Diarrheal diseases and growth retardation in preschool Guatemalan children.

The relationship between diarrheal diseases and growth increments in total body length and weight was investigated in 716 rural Ladino Gautemalan children. Data on diarrheal diseases were provided by the mothers through retrospective surveys carried out at 14-day intervals. Increments in length and weight, semestral from near birth at four years and yearly thence to seven, were related to days ill with diarrheal diseases during the same time interval. Because the data here reported were collected over a two year period, a child may have had information for more than one period. In total, 1,343 child periods were investigated. Days ill with diarrheal diseases were found to be significantly associated with reduced growth in length and weight. It was assumed that the average differences in growth by seven years of age between children in the present sample and children from well-to-do societies, are mainly a function of environmental differences and consequently, a measure of the extent of growth retardation. By expressing the growth retardation specifically associated with diarrheal diseases as a fraction of the above differences it was then estimated that around 10% of this growth retardation was associated with diarrheal diseases.


The indentification and evaluation of measurement variability in the anthropometry of preschool children.

Measurement variability estimates for 18 different anthropometric dimensions were collected within the context of an ongoing longitudinal in vestigation of preschool Guatemalan children. Estimates of total measurement variance, intra-observer variance, and short-term intra-subject variance are presented for each variable. A simple procedure for the evaluation of measurement variance in cross-sectional and longitudinal investigations is described in which the total measurement variance is expressed as a percentage of the appropriate inter-subject variance. This statistic serves as an index of the relative reproducibility of anthropometric variables.


Mandibular precedence in the prenatal development of four permanent teeth.

As shown in 62 pairs of dental opponents from 32 grossly normal human fetuses in the 75-378 mm crown-rump range, mandibular precedence is the rule for 11, 12, C and M1, a trend in agreement with mandibular precedence for deciduous teeth through dm1 and in the gingival emergence of the same permanent teeth during postnatal development.


Rethingking human pigmentation.

Though pigmentation has been of interest to anthropologists for a long time, its inheritance, and particularly the reasons for the incomplete correlation of skin, hair and eye, is poorly understood. It is suggested that this is largely due to lack of genetically plausible hypotheses. Taking into account racial and individual variation in pigment traits, and knowledge of pigmentation in other mammals, a minimum set of genetic factors for pigmentation in man is suggested. These include: (1) a set of polygenes affecting skin color only; (2) one locus for depigmentation of the eye, not affecting skin or hair, (3) one pleiotropic gene for reduction of pigment at all sites, and (4) one or more loci with multiple alleles producing blondness or rufosity of the hair in symmetrical patterns over the body.


Role of light in human skin color viariation.

The major source of color in human skin derives from the presence within the epidermis of specialized melanin-bearing organelles, the melanosomes. Tanning of human skin on exposure to ultraviolet light results from increased amounts of melanin within the epidermis. Melanosomes synthesized by melanocytes are acquired by keratinocytes and transported within them to the epidermal surface. In some cases, the melanosomes are catobolized en route. New information indicates that the multicellular epidermal melanin unit (melanocyte and associated pool of keratinocytes) rather than the melanocyte alone is the focal point for the control of melanin metabolism within mammalian epidermis. Gross human skin color derives from the visual impact of the summed melanin pigmentation of the many epidermal melanin units. In theory, constitutive skin color in man designates the genetically-determined levels of melanin pigmentation developed in the absence of exposure to solar radiation or other environmental influences; facultative skin color or "tan" characterizes the increases in melanin pigmentation above the constitutive level induced by ultraviolet light. The details of genetic regulation of pigment metabolism within the epidermal melanin units are being clarified. In some mammals at least, the function of epidermal melanin units is significantly influenced by hormones which may be regulated by radiations received through the eyes. Based on an evolutionary history of the human family which exceeds ten million years, it is proposed that melanin pigmentation may have played a number of roles in human adaptions to changing biologic and physical environments.


The evolutionary significance of vitamin D, skin pigment, and ultraviolet light.

Vitamin D is essential for normal growth, calcuim absorption, and skeletal development. Vitamin D deficiency can cause death, immobilization, or pelvic deformities which prevent normal childbirth. In the past these problems were extremely common in North America and Europe, and were only elminated by adding vitamin D to food. Prior to that, variations in available vitamin D affected health, survival and reproductive efficiency sufficiently to have evolutionary significance. Vitamin D is naturally present in few foods; most comes from the photo-conversion of 7-dehydrocholesterol in skin. The limiting factor in this conversion is the availability of ultraviolet light less than310 nm. Seasonal and geographic variations in natural ultraviolet radiation cause parallel variations in blood vitamin D levels, intestinal calcuim absorption, and clinical vitamin D deficiency. These physiological variations can be abolished by exposure to comparable artificial ultraviolet radiation, or by dietary vitamin D supplements. Ultraviolet radiation less than310 nm is absorbed by skin pigment, but is also increases skin pigmentation. This has led to the hypothesis that skin pigment regulates skin vitamin D production. Little direct evidence exists to test this reasonable hypothesis, but necessary and sufficient conditions for establishing it can be outlined. Until this hypothesis is experimentally tested, it is impossible to evaluate the corollary hypothesis: that racial variations in the efficiency of cutaneous vitamin D production restricted the evolution of dark-skinned peoples to tropical latitudes and thereby caused the geographic distribution of the races.


Retinal pigmentation, visual acuity and brightness levels.

This study investigates the hypothesis that the degree of retinal pigmentation in the human eye is adaptive as it relates to the maintenance of visual acuity in optically stressful environments, deserts and snowfields. Eighty-four subjects were examined, an estimation of their degree of retinal pigmentation made by ophthalmoscopic examination and their binocular visual acuity tested over ten levels of brightness. The general level of retinal pigmentation did not influence mean visual acuity within the levels of brightness used in this study. The hypothesis was, therefore, rejected, but with the proviso that this study should be extended to even higher levels of brightness than were obtained here. There was no difference in mean pupil size at various levels of illumination between individuals grouped by degree of retinal pigmentation.


Iris pigmentation and photopic visual acuity: a preliminary study.

Visual acuity under varying conditions of light stress was tested in four human populations. It was found that the density of iris pigmentation had no significant effect on visual acuity under conditions of bright light. While some acclimatization to local light levels was observed, significant population differences in visual acuity were obtained. A hypothesis is advanced at to the adaptive value of varying densities of pigmentation of the iris based on the known heat absorption properties of melanin granules.


A quantitative and morphological study of the pigmentary system of the chimpanzee with the light and electron microscope.

The epidermal melanocyte system of the chimpaneze was studied by the combined skin-splitting DOPA, and electron microscopic techniques. It is very similar to man. There are DOPA-positive epidermal melanocytes in all body regions regradless of the degree of macroscopic skin pigmentation or hirsutism. Furthermore, as in man, but in contrast to rodents, chimpanzee skin contains a very high level of melanocytes in the epidermis; approximately 3,320+/-350 per square millimeter skin. Chimpanzee melanosomes are long, wide, and fully melanized. In keratinocytes, these organelles are individually dispersed in all body regions, regardless of the degree of skin color, as is true for other mammalian species with large melanosomes.


Capillary and cell wall permeability to potassium in isolated dog hearts.

From venous tracer-dilution curves recorded after 36 pulse injections of 42KCl and 131I-labeled albumin into the coronary artery inflow of 15 isolated canine heart preparations, we calculated maximal fractional extractions (Emax) and capillary permeability-surface area products (PScap) for 42K+ over a range of plasma flows (FP) from 0.3 to 1.7 ml min-1 g-u. At low FP (less than 1.0), Emax was 0.60 +/- 0.0l (mean +/- SD) and PScap was 0.72 +/- 0.20 ml min-1 g-1; at high FP (greater than 1.0), Emax decreased to 0.49 +/- 0.05 and PScap increased to 1.06 +/- 0.18. Continuous recording (gamma detector) of residual myocardial 42K+ in seven hearts showed that the mean fractional escape rate of tracer between 30 and 60 min after injection was 0.011-0.023 min-1; higher rates were observed at high FP, when the residue of 42K+ decreased to less than 10% of the injected dose by 60 min. Using PScap measured at high FP and considering the virtual intracellular volume of distribution for K+ to be 20 ml/g, we calculated the permeability-surface area product for sarcolemma (PScw) as 0.54-0.73 ml min-1 g-1, or about 50% of PScap. Considering sarcolemmal surface area (Scw) as 4,200 cm2/g and capillary surface area (Scap) as 500 cm2/g, cell permeability is low, with Pcw:Pcap being less than 0.08.


Satiety and hunger induced by small and large duodenal loads of isotonic glucose.

Hepatic-portal infusions of small or large flucose loads in the rabbit had little or no stimulating effect on postinfusion food intake. However, marked differential changes in appetite were observed when small and large glucose loads were infused into the duodenum. The satiating effect of small glucose loads contrasted sharply with an unusually high increase in food intake triggered by the infusions of larger amounts of glucose into the duodenum. The results are interpreted in terms of a possible involvement of the enteroinsular mechanism in the regulation of food intake. This mechanism is bypassed and its influence on food intake eliminated when glucose is infused directly into the portal circulation. The positive relationship between large amounts of alimentary carbohydrates and overeating is seen as a factor that may actively promote the development of obesity and diabetes mellitus.


Subepithelial capillary blood flow estimated from blood-to-lumen flux of barbital in ileum of rats.

The outflux of barbital from the blood into the small intestine perfused with an isosmotic buffer of pH 9.5 in anesthetized rats was measured to determine the subepithelial capillary blood flow in the gut. It was shown that barbital clearance is blood flow limited when total blood flow to the small intestine varied between 0.3 and 1.3 ml/min per g wet gut. The barbital clearance amounted to an average of 50.3% of the total blood flow. The total mucosal blood flow determined by the use of the distribution of microspheres in the layers of gut wall was 62.76% of the total blood flow. It is concluded that, because of anatomical reasons, a subepithelial blood flow available for the transport process is somewhat less than the measured total mucosal blood flow.


Dispersed rat parotid acinar cells. III. Characterization of cholinergic receptors.

The in vitro characterization of cholinergic receptors in dispersed rat parotid acinar cells was accomplished through investigations of the net transmembrane fluxes of K in response to exposure of the cells to selected cholinergic agonists and antagonists. Interaction of acetylcholine bromide (ACh) and carbamylcholine (carbachol) with the cholinergic receptors resulted in rapid net efflux of K from the cells. This cellular response was demonstrable in concentrations of carbachol as low as 10(-8) M. With gradual increase in the concentrations of the agonist an increase in the K efflux was observed up to 10(-5) M. At higher concentrations of this cholinergic agonist no further increases in the net K efflux were observed. The response of the cells to cholinergic agonists was inhibited by atropine but not by the adrenergic antagonists phentolamine or propranolol, suggesting cholinergic agonist-antagonist interactions at the receptor site. The dispersed rat parotid acinar cells appear to have functionally intact cholinergic receptors and could be used as valuable experimental tools for the study of receptor physiology and pharmacology as well as of other aspects of secretory function at the cellular level.


