The serratus anterior muscle on chest radiographs. The radiographic appearance of the serratus anterior muscle shadow is analyzed. In frontal and near-frontal views, it produces a "bowling-pin" silhouette. When the muscle is well developed, the medial edge of this silhouette may be superimposed upon the air shadow of the lung in a variety of ways. When it overlies the apex of the lung, it gives rise to the companion shadow; when overlying the midlateral lung edge and costophrenic angle it may mimic pleural and/or extrapleural disease. Recognition of the various possible patterns is important to prevent overdiagnosis of disease, particularly asbestosis.


Sarcoidosis of the larynx.

Sarcoidosis of the larynx. Sarcoid involvement of the larynx is a rare but potentially life-threatening complication of systemic sarcoidosis. A classic, clinical, radiologic, and pathologic case is presented.


Acute bowing fracture of the fibula in an adult. Acute traumatic bowing of bone has only recently been recognized. Although most of these unusual fractures have been described in the pediatric forearm, bowing fractures of other juvenile long bones have also been reported. The authors describe a case of an acute bowing fracture of the fibula in a young adult.


Acute plastic bowing fractures of the fibula. Two cases of acute plastic bowing fractures of the fibula are described. A brief description of the mechanism of bone deformation under stress and the pathological cortical microfractures involved in bowing fractures is given.


Lymphangiography in staging of carcinoma of the prostate: the potential value of percutaneous lymph node biopsy. Bilateral pedal lymphangiography was performed in the staging of 208 patients with prostatic carcinoma. Forty-seven (23%) were found to have lymph node involvement, and 40 of these 47 had Stage C disease. Nine per cent of the Stage C1 patients (moderately advanced disease) and 37% of Stage C2 (massive carcinoma) had lymph node metastases. The distribution of the abnormal nodes was in continuity with the lymph node drainage from the prostate. The external iliac nodes were the most frequent site of metastases. Histological confirmation was obtained in 20 of the 40 positive Stage C2 cases. More recently, percutaneous aspiration biopsy of the opacified nodes was used to document the presence of metastic disease, thereby extending the value of lymphangiography.


Percutaneous transperitoneal lymph-node biopsy as a means of improving lymphographic diagnosis. Percutaneous transperitoneal fine-needle lymph-node biopsy was performed in 52 patients to establish a diagnosis of metastatic disease in nodal defects detected during lymphography. The procedure was found to be highly accurate, with few false-negatives and no false-positives.


Pneumonia of atypical measles.

Pneumonia of atypical measles. Infection with rubeola virus after previous immunization with killed measles virus vaccine produced abnormal chest radiographs in 9 patients. Variable pneumonic consolidation occurred in all cases and was mainly lobar or segmental in distribution. Four patients had hilar adenopathy, 3 pleural effusion, and in 1 instance a pulmonary nodule remained 9 months after clearing of the acute pneumonia. Atypical measles pneumonia is a presumed hypersensitivity response in incompletely immunized patients.


Hamartoma (mesenchymoma) of the chest wall in infancy. Chest wall hamartoma, commonly known as mesenchymoma, is very rare in infants and usually present at birth. This lesion is a focal overgrowth of normal skeletal elements, Histologically, it is benign. The radiographic appearance is that of a partially mineralized extrapleural mass involving one or more ribs. Surgical ablation seems to be the proper treatment and is curative. Nine cases of this condition are presented, including long-term follow-up in 4.


Polyvinyl foam embolization of vascular and neoplastic lesions of the head, neck, and spine. Embolization of vascular and neoplastic lesions of the head, neck, and spine may be performed either as primary therapy (particularly for lesions which are difficult to approach surgically) or preoperatively to decrease blood loss. Polyvinyl alcohol foam (PAF) offers a number of advantages over other embolic material, including biocompatibility, promotion of progressive thrombosis and fibrosis, permanence, compressibility, and manageability. The clinical cases illustrate the kinds of lesions that are amenable to embolization, including arteriovenous malformations, arteriovenous fistulas, meningiomas, and nasopharyngeal tumors. Techniques and possible complications are discussed.


Cerebral thrombosis associated with Amicar therapy. Amicar (epsilon-aminocaproic acid) has been used in patients with subarachnoid hemorrhage to promote clotting. However, cerebral thrombosis has been reported in various vascular compartments following its use. The authors describe 2 patients who had cerebral angiography after Amicar therapy and demonstrated thrombosis unrelated to vascular spasm or technical complications of angiography. Careful screening is needed in patients treated with Amicar to determine if an increased risk of thrombosis exists.


Computed tomographic positive contrast peritoneography. Despite the use of intravenous and oral contrast material and antiperistaltic pharmaceuticals, abdominal computed tomography has limitations in the morphological study of the gastrointestinal tract, retroperitoneum, and pelvis. To better define these regions, positive contrast material was infused into the peritoneal space prior to abdominal CT. Results included: improved visualization of the peritoneal cavity and its contents; evident demarcation between the retroperitoneal space and intraperitoneal structures; sharp delineation of serosal surfaces of the bowel and solid viscera; and an obvious distinction between impinging bowel loops and pelvic organs.


Gray-scale ultrasonic features of ovarian teratomas. Forty patients with pelvic masses were examined with ultrasound; surgical exploration subsequently revealed an ovarian teratoma. The echographic appearance of the lesions was extremely variable. Although a number of characteristic features of teratomas have been described (axial location, solid mural component, acoustic shadow, and "hair/fluid level"), these occurred only in a minority (17/40) of patients. When the clinical setting suggests an ovarian teratoma, the ultrasonographer should consider it regardless of the internal architecture and consistency of the mass.


High-resolution ultrasonography of scrotal pathology. A prototype high-resolution (10-MHz) real-time ultrasonic system was used to study 22 patients who were ultimately proved to have intra- and extratesticular tumors, scrotal fluid collections, and inflammatory processes. In 5 of 6 patients with primary testicular masses, there were areas of decreased echogenicity within the testis when compared with surrounding normal tissue. In general, the method was highly effective in differentiating and characterizing testicular and extratesticular processes.


67Ga scanning in the evaluation of esophageal carcinoma. Eighty-nine patients with histologically proved esophageal carcinoma were scanned with 67Ga to screen for extramural tumor extension and lymph-node involvement. Radiation dose and reduction of uptake were correlated. 67Ga accumulation indicated extramural extension with a sensitivity of 67% and a specificity of 93%. Marked uptake in an extraprimary site in the mediastinum or upper abdomen indicated lymph-node involvement with a sensitivity of 27% and a specificity of 100%. Irradiation with more than 20 Gy (2,000 rad) reduced uptake (P less than 0.05). 67Ga scanning appears to be useful in the evaluation of esophageal carcinoma.


Scintigraphic features of nonosteogenic fibroma. Three cases of nonosteogenic fibroma or fibrous cortical defect are presented which demonstrated scintigraphic findings of minimal to mild increased uptake of bone-seeking radiopharmaceutical and thus helped to distinguish these lesions from other benign or malignant abnormalities. The authors suggest that the two types of lesion are not fundamentally different from one another.


The opossum as an animal model for studying radiation esophagitis. Six opossums were evaluated as a possible animal model of radiation esophagitis. In a single exposure to the esophagus, four animals received 60Co radiation of various doses; two served as controls. Pre- and postirradiation evaluations using fiberoptic endoscopy, mucosal biopsy, barium esophagography, and manometry were performed. Esophagitis developed at one week in irradiated animals. Opossums receiving 17.5, 20, and 22.5 Gy (1,750; 2,000; and 2,250 rad) became anorexic one week postirradiation, and abnormal motility subsequently developed. The controls and the animal receiving 15 Gy (1,500 rad) remained normal. Histological changes in the irradiated opossum esophagus resembled those found in humans.


Light output and x-ray attenuation measurements at mammographic beam qualities for nine commercial intensifying screens. X-ray attenuation and intensity of light emitted were measured for nine intensifying screens used in mammography. Incident beam qualities with half value layers in the range of 0.38 to 2.68 mm Al were used to simulate the range of clinical conditions encountered in mammography. All the screens attenuated the x-ray beam to a similar extent at these beam qualities, but a wide variation in the intensity of light emitted was observed. The interrelation of the measured physical parameters in determining both the system speed and noise properties is discussed.


Magnification mammography: a low-dose technique. Image quality and radiation exposures of a mammographic technique using direct radiographic magnification at 2 X with a microfocal spot x-ray tube and a fast, double screen-film system were compared to those of conventional contact mammography with a rare-earth screen and molybdenum target tube. The results indicate that the magnification technique yields improved detection of microcalcifications and comparable visualization of soft-tissue details, with a large reduction in radiation exposure. This technique has demonstrated the feasibility of carrying out high-quality mammography with an entrance dose of 1.35 X 10(-3) Gy (135 mrad) for the average breast.


Modification of radiation-induced pulmonary fibrosis in rats. Male rats received 25 Gy (2,500 rad) of gamma rays to the right hemithorax and were killed three or six months later. Microscopic pulmonary abnormalities developed sooner and progressed more rapidly in animals given control feed than in those given the collagen antagonist D-penicillamine (10 mg/day, p.o.). Three and four months after irradiation, hypoperfusion and radiographic hyperlucency of the right lung were observed in both the treated and control animals.


