study of post-thoracotomy purulent pericarditis. A continuing problem of diagnosis and therapy. Cardiac infections after operations are infrequent but, when present, are often fatal. The 14 autopsied patients in whom purulent pericarditis developed after thoracic operations over an 88 year period at The Johns Hopkins Hospital were studied. Purulent pericarditis developed after cardiac operations in 10 and after pulmonary resections  in 4. In 12 of the 14 cases the pericardial sac had been opened. Associated postoperative infection, present in 13 patients, included mediastinitis in 7 and empyema in 3. Staphylococcus was the infection organism in half of the patients. Associated cardiac infection, including endocarditis, myocardial abscess, and graft infection, was present in 5 (36 per cent) patients. Death occurred within 2 months of operation in 11 (79 per cent) patients; it was due to infection in 9, cardiac tamponade in 4, and arrhythmias and heart failure in one. The diagnosis of purulent pericarditis was made before death in only 5 (36 per cent) cases, in part owing to masking of the usual signs of pericarditis in the postoperative patient. Since the introduction of antibiotics, the over-all incidence of purulent pericarditis has decreased. However, pericardial infection after thoracotomy has increased tenfold, and patients undergoing cardiac operations in particular provide a new and increasing population at risk for this disease.


Recent results after repair of atrioventricular canal. Tweleve patients with the complete form of persistent atrioventricular (AV) canal were operated upon at the University of Wisconsin between May, 1972, and November, 1975. The technique originally described by Rastelli and his associates was used. All 12 patients are asymptomatic and well, with no hospital or late deaths. Postoperative cardiac catheterization in 8 patients showed a return to near normal dynamics, with minimal residual mitral insufficiency. Half of these children had type A and half type C malformations; both types could be repaired without the need for valve replacement. Since 3 of these patients were less than 2 years of age, we now feel that complete repair of the AV canal can be undertaken in children between 12 and 18 months of age for optimal management.


Prosthetic valve endocarditis. The case for prompt valve replacement. Treatment of patients with prosthetic valve endocarditis with existing guidelines has failed to reduce the over-all mortality rate to below 50 per cent. However, subgroups with high or lower risk of death can be delineated on the basis of risk factors such as early onset following surgery, high-risk causative organisms, cardiodynamic failure, and septic emboli. High-risk patients comprise more than 70 per cent of those with prosthetic valve endocarditis in recent series. Analysis of previously reported series indicates that the mortality rate for high-risk patients with late onset of prosthetic valve endocarditis treated by valve replacement was less than that of patients receiving only medical therapy. We have treated 6 consecutive patients with prosthetic valve endocarditis (3 early onset, 3 late onset) by valve replacement before completion of a course of antibiotics. All patients survived surgery but one patient died after 4 1/2 months of noninfectious causes. Prompt valve replacement is technically feasible and should become the standard therapy for patients with prosthetic valve endocarditis who do not fall into the lower risk group.


The lithium iodide--powered cardiac pacemaker. Clinical experience with 250 implantations. A long-life cardiac pulse generator powered by the lithium-iodide fuel cell is described and our experience with 250 implantations is documented. The compact, hermetically sealed pulse generator unit is easily implanted, is reliable, and is well accepted by patients. There have been no pacemaker-related deaths and only minimal morbidity. There was a single instance of electrical circuit failure of the pulse generator early in our experience; however, to date, after 15.9 months' average follow-up representing 3.988 patient months of cardiac pacing, there have been no battery failures and no further electrical component failures. The pulse generator unit is now guaranteed by the manufacturer for 6 years. We believe that the lithium-iodide powered pacemaker represents a significant advance in pacemaker generator technology and is recommended for long-term cardiac pacing.


A study of methods for surgical interruption of the His bundle. The relationship of the atrioventricular (AV) node and His bundle to surrounding structures is described from the viewpoint of the surgeon. A series of experiments were carried out for interruption of atrial to ventricular conduction that included electrocauterization of the His bundle, incision just above the tricuspid annulus to attempt to divide the His bundle, and finally excision of the right atrial wall and the insertion of the atrial septum into the right fibrous trigone to remove all connections from the AV node and atrium to the His bundle. The last procedure was the most satisfactory method, as judged by the certainty of accomplishing both His bundle interruption and interruption at its highest possible point.