Uric acid excretion by the rat kidney.

The renal excretion of uric acid was studied in nondiuretic (ND) male Wistar rats and in the same animals subsequently made diuretic (D) by the infusion of hypertonic saline. Clearances of endogenous urate and of inulin, determined chemically, were compared with the simultaneous clearance of 14C infused as [6(-14)C]urate or [2(-14)C]urate. In rats infused with [6(-14)C]urate the isotope/inulin clearance ratios were 0.29 +/- 0.09 (ND) and 0.31 +/- 0.11 (D) ml/min; the simultaneous urate (chemical)/inulin ratios were 0.21 +/- 0.07 (ND) and 0.24 +/- 0.08 (D) ml/min. In rats infused with [2(-14)C]urate the isotope/inulin clearance ratios were 1.02 +/- 0.5 (ND) and 1.13 +/- 0.9 ml/min (D); the simultaneous urate (chemical)/inulin clearance ratios were much lower-0.19 +/- 0.09 (ND) and 0.32 +/- 0.19 (D) ml/min. Thin-layer chromatography of urine after [6(-14)C]urate inl uric acid. In contrast, a similar analysis of urinary radioactivity after [2(-14)C]urate infusion revealed that more than 70% of the 14C was excreted as allantoin and not as uric acid.


Bile acid kinetics and bile secretion in the pony.

Bile acid pool size and synthesis rate were determined by both isotope-dilution and washout methods in ponies with chronic external biliary fistulas. Bile acid pool size (10.9 mumol/kg) and synthesis rate (11.2 mumol/day per kg) estimated by the isotope-dilution method did not differ significantly from pool size (9.4 mumol/kg) and synthesis rate (9.5 mumol/day per kg) estimated by washout method. Bile acid-dependent and -independent fractions of bile flow, determined by a method that circumvents any inevitable correlation of flow to bile acid secretion due to common factors in both parameters, did not differ from those values obtained by linear regression of bile flow versus bile acid secretion. The choleretic effect of infused chenodeoxycholic acid was higher than that of both endogenous bile acid and infused taurocholic acid.


Recirculation and reutilization of micellar bile lecithin.

Bile lecithins, solubilized in micellar bile salt and radiolabeled in the 1-acyl fatty acid, phosphorus, and choline positions, were infused in the small bowel of fasted rats. Absorption of each label was virtually complete after 24 h. However, these lecithins were extensively hydrolyzed in the bowel lumen as well as after absorption, and neither the fatty acid nor phosphorus was significantly retained in the enterohepatic circulation or reutilized for biliary lecithin synthesis. In contrast, while choline was also dissociated from absorbed lecithin, choline was instead retained in the liver, reincorporated into newly synthesized hepatic lecithin, and sercreted in biliary lecithin in 10-fold greater amounts than either the fatty acid or phosphorus. However, the extent of choline incorporation into bile lecithin was limited and was not further increased when free choline was directly injected into the portal vein. The data therefore suggest that although only choline of absorbed lecithin is retained in the enterohepatic circulation and preserved for new biliary lecithin synthesis, exogenous choline utilization is regulated by the size of the available hepatic pool.


Reevaluation of the needle method for measuring interstitial fluid pressure.

Inserting a needle into subcutaneous spaces should allow a subatmospheric pressure to be measured if interstitial fluid pressure is truly negative as measured by the capsule and wick techniques. Previous needle measurements of interstitial fluid pressure have produced a positive value, but in most instances fluid has been injected into the tissues prior to recording of pressure. Therefore, we measured subcutaneous needle pressure in anesthetized dogs without fluid injection into the tissues. Approximately 30 min are required for an equilibrium pressure after insertion of the needle. The mean 30-min pressure was 4.6 +/- 0.5 (SE) mmHg (n equals 41). With observable edema, interstitial fluid pressures as measured with the needle were always positive. However, the needle method for continuous recording of pressure lacks rapid sensitivity to changes in tissue fluid pressures. In order to develop a needle method that would follow changes in interstitial fluid pressure, 0.5-1 mul of saline was injected into or withdrawn from the tissue. With this method, pressure plateaued in 10-20 min. This plateau pressure increased with tissue hydration and decreased with dehydration.


Phase lock of electrical slow waves and spike bursts in cat duodenum.

The phase relationship between slow waves and spike bursts was studied in vitro in the cat duodenum. Electrodes were arranged radially about the duodenum. Records were read for T1, the time between the slow-wave "valley" and the first spike, and T2, the time between successive valleys. The distributions of the ratio T1/T2 showed very small differences, not uniquely attributable to radial electrode position. The distribution of T1/T2 indicated that spike bursts began 58.8% of the way through a slow-wave cycle, measured from the valley. Also, electrodes were arranged longitudinally and records were read to determine deltaSW, the slow-wave delay time between adjacent electrode positions, and deltaS, the spike burst delay time between adjacent electrode positions. The correlation of deltaS and deltaSW suggested a linear relation, and a regression resulted in a good linear description. These results are consistent with an assumed phase lock of spike bursts to slow waves.


Properties of canine tissue thromboplastins from brain, lung, arteries, and veins.

Properties of the protein moieties of canine tissue thromboplastins (TTP's) from brain (BTTP), lung (LTTP), arteries (ATTP), AND VEINS (VTTP) were determined. The maximum specific activity of each protein moiety after its relipidation was obtained when the phospholipid-delipidated TTP ratio was 0.32 and was 1,395 U/mg BTTP, 1,130 U/mg LTTP, 630 U/mg VTTP, and 435 U/mg ATTP. The amino acid contents of the protein moieties of LTTP, ATTP, and VTTP were closely similar, but that of BTTP was significantly different. The Ouchterlony analysis showed that BTTP did not react at all with the antibody against VTTP, but that three other TTP's did and showed the reaction of complete identity. Then, the reactivity of 125-I-labeled TTP's with the anti-VTTP antibody was studied. The results showed that 0.79 +/- 0.01 (SD) % of [125I]BTTP, 10.24 +/- 0.5 (SD) % of [125I]LTTP, 19.4 +/- 0.2 (SD) % of [125I]VTTP, and 5.88 +/- 0.4 (SD) % of [125I]ATTP added were bound to the antibody in 2 h. Next, the molecular weight of each was determined by Sephadex G-200 filtration, which averaged 80,000 +/- 4,000 (SD) ([125I]BTTP), 113,000 +/- 5,000 (SD) ([125I]LTTP), 62,000 +/- 3,000 (SD) ([125I]ATTP), and 47,000 +/- 2,000 (SD) ([125I]VTTP). Finally, the plasma behavior of each was studied in four dogs. The plasma half-life averaged 8.1 +/- 0.24 (SD) h ([125I]BTTP), 14.6 +/- 0.5 (SD) h ([125I]LTTP), 7.38 +/- 0.48 (SD) h ([1252]ATTP), and 24.3 +/- 0.9 (SD) h ([125I]VTTP). These results indicate that the protein moieties of canine TTP's from brain, lung, arteries, and veins are closely similar in some aspects but dissimilar in others and are definitely not identical.


Effect of renal decapsulation on renal function.

Marked increases in renal volume commonly occur in acute tubular necrosis and acute transplant rejection. Based on studies in the dog, we have previously suggested that the renal swelling observed in states of acute renal injury may be due principally to an increase in compliance of the kidney. The present study was undertaken in an effort to assess whether compliance-mediated increases in renal volume might affect renal function. In 15 dogs we compared the function of a decapsulated kidney (DK) to that of the contralateral intact kidney (IK); in 12 dogs we compared the function of a partially decapsulated kidney (PDK) to that of the contralateral IK. We compared the function of DK or PDK to IK, first under control conditions (ureteral pressure (UP) equals 0 mmHg), then at increased intrarenal pressure (UP equals 30 mmHg for both kidneys plus iv saline loading), and then during a recovery period (UP of both kidneys restored to 0 mmHg). The rationale is that probably DK is more compliant than IK; thus at increased intrarenal pressure DK volume should increase more than IK volume. Under control conditions DK and IK function were normal and equal; however, during increased intrarenal pressure, glomerular filtration rate (GFR) was about 20% less and Na and H20 excretion were about 30% less in DK than in IK. When intrarenal pressure was restored toward control by lowering UP to 0 mmHg, DK and IK function were once again equal. Similar but less marked changes occurred in the experiments comparing PDK and IK function. The impairment of renal function in DK vs. IK at increased intrarenal pressure was not explained by renal blood flow distribution, backdiffusion of glomerular filtrate, or by surface losses of fluid from DK. We suggest that impairment of renal function in DK vs. IK during increased intrarenal pressure is in some way related to the greater expansion of DK (21.0 +/- 0.02%) vs. IK (9.7 +/- 0.03%) at increased intrarenal pressure.


Effect of [Sar1, Ala8]angiotensin II on renal vascular resistance.

Partial occlusion of the renal artery (RAO) was induced in dogs anesthetized with pentobarbital or morphine chloralose-urethan. The effect of [Sar1, Ala8]angiotensin II (P-113) was compared before and during RAO on blood flow and vascular resistance of the contralateral kidney. An increase in renin secretion rate was obtained in the ischemic kidney, which was accompanied by an increase in renal vascular resistance (RVR) in the contralateral kidney and a rise in systemic blood pressure. P-113 given intra-arterially to the contralateral kidney consistently increased renal blood flow and decreased RVR during RAO, but did not alter RVR significantly before RAO. The elevation in renin secretion rate decreased between 30 and 122 min after the initiation of RAO in the pentobarbital-anesthetized dogs but not in the chloralose-urethan-anesthetized dogs. These experiments indicate that during RAO release of renin causes, through formation of angiotensin, an increase in RVR in the contralateral kidney and intra-arterial administration of P-113 restores the vascular resistance to a near-normal level.


Isotonic relaxation in cardiac muscle.