Comparison of the protective action of glutathione and cysteamine on radiation-induced mitotic delay in cultured S-5 cells. The protective effect of glutathione (GSH) and cysteamine (MEA) on radiation-induced mitotic delay in cultured mammalian L-5 cells was studied. Cells treated with 20 mM of GSH during irradiation with 2 Gy (200 rad) showed faster recovery of the mitotic index than control cells irradiated without chemical treatment; however, GSH had no effect on mitotic delay time. Inhibition of mitosis was observed with 80, 100, and 120 mM of GSH. Cells treated with 5 mM of MEA during irradiation also showed faster recovery of the mitotic index than the controls, but in addition the delay time was shortened. Progression of G2-phase cells treated with 5-fluorouracil to mitosis after irradiation was protected by MEA but not by GSH. Progression of S-phase cells labeled with 3H-thymidine to mitosis was accelerated by both agents during irradiation.


Irradiation of the microvasculature with fast neutrons. Single- and split-dose irradiation of the eyes of dogs was performed with cyclotron-produced polyenergetic neutrons at a rate of about 0.2 Gy (20 rad) per minute. Neovascularization was subsequently induced surgically in the avascular corneas and stimulated for 7 days to study the response of slowly proliferating capillary endothelial cells. Corneal tissue samples were evaluated quantitatively by morphometric methods. A dose-response curve was drawn by plotting per cent capillary volume versus dose. D0 was 2 Gy (200 rad), and the recovery ability was determined to be equivalent to 1.3 Gy (130 rad). Depending on the level of damage, relative biological effectiveness (RBE) values were 1.9 to 2.3.


Transmission computed tomographic diagnosis of experimentally produced acute pulmonary vascular occlusion in the dog. Acute experimental pulmonary arterial occlusions were produced in 5 dogs. The chest was subsequently imaged with computed tomography (CT), 99mTc-MAA scintigraphy, and plain radiography. Gamma images revealed all 6 lesions, and plain radiographs were uniformly negative. Enhanced CT scans demonstrated 3 of 5 lesions, and unenhanced scans revealed 1 of 6. CT findings were variable.


Heparin-induced thromboembolism: angiographic features. Angiographic evaluation of heparin-induced thromboembolism in 3 patients who suffered disastrous consequences revealed a distinctive radiographic appearance consisting of mural filling defects quite unlike atheromatous plaques. These lesions were broad-based, isolated, gently lobulated excrescences which produced 30-95% narrowing of the arterial lumen. In eache case, the lesions were located proximal to sites of arterial occlusion.


Desferoxamine mesylate (Desferal): a contrast-enhancing agent for gallium-37 imaging. Desferal (desferoxamine mesylate) was investigated as a contrast-enhancing agent for tumor and abscess imaging with 67Ga-citrate. Tumor studies were performed in mice with Cloudman S-91 melanoma. Abscess studies were performed with a subcutaneous abscess model in rabbits. When Desferal is administered 16 to 18 hours after injection of 67Ga, rapid blood clearance of 67 Ga occurs with only slight (tumor) or no (abscess) loss of activity from the lesion. Retention in other organs is variable. Tumor-to-blood ratios are improved eightfold in tumor and fourfold in abscess in studies performed with single Desferal injections of 150 mg/kg. Blood and total body clearance studies in rabbits reveal that maximum Desferal effect is achieved in the 17 to 50 mg/kg dose range and that only minimal improvement occurs at higher doses.


Ultrasonic measurement of the fetal ventricular system. The ventricular systems of 178 fetal heads, ranging from 13 weeks gestation to term, were examined with ultrasonic "B" scans. The width of the frontal horns and of the third ventricle was measured. The distances between the temporal horns and between the sylvian fissures were also examined. The most important clinical measurement is that of the frontal horns. The combined width of the two frontal horns averaged 1.1 cm at 13 weeks and grew to an average of 2.4 cm at term. The 99% upper limits of confidence for these measurements were 1.45 cm and 2.78 cm, respectively. The frontal horn to BPD ratio decreased from 0.48 at 13 weeks to 0.25 at term. These measurements are considered important for the evaluation of possible ventricular dilatation in utero.


Real-time high resolution ultrasound in the detection of biliary calculi. A high-resolution real-time ultrasound sector scanner was used in the evaluation of patients with suspected gallbladder disease. This technique is noninvasive, requires minimal preparation, and takes less than five minutes for a thorough examination of the gallbladder and related anatomy. In 17 months, 959 patients were examined for suspected gallbladder disease and the gallbladder was adequately visualized in all but 5 patients. Follow-up information was obtained from surgery in 153 cases. There were 132 true-positive studies, 15 true-negative, 5 false-negative and one-false positive study. In a correlative study with oral cholecystography, calculi were detected ultrasonically in 5 cases that had been missed on the oral cholecystogram.


The effect of penicillamine on radiation-induced pulmonary lethality in mice. The collagen inhibitor D-penicillamine was evaluated as a potential radiation reaction preventive agent by studying its effect on deaths attributed to pulmonary damage in mice. Long-term administration of D-penicillamine at a rate of 100 mg/kg/day had no significant effect on the LD50/160 in mice following pulmonary irradiation.


Low-reflectance eyeglass lenses: a viewing aid to radiologists. Low-reflectance coatings can significantly improve the low contrast resolution (MTF) of eyeglass lenses. The reflectance per surface can be reduced from 4.25% for uncoated lenses to 0.5% for multi-layer coated lenses. The radiologist who wears glasses will note improved viewing comfort with coated lenses and possibly a reduced error rate.


Simplified solid-particle embolization with a new introducer. A new and simple introducer for solid embolic particles consists of teflon tubing sized to prevent particle overriding, coupled with a backflow-limiting end adaptor, and has sterilization caps. The size-coded introducers can be of a preselected diameter and easily introduce from 1 to 30 emboli at a time.


Radiation measurement with a solid-state-matrix camera. A solid-state-matrix camera containing 32 X 32 photodiode array served as the output device on an image intensifier tube. The resulting images had poor spatial resolution but permitted precise measurement of x-ray intensity. Transmission differences of 1% were detectable.


The pediatric tracheostomy: simple roentgen studies of morphology and function. Following tracheostomy, simple roentgen studies coordinated with decannulation permit accurate evaluation of the pediatric patient. These studies require alertness to the child's clinical condition as well as a selective, monitored roentgen technique. The conventional lateral neck radiograph and the high-kV frontal tracheogram complete the evaluation in most cases. Fluoroscopy and xerography can be of additional value if decannulation is difficult, though xerography should be used only to confirm the presence of a granuloma seen on the conventional radiograph.


Smooth muscle tumors of the stomach and small bowel. Smooth muscle tumors of the stomach and small bowel, although rare, have a favorable prognosis when recognized and treated promptly. This review of 33 patients with leiomyoma, leiomyblastoma, or leiomyosarcoma of the stomach and small intestine reveals that all but two were treated by resection of the tumor, with good results.


Electroconvulsive therapy: an overview.

Electroconvulsive therapy: an overview. Modifications in technique, including the use of anesthesia and muscle-relaxing drugs, make electroconvulsive therapy safe and easy to administer. There are few contraindications, complications are rare, and efficacy is well-documented.


Kidney neoplasms.

Kidney neoplasms. The author reviews the diagnosis and treatment of carcinoma of the kidney. Surgery remains the most effective therapy. The management of metastatic disease is discussed.


Rupture of the uterus following treatment with 16-16-dimethyl E 2 prostaglandin vagitories. Rupture of the uterine body was found after induction of therapeutic abortion with vaginal suppositories containing 16, 16-dimethyl prostaglandin E 2 in a 20-year-old primigravida. A short discussion is given on the cervical complications that can occur after prostaglandin induction of abortion, stating that rupture of the uterine body also can be seen. So far, no prostaglandin compound seems to avoid such complications.


Cervical ripening prior to induction of labor (intracervical application of a PG E2 viscous gel). In 38 pregnant patients at term with unfavorable cervices labor induction was initiated with PG-E2 after a preceding intracervical application of 0.1, 0.2 or 0.3 mg PG-E2 in 1 ml viscous gel. The mean Bishop score improved from 3.36 to 7.0 in an average time of 2 h 37 min. The cervical diameter increased from 14 mm to 22.7 mm. 31 patients delivered their babies spontaneously, while 7 patients were delivered by cesarean section due to cervical dystocia and delayed labor. Fetal outcome was normal in all cases, with an average Apgar score of 8.7 and an average pH-value in the umbilical artery of 7.245. The study indicates that local application of PG-E2 induces cervical dilatation, and is of particular use in patients presenting a low Bishop score. A possible local effect of PG E2 is discussed.


Relationship between seminal PGE and 19-OH PGE and seminal fructose in man. Seminal PGE, 19-OH PGE and fructose were assayed in normal volunteers and in infertile patients. From data obtained it appears that seminal PGE are probably not synthesized exclusively at seminal vesicles level since no relationship was observed between PGE and fructose. On the other hand the seminal vesicles appear to be the preferential site of seminal 19-OH PGE production since a close relationship was observed between 19-OH PGE and fructose in those case in which these prostaglandins were below minimum normal values. Various hypotheses are advanced in order to interpret the lack of correlation in the presence of high 19-OH PGE levels.


Lysozyme in amniotic fluid during rivanol-induced second trimester abortion. The concentrations of lysozyme and free arachidonic acid in amniotic fluid were determined in eight patients during induction of second trimester abortion. Abortion was induced by extraamniotic instillation of 150 ml 0.1% Rivanol. Lysozyme increased in all patients during the induction reaching significancy after 60% of the induction-abortion time. This suggests a leakage of lysosomal enzymes from the fetal membranes. Free arachidonic acid relative to total free fatty acids increased parallell to lysozyme.