The effects of isoproterenol and dopamine on regional myocardial blood flow after stenosis of circumflex coronary artery. The effects of isoproterenol and dopamine on regional myocardial blood flow were studied in 10 open-chest dogs after acute stenosis of the proximal circumflex coronary artery. Blood flow was determined by the radioactive microsphere technique. Isoproterenol led to a homogenous increase in blood flow in the normal myocardium. In the myocardium with compromised coronary blood flow, isoproterenol led to a relative subendocardial ischemia. This occurred despite increased aortic flow and peak left ventricular dp/dt. Dopamine also increased aortic flow and peak left ventricular dp/dt, but it did not cause regional myocardial ischemia. The findings suggest that dopamine is the preferable inotropic agent in managing low cardiac output in patients with significant coronary artery disease.


Wire holder: a new adjunct for sternal closure. A new 5 inch clamp with a tungsten carbide insert used for holding the sternal closure wires on an end-to-end fashion is described. This clamp provides a much better grip and longer wear than stainless steel owing to the tungsten carbide insert. The length of the clamp allows the surgeon a firm grip on the wire, and the wire can be easily twisted. Also, the small size of the clamp avoids the crowding which occurs with the regular Kocher clamps at the operating table.


The role of multiple noncritical arterial stenoses in the pathogenesis of ischemia. The hemodynamic effects of multiple noncritical lesions in series were studied in in vitro experiments and in 15 animals. Flow visualization studies were also carried out to obtain insight into the flow pattern in the region of stenosis. Symmetrical stenosis pieces with a 50 per cent reduction in area were placed inside a plexiglass tube and used for both in vitro and in vivo experiments. Varying the number of stenoses and the spacing between them enabled us to study twelve different stenosis configurations during both pulsatile and steady flow. Flow conditions encountered clinically were simulated by varying the average Reynolds number between 30 and 380. Pressure drops across the stenosis test section were measured with a differential pressure transducer and used to calculate critical values for multiple, uniform, noncritical stenoses and for combinations of stenoses of different degrees. Results from steady and pulsatile flow in vitro were comparable, as were those results from the in vivo experiments. The pressure drop across a series of noncritical stenoses was nearly the sum of the individual pressure drops, with only slight dependence upon the spacing between stenoses, Thus it is concluded, from both experimental results and from the theoretical calculations, that the total effect of a series of noncritical stenoses may become critical and produce symptoms of arterial insufficiency.


The intrathoracic kidney.

The intrathoracic kidney. Two cases of intrathoracic kidney are discussed, both diagnosed by intravenous pyelography when other studies failed to disclose the nature of a left thoracic mass. The potential valve of intravenous pyelography in the study of a posterior mediastinal mass is emphasized. Review of the literature and of these 2 cases indicates that if the intrathoracic kidney occurs as an isolated anomaly it usually functions normally and requires no treatment.


Pericardial drainage operations in the management of uremic pericardial effusion. Because of frequent failures in nonoperative therapy, we have adopted early surgical drainage of the pericardium in the management of uremic pericardial effusion. This series presents the longest follow-up period of any group of patients with uremic pericardial effusion treated by surgical drainage. There have been no intraoperative deaths and no recurrences. The total hospital mortality rate was 8.3 per cent and the late mortality rate over a 72 month period was 25 per cent. Internal pericardiostomy drainage is a simple yet effective surgical solution to the life-threatening problem of uremic pericardial effusion.


Histology of bronchial carcinoma and regional lymph nodes as putative immune response of the host to the tumor. Two hundred forty-two patients who had bronchial carcinoma and who underwent radical surgery were studied in order to determine putative host resistance to the tumor at histologic level, i.e., lymphocytic infiltration in the center and around the tumor, together with sinus histiocytosis and follicular hyperplasia in the regional lymph nodes. These features were evaluated in a semiquantitative way, giving rise to three groups of patients: D- (reaction absent or poor), D+ (reaction present), and D++ (strong reaction present). Five-year survival rates and the incidence of metastases in regional nodes were significantly related to the putative host resistance against the tumor, but no clear-cut correlation between grade of malignancy of the tumor and histologic type was evidenced. The significance of these reactive changes is fully discussed.