The force-velocity-length determinants of isotonic relaxation were studied in 12 cat papillary muscles. Isotonic relaxation velocity (VL) was found to be a function of total load (preload + afterload), with peak VL increasing to a maximum at loads approximately .3 to .4 Po(L') (Po(L') defined as maximum isometric force developed during a twitch at the experimental length) and falling with increasing loads. Initial muscle length (ML) had no effect on the peak VL with constant load. Increasing the initial length at which isotonic relaxation occurred (LL) decreased peak VL but did not alter the unique length-velocity trajectory at constant load. This unique length-velocity trajectory occurred, despite a wide variation in time during the contraction when peak VL was measured. Increasing Ca++ from 2.5 to 7.5 mM increased peak VL (1.73 +/- .16 to 2.32 +/- .20 ML/s) and shifted the entire length-velocity trajectory toward higher velocities of lengthening. The addition of 10 mM caffeine increased peak VL also (1.67 +/- .18 to 2.54 +/- .20 ML/s) and had a similar effect on the length-velocity trajectory during lengthening as Ca++. Both increased Ca++ and caffeine (10 mM) augmented the maximum VL measured on addition of load.


Sex differences in reflex tachycardia induced by hypotensive drugs in unanesthetized rats.

Possible sex differences in autonomic regulation of the heart were studied by injecting standard hypotensive doses of histamine or bradykinin to induce reflex tachycardia in awake rats. Although depressor responses to both drugs were unaltered, the tachycardia was greatly reduced by beta-adrenergic blockade with propranolol and abolished almost completely after combined blockade with propranolol and atropine. These findings indicate that the tachycardia was mostly due to increased sympathetic stimulation wiht a minor contribution from parasympathetic withdrawal. With large doses of bradykinin, direct myocardial stimulation also seemed likely, since some residual tachycardia remained even after combined blockade. Reflex tachycardia was generally more pronounced in male than in female rats. Because males had lower base-line heart rates and more tachycardia that was resistant to beta-adrenergic blockade than females, autonomic regulation was concluded to be predominantly parasympathetic in males and sympathetic in females. Whereas the exact cause of these variations in chronotropic regulation is unknown, it was considered possible that differences in sex hormones may have affected sensitivity of some component of the reflex arc.


Effects of elevated magnesium on discharge of myenteric neurons of cat small bowel.

Electrical discharge of single units in myenteric ganglia of cat intestine was recorded extracellularly, and the effects on the electrical discharge of elevating the concentration of Mg++ in the Tyrode solution from 0.2 to 10.2 mM were determined. The ongoing discharge of 83% of the burst-type units was blocked by elevation of Mg++. The remainder of the burst-type units and all of the single-spike units tested continued to discharge in elevated Mg++. Frequency distribution histograms of interburst intervals of burst units that were unaffected by elevated Mg++ showed low variance of interburst interval, and multimodes on the histograms were multiples of the first mode. The variance of interburst intervals of burst-type neurons that were blocked by elevated Mg++ was greater than variance of the burst-type neurons that were unaffected by increased Mg++. If it is assumed that the action of elevated Mg++ is blockade of synaptic transmission, then the results indicated that the ongoing discharge of the neurons that were blocked by elevated Mg++ was dependent on synaptic input to the cell. The burst-type units that were unaffected by elevated Mg++ may be endogenous oscillators that do not receive synaptic input. The burst-type units that were blocked by elevated Mg++ may be driven by synaptic input from the burst-type oscillators.


Metabolic effects of calcitonin in the newborn.

Calcitonin was injected in newborn rats and newborn lambs to study the metabolic effects of the hormone. Subcutaneous injection of salmon calcitonin (140 MRC U/kg) induced a clearing effect on plasma from suckling newborn rats that was naturally lactescent. A lower dose given by the same route (14 MRC U/kg) strongly decreased plasma triglyceride and amino acid levels in suckling newborn rats. This was mainly the result of gastric emptying inhibition. The gastrointestinal action of calcitonin in suckling newborn rats was substantiated by the absorption of [14C]triolein and 14C-labeled amino acids. Hormonal changes that were associated were a decrease in plasma insulin level and an increase in plasma growth hormone concentration. Intravenous calcitonin at a physiological dose (0.03 MRC U/kg) injected into newborn lambs inhibited increases in total plasma lipids, amino acids, and blood-glucose levels at the time of the first suckling period without changing serum calcium levels. One of the physiological roles of calcitonin in the newborn may be the regulation of nutrient absorption from milk rich in lipids.


Thermoregulation in the rabbit following intracranial injection of norepinephrine.

The release of norepinephrine (NE) from nerve terminals in the anterior hypothalamic/preoptic area (AH/POA) of the rabbit may serve to raise body temperature. To further examine the putative neurotransmitter role of NE, bilateral microinjections of 5 or 10 mug NE were made into or near the AH/POA of 44 conscious rabbits exposed to an ambient temperature of 15 degrees C. Microinjections into the AH/POS did not cause fever; they either had no influence on thermoregulation or rapidly induced ear vasocilation and increased ear temperature accompanied by slight falls in rectal temperature. The latter averaged 0.32 degrees C (range: 0.16-0.45 degrees C) in 18 rabbits in which the effects were prominent. In contrast, the injection of 100 or 250 mug NE into the lateral cerebral ventricles of conscious rabbits in the 15 degrees C environment caused mean fevers of 0.62 +/- 0.0, and 1.04 +/- 0.14 degrees C (+/- SE, n equals 6), respectively, within 70 min. The febrile response to intraventricular injection of NE may be due to an action of the drug at a site other than the AH/POA. Alternatively, the response may depend critically on the particular distribution of NE that results from its diffusion from the third ventricle into the AH/POA.


Effects of theophylline on Na and alanine transport across isolated rabbit ileum.

Addition of theophylline to isolated rabbit ileal mucosa resulted in a persistent increase in short-circuit current (SCC) and a persistent decrease in DC conductance. Under short-circuit condition, net Na flux (JNanet) was reversed by theophylline from absorption to secretion (-0.6 mueq/h cm2) and was due to a decrease in unidirectional mucosal- (M) toserosal (S) flux (JNams). Addition of L-alanine to theophylline-treated m-ucosa increased SCC, JNanet, and JNams. Theophylline reduced JAlanet by 25%. Na flux ratios, determined in the presence of theophylline at +26 and -11 mV (mucosal reference), differed from flux ratios expected for a diffusional process by less than 8%. In contrast, Na flux ratios, determined in the absence of theophylline and presence of glucose at +26 and O mV, differed from diffusional ratios by 35%. The results are consistent with the hypothesis that theophylline inhibits active Na absorption, but the data do not conclusively demonstrate the diffusional nature of unidirectional Na fluxes in the presence of theophylline.


Intestinal CaBP: a new quantitive index of vitamin D deficiency in the rat.

Rats raised from weaning on regiments adequate in calcium and phosphorus but deficient in vitamin D will have no detectable intestinal calcium-binding proteins (CaBP), whether or not they show other signs of vitamin D deficiency, such as hypocalcemia. When hypocalcemic, vitamin D-deficient animals were treated with 25-hydroxycholecalciferol, a vitamin D metabolite, they showed a dose-dependent increase in plasma calcium and CaBP; both responses can be described by a single linear relationship, which appears to apply whether the metabolite is 25-hydroxycholecalciferol or dihydrotachysterol. Since vitamin D status is only one determinant of plasma calcium, whereas CaBP (or its expression) appears to depend on vitamin D quantitatively, CaBP may be used as an index of vitamin D status, provided calcium intake is controlled.


Tubular organization and vascular-tubular relations in the dog kidney.

Tubular organization and vascular-tubular relations were studied by double injection in canine kidneys. Blood vessels were injected via the artery after perfusion fixation. Tubules were injected by micropipettes inserted into the urinary spaces of selected glomeruli in cleared slices. One hundred proximal convoluted tubules, 16 Henle loops, and 5 distal convoluted tubules were defined. Only subcapsular proximal convolutions were perfused by efferent vessels arising from the same glomerulus (43 of 55). In midcortex, proximal convolutions were generally perfused over less than half their length by the parent efferent (21 of 31). Here tubules entirely perfused by the parent efferent were rare (2 of 31). No inner cortical proximal convolutions were perfused by the efferent from the same glomerulus (0 of 14). Henle's loops were found to be perfused by the efferents of many glomeruli regardless of the cortical position of the parent glomerulus. Distal convolutions shared the perfusion of proximal convolutions of the same glomerulus. Thus, each nephron is apparently functionally dependent on efferent blood from glomeruli of many other nephrons. New synoptic diagrams of canine renal organization are presented.


Effect of primary bile acids on bile lipid secretion from perfused dog liver.

An isolated canine liver perfusion technique featuring a second dog as the pump oxygenator was used to compare biliary lipid secretion during randomized, steady-state perfusions at two different rates of cholyl taurine or chenodeoxycholyl taurine infusions. The hepatic extraction of the trihydroxy-conjugated bile acid was considerably greater than that of the dihydroxy conjugate, possibly explained by ultrafiltration experiments which indicated that cholyl taurine was less protein bound than chenodeoxycholyl taurine. Both bile acids induced phospholipid and cholesterol secretion that was linearly proportional to bile acid secretion. However, each mole of secreted chenodeoxycholyl taurine induced a greater relative secretion of phospholipid and cholesterol than did that of cholyl taurine. Thus in the canine liver, the two primary bile acids are extracted at different rates and induce biliary secretion of different relative lipid composition.


ADP, thrombin, and Bothrops atrox thrombinlike enzyme in platelet-dependent fibrin retraction.

Clots formed upon the addition of thrombin to human platelet-rich plasma (PRP) retracted readily but the clotting enzyme from Bothrops atrox venom did not cause retraction in PRP unless ADP, collagen, epinephrine, or low concentrations of thrombin (0.1 U) were added. The latter type of retraction was inhibited by apyrase and creatine phosphate kinase in the presence of creatine phosphate, but that induced with higher concentration of thrombin (2 U) was not. In a system composed of washed human platelets and purified fibrinogen, Bothrops marajoensis (BM) thrombinlike enzyme (highly purified preparations of viper venom) did not cause clot retraction. Addition of ADP to the platelet-fibrinogen mixture prior to BM enzyme resulted in stimulation of clot retraction that could be dissociated from the release of platelet constituents. Addition of low concentrations of thrombin (0.1 U/ml) caused retraction associated with a considerable release of adenine nucleotides that was inhibited by potato apyrase. Electron micrographs showed platelet-fibrin aggregates in all types of retracted clots. Nonretracted clots formed in the presence of potato apyrase contained discoidal platelets that were not in close association with fibrin. It has been postulated that platelet-dependent fibrin clot retraction induced by collagen, epinephrine, and low concentration of thrombin is mediated by ADP. High concentrations of thormbin may possibly promote clot retraction independently of ADP.


Pressure-flow and volume-flow relationships of the systemic circulation of the dog.