Influence of the arachidonic acid cascade on the in vitro hepatic response to hypoxia. Studies were undertaken to determine the effect of arachidonic acid, the precursor of bisenoic prostanoic acid derivatives, on the response of the isolated, perfused rabbit liver to hypoxia. Two and one half hours of severe hypoxia resulted in significant increases in hepatic vascular perfusion pressure, tissue wet weight, and the rates of cellular loss of lactic dehydrogenase, malic dehydrogenase, and acid phosphatase into the perfusing medium. Hypoxia also increased the rate of hepatic PGF2 alpha production by 25% after 2 1/2 hours (p less than 0.05, hypoxia vs sham). The addition of arachidonic acid (0.1 microgram/g/min for 150 minutes) to the perfusion medium of hypoxic livers significantly attenuated the changes in perfusion pressure, tissue wet weight, and loss of cellular enzymes. Arachidonic acid administration increased the rate of PGF2 alpha production by 100% (p less than 0.05, sham vs hypoxia + arachidonic acid) within 30 min after hypoxia and maintained this rate for the duration of the study. These results demonstrate that hypoxia mediated prostaglandin F2 alpha synthesis in the rabbit liver can occur in the absence of neural and blood borne components and that significant activation of the arachidonic acid cascade via the administration of exogenous arachidonic acid has a salutary effect on hepatic hemodynamics and cellular integrity during hypoxia.


Does 15-hydroxy prostaglandin dehydrogenase contribute to prostaglandin inactivation in brain? 15-Methyl prostaglandin E2, a compound which is not a substrate for 15-hydroxy prostaglandin dehydrogenase, is a more potent pyretic agent than prostaglandin E2 when injected into the third ventricle of conscious cats. This finding raises the possibility that 15-hydroxy prostaglandin dehydrogenase contributes to prostaglandin inactivation in brain, notwithstanding its low activity.


Prostaglandin synthesis in isolated glomeruli. Prostaglandins are thought to play an important role in the local regulation of glomerular blood flow and in the release of renin from the juxtaglomerular apparatus. We therefore examined prostaglandin synthesis by isolated rat glomeruli. Isolated glomeruli were either prelabeled with [14C] arachidonic acid or were incubated with [14C] arachidonic acid for the entire experimental incubation in Krebs buffer. Prostaglandin synthesis was determined by thin layer radio-chromatography of acid extracts of the supernatant solutions. Indomethacin inhibitable synthesis of small amounts of 6-keto-PGF1 alpha, the metabolite of prostacyclin (PGI2,) and larger amounts of PGF2 alpha, and PGE2, and possibly thromboxane B2 (TXB2) by isolated glomeruli could be demonstrated with either prelabeling or direct incubation. These findings support the hypothesis that prostaglandins are produced within the glomerulus where they may affect local glomerular blood flow and function.


Effect of low and high methional concentrations on prostaglandin biosynthesis in microsomes from bovine and sheep vesicular glands. The effect of methional on prostaglandin biosynthesis from 5,8,11,14-eicosatetraenoic acid was studied with microsomes from both bovine vesicular glands (BVG) and sheep vesicular glands (SVG). Ethylene was identified when methional was added to the fatty acid-microsome incubation systems showing that oxygen centered radicals such as hydroxyl radical were generated during incubation. A low methional level, 1 mM, enhanced the rate of prostaglandin biosynthesis in both BVG and SVG. A high methional level, 10 mM, inhibited prostaglandin biosynthesis in both BVG alone and SVG solubilized with 1% Tween 20. The inhibitory effect of 10 mM methional was reversed by lyophilization. These data suggest that oxygen centered radicals are used in prostaglandin biosynthesis even though they inactivate the enzyme complex.


Comparison of the effects of prostaglandins E1 and A1 on coronary occlusion induced arrhythmia. The present study compares the effects of PGE1 and PGA1 on ventricular arrhythmias following coronary artery occlusion. The left anterior descending coronary artery (LAD) was occluded abruptly in 55 cats anesthetized with alpha-chloralose. Lead II of the ECG along with arterial blood pressure were monitored for one hour after occlusion. Either vehicle or prostaglandin was infused into the left atrium (LA) or femoral vein (IV) 15 min prior to and for 1 hour after LAD occlusion at a rate of 0.15 ml/min. Prostaglandin was infused at either a high dose (1.0 microgram/kg/min) or a low dose (0.1 microgram/kg/min). Infusion of either PGE1 or PGA1 produced a marked fall in blood pressure and heart rate which returned toward control before occlusion. Abrupt occlusion of the LAD produced ventricular arrhythmia in all cats ranging from ventricular premature beats to ventricular fibrillation (VF). The control animals had a 38% incidence of VF. VF occurred in 75% of the animals in which PGE1 was administered into the LA at either the high or low dose while the occurrence in those administered PGA1 was 67% and 50%, respectively. Intravenous administration of the high dose of PGE1 or PGA1 resulted in VF in 13% and 67% of the animals after LAD occlusion, respectively. These data indicate that the IV administration of PGE1 may protect the heart from VF while the infusion of PGE1 or PGA1 into the LA may enhance VF after LAD occlusion.


Cancer growth, response to treatment and survival time in mice: beneficial effect of the prostaglandin synthesis inhibitor flurbiprofen. Adult mice were injected subcutaneously with cells from a syngeneic metastasizing mammary cancer. Daily treatment with flurbiprofen starting before injection of the cancer cells reduced tumour growth and lengthened the survival of mice whose tumours were excised at 3 weeks. When low doses of radiotherapy and chemotherapy were given, additional treatment with flurbiprofen starting 25 days after injecting the cancer cells substantially inhibited tumour growth.


Effect of prostaglandins E1, E2 and F2alpha on neutrophil aggregation. Recently we have found that chemotactic factors stimulate neutrophils in suspension to aggregate. Because of an obvious analogy to platelet aggregation, we examined the influence of three prostaglandins on this process. Prostaglandins E1, E2 and F2alpha alone did not cause aggregation of the neutrophils but were able to partially inhibit the aggregation response induced by the synthetic chemotactic tripeptide, formyl-methionyl-leucyl-phenylalanine. The minimal inhibitory concentrations for prostaglandins E1, E2 and F2alpha were 10(-7), 10(-6) and 10(-5)M, respectively. These results are similar to those found for the prostaglandin-induced inhibition of platelet aggregation. It may be, therefore, that neutrophil aggregation, like platelet aggregation, is modulated by intracellular prostaglandins and other products of arachidonic acid metabolism.


Synthesis of the sultam analog of 11-deoxy PGE2. As an extension of our work on the series of N-alkylmethanesulfonamidoheptanoic acids, we have prepared the cyclic-sulfonamide (sultam) analog of 11-deoxy PGE2. Although numerous publications have described the introduction of heteroatoms into the 5-membered ring of the prostaglandins, the cyclic-sulfonamides have remained a heretofore unexplored class. The synthetic scheme for the preparation of this unique PG analog is presented in this paper.


Effects of prostaglandin E1 and indomethacin on fetal and neonatal lamb mesenteric artery responses to norepinephrine. The effects of prostaglandin E1 (PGE1) and indomethacin on isolated fetal and neonatal lamb mesenteric artery responses to norepinephrine were investigated. PGE1 (1.5 micrometer) significantly reduced vasoconstriction responses to 0.5 to 5 micrometer norepinephrine. Indomethacin (1 micrometer) markedly potentiated the constrictor effects of 0.5 to 10 micrometer norepinephrine. PGE1 prevented the potentiating effect of indomethacin. Neither PGE1 nor indomethacin altered basal muscle tension. These results suggest that endogenous PGs modify adrenergic responses in the isolated mesenteric arteries of preterm and newborn lambs.


The 8-isoprostaglandins: evidence for eight compounds in human semen. Evidence is presented for the existence of a group of 8-iso prostaglandins in human semen, comprising 8-iso PG E1, 8-iso PG E2, 8-iso PG F1 alpha, 8-iso PG F2 alpha and the four corresponding 19-hydroxy prostaglandins. The E and F compounds have been positively identified by comparison of their mass spectra and chromatographic properties with those of authentic standards. Preliminary measurements of levels of these compounds in pooled semen are presented.


On the mechanism of action of 15-methyl-PGF2 alpha as an abortifacient. Several hours following administration of long acting vaginal suppositories containing 3.0 mg of 15-methyl-PGF2 alpha for interruption of second trimester pregnancies there is an up to 10-fold increase in endogenous production of PGE2 and PGF2 alpha before abortion as reflected by gas chromatographic-mass spectrometric determination of the major plasma metabolites of PGE2 and PGF2 alpha. The data suggest that this increased formation of endogenous prostaglandins contributes to the induced uterine activity during the latter part of the abortion process.


The mechanism of prostaglandin action on the pregnant human uterus. The concentrations of 15 methyl PGF2 alpha, progesterone and estradiol in the peripheral plasma were assayed sequentially and the resting and active pressures of the uterus were quantitated in 10 first trimester pregnant patients, treated with a vaginal suppository containing 3 mg U-36,384. The purpose of the study was to determine the sequence of the prostaglandin induced changes in regulatory profile and uterine function and thus expose further the mechanism of prostaglandin action. The temporal relationships of the changes revealed that the primary action of exogenous prostaglandin is the disruption of the normal endocrine function of the conceptus and that the delayed oxytocic effect of this compound is secondary, a consequence of the primary action. Apparently prostaglandins are only effective as postconceptional agents if they convert the refractory normal pregnant uterus into a reactive organ. The academic and therapeutic significance of this finding is discussed.