Anatomic correction of transposition of the great arteries. Complete anatomic correction of transposition of the great arteries (TGA) and ventricular septal defect (VSD) was performed on 2 infants with high pulmonary arterial resistance. Both patients were operated upon under deep surface-induced hypothermia and limited cardiopulmonary bypass. Direct repair of the anomaly was accomplished by switching the aorta and the pulmonary artery with reattachment of the coronary arteries. The clinical result in the first patient was satisfactory. The postoperative cardiac catheterization and angiogram demonstrated no gradient across either outflow tracts and normal arrangement of the great vessels. The second patient died in the operating room, probably owing to compression or kinking of the left coronary artery.


Carbohydrate and lipid metabolism in open-heart surgery. Carbohydrate and lipid metabolism was studied in 8 patients who underwent open-heart surgery with the aid of extracorporeal circulation. Hyperglycemia was observed during perfusion. Despite the high glucose levels during perfusion, insulin responses were depressed. A rise of insulin levels was observed one hour after perfusion, and at the same time the glucose levels dropped. Suppression of insulin secretion during perfusion may be the result of increased catecholamine secretion, induced hypothermia, or heparin administration. High levels of non-esterified fatty acids (NEFA) and low levels of triglycerides were observed immediately before, during, and after perfusion while heparin was being utilized. This phenomenon was considered to be strongly affected by the use of heparin. The levels of growth hormone were depressed during perfusion but significantly elevated one hour after the end of perfusion. These phenomena may be caused by the fluctuations in glucose and NEFA levels.


An aortic--left ventricular pulse duplicator used in testing prosthetic aortic heart valves. A pulse duplicator for the testing of prosthetic valves has been produced which accurately simulates physiological pressure and flow wave forms in the left ventricle and ascending aorta. The model consists of two components--the ventricle and the artificial systemic circulation. The ventricle is a collapsible bag which is externally pressurized and produces an accurate ventricular pressure-time history. The artificial circulation is externally pressurized and produces an accurate ventricular pressure-time history. The artificial circulation is a development of the lumped parameter model of Westerhof13 in which the physiological input impedance is modeled by a characteristic resistance, a capacitance, and a peripheral resistance connected in series. The model allows for a wide range of heart rates, systolic-diastolic ratios, mean pressures, flow rates, and fluid viscosity. A Fourier analysis of the model pressure and flow waves shows excellent quantitative agreement with physiological data, as does the vascular input impedance. The Oxford aortic heart valve exhibited a regurgitation of 1.9 per cent and no measureable pressure drop or power loss.


The prediction of postoperative potassium excretion after cardiopulmonary bypass. Potassium excretion following cardiopulmonary bypass has been studied in 11 patients. After an initial period of 4 to 5 hours, potassium excretion was found to be directly related to urine flow provided diuretics had not been administered. Triamterene altered the slope of the regression line so that, for any given urine flow rate, less potassium was excreted. A simple program for postoperative potassium therapy is described.


Radiopaque marker in the tilting disc of the Björk-Shiley heart valve. Evaluation of in vivo prosthetic valve function by cineradiography. This paper describes a new, noninvasive method for evaluating the in vivo function of the Björk-Shiley tilting disc valve in the aortic, mitral, and tricuspid positions. The tilting disc was equipped with a ring-shaped radiopaque marker, which permits visualization of the motion of the disc by both cineradiographic and fluoroscopic studies. A beam direction corresponding to the axis of motion of the disc should be sought for calculation of the prosthetic opening angle, whereas prostehtic valve closure is demonstrated by a beam direction deviating 20 to 30 degrees from the valve ring plane. Complete opening to 60 degrees and closure of the prosthetic valve, indicating free motility of the tilting disc, were confirmed by cineradiograms. The error of estimation of the in vivo opening angle is small with deviations of less than 15 degrees from the ideal beam direction and negligible for opening angles approaching 60 degrees. Deviations in two planes simultaneously cause less error than deviation in one plane. The radiopaque marker was designed to detect mechanical valve failure owing to thrombotic obstruction. The incidence of this particular complication was 8.1 per 100 patient-years after aortic valve replacement without anticoagulation treatment. With anticoagulation, this incidence was zero after aortic and 2.5 after mitral valve replacement. In our clinical experience to date, which comprises over 1,250 implants, we have not encountered a single case of primary mechanical valve dysfunction. Our current program includes a change-over to the radiopaque tilting-disc model of the Björk-Shiley prosthesis, which was introduced at this clinic in March, 1975.