Mean systemic pressure-flow (Ps-Q) and volume-flow (V-Q) relationships of the systemic vascular bed were determined in two groups of dogs anesthetized with sodium pentobarbital (group I) and with methoxyflurane (group II). All blood returning to the heart (Q) was removed from the right atrial appendage and passed through a Starling resistor, a pump, a flowmeter , and then returned directly into the pulmonary artery. Ps was estimated from plateau values of right atrial pressure obtained during stop-flow procedures. Both the Ps-Q and V-Q relationships were nonlinear. This nonlinearity may be attributed to a redistribution of blood flow between systemic vascular compartments of unequal time constants. With group II, the Ps-Q and V-Q curves were shifted markedly to the right along the Ps and V axes, respectively. Evidence is presented which suggests that this shift was due to an effective back pressure other than right atrial pressure produced by a hepatic waterfall. The beta-adrenergic antagonist practolol increased the effective back pressure and augmented the shift in the Ps-Q and V-Q curves.


Neural mechanisms of sneeze.

Sneezes were induced in anestized cats by repetitive stimulation of the ethmoidal nerve. Activity of bulbar respiratory neurons during sneezing was recorded extracellularly through tungsten microelectrodes. Most expiratory neurons could be locked onto the stimulus pulses so that they responded either throughout inspiration as well as expiration or so that they began responding at some time during inspiration. As inspiration approached termination, multiple spiking occurred, finally to result in high-frequency bursts which just preceded active expiration. A fraction of expiratory neurons were activated only in bursts. Latent expiratory neurons were recruited in sneezing. Inspiratory neurons near nucleus ambiguus and most of those near fasciculus solitarius displayed similar response patterns consisting of silent periods followed by delayed smooth activations. Temporal characteristics of the silent periods, "inhibitory gaps," suggested that they resulted from inhibition whose source was the expiratory neurons which were driven throughout inspriation. Some inspiratory neurons in the area of fasciculus solitarius failed to exhibit inhibitory gaps.


Aortic nerve-activated cardioinhibitory neurons and interneurons.

Unit activity evoked by electrical stimulation of the aortic and vagus nerves was recorded in the dorsal motor nucleus and nucleus solitarius of unanesthetized rabbits. Cardioinhibitory cells which showed antidromic activation to stimulation of the vagus nerve and synaptic activation to stimulation of the aortic nerve were localized in lateral dorsal motor nucleus 0.5-0.8 mm anterior of the obex. Additionally, units were found that appeared to be interneurons in the medullary pathway subserving baroreceptor reflex effects on cardioinhibitory neurons. These cells were activated by aortic, and usually vagus, nerve stimulation, appeared to be polysynaptically activated, and were located in medial nucleus solitarius rostral to the obex. Neurons reflecting a cardiac rhythm but not activated by aortic nerve stimulation were also observed.


Active transport of iron to mucosal surface of rat jejunum.

Estimations of steady-state fluxes of divalent Fe across rat intestinal segments in vitro provide evidence for two active transport mechanisms. Segments of the distal small intestine transport the mineral against electrochemical potential gradients from the serosal to the mucosal surface. Active transport in the reverse direction was confirmed with segments of proximal duodenum. The distal mechanism is dependent on cellular metabolism and is markedly decreased by metabolic inhibitors or in the absence of a metabolizable hexose. Cycloheximide, which inhibits protein biosynthesis, also blocks the active transport. Perfusion of jejunal and duodenal intestinal loops in situ in anesthetized rats provides evidence that endogenous Fe can be transferred to the lumen by a process otherthan shedding of mucosal cells. It is suggested that such transfer may occur via the active transport mechanism.


Relationship of mammary blood flow to parturition in the ewe.

Mammary blood flow was measured in conscious, unanesthetized ewes with electromagnetic flow probes prior to spontaneous labor (four animals) or during the induction of premature labor (four animals) by administration of dexamethasone, 1 mg/24 h, to the fetus. In all animals an increase in mammary blood flow was noted prior to delivery. Dexamethasone administered to one mother in the same dose did not induce labor or produce an increase in mammary blood flow. These results suggest that the fetal adrenal gland influences maternal mammary blood flow prior to delivery.


Arterial wall mechanics and composition and the effects of smooth muscle activation.

A comparison of passive mechanics and the effects of smooth muscle (SM) activation has been made in canine carotid and iliac arteries. Measurements of external diameter and axial force were made on isolated cylindrical segments in response to internal pressure variations. Data were obtained during maximal norepinephrine (NE) and potassium (K) activation, and following metabolic inhibition of SM. These data were used to determine wall tangential stress-strain relations. The maximum increase in wall stress after K and after NE was greater for the iliacs and occurred at smaller values of wall strain. Passive stress-strain curves for the iliacs were likewise shifted to smaller strains, suggesting an important role of passive wall elements in setting the length of contractile elements. Diameter responses to K at low values of pressure were the same for iliacs and carotids, but were better maintained at higher pressure levels for the iliacs. Similar findings were found for iliac responses to NE and K. The results suggest that at low values of wall stress, active diameter responses are not strongly dependent on the maximum isometric stress development. However, higher pressure-diameter responses are also determined by the force-generating capacity of SM.


Role of luminal hydrostatic pressure in proximal tubular fluid reabsorption in the rat.

The effect of small changes in intraluminal hydrostatic pressure (P) on the tubular radius (r) and the net fluid reabsorption per unit of surface area of the tubular wall (Js) has been studied in the proximal tubule of the rat kidney. The split-drop method was used to simultaneously determine Js and r. Two standardized split-drop techniques A and B allow selective change in P. P was 31.6 +/- 1.3 mmHg in technique A and 15.5 +/- 1.5 in technique B. The pressure difference significantly affected the tubular radius; r was 21.9 +/- 0.4 and 18.6 +/- 0.5 mum in the split drop A and B, respectively. In contrast, net transepithelial fluid reabsorption Js was unchanged. Js amounted to 2.72 +/- 0.20, and 2.78 +/- 0.33 10(-5) cm3 cm-2 s-1 in split drop A and B. The absence of variations in Js could result from two opposite effects of pressure. P might enhance Js by increased ultrafiltration. However, the rise in r might decrease the density of the intraepithelial transport paths per unit area of tubular wall and therefore might decrease Js.


Localization of renal tubular uric acid transport defect in gouty chickens.

Chickens genetically selected for high incidence of articular gout and hyperuricemia were used to determine the site of defective uric acid (UA) transport in gout. The Sperber technique was used to compare the tubular secretion of preformed UA with the tubular secretion of UA formed within the tubular cells in gouty and nongouty chickens of the same strain. In gouty chickens, the tubular excretion ratio of preformed [14C]UA was 36% of the value obtained in nongouty chickens of the same strain, whereas the tubular excretion ratios of [14C]UA formed within the tubular cells from [14C]guanine were equal in the two types of chickens. This suggests that a UA transport is located at the peritubular membrane and that this mechanism is defective in gouty chickens. In addition, the transport of p-aminohippurate (PAH) was normal in gouty chickens, which suggests that the transport mechanism for UA is distinct from that for PAH.


Prostaglandin control of renal circulation in the unanesthetized dog and baboon.

Effects of indomethacin and meclofenamate, inhibitors of prostaglandin synthesis, were evaluated in the regulation of renal blood flow in conscious and anesthetized dogs and in tranquilized baboons, instrumented with arterial pressure catheters and renal blood flow probes. Indomethacin, 10 mg/kg, did not alter renal blood flow or resistance significantly in the conscious dog. In the anesthetized dog, however, indomethacin caused a reduction in renal blood flow (25 +/- 3% of control) and an elevation of renal vascular resistance (45 +/- 8% of control). Meclofenamate, 4 mg/kg, reduced renal flow (12 +/- 2%) and increased renal vascular resistance 15 +/- 4% in conscious dogs. In conscious dogs and tranquilized primates, indomethacin and meclofenamate reduced the reactive hyperemia in the renal bed after 15 s occlusion from a control of 36 +/- 5 ml to 6 +/- 2 ml, and after 45 s occlusion from a control of 98 +/- 9 ml to 17 +/- 5 ml. Methoxamine (10-50 mug/kg per min) and angiotensin II (0.03-0.12 mug/kg per min), infused in graded doses, induced significantly greater renal vasoconstriction in conscious dogs in the presence of indomethacin. Thus, in the conscious animal, prostaglandins appear to play only a minor role in the control of the renal circulation at rest, but are of greater importance in mediating the renal responses to reactive hyperemia and to vasoconstriction.


Metabolic and hemodynamic consequences of mannitol following myocardial anoxia.

The mechanism of action of hyperosmolal mannitol was evaluated by hemodynamic and metabolic studies in 79 isovolumic nonrecirculating paced perfused rat hearts during sequential 15-min periods of aerobic, anoxic, and reoxygenated perfusion. Hyperosmolality induced by addition of mannitol significantly decreased myocardial water content (wet/dry wt ratio). It improved recovery of hemodynamic function during reoxygenation. With isomolal perfusion (290 mosmol/kg) left ventricular systolic peak pressure (LVSP) decreased 32% (127 +/- 5 to 86 +/- 6 mmHg) and maximum dP/dt fell 50% (3,513 +/- 328 to 1,758 +/- 172 mmHg/s) during the postanoxic recovery period. With hyperosmolal perfusion (350 mosmol/kg), LVSP decreased 23% (132 +/- 5 to 102 +/- 7 mmHg) and dP/dt fell 21% (3,817 +/- 215 to 2,998 +/- 234 mmHg/s) (P less than .01). Hyperosmolal perfusion did not affect postanoxic total coronary flow, lactate and glucose metabolism, tissue glycogen, creatine phsophate, or adenine nucleotide concentrations. Coronary perfusion with hypersmolal solution aided recovery, enhanced postanoxic myocardial performance, and minimized tissue swelling. The most tenable explanation for the locus of action of hyperosmolal mannitol during anoxia under our experimental conditions is its direct effect on myocardial water content.


Effects of mannitol on cardiac ultrastructure and microcirculation following anoxia.

Electron microscopic and microcirculatory effects of hyperosmolal mannitol were evaluated in the isolated perfused isovolumic rat heart. Specimens for ultrastructural examination were obtained in 26 experiemnts after 15 min of sequential aerobic, anoxic, and reoxygenated perfusion using an isosmolal perfusate of Krebs-Ringer-Henseleit bicarbonate buffer (KRB) (osmolality equals 290 mosmol/kg) vs. a hyperosmolal solution of KRB + mannitol (equals 350 mosmol/kg). No significant changes were noted during aerobic perfusion. Anoxic hearts perfused with isosmolal KRB demonstrated the most severe ultrastructural alterations including: mitochondrial swelling with disruption of cristae, myofibrillar fusion and contraction bands, and subsarcolemmal edema and vacuolization. These subcellular changes were not only partially reversed by oxygenated isosmolal perfusion but were significantly reversed during both the anoxic and reoxygenation perfusion periods with mannitol added. Following silicone rubber injection of the microcirculation, only focal capillary endothelial cell swelling was noted, and no difference in arteriolar or capillary filling was observed with either perfusate. Thus, mannitol significantly reversed the postanoxic ultrastructural changes consistently observed in the absence of increased osmolality. No gross effect on vascular patency could be demonstrated.