Luteolytic prostaglandins. Synthesis and biological activity. Analogues of PGF2 alpha with enhanced luteolytic activity were synthesized using the Corey synthesis. The luteolytic activity of the new prostaglandins was tested in the hamster. In addition the smooth muscle activity of the new compounds was compared with that of PGA2 on the longitudinal strip of rat stomach fundus. Structure-activity relationships in the new series of 17,18,19,20-tetranor-16-thienyl-oxy-PGF2 alpha are discussed.


Neutron activation analysis of selenium and 17 elements in sediment. Instrumental neutron activation analysis was performed to determine Na, Mg, Al, Cl, Sc, V, Cr, Mn, Fe, Co, Ni, Rb, Sb, Cs, Ba, Ce and Eu in the Pacific core sediment. Selenium was also determined by neutron activation analysis, by applying a solvent extraction method with 2,3-diaminonaphthalene (DAN) as a post-irradiation procedure, after the wet-ashing of the sediment. Homogeneity of trace constituents in the sediment and neutron flux corrections for accurate determination were also investigated.


Clinical evaluation of thyroid imaging with 201T1-chloride. Clinical value and limitation of thyroid imaging with 201T1Cl were studied. The positive rate of 201T1 was 82% in 22 malignant thyroid lesions and 46% in 37 benign lesions. A 201T1 positive image was obtained when a lesion was parenchymatous and a 201T1 negative one when it was cystic, filled with colloid or hyaline and had massive necrosis or bleeding. Thus 201T1Cl localized in a parenchymatous lesion and did not in a nonparenchymatous one regardless of a malignant or benign disease. An increasing positive lesion in contrast with the surrounding thyroid tissue implies that it may be malignant and a decreasing one benign as a results of review of serial scintiphotos. Scintigraphic methods with 131I and 201T1 are complementary each other and a 201T1 negative image itself has a high diagnostic value but it seems to be better to attach much value to the finding of imaging with 131I when a 201T1 positive image is obtained.


[Coprecipitation of rare earth elements with hydroxyapatite (author's transl)]. The distribution behavior of trace rare earth elements between an aqueous phase and hydroxyapatite crystals was investigated. The apatite prepared by adding phosphate ion extremely slowly to an aqueous solution containing calcium, rare earth elements, ethylenediamine and nitrilotriacetate ion at 80 degrees C. Apparently the coprecipitation reaction seems to be anomalous, because the apparent distribution coefficient did not have a constant value through the reaction. But when the true distribution coefficient was calculated by using the thermodynamic data at 80 degrees C, it was revealed that rare earth ions were coprecipitated obeying logarithmic distribution law. The true distribution coefficient values of tervalent yttrium, scandium, europium and cerium ions were about 10(7.3), 10(9.8), 10(7.4) and 10(6.5), respectively.


Role of the hypophysis in thyroid regeneration after partial thyroidectomy. The role of the hypophysis in thyroid regeneration was investigated by measuring the mitotic activity of the thyroid remnant in hemithyroidectomized rats as well as the blood levels of thyroid hormone at various time-intervals after hemithyroidectomy. Mitotic activity underwent a significant increase to reach a peak (a 5- to 8- fold increase) 2 days after hemithyroidectomy. The thyroid hormone level in blood was lower than in controls. Histologically, the thyroid gland showed signs of an elevated rate of functional activity, as indicated by losses of colloid and cell hypertrophy. In a second approach, the mitotic activity of the thyroid remnant was estimated in hypophysectomized and in thyroxine treated rats. Both hypophysectomy and thyroxine injection prevented occurrence of the mitotic peak at 2 days. The regeneration of the thyroid after hemithyroidectomy, as it occurred in the present work, may be explained by a release of thyroid stimulating hormone from the pituitary, brought about by the low level of circulating thyroid hormone, itself resulting from a loss of thyroid tissue.


[Relationship between anatomical structure and metabolism of plant tissues. I. Differences between the qualitative and quantitative composition of phenolic substances of apple explants and that of callus and cells produced by the culture]. Relationship between anatomical structure and metabolism of plant tissues. I. Differences between the qualitative and quantitative composition of phenolic substances of apple-fruit explants and that of calli and cells cultured from these explants. Phenolic compounds of intact apple-fruits (CV. Golden delicious), fruit fragments cultured on agar medium, newly formed calli and cell suspensions prepared from these calli, were studied quantitatively and qualitatively. The phenol content of the tissues decreased during the first days of culture, then recovered practically the initial level just before the initiating calli became visible. This content is very low in the calli and in the cultured cells. But the most remarkable result is that the qualitative compositions of the phenols extracted from the fruit tissues, the calli and the cells were different : p-coumaryglucose, which is abundant in the fruit, disappeared almost completely in the calli, in which three compounds were formed de novo, X1 which was tentatively identified as ferulylquinic acid, X2, a glycoside of p-coumaric acid different from p-coumarylglucose, and X3 not yet identified; the cells synthesized also X1 and X3 but not X2, and contained no p-coumaryglucose while feruylquinic acid was abundant. The study on the processes of induction or regulation of the enzymes implied in these metabolic modifications is under way.


The effect of luminance upon the distribution and behavior of the Eleotrid fish Gobiomorus dormitor, and its prey. Gobiomorus dormitor success in capturing prey, cichlids, poeciliids and atherinids, is correlated with low luminance. Both prey and predator populations inhabiting rocky areas in Lake Jiloa, Nicaragua shift to deeper water during the dry season when luminance is greater. Predator and prey populations are also deeper over bright sandy areas than over rocks. Predators, during the middle of the day, attack prey significantly less in water above 3 m than in water between 3-12 m, but there is a significant increase in the number of attacks occurring above 3 m at twilight. The predator becomes more active, and the prey disappear into holes at twilight. These data suggest that conclusions concerning the importance of light in structuring the community and behavior of marine fishes can be generalized to tropical freshwater systems.


Diel locomotor activity pattern of juvenile Limulus polyphemus Linnaeus. Ten juvenile Limulus polyphemus, tested individually for 3-day periods in electronic shuttleboxes, exhibited a nocturnal activity pattern; activity was four times as great at Night as during the Day.


Behavioral thermoregulation in the grass shrimp Palaemonetes vulgaris (Say). Grass shrimp (Palaemonetes vulgaris) tested in a horizontal linear gradient trough exhibited a modal final thermal preferendum of 27 degrees C, and voluntarily occupied a 24-31 degrees C range.


[Ultrastructure of the mid-intestine muscle of the larva of Calliphora erythrocephala Meig]. The fine structure of the mid-gut muscle in larval Calliphora Erythrocephala Meig. Electron microscopy reveals and mid-gut muscle fibres to be composed of an array of actin and myosin myofilaments. The perforated Z-band divides the fibril to sarcomeres. The average length of the sarcomere in 5,34 micrometer for the non contracted muscle and 2,09 micrometer for the fully contracted muscle. The thick filaments of the fully contracted muscle pass through the spaces of the Z-structures.


Nylidrin: a potent anti-hypertensive agent in hypertensive rats. Nylidrin HCl lowered the blood pressure and increased the heart rate of conscious, spontaneously hypertensive rats (SHR), Goldblatt hypertensive rats, and DOCA hypertensive rates. In SHR, the minimum effective dose was 0.5 mg/kg, s.c. At that dose, the anti-hypertensive activity of nylidrin lasted more than 3 hours. Propranolol reversed both effects on blood pressure and heart rate by nylidrin, whereas atenolol, a specific cardiac beta 1 blocker, only blocked or reversed the tachycardia caused by nylidrin but did not block the anti-hypertensive effect of the compound. In normotensive rats of Wistar/Kyoto strain (WKY) and Holtzman strain, nylidrin at 5 or 10 mg/kg, s.c., produced a transient hypotensive effect which lasted less than an hour and tachycardia that persisted for several hours. In WKY, atenolol prolonged the hypotensive activity of the compound by partially reversing the tachycardia. These observations indicate that SHR is more sensitive than WKY to the anti-hypertensive activity of nylidrin, which is probably caused by vasodilatation mediated by beta 2 receptors.


Delayed sexual maturation in female C57BL/6J mice prenatally exposed to alcohol. Prenatal exposure of mice to alcohol during days 5 to 11 of gestation resulted in delayed sexual maturation as measured by the time of vaginal opening. Data from some of these mice suggest that vaginal epithelial differentiation may also be altered.


Renal anomalies in mice prenatally exposed to ethanol. The current observations confirm and extend earlier data demonstrating the deleterious effects of ethanol in the C57BL/6J mouse. Ethanol given to pregnant mice from gestation-day 5 to gestation-day 11 reduced the number of mice going to full term, decreased the number of pups per litter, and lowered the birthweight of the live pups. Prenatal exposure to ethanol also produced a high incidence of hydronephrosis in the offspring.


Post mortem stability of catecholamines in discrete regions of rat brain. Male Sprague-Dawley rats (200-300 g) were sacrificed by cervical dislocation and left either at room temperature (21-23 degrees C) for periods of 1, 2, and 4 hours or in the refrigerator (4-5 degrees C) for periods of 1, 2, 4, 8, 16, and 24 hours. The brains were left in the intact animals in order to stimulate human autopsy materials. At the end of each period, the rat was decapitated and the brain removed and immediately dissected into the following regions: cerebral cortex, striatum, midbrain, pons and medulla, and cerebellum. The levels of norepinephrine (NE) and dopamine (DA) in brain regions were determined fluorometrically. In animals kept at room temperature the level of NE decreased gradually with time reaching 61%, 76%, 68%, and 68% of control in the cerebral cortex, midbrain, pons and medulla, and cerebellum at 4 hours post mortem respectively. Striatal DA reached 61% of control at 2 hours and remained the same at 4 hours post mortem. The NE level declined at a slower rate in brain regions obtained from refrigerated animals, reaching 65%, 81%, 77%, and 77% of control in cerebral cortex, midbrain, pons and medulla, and cerebellum at 24 hours post mortem. Striatal DA reached 54% of control at 16 hours and showed no further decline at 54 hours post mortem. There was a significant post mortem decrease in NE and DA levels in all brain regions examined, however, the rate of this decline varied from region to region. The tissues obtained from refrigerated animals showed statistically less of a decline in amine levels.


Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide. To investigate the pathophysiologic mechanisms of nicekl-induced erythrocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of alpha Ni3S2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 hr intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was congruent to 20 I.U./liter of serum. In mice which received pooled serum from alpha Ni3S2-treated rats, erythrocyte 59Fe-uptake averaged 28% (S.D. +/- 5) (vs 3.7 +/- 1.1% in control rats; P less than 0.001). Based upon a 7-point calibration plot, the erythropoietin activity in pooled serum from alpha Ni3S2-treated rats averaged 130 I.U./liter (S.D. +/- 18) (vs 27 +/- 6 I.U./liter in control rats; P less than 0.001). In vitro addition of Ni(II) to rat serum (100 microgram/liter) had no effect upon serum erythropoietin activity. This study demonstrates that induction of erythrocytosis in rats by intrarenal injection of alpha Ni3S2 is mediated by increased serum erythropoietin activity.


Amino acid conferred protection against melphalan: comparison of amino acids which reduce melphalan toxicity to murine bone marrow precursor cells (CFU-C) and murine L1210 leukemia cells. The effect of the naturally occuring amino acids upon melphalan (L-phenylalanine mustard, L-PAM) toxicity to a host sensitive tissue, the granulocyte and macrophage precursor cells of murine bone marrow (CFU-C), was investigated. At physiological concentrations the L isomers of leucine and glutamine were found to be the most effective of the naturally occurring amino acids in reducing drug toxicity. Tyrosine, phenylalanine and methionine also protected murine CFU-C from melphalan toxicity although the amount of protection provided by these amino acids at physiological concentrations was less than that provided by leucine and glutamine. Little difference was observed in the pattern of amino acid protection of murine CFU-C and murine L1210 leukemia cells. Murine CFU-C however were more sensitive to melphalan both in the absence and presence of amino acids.


Influence of perfusion and mechanical activity of ornithine decarboxylase activity in the isolated rat heart. A small, but not significant, decrease in ornithine decarboxylase activity occurred in isolated hearts during one hour of recirculating perfusion with Krebs-Henseleit solution. A significantly greater decrease occurred with a non-recirculating system. Ornithine decarboxylase activity was the same in the working heart preparation as in the non-working preparation. It is concluded that a substance, necessary for the maintenance of ornithine decarboxylase, is removed during perfusion. The nature of the mechanical activity of the heart did not appear to be a determining factor.


Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats. The administration of adriamycin (ADM) to rats has consistently caused a widening of the QRS complex of the electrocardiogram. When coenzyme Q10 was also administered, beginning two days before ADM, this widening of the QRS complex and the elongation of the Q-T interval were reduced or totally prevented, depending upon conditions. ADM alone or with coenzyme Q10 did not alter the P-R interval. Some control by coenzyme Q10 of the cardiotoxicity of adriamycin in cancer patients is promising.


Comparative first dose effects of prazosin and tiodazosin (BL-5111) in spontaneously hypertensive rats. Prazosin produces a "first-dose" phenomenon in man clinically characterized by an exaggerated hypotensive response to the initial dose of the drug, with subsequent doses not producing this exaggerated effect. In spontaneously hypertensive rats (SHR), prazosin (1 mg kg po) produced a similar effect, appreciably reducing systolic blood pressure at 12 hours after the first dose but having little or no effect at 12 hours after the subsequent doses. In contrast, BL-5111, an antihypertensive agent similar in chemical structure and shown in previous studies to be slightly less potent than prazosin but with appreciably less alpha-adrenergic receptor antagonist activity, had no effect on blood pressure at 12 hours after dosing (1 and 2 mg/kg po). Pretreatment of rats with an ineffective blood pressure lowering dose of prazosin (0.03 mg/kg po) significantly attenuated the first dose effect of prazosin, resembling the clinical observations seen in patients. Thus, the SHR may be a useful model for predicting the prazosin-like "first-dose" phenomenon with related analogs.


Effects of clenbuterol on bronchial, cardiac and hypothalamic adenylate cyclase. Present experiments have shown that clenbuterol produces (at the bronchial level) powerful stimulation of adenylate cyclase. This effect is due to a specific stimulation of beta-adrenergic receptors.


Morphine as a discriminative stimulus: role of periaqueductal gray neurons. The present study investigated the degree of involvement of the periaqueductal gray (PAG) in the mediation of the discriminative stimulus (DS) effects of morphine sulfate (MS). Eleven rats were trained to discriminate MS (3 mg/kg; s.c.) from saline (1 ml/kg; s.c.) using a two-bar operant procedure. After the rats learned the discrimination to the criterion of 80% correct responding, cannulae were unilaterally implanted into the PAG. Intracerebral (i.c.) injection of MS (1 microliter) into the PAG produced stimulus control similar to that observed following systemic MS. Doses of 0.5, 1.0, 2.0 and 4.0 microgram elicited MS-correct responding of 27, 57, 63 and 77% respectively. The highest intraPAG MS dose elicited significantly more MS correct responding than did either systemic or the i.c. injection of saline, while not differing from systemically-administered MS. These results suggest that the PAG may at least be partially responsible for the generation of morphine's DS effect when administered s.c.


Antagonism of cisplatin induced emesis in the dog. Cisplatin (cis-diammine-dichloro-platinum) administered at a dose of 3 mg/kg iv induced a reproducible and characteristic emetic response in the dog. It was characterized by a latency period (90-120 min) and multiple emetic episodes occuring within 5 hours following drug administration with sporadic delayed emesis later within the first 24 hours. There was a qualitative similarity between the emetic response of Cisplatin seen in dogs and cancer patients. Metoclopramide (1, 3 mg/kg sc) was found to be the most effective antagonsit of Cisplatin emesis in the dog while haloperidol (1 mg/kg sc) and chlorpromazine (0.3, 1, 3 mg/kg sc) offered a less complete protection. Nabilone (0.1 mg/kg iv) and AL-1612 (1 mg/kg sc) failed to to demonstrate any significant activity. A relationship between antagonism patterns of emetic responses induced by Cisplatin and apomorphine was discussed.


Dantrolene inhibition of the hepatic mixed function oxidase system. The effect of dantrolene sodium, a skeletal muscle relaxant, on the hepatic MFO system has been investigated. The dantrolene produces a dose related inhibition of the system. Single doses of 100 mg/kg and accumulative doses up to 125 mg/kg prolong pentobarbital sleeping time and decrease the rate of aminopyrine N-demethylation without altering cytochrome P450 content. However, single doses of 400 mg/kg and accumulative doses of 500 mg/kg do cause a decrease in cytochrome P450 content as part of the dantrolene induced inhibition of the hepatic MFO system.


Antagonistic effects of prostaglandin E1 and nicotinic acid on the human fat cell adenylate cyclase. Both prostaglandin E1 and nicotinic acid markedly reduce 3',5'-cyclic AMP-accumulation and lipolysis in adipose tissue. These effects were assumed to be mediated via inhibition of the fat cell adenylate cyclase. Therefore, the effects of prostaglandin E1 and nicotinic acid on the human fat cell adenylate cyclase were compared. Prostaglandin E1 caused a dose-dependent stimulation of the enzyme, whereas nicotinic acid was found to act as an unspecific inhibitor depressing all expressions of enzyme activity including prostaglandin E1-stimulated rates of 3',5'-cyclic AMP formation. It is concluded that the common metabolic effects of nicotinic acid and prostaglandin E1 are unlikely to be mediated via the membrane-bound adenylate cyclase in human adipose tissue.


Antagonism of prostaglandin E1 and E2 fever by catecholamines. Antagonism of PGE1 and PGE2 fever by catecholamines in adult fowls was studied by infusing these substances into the brain. PGE1 and PGE2, given into the third cerebral ventricle or into the hypothalamus, produced an immediate, intense and long-lasting increase in body temperature. Noradrenaline and alpha-methylnoradrenaline infused into the hypothalamus or into the third cerebral ventricle during the fever peak were able to antagonize it and to revert the hyperthermic effect into an hypothermic effect. The possible modes of action of PG's and relations with catecholaminergic neurons in the hypothalamus are discussed.


Neurochemical effects of peroral administration of technical pentachlorophenol. Administration of technical pentachlorophenol in drinking water (20 mg/l) to male Wistar rats caused significant liver concentration of tetrachlorophenol which remained stable during the exposure of 14 weeks. Pentachlorophenol and tetrachlorophenol accumulated to some extent in the perirenal fat whereas only pentachlorophenol could be found in brain. A period of four weeks of chlorophenol-free diet was sufficiently long to allow removal of the major part of the chlorophenol burden. The neurochemical effects included increased acid proteinase activity at the 8th week of exposure. It levelled off while superoxide dismutase activity increased to twice the control level. Glial glutathione peroxidase activity did not change whereas glial glutathione concentration was below the control range at the 12th week of exposure. Cerebral diaphorase activity was below the control range initially, and its activity increased above the control level during the recovery period whereas other biochemical changes levelled off.