Signal enhancement for detection of specialized atrioventricular conduction system electrograms during open-heart surgery. A method for signal enhancement of electrograms of the specialized atrioventricular conduction system is presented. This method allows a single electrogram to replace the tracings of bipolar electrograms previously required to ensure recognition of the specialezed conduction system and yet maintains the safety afforded by use of three pairs of recording electrodes. In addition, this new signal is enhanced in magnitude and is always unidirectional (positive). These features are desirable for automated signal recognition. This method therefore provides an important step toward future automation and signal recognition of specialized conduction system electrograms during open-heart surgery.


Effects of dipyridamol and methylprednisolone on intimal thickening in vein grafts. Fibrous intimal proliferation severe enough to produce occlusion has been observed in vein segments used for aorta-coronary bypass grafts. In an attempt to improve graft patency and decrease intimal fibrous thickening, animals with vein grafts were treated with dipyridamole or methylprednisolone for 8 to 12 weeks. Femoral vein segments were used to bypass the femoral artery in 36 dogs. Thirty-four of these grafts were patent at 8 weeks, with no statistically significant differences between control and drug treatment groups. Intimal thickness measurements were taken at three different points along the graft: proximal (upstream end), middle,and distal (downstream end). Dogs treated with methylprednisolone had significantly less intimal thickening (214 versus 125 mu, p less than 0.05) than did control animals in the middle of the veins but there was no difference in thickness measurements at the proximal and distal ends. Dipyridamole-treated animals did not differ from control dogs. Although these data show decreasing intimal thickening in the middle of grafts with methylprednisolone therapy, the intimal thickness was still considerably greater than normal. The lack of response near the anastomotic sites suggests that clinical application of either agent to improve long-term patency is unwarranted.


The significance of intraoperative ventricular fibrillation during aortic valve replacement. The effect of the spontaneous occurrence of ventricular fibrillation during aortic valve replacement and coronary arterial perfusion was studied in a consecutive series of 361 such operations. All operations were performed in a standard manner before 1972. One fourth of the patients experienced ventricular fibrillation,and the early mortality rate of this group was significantly (p less than 0.005) higher 7.3 per cent) than in the nonfibrillating group (1.5 per cent). The total mortality rate was 3 per cent. However, late results among survivors of the operations showed no effect of fibrillation. These findings indicate that ventricular fibrillation should be avoided in these patients. Whether or not countershock is advisable if and when fibrillation occurs remains an unanswered question.


Repair of double-outlet right ventricle. The results of repair of double outlet right ventricle in 26 children are reported. Eighteen of these patients had subaortic ventricular septal defect (VSD), without pulmonary stenosis (PS) in 5 and with PS in 13. Another 8 patients had subpulmonic VSD, without PS in 6 and with PS in 2. All had concordant atrioventricular relationships. There were six early deaths and two late deaths of the 26 patients in our study. Of these, 5 patients had severe associated cardiac abnormalities, and 2 who died early had had an incision in the systemic (right) ventricle.


Antibiotic prophylaxis for open-heart surgery. A randomized, prospective study of the relative effectiveness of broad-spectrum versus specific antistaphylococal antibiotic prophylaxis in patients having open-heart surgery was performed between May, 1972, and June, 1973. All patients undergoing open-heart surgery was assigned randomly (by hospital number) to receive either methicillin or cephalothin beginning the night before operation. There were 132 patients in the cephalothin group and 129 in the methicillin group. There was no statistically significant differences in age or duration of hospitalization, cardiopulmonary bypass, urinary tract drainage, or postoperative fever. There was a significant difference in the ratio of male to total patients (cephalothin group, 0.67; methicillin group, 0.52; p less than 0.02) and duration of operation (cephalothin group, 4.27 hours; methicillin group, 3.87 hours; p less than 0.05). The methicillin group had a statistically significant higher rate of urinary tract infection (cephalothin group, 3 cases; emthicillin group, 22 cases, p less than 0.05), pneumonia (cephalothin group, no cases; methicillin group, 9 cases; p less than 0.01), and episodes of sepsis and prosthetic valve endocarditis (cephalothin group, no cases; methicillin group, 11 cases, p less than 0.001). The incidence of wound infections and positive blood cultures from blood obtained immediately after termination of cardiopulmonary bypass was not significantly different between the two groups. Cephalothin has replaced methicillin as the routine prophylaxis for open-heart surgery at our institution.