Physiological temperature response and embryonic mortality in stressed swine.

Physiological responses and some aspects of reproductive function were examined in mated female pigs subjected to a short-term heat stress during two intervals of early gestation. Trial 1 control and treated animals experienced temperatures of 24.0 and 40.2 degrees C, respectively, from days 2 through 13 of pregnancy. Trial 2 control and treated pigs were exposed to 23.3 and 40.4 degrees C, respectively, from days 14 through 25 of pregnancy. Both high thermal exposures caused significant increases (P less than 0.05) in rectal temperature. At body temperatures of 41.1 degrees C or above, animals became more active and behavioral patterns erratic. Stressed pigs in both trials exhibited adaptation to the short-term high thermal environment as treatment days progressed. Embryonic mortality in the stressed animals in trial 1 was greater than in controls, with the animals in the former group retaining a normal size litter or losing the entire litter by day of slaughter. A significant proportion (P less than 0.01) of litters from stressed animals contained degenerating fetuses at day 42 of gestation, suggesting a continuous or delayed effect of thermal stress on embryo survival.


Influence of altered O2 tension on substrate metabolism in perfused rat lung.

Effects of hypoxia (1.5 h) on glucose and palmitate metabolism were investigated in perfused lungs from normal rats and rats exposed for 24 h to hypobaric conditions (simulated altitude of 24,000 ft). Hypoxic lungs were ventilated with 5% O2-5% CO2 and control lungs with 21% O2-5% CO2. Blood gases and pH remained stable during the 1.5-h perfusion period. Exposure of normal rat lungs to 1.5 h of in vitro hypoxia (blood Po2=34 mmHg) significantly increased lactate production and mean arterial pulmonary pressure, but did not alter glucose uptake, pyruvate levels, and oxidation of either [U-14C]glucose or [1-14C]palmitate to CO2. Incorporation of labeled glucose and palmitate into lung lipids was also unaltered. In contrast to normal lungs, prior exposure to hypoxia for 24 h and subsequent perfusion under hypoxic conditions significantly stimulated glucose uptake (74% increase), markedly increased glucose incorporation into lung lipids, and increased oxidation of glucose to CO2. Lactate/pyruvate ratios also showed a significant 38% increase. Lung glycogen was unchanged following 24 h hypoxia. These data indicate that adaptive changes occur in metabolic processes within the lung during acute changes in O2 tension.


Mechanism of diuretic response associated with atrial tachycardia.

Left atrial pacing was performed in three groups of anesthetized dogs. In the first group of eight intact dogs a mean increase in atrial rate (AR) from 140 +/- 7 to 244 +/- 6 was associated with a decrease in urinary osmolality (U osmol) from 631 +/- 72 to 264 +/- 43 mosmol/kg (P less than .001), and free-water clearance (CH20) increased from -.325 +/- .06 to +.355 +/- .15 ml/min (P less than .001). At the same time left atrial pressure (LAP) increased from 6 +/- 1 to 15 +/- 1 mmHg (P less than .001). A second group of studies was performed in six hypophysectomized, steroid-replaced animals receiving 40-50 muU/kg per min of antidiuretic hormone (ADH). In these animals AR was increased from 148 +/- 17 to 250 +/- 17 but diuresis did not occur. In these studies Uosmol was 690 +/- 55 before and 704 +/- 49 mosmol/kg after atrial pacing and CH20 also did not change. Left atrial pressure increased from 10 +/- 2 to 19 +/- 2 mmHg during atrial pacing. A third group of studies was performed in five animals with bilateral cervical vagotomy. In these animals AR was increased from 159 +/- 6 to 258 +/- 17 and LAP increased from 7 +/- 1 to 16 +/- 2 mmHg. Osmolality increased from 808 +/- 72 to 1,049 +/- 65 musmol/kg (P less than .005) and CH20 was unchanged. These results, therefore, indicate that atrial tachycardia primarily increases renal water excretion by suppressing ADH release. This reflex is dependent on the integrity of cervical vagal pathways.


Negative inotropic influence of hyperosmotic solutions on cardiac muscle.

In cardiac muscle, moderate degrees of hyperosmolality of the type encountered physiologically or clinically (i.e., less than 200 mosM above control) characteristically exert a positive inotropic effect, which presumably is mediated by increased Ca2+ availability for binding to troponin. In contrast, skeletal muscle displays significant contractile depression on exposure to hyperosmotic solutions, even at mild degrees of hypertonicity. To determine whether a similar potential for hyperosmolarity-induced depression also exists in cardiac muscle, right ventricular papillary muscles from cats were exposed to hypertonic solutions of mannitol or sucrose under circumstances in which positive inotropic effects were precluded by prior exposure to a bathing solution of 4.0 mM Ca2+ and paired electrical stimulation to maximize intracellular Ca2+ before addition of the hyperosmotic substances. In contrast to their usual positive inotropic effects, hypertonic solutions under these conditions caused cardiac depression at all osmolarities tested. Developed tension and its maximal rate of development (dT/dt) decreased by 18% at 50 mosM above control, by 30% at 100 mosM, by 36% at 150 mosM, and by 42% at 200 mosM (P less than 0.01 for all). Time to peak tension and resting tension were not changed significantly. When the muscles were returned to control solutions, tension development also returned toward normal. The data are compatible with the hypothesis that, within the range tested, all degrees of hyperosmolarity exert a significant negative inotropic influence on cardiac muscle, as is true in skeletal muscle; manifestation of this effect of increased tonicity normally would be obscured at low degrees of hyperosmolality, however, by an overriding positive influence that is absent in skeletal muscle.


Mesenteric baroreceptors.

Occlusion of the mesenteric vessels in the cat and injection of catecholamines produced significant changes in skin and muscle blood flows. These were abolished by cutting the mesenteric nerves. The occurrence of systemic pressure and peripheral resistance changes in cross-perfused mesenteric preparations indicates that hemodynamic factors alone, such as might result from occlusion of a large vascular region, were not initiating the reflex. This also excludes extramesenteric receptors within the heart and large vessels from the reflex. Since both intravascular pressure and catecholamines have been shown to modify Pacinian receptor discharge in vivo, the evidence suggests that the mesenteric Pacinian corpuscle is the baroreceptor probably initiating the vasomotor reflexes in skin and muscle. The net effect of mesenteric receptor activity appears to be an inhibition of vasomotor neurons supplying skin and muscle.


Responses to cold in the midbrain sonar center of hibernating and tropical bats.

The central gray matter of the bat midbrain, when electrically stimulated, causes the animal to produce a string of species-specific biosonar cries. Changes in this response with progressive cooling were studied in tropical homeothermic bats and in temperate hibernating bats. The species of hibernators chosen often move between hibernacula in the winter, flying and echolocating at low body temperatures (Tb). It was found that the midbrain "sonar center" exhibits a differential response to cooling that depends on the thermal propensities of the animal and its natural environment. Tropical bats followed a Q10 similar to that reported for other nonhibernating mammals and ceased responding at Tb 14-15 degrees C. Temperate zone-hibernating bat brains showed a relative insensitivity to temperature change and still responded at Tb 4-5 degrees C. Individual sonar cries within a string showed that duration was correlated with temperature but amplitude was unaffected. The study provides data for the functional separation of some parameters of biosonar and gives further evidence for differential nervous function in eurythermal versus stenothermal animals.


Nutritional effects on heart acetylcholinesterase and butyrocholinesterase activity.

Male rat pups were undernourished in energy and protein by assigning them at birth to lactating dams receiving a low-protein diet (12% casein) to decrease the maternal milk supply. A normal diet (25% casein) was fed to the dams of control pups. On day 21 the pups were killed and hearts were removed and examined from both groups. Hearts from the undernourished animals weighed less and contained less DNA, RNA, and protein. The chemical indices of cell number (DNA) and cell size (wt/DNA) were reduced in the hearts from undernourished animals. Assays of the cardiac tissue for the activity of acetylcholinesterase and butyrocholinesterase indicated that undernutrition altered the activities of both enzymes, but in opposite directions. Protein-energy undernutrition resulted in an increase in acetylcholinesterase activity and a decrease in butyrocholinesterase activity. The specific activities of choline acetyltransferase and cholinesterase were unchanged. The total activity of both cholinesterase and butyrocholinesterase was reduced in the hearts of the undernourished animals. The data indicate that nutritional status can alter the activity of cardiac enzymes which have been associated with controlling the rate and rhythmic contractions of the heart.


Osmotically induced changes in electrical resistance of distal tubules of rat kidney.

Changes in peritubular oncotic pressure do not alter the electrical resistance of distal convoluted tubules. Transverse specific electrical resistance decreases along the distal convoluted tubule in nondiuretic rats. This drop in resistance can be at least in part accounted for by the relative increae in osmolality of late distal fluid. Osmotic gradients influence the magnitude of intercellular rather than transcellular conductance. Hyposmolality of tubular fluid leads to reduced shunting, whereas increased tubular osmolality has the opposite effect. The osmotic effect forms part of an intraepithelial positive feedback loop for sodium reabsorption in the diluting segment of the renal nephron.


Evoked release of [14C]norepinephrine from the rat hypothalamus during feeding.

The pattern of catecholamine release was studied at sites adjacent to the lateral ventricle or in the anterior, dorsomedial or ventromedial hypothalamus of the rat as it was feeding. Endogenous stores of norepinephrine (NE) were first labeled by the microinjection of [14C]NE into these circumscribed sites. Subsequently, [14C]NE release was examined by repeated perfusions of an artificial cerebrospinal fluid through a push-pull cannula at the rate of 23 mul/min for 5-10 min every 30 min. After successive control perfusates were collected, food or water was given to the animal. During an interval of feeding, a significant efflux of [14C]NE and its metabolites occurred reliably from midline structures of the hypothalamus at the level of the ventromedial nucleus. Although the feeding-related output of [14C]NE detected within the anterior hypothalamus was lower, [14C]NE was also released from this region when the rat pressed a lever to obtain food pellets. These results support the view that endogenous catecholamines underlie, at least partially, diencephalic mechanisms controlling food intake, including sensory, motor, or motivational components.