Inhibition of human intestinal alpha-glucosidehydrolases by a new complex oligosaccharide. The effect of a new complex oligosaccharide (Bay g 5421) of microbial origin on human intestinal alpha-glucosidehydrolase activity was tested in mucosal homogenate from human small bowel biopsy specimens. The alpha-glucosidehydrolase inhibitor (alpha-GHI) exerted a potent inhibitory effect on glucoamylase, sucrase, and maltase, was minimally effective on isomaltase, and did not affect trehalase and lactase activity. Kinetic analysis revealed a fully competitive type of inhibition with a Ki of 1.3 x 10(-6) M; thus the inhibitor had a 15,000-fold higher affinity to the enzyme sucrase than its natural substrate sucrose. The new compound may prove to be useful in the study of carbohydrate maldigestion and malabsorption and may possibly be of therapeutic benefit in diabetes and obesity.


Proximal and distal intestinal calcium transport in vitro as influenced by low calcium diet, uremia, parathyroidectomy and 1,25-dihydroxycholecalciferol treatment in rats. Duodenal and ileal in vitro calcium transport was studied in 5/6 nephrectomized rats. Low calcium diet resulted in an increase of the duodenal calcium transport in kidney intact control animals but not in uremic rats; the ileal transport however increased in controls as well as in uremic rats. Parathyroidectomy decreased this adaptive transport at both gut sites in intact and uremic rats. Supplementation with low doses of 1,25-dihydroxycholecalciferol (1,25-DHCC) restored the duodenal transport in nephrectomized rats to the level of controls; nephrectomized plus parathyroidectomized animals increased the duodenal but not the ileal calcium transport. A close correlation between calcium transport and serum phosphorus concentrations of all groups of rats studied points towards a possible role of phosphate for intestinal calcium transport. It is concluded that duodenal calcium transport is regulated by the parathyroid-1,25-DHCC axis with 1,25-DHCC as effector; ileal calcium transport in contrast is regulated by combined direct effects of 1,25-DHCC and parathyroid hormone, the latter being essential for active transport.


[The effect of unconjugated bile salts on the intestinal absorption of electrolytes and water in the proximal jejunum. Studies in conscious rats (author's transl)]. With an in vivo-perfusion-technique the influence of unconjugated bile salts (cholate, desoxycholate) on the net electrolyte and volume absorption is studied in the jejunum of conscious rats. The applied doses correspond to physiological concentrations in the intestine of rats. Control experiments were performed in the same animal. Cholate and desoxycholate diminish the net electrolyte and volume absorption resp. cause a net secretion. The effects are largely reversible. The extent of net volume absorption depends on the applied dose of each bile salt. The possible mode of action of unconjugated bile salts on the electrolyte and water absorption in the small intestine is discussed.


The effect of normovolemic hemodilution on microvascular hemostasis in the rabbit. Hemostatic plug formation has been studied in the rabbit mesenteric microcirculation during normovolemic hemodilution. A hemodilution method has been developed which maintains a constant platelet count. Using this method the primary hemostatic plug formation time (PHT) and the total hemostatic plug formation time (THT) has been assessed for different degrees of hemodilutions. Both PHT and THT are significantly prolonged for arterioles perfused with low hematocrits (10.6 and 14.2). At a hematocrit of 19.0 the hemostasis is most effective with the shortest hemostatic plug formation times.


Lymphocyte proliferation to phytohemagglutinin (PHA) in hepatitis B antigen-positive and -negative hepatitis. Lymphocytes from patients with HBs-Ag-positive and -negative acute, chronic-persistent, and chronic-active hepatitis, from healthy controls and from patients with alcoholic liver cirrhosis were tested under standardized conditions. These included use of a single charge of Phytohemagglutinin (PHA-P) dissolved and diluted in one operation, of a single pool of homologous serum of the major blood group AB found free of HBs-Ag and cytotixic factor, and elaboration of PHA dose response curves in the presence of autologous and homologous serum in each case examined. During the early phase of acute virus hepatitis B and non-B, and in HBs-Ag-positive chronic persistent and active hepatitis, hyperresponsiveness of lymphocytes to PHA was observed independently of the source of the serum present in the culture. Lymphocyte responsiveness returned to normal in the later phase of acute hepatitis and depressed in alcoholic liver cirrhosis and in cases of HBs-Ag-positive chronic active hepatitis in which cirrhosis had developed. Although the cause of these alterations in lymphocyte responsiveness is not completely understood, the central role of a primary change of the lymphocytes themselves affecting their ability to react to PHA seems probable.


Therapeutical influence of vagus blockade on antigen-induced airway obstruction. The influence of bilateral vagus blockade on airway resistance induced by allergen exposure, while aerosol was given, was tested on 3 dogs. The therapeutic effect of vagus blockade could be demonstrated, which showed to be in a same degree as its prophylactic effect demonstrated in experiences before.


[Computation of the average in- and expiratory airway resistance (author's transl)]. This paper extends the mathematical model of Jaeger and Otis to a separate computation of the mean airway resistance in the in- and expiratory phase. The extended method is illustrated and compared to known methods by means of data on 12 healthy subjects and 12 patients with obstructive airway diseases.


Resistance of airways in animals following tracheal plastic surgery. A simple method for the evaluation of the tracheal lumens in rabbits following tracheal plastic surgery is described. The results are compared with those obtained by blood gas analysis and ray cinematography.


Bronchial aspirate alkaline phosphatase: a sensitive marker enzyme to evaluate bronchial cell damage. A correlation between the number of bronchial cells and alkaline phosphatase levels in bronchial aspirates obtained from patients was demonstrated.


A comprehensive on-line computerised lung function screening test. An on-line computerised lung function screening test is described which prints out 22 lung function parameters and a functional diagnosis. The complete test with print-out data takes less than 8 min per patient which implies that more than 60 out-patients can be 'screened' per day. Furthermore, for patients about to undergo major surgery a lung function operative risk grading is also available. The developed computer system is comparatively inexpensive, simple to operate and can be immediately on-lined to most apparatus without special interfacing. The total screening system can be operated by a single technologist and the required respiratory manoeuvres can be performed by almost all patients irrespective of the degree of lung function impairment. Although comprehensive in itself the screening test has been invaluable in deciding upon which patients require more intensive and time-consuming lung function investigations.


Tracheal contractility and flow resistance in anesthetized dogs with and without vagal block. The study was carried out on 8 boxer dogs in three groups. They were anesthetized, intubated and breathed spontaneously. The animals were exposed to inhalative acetylcholine (ACH) aerosol, mechanical stimulus to the bronchial tree, intrabronchial and intravenous application of ACH solution. Dynamic elasticity, lung resistance, tracheal resistance and breathing rates were determined. A special method was used for recording tracheal activity in spontaneously breathing animals and noted as tracheal pressure. Those parameters were noted before and after partial blocking of the cervical vagus nerves on both sides. Bilateral vagal block entirely prevented the response produced by mechanical irritation and intrabronchial ACH. Inhalative and intravenous ACH produced significantly less response after vagal block, but certain residues remained. It is concluded that mechanical irritation works entirely through the reflex path, but ACH mostly follows the reflex path a little on the smooth muscle directly.


Effect of furosemide on altitude tolerance in experimental animals. Furosemide which is claimed to prevent acute mountain sickness and pulmonary oedema of high altitude was tried in experimental animals to evaluate its usefulness or otherwise as a measure of prophylaxis. 90 mice, 128 rats and 44 guinea pigs--all males--were used for the studies. Half the number in each species were kept as controls. The remaining half were further divided into two batches. The first batch was given furosemide 10 mg/kg body weight. Two h later they were exposed to simulated altitude of 30,000 ft for 6 h. The second batch was given two injections of furosemide at intervals of 24 h before exposure to simulated altitude. The controls were given distilled water. Our results show that the death rate was more in the furosemide-treated groups, both under mild as well as severe dehydration in all species. The present study does not substantiate the claim than the drug can be used as prophylactic against acute mountain sickness and pulmonary oedema of high altitude.


A new lung function index: the area under the maximum expiratory flow-volume curve. A new lung function index, the area under the maximum expiratory flow-volume curve (AFVx) is described. A predicted AFVx based on age, sex and height is determined, and the measured to predicted AFVx ratio is assessed by comparison with other established lung function parameters. This ratio appears to be a very sensitive indicator of the degree of lung function impariment.


A single-breath method of alveolar O2 determination. We designed a single-breath method of alveolar O2 determination, requiring only a single tidal breath expirate and concomitant arterial blood sample. The PAO2 equation used in our method was derived by applying the Bohr equation to both O2 and CO2 and independant of VO2, VCO2 and RQ. In 35 patients with different degrees of airway obstruction, at rest and during exercise, the single-breath method agreed well with the classic method of PAO2 determination which required 3 min of expired gas collection and derivation of VO2, VCO2 and RQ. The mean difference between the PAO2 estimates by the two methods was 0.36 mm Hg as calculated for all patients, both at rest and during exercise. At rest, in 2 out of 35 cases the difference was greater than 2 mm Hg and such difference happened only in 1 case during exercise. A good correlation existed between the two PAO2 estimates by the two methods (r ranging from 0.977 to 0.996). The data indicated that single-breath method of PAO2 determination was reliable. Its extreme simplicity would facilitate greatly the assessment of gas exchange efficiency in situations where both patient's cooperation and laborator equipment are less than optimum.