Survival for 145 days with a total artificial heart. A calf into which a biolized, total artificial heart (TAH) had been implanted survived for 145 days. All measured physiological parameters except central venous pressure (CVP) were back to normal one month after implantation, and thereafter the animal's physiological development was similar to that of a normal calf. The intimal weight, which was 96 kilograms at implantation, reached 190 kilogram at the end of experiment, with a daily gain rate of 0.9 kilogram per day. After the nineteenth postoperative week, signs of congestive heart failure appeared, such as high venous pressure, ascites, and enlarged liver although the calf outwardly appeared well. On postoperative day 146, the animal started foaming at the mouth, and a convulsion occurred; then, the experiment was terminated after 3,494 hours of pumping. At autopsy, there were acute bilateral bronchopneumonia involving mostly both upper lobes, pulmonary edema, slight chronic pneumonitis, and hepatomegaly. There were no serious thrombotic deposits inside the cardiac prosthesis.


Increased cardiac output by downstream pumping with a reversed unidirectional intra-aortic balloon. Downstream and upstream pumping with unidirectional intra-aortic balloons was compared in 8 open-chest normal mongrel dogs anesthetized with pentobarbital. Downstream pumping effect a 32 per cent increase in cardiac index, a 24 per cent decrease in systemic resistance, and a 2 per cent decrease in heart rate. Upstream pumping did not significantly affect these parameters. Mean aorta pressure proximal and distal to the balloon was not altered significantly by pumping in either direction. This unique observation of increased cardiac output may have important implications for the treatment of low output cardiac failure. Preliminary studies including baroreceptor denervation suggest that a reflex mechanism may be involved.


Conformational analysis of the 20 naturally occurring amino acid residues using ECEPP. Conformational energy calculations using ECEPP (Empirical Conformational Energy Program for Peptides) were carried out on the N-acetyl-N'-methylamides of the 20 naturally occurring amino acids. Minimum-energy conformations were located, and the relative conformational energy, librational entropy, and free energy each minimum were calculated. The effects of intrinsic torsional potentials, intramolecular hydrogen bonds, and librational entropy on relative conformational energies and locations of minima are discussed. The results are categorized most easily by use of a new conformational letter code that is introduced here.


Intrachain reactions of a pair of reactive groups attached to polymer ends. 3. Intrachain charge-transfer complex on polysarcosine chains having terminal electron donor and terminal electron acceptor groups in chloroform solution. Polysarcosine having a terminal p-dimethylaminoanilide group and a terminal 3,5-dinitrobenzoyl group was synthesized. The number-average degree of polymerization n was varied from 6 to 25. In chloroform solution this polymer showed a distinct absorption band around 455 nm, which was attributed mostly to intramolecular charge-transfer interactions. The extinction coefficient of the charge-transfer complex was determined for low molecular weight model compounds. Using the same extinction coefficient, the fraction of polymers forming intrachain charge-transfer complex was evaluated at infinite dilution. The fraction was about 0.15 for n = 6 and decreased asymptotically with increasing n finally to 0.03 for n = 25. These values are almost 20-100 times as large as those estimated from the Monte Carlo calculation and on the basis of the intramolecularly catalyzed hydrolysis of polysarcosine chain. This indicates that the cyclized conformations of polysarcosine chain are greatly stabilized by the formation of intrachain charge-transfer complex. The fraction of the cyclized polymer was decreased with increasing temperature for short chains. The thermodynamic parameters characterizing the conformational change required for cyclization in chloroform were obtained and compared with those for the same reaction in ethanol solution, as well as those for the intramolecularly catalyzed hydrolysis on polysarcosine chain in aqueous solution.