Distal site of action of parathyroid hormone on phosphate reabsorption.

The sites of inhibited phosphate transport following administration of bovine parathyroid hormone (bPTH) to thyroparathyroidectomized (TPTX) dogs were investigated. Phosphate reabsorption by the proximal and distal nephron was studied using recollection micropuncture, stop-flow methodology, and electron-probe microanalysis. Following bPTH, delivery of phosphate from the proximal tubule increased from 26 to 37% of the filtered load, P less than .01. Fractional phosphate excretion increased from 2.3 +/- 1.5 to 21.4 +/- 2.3%, P less than .001. The increased delivery of phosphate at the point of micropuncture in the proximal tubule accounted for approximately half of the phosphaturia. In six TPTX dogs, which were saline loaded, similiar increases in phosphate delivery from the proximal tubule from 27 +/- 1 to 36 +/- 2% of the filtered load resulted in a strikingly smaller phosphaturia, 5.1 +/- 1 to 9.8 +/- 2.4%, NS. In stop-flow experiments, phosphate concentratin ratios were slightly increased in the proximal nephron and markedly increased in the distal nephron following bPTH. It is concluded that parathyroid hormone markedly decreases phosphate transport in the distal nephron.


Acute suppression of hepatic gluconeogenesis by glucose in the intact animal.

Within 2 h after glucose administration to fasting rats the incorporation of radioactive lactate into blood glucose and liver  glycogen is decreased. Using tryptophan, which facilitates the study of gluconeogenesis prior to the phosphoenolpyruvate (PEP) carboxykinase step by increasing the level of certain hepatic metabolites, we have found that in animals fasted for 24 h glucose markedly decreased hepatic malate and aspartate concentrations without a corresponding fall in that of pyruvate, suggesting a decrease in pyruvate carboxylase activity. An inhibitor of fatty acid oxidation, 4-pentenoic acid, similarly decreased the accumulation of these intermediates, and octanoic acid significantly lessened the fall in malate and aspartate with glucose. The changes in tissue metabolite levels were consistent with inhibition of the liver pyruvate carboxylase reaction by glucose treatment, and with abolition of this inhibition by octanoate administration. Alanine and glutamate levels in the liver of tryptophan-treated animals were decreased 90 and 32%, respectively, by glucose. Thus, glucose administration in the whole animal acutely decreases gluconeogenesis by apparently inhibiting the pyruvate carboxylase step and decreasing alanine levels in the liver.


Impermeability of rabbit erythrocytes to prostaglandins.

Washed rabbit erythrocytes were suspended in Tris-electrolyte buffer containing [3H]prostaglandin (PG) E1, F1alpha, F2alpha, or A1 and one 14C-labeled compound such as sucrose. After up to 24 h of incubation, aliquots of centrifuged, packed cells and supernatant were oxidized and the 3H and 14C samples were counted. The mean sucrose space of the packed cell was 7.4%. After 1 min the E1, F1alpha, and F2alpha spaces were 16, 15.4, and 10.0%, respectively, and showed no increase even after 24 h of incubation at either 23 or 5 degrees C. At 23 degrees C the initial (0.5 min) PGA1 and thiourea spaces were 94 and 75%, respectively, whence the PGA1, but not the thiourea, space declined, reaching 30% at 4 h. The large initial uptake of PGA1 was eliminated at 5 degrees C, while it was accentuated at pH 6.8 or at a PGA1, concentration of 10(-3) M. 14C-Labeled arachidonic, octanoic, and other non-PG fatty acids gave apparent distribution spaces of 140-300%. These results show that PG's can partition  into rabbit erythrocyte membranes, but the intracellular volume of the erythrocytes is not freely accessible to these autacoids. The implications of the finding that some cell membranes are impermeable to prostaglandins are discussed.


Effect of calcium on magnesium absorption.

The effect of calcium on magnesium absorption was studied in the rat ileum in vivo. The increase in the luminal concentration of calcium led to a progressive decrease in magnesium absorption, which was accompanied by a parallel decrease in net sodium absorption. This calcium effect was also observed when sodium chloride was replaced by urea. However, a consistent correlation was observed between the magnitude of net magnesium absorption and the rates of net water absorption of all calcium concentrations. These findings suggest that calcium decreases magnesium absorption by a nonspecific reduction in membrane permeability to solutes that induce net water flow and are consistent with the concept that magnesium is transported by solvent "drag". The increase in the luminal concentration of calcium resulted in an increase in tissue accumulation of magnesium. This increase in tissue accumulation of magnesium was associated with a decrease in net sodium absorption and in the negativity of the transmural PD. These findings suggest an additional mechanism of magnesium transport operating independently of net water flow.


Absence of estimated glomerular pressure autoregulation during interrupted distal delivery.

Micropuncture studies in dogs have suggested that a distal tubule-to-afferent arteriole feedback system may participate in the autoregulation mechanism at the single-nephron level. To evaluate the effect of interrupted distal delivery on glomerular capillary pressure (GP) and its autoregulation, the proximal tubule was blocked with oil and maximal stop-flow pressure was measured with a micropressure servo-null system. The GP was estimated from the sum of stop-flow pressure and the plasma colloid osmotic pressure (membrane oncometer). In 18 dogs given a mild mannitol load, average +/- SD control arterial pressure was 118 +/- 16 mmHg, proximal tubule pressure was 24 +/- 5 mmHg, and estimated GP averaged 70 +/- 10 mmHg. There was a highly significant relationship between estimated GP and arterial blood pressure. Similar results were obtained in hydropenic dogs. In response to decreases in renal arterial pressure in individual dogs, stop-flow pressure and estimated GP failed to exhibit autoregulation although autoregulation of renal blood flow, GFR, and proximal tubule pressure was observed over an arterial pressure range of 150-95 mmHg. These results indicate that interruption of normal distal delivery by proximal tubule blockage interferes with the ability of the nephron to autoregulate glomerular pressure. They provide further evidence in support of the concept that a distal tubular feedback mechanism participates, at least in part, in the autoregulatory control of glomerular pressure.


Stimulation of intestinal smooth muscle by atropine, procaine, and tetrodotoxin.

In order to determine whether or not atropine, procaine, and tetrodotoxin (TTX) can stimulate intestinal smooth muscle directly, we examined the effects of these drugs on the mechanical and electrical activities of several types of cat intestinal smooth muscle preparations. The preparations consisted of isolated rings of 1) intact intestinal wall, 2) intact longitudinal and circular muscle, 3) ganglion-free circular muscle, and 4) ganglion-free circular muscle devoid of its dense layer and plexus muscularis profundus. Atropine and procaine (greater than 10(-4) M) stimulated all four types of preparation. On the other hand, TTX (up to 5 X 10(-6) M) stimulated only preparations 1 and 2. It is concluded that whereas atropine and procaine can directly stimulate intestinal smooth muscle, the excitatory effect of TTX is neurally mediated.


Skeletal buffering of acute metabolic acidosis.

Decreases in the sodium content of bone were measured to evaluate the role of this tissue in the buffering of acute metabolic acidosis. The bones of rats and dogs were labeled with radiosodium prior to the infusion of HCl, and changes in the radioactivity were used to indicate the loss of bone sodium. Significant reductions in the skeletal sodium occurred within the first 5 h of acidosis, and these losses can only be partially attributed to the hyponatremia accompanying the acid infusion. Decreases were greatest in the smaller bones of the rat; and, in the dog, the losses from flat bones exceeded those of the long bones. Only the rapidly exchangeable sodium of bone was involved in the changes due to acidosis. Soft tissue buffering may be more important initially; during 1.5-h experiments, the skeletal losses were small and could be ascribed almost entirely to the decrease in the amount of sodium contained in bone water. However, at the end of 5.0 h, the quantity of sodium released from the skeleton is sufficient to account for much of the tissue buffering.


Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation.

Adenosine is a possible mediator of myocardial and skeletal muscle blood flow regulation. Whether adenosine plays a similar role in modulating the pulmonary pressor response to acute alveolar hypoxia is not known. Adenosine levels (nmol/g tissue) in lung in six dogs ventilated with 95% N2, and 5% CO2 for a period of 3 min increased nearly 10-fold. Inosine and hypoxanthine, adenosine enzymatic degradation products, sustained a 10- and 7-fold increase, respectively. These degradative products are mainly formed in the capillary endothelial cells that contain the degradative enzyme nucleoside phosphorylase as demonstrated by histochemical techniques. To determine the effect of ATP, ADP, AMP, and adenosine on the pulmonary circulation, the in situ left lower lobe of 10 dogs was perfused at either free flow or constant flow via its pulmonary artery. ATP and ADP increased lobar vascular resistance; AMP and adenosine decreased the resistance. During hypoxic ventilation, adenosine infusions (100 nmol/ml blood) entirely abolished the increase in vascular resistance that was due solely to hypoxia. Dipyridamole produced similar responses. These data indicate that adenosine is a pulmonary vasodilator and that it may modulate the pulmonary pressor response to acute alveolar hypoxia. The findings suggest that the use of adenosine or dipyridamole may be beneficial in patients with pathologic elevations of the pulmonary vascular resistance which are a result of an exaggerated pulmonary pressor response to hypoxia, as seen in high-altitude pulmonary edema or that following cerebral injury.


In vitro measurement of margin of safety of neuromuscular transmission.

The margin of safety of neuromuscular transmission was measured in isolated guinea pig lumbrical muscles. Twitch height of an indirectly stimulated muscle was reduced stepwise by suitable concentrations of tubocurarine for comparison with the associated occlusion of receptors by the drug. Receptor occlusion was estimated from the effect of tubocurarine on carbachol depolarization measured extracellularly by the moving-fluid electrode technique. Roughly 75-80% of the receptor pool had to be blocked before the twitch height began to fall, and 90-95% had to be blocked before the twitch response was completely abolished. These results agree well with those found previously in vivo. Thus, the present results add further support to the earlier measurements. In particular, artifacts that might have been present because of the complex pharmacokinetic situation in vivo have been ruled out.


Pentobarbital and contraction of vascular smooth muscle.