[Pathogenesis of acute hypercapnic hyperammoniaemia (author's transl)]. Alterations in the ammonia concentration in arterial blood due to drug-induced portal vasoconstriction (oxprenolol 1 mg/kg) or vasodilatation (phentolamine 0.5 mg/kg) were studied in anaesthetized and artificially respirated mongrel dogs during normal air ventilation, during hypercapnia induced by ventilation with an appropriate gas mixture, and during episodes. The NH3 values in arterial-blood plasma were in the region of 41 microgram/100 ml and those in portal-blood plasma 3--4 times higher. The induction of progressive levels of hypercapnia opened the portal-to-systemic venous shunt, producing an increase in arterial NH3 and, to a lesser extent, NH3 in the CSF. The portal vasoconstriction caused by oxprenolol 1 mg/kg i.v. resulted in the functional elimination of the shunt during normoxia or hypercapnia, leading to a decrease in the NH3 concentration in the arteral blood and hence also in the CSF. The vasodilating effect of phentolamine 0.5 mg/kg i.v., on the other hand, caused a transient, stastically significant increase in arterial NH3 during normoxia; during hypercapnia the NH3 values did not differ from the controls.


Analysis of the changes in ECG during status asthmaticus. An analysis was made of the changes in ECG in 61 random patients during status asthmaticus. It was found that a statistically significant increase occurred in the amplitude of the P wave in the inferior leads. P. pulmonale was noticed in lead II in 26%, in lead III in 18%, and in lead aVF in 25% during status asthmaticus, whereas corresponding values in the controls were 5%, 5% and 3%. A tendency to rS was also seen in the precordial leads, as were a small clockwise rotation, a small rotation of the frontal QRS axis to the right, and slight changes in the ST segment and T wave.


Collateral ventilation in excised human lungs. Collateral ventilation was determined in 13 isolated human lungs obtained at postmortem. These included lungs from patients with pneumonia (2 cases), metastatic breast carcinoma (3), emphysema (5), pulmonary fibrosis (2) and hemorrhagic abscess (1). The amount of collateral ventilation was variable and related to the pathological process within the lung. Flow and resistance of collateral pathways were determined for each studied lung. Demonstration of collateral flow was made with the use of 133Xe and recorded by radiographic imaging. Further demonstration of the collateral pathways was done by use of 1 micrometer sized particles of tantalum. Histological examination showed tantalum dust to accumulate at gaps in the alveolar wall at the lobar junction and to pass through this area. Although the sample population is small, no correlation was found for age and the amount of flow through the channels. This study demonstrated that alveolar pores play a role in collateral ventilation. No collateral flow was observed in six pediatric lungs tested. It is likely that collateral ventilation is an acquired phenomenon in humans.


Respiration in conscious dogs at rest and during exercise. 25 mongrel dogs (average b.w. 24.6 kg) were studied on several occasions at rest and during treadmill exercise of up to 10 mph (15% incline). Minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), tidal volume (VT) and respiratory frequency (f) were determined at rest and at each level of exercise. Individual variability in resting VO2 was considerable (71--695 ml/min). Most often the dogs panted, with VE's above 25 liters/min and f's above 100 min-1. The averate VE/VO2 was 109 at rest. VO2 was linearly related to VE (VO2 = 9.17 VE + 66.9; r = 0.80). Differences in resting VE were largely due to differences in f (f = 3.57 VE + 21.2; r = 0.82). Considerable individual variability in VO2 for a given work load was also observed during exercise. Some dogs showed significant differences in VO2 from experiment to experiment while running at a given treadmill speed. These differences were largely related to the levels of VE. VE/VO2 decreased to 50. We found a leveling off of VO2 (at about 60 ml/min/kg) at treadmill speeds of 5 mph, suggesting that the maximal VO2 in dogs is less than previously reported.


Effect of hypoxia on regional lung perfusion, by scanning. Lung scanning was performed in 12 subjects who had pulmonary oedema of high altitude (POHA) before, and in 8 men who had been at high altitude without developing pulmonary oedema. Scanning done before and after 5 min 10% O2 breathing showed (a) increased perfusion in POHA subjects after hypoxia, (b) more in the lower than in upper zones, and (c) striking increase in perfusion in localised areas. In controls, however, there was significant reduction in perfusion after hypoxia in most areas. The reduction was less marked in the lower zones than in the upper zones. POHA subjects were hyperreactors to hypoxia, compared to controls. It is concluded that scanning before and after hypoxic breathing might help in differentiating hyperreactors.


The role of upper airways in antigen-induced bronchoconstriction. The bronchoconstrictor effect of antigen was tested in 15 dogs. The upper and the lower airways were sequently exposed through a specially confected endotracheal tube. The antigen was also generally administered through a mouth mask. Bronchoconstriction was induced after each kind of exposure. The results argue for reflex bronchoconstriction. The sensory receptors localized in the upper part of the airways are responsible for about 50% of antigen-induced bronchoconstriction. The decrease of PO2a was less marked following Ascaris suum extract aerosol administration to the upper part of the airways. Control measurements demonstrated the reproducibility of antigen-induced bronchoconstriction.


Meniscus formation in airways of excised rat lungs. The object of this study was to determine the transpulmonary pressure at which menisci form in the airways of excised rat lungs. The necessary geometric requirements for meniscus formation are normally met in the airways, but a meniscus is presumably prevented from forming at large lung volumes because too little fluid is present. At lower lung volumes a meniscus could form easier since airway caliber is reduced and less fluid is required. A series of pressure-volume curves were recorded for lungs in which meniscus formation was inhibited by increasing the end expiratory pressure. Assuming the number of airways containing at least one meniscus was proportional to the amount of gas trapped in the excised rat lung, it was found that the menisci were formed in 68% of the airways between positive transpulmonary pressures of 1.4 and 3.0 cm H2O during deflation.


Static volume-pressure relationship in normal rats at various stages of growth. Static deflation air volume-pressure (V-P) curves were studied in 136 open-chested normal male rats ranging from 103 to 604 g in weight. The lungs accepted a greater volume of air as rats grew in size, but beyond 8 weeks of age, the volume expressed per g of lung weight progressively decreased. In older rats, V-P curves in precent maximum lung air volume (%MLV) were shifted upward and to the left compared to younger rats. We believe that these differences reflect various phases in the postnatal growth of rat lungs and loss of tiss elasticity due to the aging process, respectively. Lung air volume at 30 cm H2O Ptp (MLV30) showed a significantly higher linear relationship with body weight (r = 0.93) than with lung-heart weight (r = 0.80) as the independent variable. We present V-P nomograms and discuss two techniques of measuring V-P relationships with their specific applications.


Corrections to the Hazelhoff model of airflow in the avian lung. The ventilatory activity of the anterior and posterior groups of air sacs was simulated in unidirectionally-ventilated geese and the resultant flow of air in the mediodorsal secondary bronchi was used as an indicator of the route which air followed through the lung. The results were used to isolate the roles of the respective groups of air sacs in the shaping of the unidirectional pattern of airflow known to exist during normal respiration. Findings indicated that, in contrast to Hazelhoff's model, the anterior and not the posterior sacs are responsible for producing the caudo-cranial flow of air through the parabronchi during inspiration. The posterior sacs, as predicted by Hazelhoffs model, and primarily responsible for driving the caudo-cranial current through the parabronchi during expiration.


Role of PCO2 as determinant of CSF [HCO-3] in metabolic acidosis. To study regulation of CSF [HCO-3] in metabolic acidosis and in particular the role of CSF PCO2 in establishing CSF bicarbonate level, acute metabolic acidosis was induced by the intravenous infusion of HCl in three groups of anesthetized dogs for six hours when PaCO2 was changed at different rates. Plasma [HCO-3] was lowered to 12 +/- 2 meq/L within one hour and maintained at that level thereafter in all groups. (I) Seven dogs were kept isocapnic while metabolic acidosis was induced. The cisternal CSF [HCO-3] fell by only 2.6 meq/L after six hours and was not significantly different from control. (II) In 11 dogs metabolic acidosis was induced while the dogs breathed spontaneously. There was a gradual drop in PaCO2 accompanied by a similar drop in CSF PCO2 of 14.5 torr. CSF [HCO-3] fell significantly by 6.1 meq/L at 6 hours and in parallel with the fall in CSF PCO2. (III) In order to show interdependence of the rate of fall in CSF [HCO-3] with rate of fall in cisternal PCO2 six dogs were mechanically hyperventilated and PaCO2 reduced to 21 torr rapidly and maintained there for six hours. CSF PCO2 followed PaCO. CSF bicarbonate fell rapidly and by 5 meq/L. In groups II and III the fall in cisternal [HCO-3] paralleled the drop in PCO2. Therefore, in metabolic acidosis the rate of the fall in cisternal bicarbonate appears to be a function of the rate of fall in CSF PCO2. It is speculated that the coupling of CSF [HCO-3] reduction in metabolic acidosis to CSF PCO2 fall is primarily for the benefit of CNS H+ homeostasis.


An analysis of respiratory frequency alterations in vagotomized, decerebrate cats. Changes in inspiratory (TI), expiratory (TE) and total respiratory cycle (TTOT) durations with hypercapnia- of hypoxia-induced tidal volume (VT) elevations were evaluated in midcollicular decerebrate cats. As VT increased, TI, TE, and TTOT decreased for most animals having intact vagi. Following vagotomy, TI, TE, and TTOT increased with hypercapnia for cats which had TI, TE and TTOT values shorter than 1.6, 3.7 and 5.2 sec respectively while breathing 100% O2; values longer than these forecast hypercapnia-induced decreases in each parameter. Similar systematic changes were not evident for hypoxia-induced responses. Varying the midbrain transection level or pentobarbital administration altered TI, TE and TTOT values while breathing 100% O2; however, the predictability of hypercapnia-induced responses, based on data analysis from midcollicular decerebrate cats, was maintained. It is concluded that the vagally-independent brainstem frequency controller is sensitive to hypercapnia and hypoxia. The predictability of hypercapnia-induced TI, TE and TTOT changes in vagotomized animals is considered in the context of previous models for respiratory rhythm generation.