Fluorescence and energy transfer of polypeptides containing naphthyl groups in their side chains. Energy transfer in the singlet state was studied in solution at 25 degrees C for poly(beta-1-naphthylmethyl L-aspartate) and copolymers of beta-1-naphthylmethyl L-aspartate and gamma-benzyl L-glutamate. Transfer efficiencies, migration coefficients, migration lengths, and interaction radii were determined from the quenching studies using biacetyl as a quencher. The migration coefficient increases with increasing naphthyl groups in the copolymers. This means that singlet energy migrates among more naphthyl groups with increasing naphthyl groups in the polymer chain. Interaction radius for the fluorescence quenching by biacetyl was estimated to be in the range of 5.8 to 8.9 A irrespective of whether energy donor is monomer or excimer. Moreover, it was shown that energy migration via excimer does not take place and energy of the excimer is localized.


The Kell blood group, Kx antigen, and chronic granulomatous disease. The Kell blood group has 18 associated red cell antigens. One, named KX, is the product of an X-linked gene and appears to be a precursor in the Kell biosynthetic pathway. Lack of KX on red cells, caused by inheritance of a variant allele at the X-linked locus, results in gross changes in Kell antigenicity, an effect called the McLeod phenotype. Such cells also show striking morphologic changes. Normal phagocytic leukocytes lack Kell antigens but have strong KX. The leukocytes of boys with X-linked chronic granulomatous disease lack KX antigen and have defective bactericidal function. The fundamental defect in chronic granulomatous disease appears to be failure to inherit the X-linked gene that determines KX synthesis. The enzymatic and functional disorders of the leukocytes, and the structural changes in the red cells, are consequences that follow.


A statistical approach to the calculation of conformation of proteins. 1. Theory. A quantitative theory is presented for calculating the folding of a polymer, especially as applied to the renaturation of globular proteins. The theory applies to both thermodynamically and kinetically determined processes, so that not only can the equilibrium result be calculated but also the time course of folding. Since it is not automatically assumed that the folding will result in a single "native" conformation, it is possible to conclude that the polymer will exist as a random coil under appropriate conditions. A Monte Carlo method for applications is discussed in detail, and a very simple example is presented.


Chronic granulomatous disease and the Mcleod phenotype. Successful treatment of infection with granulocyte transfusions resulting in subsequent hemolytic transfusion reaction. A young man with X-linked chronic granulomatous disease of childhood, who is of the rare McLeod phenotype with antibodies in his serum shown to be hemolytic and reactive against all red cells with normal expressions of the Kell antigens, developed a severe Nocardia pneumonia with abscess formation and was subsequently treated successfully with granulocyte transfusions in spite of the presence of anti-KX in the patient's serum. The anti-KX did not appear to alter significantly the effectiveness of the transfused granulocytes; it did, however, cause a mild hemolytic transfusion reaction. The patient made a remarkable recovery from this episode and his condition has progressed to a state satisfactory enough for him to donate his own blood for storage and possible use in the future.


Blood transfusion for the patient who is difficult to transfuse. There are two types of patients who are difficult to transfuse because of the presence of red cell antibodies, those patients who have an antibody reactive against an antigen of high incidence and those who have multiple antibodies. Possible sources of blood for the patient who has an antibody reactive against a high-incidence red cell antigen include the patient's family, rare donors lacking the high-incidence antigen, and self-donation. Possible sources of blood for those who have multiple antibodies are limited to rare donors lacking the appropriate combination of antigens or to self-donation.


A statistical approach to the calculation of conformation of proteins. 2. The reoxidation of reduced trypsin inhibitor. A statistical method for the calculation of conformation is applied to the small protein, basic pancreatic trypsin inhibitor. The polypeptide geometry, energies, rotational isomers, and technique of conformation generation are discussed in detail. The calculations indicate that (i) under denaturing conditions, reduced trypsin inhibitor when oxidized should form initially 14 of the 15 possible single disulfide bridge intermediates in roughly equal proportions, and (ii) under renaturing conditions (pH 8.7, room temperature, aqueous solution) the single disulfide bridge intermediate with cys 30 and cys 51 connected is present in higher concentration than that with cys 30 and cys 55 linked. The two calculations are in agreement with experiment.