This study, with isolated rat aortic strips and portal veins, was undertaken to : 1) study the effects, if any, of pentobarbital Na (PTB) (5 x 10(-5) to 2 X 10(-3) M) on reactivity to epinephrine, serotonin, and KCl; 2) determine whether  certain concentrations of PTB induce direct actions on aortic strips and portal veins; and 3) gain some insight into how these effects are brought about. The results indicate that PTB can: a) inhibit development of spontaneous mechanical activity in these vessels in anesthetic concentrations; b) dose-dependently attenuate contractions induced by epinephrine, serotonin, and KC1; c) cause a noncompetitive type displacement of the dose response curves of these vasoactive agents; d) attenuate Ca2+- induced contractions of potassium-depolarized aortic strips and portal veins concomitant with a dose-dependent displacement of these dose-response curves to the right; and e) rapidly relax drug as well as Ca2+ -induced contractions of aortas and portal veins. In addition, the data indicate that rat portal venous smooth muscle is more sensitive to the inhibitory actions of PTB than rat aortic smooth muscle. Overall, these data suggest that concentrations of PTB used to induce surgical anesthesia can exert profound depressant effects on at least two different types of vascular smooth muscle that may be related to actions on movement and/or translocation of Ca2+.


Characteristics of urate influx in the rat nephron.

Permeability  of the tubular epithelium to urate presented on the peritubular side was studied in anesthetized rats during mannitol diuresis by capillary microinjections of [14C]urate and [3H]inulin, [14C]PAH and [3H]inulin, or [14C]urate and [3H]PAH. Recovery of isotopes was determined in urine collected serially from the injected and contralateral kidney. Appearance and peak excretion of urate in the experimental but not in the contralateral kidney preceded inulin and coincided with PAH, indicating proximal permeability to urate. Recovery of urate was higher from the injected than from the contralateral kidney. Urate precession and recovery did not change after addition of PAH (1.5-6.4 mm) to [14C]urate-[3H]inulin solutions, whereas they decreased significantly in the experimental kidney after pyrazinoate (1.6-3.2 mM) addition. On the other hand, no effect of urate on [14C]PAH-[3H]inulin injections was detectable. These findings are suggestive of a carrier-mediated transtubular influx of urate in rat proximal tubule. Absence of competition with PAH may suggest differences in the secretory mechanisms for organic acids.


Glucose turnover values in the dog obtained with various species of labeled glucose.

Recent studies proposed that [2T]glucose is preferable to [14C]-glucose as a tracer for the measurement of glucose turnover. However, higher values for glucose turnover were obtained using [2T]glucose than with [14C]glucose. The present study explores the merit of another species of tritiated glucose, [3T]glucose. Utilizing isotope-dilution principles, comparison is made of glucose turnover values determined by use of [2T]glucose, [3T]glucose, and [6-14C]glucose. Glucose turnover using [2T]glucose was 1.51 +/- 0.07 times greater than that using [6-14C]glucose, after correction for recycling of 14C. However, glucose turnover values obtained with [3T]glucose were similar to those obtained with [6-14C]glucose. There were no temporal or quantitative differences in appearance of tritium (T) in plasma water after injection of [2T]- and [3T]glucose. A methylprednisolone regimen in the normal dog increased glucose turnover as determined by all three tracers, but the increase observed using [2T]glusoce was significantly greater than that using that two other tracers. Thiement for [6-14C]glucose for measurement of glucose turnover in the dog.


Rattlesnake venom shock in the rat: development of a method.

A model in Wistar rats (n = 30, 279-345 g) was developed to study circulatory, respiratory, metabolic, and lethal effects of an intravenous infusion (30 min; 1.25, 1.5, 1.75, and 2.0 mg/kg) of rattlesnake (Crotalus viridis helleri) venom. Venom produced perfusion failure with lactacidemia, hemoconcentration, hypoproteinemia, and death. The severity of poisoning was proportional to the quantity of venom given and to the elevation in lactic acid and hematocrit. Hemorrhages in the diaphragm, intercostal muscles, and intestine were observed at necropsy. In a separate test, rats (n = 12, 311-355 g) received an infusion of 1.5 mg/kg of venom or physiological salt solution. Blood volume was measured 30 min after the end of infusion in both groups with radioiodinated (125I) human serum albumin (RIHSA) and 51Cr-labeled rat red cells. Venom produced a significant reduction in total blood volume index (35%, P less than 0.001), plasma volume index (46%, P less than 0.001), and red cell mass indec (22% P less than 0.005). The slope of the RIHSA-disappearance curve of animals that received venom was more than twice that of the control group. We conclude that perfusion failure following rattlesnake envenomation is associated with hypovolemia due to increases in vascular permeabiltiy and hemorrhage.


Chymodenin, a duodenal peptide: specific stimulation of chymotrypsinogen secretion.

Chymodenin, a basic porcine duodenal peptide, was administered to anesthetized rabbits intravenously or added to the medium bathing the isolated pancreas. In the 10(-8)M range, chymodenin rapidly increased chymotrypsinogen (ChTg) secretion, did not increase lipase secretion, and modestly enhanced protein secretion (which could be attributed primarily to augmented ChTg secretion). The increased ChTg output was too rapid to be the result of increased rates of protein synthesis and could not be attributed to the exocytosis os zymogen granule contents because of the enzyme-;pecific nature of the response. In contrast to shymodenin, cholinergic stimulation in vitro produced a relatively lipase-rich, chymotrypsinogen-poor secretion. Lipase and ChTg outputs, which varied relatively independently under unstimulated conditions, covaried in the presence of chymodenin. The existence of a duodenal peptide that produces an enzyme-specific response supports the hypothesis that the secretion of digestive enzymes during digestion is a highly regulated process in which the enzyme content of pancreatic secretion varies with differences in the composition of intestinal substrates.


Embryonic and placental development during prolonged inanition in the pig.

Pregnancy is maintained in a high percentage (79%) of pigs subjected to inanition for periods up to 37 days, but few (25%) remain pregnant when inanition continues beyond 41 days. All remain pregnant during prolonged inanition (45 days) when exogenous progesterone and estradiol benzoate are given daily. Embryo survival rates in animals on inanition remain high (88%) and similar to those (89%) found in pigs given a full diet. Nitrogen content of embryos increases at a decreasing rate after 41 and 45 days inanition; placental nitrogen is markedly reduced at those times. By 45 days of inanition, nitrogen contents of embryos and placentas are less (P  less than 0.01) than found in dams receiving a full diet. During prolonged inanition, exogenous progesterone (80 mg/100 kg) and estradiol benzoate (500 mug/100 kg) maintain embryonic and placental development at levels similar to those found in animals on a full diet. Maternal stores of protein and energy are made available for embryonic and placental developement in the presence of adequate levels of progesterone and estrogen, in spite of severe body weight loss during prolonged inanition of the dam.


Micropuncture study of renal magnesium transport in magnesium-loaded rats.

Mg transport in the deep loop of Henle was studied in 15 young rats (50-60 g) after acute systemic Mg loading (UFMg (ultrafilterable Mg) 4.77 meq/liter). Intratubular Mg was measured with a recently  described fluorometric microtechnique. The mean values of the TF/P inulin and TF/UF Mg ratios were 3.32 +/- 0.13 and 4.25 +/- 0.17, respectively. The proportion of filtered Mg recovered in this part of the nephron was therefore 131.2 +/- 5.0%, indicating that an appreciable amount of Mg entered the lumen prior to the sites of puncture. A significant correlation between the TF/P inulin and TF/UF Mg ratios suggests that water reabsorption also contributes to the high concentration of Mg in the loop of  Henle during systemic Mg loading. In another series of young rats (90-160 g), similarly loaded with MgCl2 (UFMg 5.81 meq/liter), Mg and inulin were measured in superficial proximal (PT) and distal tubules (DT). Punctures were paired at two sites of the same PT and DT. The Mg concentration increased progressively along the PT in such a way that 90.5% of the filtered load still remained in the late proximal loops. If superficial and deep proximal tubules behave in a similar manner, it may be concluded that the site of entry of Mg is located between the late accessible part of the PT and the bend of the loop of Henle. Only 58.0 +/- 3.0% of the filtered Mg was delivered to the DT, indicating that Mg is extensively reabsorbed in the ascending limb, despite systemic loading. The proportion of filtered Mg did not vary along the DT, indicating no net reabsorption.


Restriction of hepatic gluconeogenesis and ureogenesis from threonine when at low concentrations.

Experiments were carried out with the isolated perfused liver of the overnight-starved rat to study the control of the conversion of the essential amino acid threonine to glucose and urea from the point of view of its conservation when in short supply. The relationships between the concentration of added L-threonine and the rate of glucose and urea production showed that both pathways have considerable capacity and were saturated at a high (15 mM) concentration of threonine. However, these concentration-rate relationships were sigmoidal, so that at low concentrations the rates of conversion were disproportionately low. Thus at physiologic levels of threonine, no measurable stimulation of glucose or urea output was observed. Hepatic uptake of threonine was similarly disproportionately reduced at near-physiologic levels. Glucagon stimulated glucose and urea outputs in parallel fashion and stimulated the uptake and inward membrane transport of threonine at both saturating and low concentrations. This and the changes in intracellular and extracellular concentrations of threonine indicate the transport is rate limiting for both pathways. If this is so, the apparent restrictive property probably resides at the plasma membrane. Since the liver is the end point of threonine metabolism, this property would effectively limit the utilization of threonine when in short supply.


Tracheal agenesis.

Tracheal agenesis is a rare anomaly that produces neonatal respiratory distress and has been uniformly lethal to date. In this malformation the entire trachea is usually absent, air reaching the bronchi through a communication with the esophagus, and the lungs are normally formed. The diagnosis should be suspected in any infant in whom improved ventilation is obtained despite difficult intubation and abnormal tracheal tube placement. Coexistent cardiac, gastrointestinal, and genitourinary anomalies are common. The growth of the tracheoesophageal septum and the elongation of the dividing foregut are crucial phases in the morphogenesis of this malformation.


Renal hemangiomas. An  analysis of 13 cases diagnosed by angiography.

The angiographic findings in 13 patients with renal hemangiomas (one pararenal) are presented. The material suggests, contrary to earlier reports, a predominance for the female sex and the right kidney. Nine of the patients had macroscopic hematuria, of which five had renal colic. Obstruction was found at urography in seven cases. Renal angiography is the definitive diagnostic procedure and should be performed in all cases of unexplained macroscopic hematuria. Diagnosis may eventually be improved by pharmacoangiography or by hemodynamic studies using a dye dilution technique, as small arteriovenous shunts may remain undetected at angiography. Cardiac decompensation was not noted in our material, even though arteriovenous shunting within the hemangioma was seen in eight cases, suggesting that the shunt flow in renal hemangiomas usually does not reach levels high enough to impair the general circulation. Hypertension was present in only one patient, attributed to chronic pyelonephritis. Hematuria disappeared in all nine patients operated upon.


Medullary rays. Visualization during excretory urography.