Patterns of dystonia ("I-D-I" and "D-I-D-") in response to l-dopa therapy for Parkinson's disease. The clinical, biochemical, and pharmacologic responses to L-dopa were studied in 87 patients with Parkinson's disease. Eleven of the 87 patients had a long-duration response, 39 had a short-duration response, and 37 had a combination of both. Thirty-four of the 39 patients with short-duration response to L-dopa experienced a consistent and reproducible sequence of clinical and biochemical events after each dose, characterized by improvement of parkinsonism and a single phase of dystonia occurring during or shortly after the peak of dopa concentration in plasma and during maximal clinical improvement. We have called this the I-D-I- response, for Parkinsonism-Improvement-Dystonia-Improvement-Parkinsonism. The remaining five patients all had the onset of the disease at an unusually young age and showed a distinctly different response pattern consisting of a first phase of dystonia, before there was any improvement, followed by a phase of improvement without dystonia and then by a second phase of dystonia before the abrupt return of parkinsonism. We have called this the D-I-D response, for Parkinsonism-Dystonia-Improvement-Dystonia-Parkinsonsim. Dystonia occurs in the D-I-D- response when the concentration of dopa in plasma passes through a critical but relatively low level, whereas it remains absent as long as the concentration of dopa remains above that level. In the I-D-I- response, dystonia is avoided by keeping the plasma concentration of dopa low, in the D-I-D- response by keeping it high. It is postulated that in the D-I-D response postsynaptic depolarization blockade due to supramaximal stimulation of the neuronal system mediating dystonia occurs, whereas in the I-D-I response the postsynaptic members of the same neuronal population respond with excitation but not with depolarization blockade.


Carcinoma of the endometrium: Mayo clinic experience. Five hundred and twenty-three patients with endometrial carcinoma treated at the Mayo Clinic from 1952 through 1962 have been followed up for a minimum of 10 years. These patients have been assigned International Federation of Gynecology and Obstetrics classifications retrospectively; 324 were stage IA and 85 were stage IB. Only 24 patients were stage II and 90 were stages III and IV, combined. Most patients were symptomatic, and a significantly greater number of stage IV patients had symptoms for a longer duration. The average age was 59 years; most patients were postmenopausal and there was a high degree of nulliparity. Seventeen and one-half percent of all patients in this series had a second carcinoma at some time, with breast and colon being the most common second primaries. Treatment was basically total hysterectomy and bilateral salpingooophorectomy with postoperative radiation added on an individualized basis. Seventy-four percent of the 523 patients survived 5 years and 64% survived 10 years. This varied from a 90% 5-year survival in 249 patients with stage IA or IB, G1, to a 13% 5-year survival in 46 patients with stage IV lesions.


Peripheral arteriovenous fistula. Detection by contrast echocardiography. A method for detecting peripheral arteriovenous fistulas using contrast echocardiography is described. The detection of intracardiac and intrapulmonary shunts by this technique has previously been documented. After injection of indocyanine green dye into the blood stream, a dense cloud of echoes can be detected downstream as well as at the injection site. This echo-producing effect is completely lost on a single transit through a capillary bed. Thus detection of resultant echoes in the systemic venous circuit after systemic arterial injection of dye would indicate the presence of an abnormal arteriovenous communication. We have recently tested this hypothesis for the confirmation of left-to-right shunts in two patients who had suspected traumatic lower extremity arteriovenous fistulas. After injection of indocyanine green dye through a small-gauge needle into the femoral artery, a dense cloud of contrast echoes appeared in the right ventricle, which indicated the presence of arteriovenous shunting. This procedure is safe and easily performed and represents a new and relatively noninvasive technique for the detection of peripheral arteriovenous fistulas.


Health status, socioeconomic status and utilization of outpatient services for members of a prepaid group practice. When evaluating the effectiveness of medical care programs, one concern is whether receipt of care is based upon health care needs or upon socioeconomic status. This study describes the relation between health status and socioeconomic status and attempts to determine which has the greater effect on ambulatory care utilization. The study setting was an operating HMO serving a cross-sectional membership of nearly 200,000 persons. Outpatient utilization data were derived from the medical records of a five per cent sample of health plan members for 1969 and 1970. Social, economic, situational, and attitudinal data were provided by 2,603 respondents in a household interview survey. Since a population's perceived health status may reflect health need, information from the survey provided measures of health status that ranged from specific symptoms and complaints to a general measure of perceived health status. Although the findings varied somewhat according to which variables were considered, they generally showed health status to correlate more highly than socioeconomic factors with the utilization of services in this medical care system. An exception was the use of preventive services, which was not significantly related to health status measures but rather, for women, to education and, to a lesser extent, income.