The medullary rays are well-defined anatomic structures consisting of bundles of renal tubules which form in the renal cortex and continue through the renal medulla as the medullary striations. These structures are occasionally visualized during excretory urography in abnormal physiologic states characterized by tubular stasis and hyperconcentration of contrast material. Under these conditions, fine striations are visualized which correspond in position and orientation to these structures. The work of others has shown that in tubular stasis, contrast material is hyperconcentrated in the tubules. On microradiography in normal and obstructed kidneys, the highest concentrations of contrast material are seen in the lumen of collecting ducts. Lastly, retrograde injection of contrast material into the medullary rays produces a roentgen image similar to our illustrated cases.


The natural history of the upper renal tracts in adults following ureteroileal diversion (Bricker procedure).

The natural history of the upper tracts (170 renal units) of 87 patients undergoing total cystectomy and ileal loop diversion has been followed roentgenologically for up to seven years. The complications inherent in the procedure are illustrated and the appearances of new upper tract tumors demonstrated. Of 126 renal units which was obstruction of the anastomosis, seen in 29 units. The need for regular contrast material examination of the surgically modified upper tracts is emphasized.


The bleeding marginal ulcer. Catheterization diagnosis and therapy.

Superior mesenteric arteriography can often demonstrate actively bleeding marginal ulcers. Five cases diagnosed by angiography are reported. Pitressin infusions of the superior mesenteric artery stopped bleeding permanently in two cases, transiently in two cases, and was not attempted in one case. Pitressin infusions of the superior mesenteric artery should be attempted before surgery is performed for bleeding marginal ulcers.


Intracranial hemangiopericytomas. Angiography, pathology and differential diagnosis.

Intracranial hemangiopericytomas are tumors which angiographically and histologically can mimic other vascular intracranial masses. The term angioblastic meningioma has been applied to this tumor and to other vascular tumors. However, hemangiopericytomas have a unique biological behavior and prognosis as they tend to recur or metastasize and are insensitive to radiation. Hence, the importance of their specific recognition is emphasized. This is a report of the roentgenologic and pathologic fidings in five cases of histologically verified intracranial hemangiopericytomas. The angiographic findings common to these tumors include a myriad of tiny irregular feeding vessels springing from a main trunk, an intense fluffy type of stain, lack of early veins, and prolonged tumor circulation time. The major arterial supply is from the internal carotid or vertebral circulation rather than from external (meningeal) vessels. Differentiation from other vascular tumors particularly supratentorial hemangioblastoma, glioblastoma multiforme, as well as from vascular meningothelial meningioma is important from both the angiographic and histologic aspects.


Displacement of pontine arteries by fungating pontine astrocytomas.

Pontine astrocytomas may fungate, encircling the basilar artery and pontomesencephalic vein and intruding between these structures and the clivus. The tumor thus may prevent anterior displacement of these vascular structures against the clivus or produce paradoxical posterior displacement. However, the pontine arteries are usually swept forward by the tumor nodules to lie anterior to the basilar artery. These arteries are also stretched as they encircle the enlarged pons, losing their normal undulations. An increased posterior extent of the vessels may be seen, presumed due to hypertrophy or displacement or both. These findings seem highly specific for the diagnosis of fungating pontine astrocytoma.


Orifice-view roentgenography for evaluation of the aortic valve.

Plain orifice-view roentgenograms permit measurement of the area circumscribed by calcium in patients with heavily calcified aortic valves. The measurements relate well to the actual size of the orifice. Therefore, this roentgenographic technique serves in a practical fashion as a non-invasive method for the assessment of the severity of the aortic stenosis in such patients. During the injection of contrast material, orifice-view roentgenograms serve as a useful adjunct to standard aortography. Such views permit assessment of the valvular leaflets, size of the aortic ring, and the degree of stenosis.


Orifice-view roentgenography of the mitral valve.

The mitral valve can be visualized as if looking directly into the valvular orifice by obtaining roentgenograms directed obliquely through the heart at a 25 degree superior elevation, with the patient rotated 60 degrees in the right anterior oblique direction. This view was based upon trigonometrical calculations of the spatial orientation of the annulus of prosthetic mitral valves in 25 patients. Calculations based upon measurement in these patients indicate that the area of the orifice of the mitral valve can be shown with less than ten percent error due to distortion of the projected image in 80 percent of patients. During the injection of contrast material into the left ventricle, orifice-view roentgenorgram serve as a useful adjunct to satndard ventriculograms. Such views permit assessment of the size of the mitral annulus and the degree of stenosis. Plain orifice-view roentgenograms of heavily calcified mitral valves permit measurement of the area circumscribed by calcium in such patients. The measurements indicate an upper limit of the possible size of the functional orifice. Therefore, this roentgenographic technique serves in a practical fashion as a non-invasive method for the assessment of the severity of mitral stenosis in such individuals.


The reconstructed esophagus.

Reconstruction of the esophagus has been used for more than half a century. Benign as well as malignant diseases are treated in this manner. Viscera used for reconstruction are: colon, jejunum, and stomach. The different modalities of surgical intervention have been briefly summarized. Complications have been enumerated with the major ones stressed in more detail. The exact nature of surgical procedure should be known before attempting to evaluate roentgenologically a reconstructed esophagus. Preoperative roentgen evaluations, including barium study and angiography, are indicated for better postoperative results. Postoperative roentgen studies are needed to detect most of the postoperative complications.


The roentgenologic investigation of congenital subglottic stenosis.

Congenital subglottic stenosis, which is life-threatening to the infant, can be diagnosed by the correlation of the clinical and the roentgenologic findings. The main clinical sign is the persistence of stridor from birth. The indicative roentgenologic finding is a symmetrical narrowing of the subglottic segment which is constant in form and length during the various phases of the respiratory cycle. Two cases are presented, one confirmed by postmortem examination and the other by endoscopy. The etiology of this condition and the differential diagnosis are discussed.


The various forms of pulmonary varices. Report of three cases and review of the literature.

Ture pulmonary varices are congenital local dilatations of a pulmonary vein or veins, with normal or collateral transpulmonary drainage into the left atrium. Pulmonary varices do not cause pulmonary venous hypertension, but existing varices can further become dilated by pulmonary venous hypertension due to mitral valve disease. Embryologically, pulmonary varices may represent residual primitive splanchnic venous components incorporated into the pulmonary venous system, or atresia of an individual pulmonary vein which occurred at a time that enable adoption of unobstructed transpulmonary collateral drainage into the left atrium. True pulmonary varices do not produce symptoms, do not change in diameter over the years, and, usually, do not require treatment.


Evaluation of a method for quantifying the angiographic severity of major pulmonary embolism.

A method has been evaluated for the quantification of the angiographic severity of pulmonary embolism. There was close agreement between observers especially in the more severely affected cases. The method has been shown to be sensitive enough to demonstrate highly significant differences between treatment regimens and to assist in the selection of treatment at the outset.


Pathways of extrapelvic spread of disease: Anatomic-radiologic correlation.

Extrapelvic spread of disease, particularly from gastrointestinal tract perforations which may be clinically occult, may first present in the buttock, hip, thigh, and even lower leg, and the extraperitoneal space of the abdomen itself. Clinical manifestations at these remote sites may be very misleading. Anatomic and roentgenologic observations establish the preferential pathways of extrapelvic spread. These are related to the insertions and fascial investments of the iliopsoas, pyriformis, and obturator internus muscles and the ensheathed penetrations of the superior gluteal arteries. Superiorly, extension from the pelvic tissues seeks out the posterior pararenal compartment of the extraperitoneal region of the abdomen. Roentgenologic signs may first identify the presence, extent, and localization of the primary process.


Improved roentgenologic diagnosis of osteomalacia by microradioscopy of hand bones.

Microradioscopic study of metacarpals in 24 osteomalacic and 34 osteoporotic patients revealed excessive intracortical resorption (striations) in approximately 60 percent of patients suffering from osteomalacia, but in none of the osteoporotics. Phalangeal periosteal resorption was found less frequently in osteomalacia than metacarpal striations, and was absent in osteoporotics. On the other hand, quantitative evaluation of cortical thickness, percent cortical area, bone mineral mass, and density did not show any clear differences between the two study groups. It is concluded that the differential diagnosis between osteomalacia and osteoporosis may be considerably improved by microradioscopy of hand bones.


The association of cleidocranial dysostosis with hearing loss.

Three new cases of cleidocranial dysostosis with hearing loss are reported in this paper. The significant points concerning this association are: (1) the hearing deficit is predominantly a middle ear conduction problem secondary to structural abnormalities of the ossicles; (2) there is sometimes a small bone conduction deficit indicating either a cochlear or an eighth nerve problem; (3) the middle ear hearing loss was corrected surgically in one reported case; (4) there is dense sclerosis of the temporal bone which makes a middle ear operation technically difficult; and (5) hearing loss with cleidocranial dysostosis may be more common than the number of cases in the literature suggests.


Gastrointestinal manifestations of the muscular dystrophies.

Five patients with acute megacolon with varied types of progressive muscular dystrophy are presented. Dysfunction of smooth muscle among patients with muscular dystrophy is reviewed. The extra gastrointestinal roentgen features are summarized. Recognition of the diffuse smooth muscular involvement among patients with muscular dystrophy is stressed for proper diagnosis and patient management.


Transient post-vagotomy dysphagia: A distinct clinical and roentgenographic entity.

Dysphagia is a relatively infrequent complication of vagotomy in the postoperative period. The most common form is a transient post-vagotomy dysphagia which requires not treatment other than the temporary exclusion of solid food. Accurate diagnosis is possible on the basis of clinical history and typical roentgenographic findings. The onset of dysphagia characteristically occurs with the first ingestion of solid foods on the seventh to fourteenth postoperative days. A barium swallow examination reveals persistent tapered narrowing of the therminal three to four centrimeters of the esophagus. Most cases are relieved in two to six weeks without clinical or roentgenographic residua. Five cases of transient postvagotomy dysphagia are presented.


Localization with the EMI scanner.

Accurate localization of lesions seen on computerized tomographic scans obtained with the EMI unit is often difficult due to a paucity of reliable landmarks and to varying head angulation. A simple and accurate system of transposing the location of any particular lesion to a roentgenogram obtained with the scanner tube is described.


Spontaneous resolution of pancreatic pseudocysts: implications for timing of operative intervention.

Approximately half the clinical diagnoses of pancreatic pseudocysts will be erroneous if made during the acute phase of coexisting pancreatitis. Since self-limiting peripancreatic edema may clinically simulate pseudocyst, previous natural history information is subject to question. Occasional spontaneous resolution of a pseudocyst has been confirmed in five patients using serial ultrasound studies. It appears that although most pseudocysts maintain dimensional stability, a few may exhibit relatively rapid changes in volume. The pathophysiologic and surgical implications of these observations are discussed.