From professional monopoly to corporate oligopoly:the clinical laboratory industry in transition. Until the mid-1960s the nonhospital clinical laboratory industry was dominated by pathologists. The ethics of medical professionalism protected the pathologists' market from price competition and from any serious threat from new entrants into the market. Immune from the competitive pressures of the marketplace, pathologists exerted monopoly control in local markets. That power was eroded by laboratories operated by technologists and bioanalysts and was finally overcome by the entry of large corporations into the industry. The market power of the largest corporate laboratories is now growing to a point where competition may again be thwarted. The professional ethics of pathologists allowed high prices, but there was little push toward higher volume. The commercial ethics of the corporate entrants brought lower prices but resulted in strong pressure for greater test quantities. In either case, the power wielded by the dominant producer would seem to go against the consumer's interests.


An analysis of selected blood service policy changes. Prinicipal national goals for a blood service system are concerned with shortage, quality, acessibility, and efficiency. Since regional blood service operating objectives based on these goals are in partial conflict, a single policy does not exist. Using a computer-based planning system, four policies are examined and tested for their effects on these objectives. [corrected] The policies are: use of frozen red cells ( a technological alternative); extension of the useful life of fresh blood (a legal alternative); improved collection planning (a planning alternative), and improved inventory management (a management alternative). Model projections of the effects of each policy and comparative performance of each policy with respect to the principal objectives are discussed.


Getting care to nursing-home patients: a problem and a proposal. Data abstracted from transportation company records showed that nursing home patients made an average of 3.6 trips per year for care out of the nursing home. The bulk of this care (55 per cent) was provided at University Hospital with over a quarter provided at private physicians' offices and community health centers. On the basis of chart abstracts over half the patients had been seen within the previous month, but the quality of that visit was open to question. A means of providing cost-effective primary medical care in the nursing homes using a team of nurse practitioner and social worker is proposed.


Communication Style: a clue to unplanned pregnancy. This investigation compared the communication patterns of women who had never been pregnant with those of women who had had two or more unplanned pregnancies. A six-part questionnaire assessing communication skills, social orientation and involvement, self-disclosure, physical accessibility and verbal defensiveness was administered to fifty-six paid subjects from family planning clinics in the San Francisco Bay Area. Significant differences in communication skills, depth of self-disclosure, physical accessibility, and verbal defensiveness were found. The study suggests that the communicative inadequacies in the women with multiple unplanned pregnancies may be critical factors in contraceptive failure.


Enrollment choice in a mutli-HMO setting:the roles of health risk, financial vulnerability, and access to care. Results of an analysis of enrollment decisions in HMO-type plans are reported. Previous studies concern dual-choice situations; this paper deals with a quadruple-choice situation involving one open- and two closed-panel HMO-type plans as well as Blue Cross/Blue Shield (BC/BS). The risk-vulnerability hypothesis is disaggregated into its components and the results show that there is no adverse health risk self-selection in an employed population. The hypothesis of economic vulnerability is maintained when tested in terms of per capita income rather than the previously used measure of family income. It is shown that those who enroll in any HMO-type plan are younger and have younger and larger families and lower per capita income than those who do not. No meaningful differences in terms of health status, health concerns, or prior utilization are found. Of the few differences found between those who enroll in closed- and open-panel HMO-type plans, having a private physician as the usual source of care is the most significant: those with an established physician relationship who join any HMO-type plan tend to follow their physician into the open-panel plan. The results should not be generalized to situations involving premium differences since the premium cost to subscribers in any of the plans considered here was fully paid by the employer. The validity of the results in terms of nonfinancial factors, on the other hand, is enhanced by the removal of cost considerations.


[Serum levels of magnesium and zinc after a controlled thermal trauma of the rat (author's transl)]. After a thermal trauma similar changes of Mg and Zn levels in serum are observable. During the initial period of shock the concentration of both elements increases as a consequence of damage of cellular and subcellular compartments. During the catabolic phase a deficiency syndrome occurs as a result of renal excretion, loss through the wound secretion, and demarcation of necrotic tissue. On the other hand increasing requirements of Mg and Zn appear because of the anabolic process of wound healing. From these reasons a substitution of both elements is recommendable in all cases of proved deficiency after burns.