Regulation of ventilatory responses in vagotomized cats by caudal brainstem sites. Respiratory responses to hypercapnia and isocapnic hypoxia were evaluated in vagotomized decerebrate cats prior to and following lesions in the midline at the pontomedullary junction. Subsequent to these lesions, frequency responses to hypercapnia were significantly elevated whereas the concomitantly determined tidal volumes were significantly lowered. In the post-lesion phase, the durations of inspiration, expiration and the total respiratory cycle at maximum hypercapnia-induced tidal volumes were lower than comparable values at maximum tidal volumes in the pre-lesion phase. The same lesions produced no significant alteration of respiratory responses to hypoxia. Mesencephalic or rostral pontile lesions caused no systematic changes in either hypercapnia- or hypoxia-induced responses. It is concluded that the lesions at the pontomedullary junction produce ventilatory alterations by interrupting a pathway interconnecting the caudal pontile apneustic center with the medullary respiratory complex. The possibility that this interruption produces an alteration in the threshold of the inspiratory off-switch mechanism of the brainstem respiratory controller is considered and discussed.


Pentobarbitone effects on respiration related units; selective depression of bulbopontine reticular neurones. Respiration related units (RRUs) were recorded in cats, locally anesthetized, vagotomized and immobilized, under two different experimental conditions: (1) receiving pentobarbitone intravenously at a dose inducing slight but highly significant changes in phrenic discharge; (2) unanesthetized, with a spinal section at C6. RRU characteristics were analysed in unitary volumes constituted by cubes of a matrix including the brain stem. Four parameters of RRU discharges were compared in cubes = RRU density (RRUD), RRU proportion and two indices of respiratory modulation. Cubes were sampled in: (1) dorsal and ventral bulbar respiratory nuclei, (2) pneumotaxic centre (PC), and (3) seven fields of the bulbopontine and mesencephalic reticular formation. Using the paired sample method for comparing data cube by cube in the two conditions it was shown that under pentobarbitone, RRU activity was profoundly depressed in the reticular formation surrounding dorsal and ventral bulbar respiratory nuclei, in the region bridging the gap between these and the pneumotaxic centre and extending from the pneumotaxic level to the decussation of the brachium conjunctivum. In contrast RRU activity was unchanged at the level of dorsal and ventral bulbar respiratory nuclei and in the nucleus parabrachiallis medialis (NPBM) and was increased in the Kölliker-Fuse nucleus (KF). In the mesencephalic reticular formation, increased activity was observed for non-modulated units and to a larger extent for units driven by the bulbopontine respiratory system.


Histamine and phenyldiguanide induced tachypnea in hypercapnia and hypoxia. The rapid shallow breathing of pulmonary vagal origin following administration of histamine (H) and phenyldiguanide (PDG) was studied at different levels of hypercapnic and hypoxic stimulation. At all levels of chemical drive H and PDG caused an excitatory effect on timing of breathing and an inhibitory effect on the respiratory output. The latter was evaluated from the mean inspiratory flow rate and the mean rate of change of pressure developed in the lungs during an inspiratory effort against closed airways. The timing effect was greater at low than at high PaCO2 while the opposite was true for the output effect. At all PaCO2, H and PDG decreased the volume-threshold for termination of inspiration (leftward displacement of the VT vs TI relationship) of the VT Vs TI relationship). Hypoxia increased the respiratory output in control as much as with drug stimulation. Moreover, hypoxia did not affect the volume-threshold curve both in control and with H and PDG. We concluded that vagal afferents stimulated by H and PDG (irritant and/or J receptors) interfere with the timing and output response to central chemoreceptors stimulation (CO2 sensitivity) without affecting the response to peripheral chemoreceptors stimulation (mainly hypoxic chemosensitivity).


Role of glucose in contractility of airway smooth muscle. This study investigated the response of isolated tracheal preparation (ITP) from guinea pigs to three bronchoconstrictive drugs: histamine (H), carbachol (CAR), and acetylcholine (ACH). Cumulative dose-response curves were obtained in substrate-rich (5.50 mM of glucose) and substrate-free physiological salt solutions under aerobic conditions (PO2 = 95 +/- 0.5 Torr) or in acute 30-min hypoxia (PO2 = 30 +/- 2 Torr). The reactivity of ITP was measured by ED50 (effective dose developing 50% of maximal response); and the contractility of ITP was measured by a maximal developed isometric tension. This study showed that the contractile response of isolated segments of tracheas to H, CAR, and ACH was significantly decreased (P less than 0.05) when the experimental medium contained no glucose, or when glucose was replaced with metabolic inhibitor 2-deoxyglucose. This data contrasted with findings obtained with main pulmonary arteries (MPAs) isolated from the same species, where the absence of glucose in the experimental medium did not affect patterns of histamine cumulative dose-response curves. It was also shown that pretreatment of isolated tracheas with a small dose of insulin significantly decreased (P less than 0.05) the contractile response of airway smooth muscle to histamine. In both experiments, either with or without glucose in the experimental medium, acute hypoxia (30 min) had a significantly greater effect (P less than 0.05) on the development of isometric tension of MPA compared with that on ITP. Both removal of glucose from the experimental medium and/or acute hypoxia significantly decreased (P less than 0.001) adenosin triphosphate and creatine phosphate contents of tracheal segments but did not influence the high-energy phosphate content of main pulmonary arteries exposed to similar conditions. In addition to pointing out the physiological and metabolic differences between pulmonary vascular and airway smooth muscle, this study showed the important dependence of airway smooth muscle on glucose as a substrate.


Respiratory responses to changes in airflow resistance in conscious man. The time course and magnitude of adjustments in respiratory activity during the application and following the removal of inspiratory resistive loads were determined in conscious men. Changes in airflow resistance were made periodically during rebreathing of a gas mixture of carbon dioxide and oxygen. Ventilation, the ratio of tidal volume to inspiratory duration and the mouth pressure during airway occlusion, 100 ms after the onset of inspiration were used as measures of inspiratory neuromuscular activity. The occlusion pressure was measured during each breath using an electrically activated solenoid shutter which obstructed the airway for only the first 100 ms of each inspiration. During the second breath following the application of the resistive load, there was an increase in inspiratory output which occurred independently of changes in PCO2 and PO2. Further increases in inspiratory activity during successive loaded breaths, however, were due exclusively to changing chemical drive. The level of inspiratory neuromuscular activity remained elevated for a single breath following removal of the added resistance. Adjustments in respiratory activity were greater the more severe the load. The results suggest that non-chemically mediated respiratory compensation in conscious individuals develops rapidly and is important in maintaining ventilation when breathing is encumbered.


The measurement of metabolic gas exchange and minute volume by mass spectrometry alone. Metabolic gas exchange and respired minute volume were measured on 37 occasions in 9 normal adults on exercise and at rest, using the concentration of an injected gas, argon, as a measure of flow. These measurements were compared with simultaneous Douglas bag collections in which volumes were determined with a dry gas meter. The two types of measurements agreed within +/- 5%. It was concluded that this technique, designed for the remote monitoring of unconscious patients was suitable for a wide variety of clinical and experimental situations.


Hen's eggs with retarded gas exchange. I. Chorioallantoic capillary growth. The diffusing capacity of the hen's egg for carbon monoxide (D tau co) increases during incubation, reflecting the development of the chorioallantoic circulation. Previous work showed that the increase in D tau co could be diminished by incubating eggs in a 60% oxygen environment. The present work explored the effects of impeding gas exchange on the development of D tau co. Half the shell area was covered during incubation by a removable neoprene membrane which limited D tau co by approximately 20%. No difference could be detected between the D tau co values (measured with the membrane removed) of these eggs and control eggs incubated in the same 21% oxygen environment without a neoprene membrane. We conclude that the development of the chorioallantoic circulation is at its maximum under normal conditions of incubation and cannot be accelerated by restricting gas exchange.


Decay rate of inspiratory muscle pressure during expiration in man. Decay rate of inspiratory muscle pressure (PmusI) was studied in 4 subjects during post-inspiratory period of zero flow (TEz) occurring under discontinuous inspiratory elastic load (DIL). End-inspiratory pressure (PmuseI) was increased by dead spaces or exercises. Decay rate was related to PmuseI by a power function with exponent greater than 1. It was not directly affected by concomitant changes of PCO2. It did not increase when an expiratory resistive load was added, i.e. when braking action of inspiratory muscles was no longer required. Time course of PmusI during TEz was more straight than exponential. Relative decay rate increased with PmuseI and with decrease of inspiratory or expiratory time. Experiments with resistive loads suggest that relative rate is mainly related to timing factors. During voluntary inspiratory efforts with closed airways, relative decay rate was not related to PmuseI, while decay rate increased linearly with PmuseI.


Mechanical properties of the harbor porpoise lung, Phocoena phocoena. The pressure-volume and pressure-flow characteristics of the excised lungs of 5 harbor porpoise were determined. It was found that: (1) in comparison to terrestrial mammals the lung volume relative to body weight is large, (2) the lungs are capable of emptying to less than 17% of total lung capacity, (3) peak expiratory flowrates of 5 to 10 vital capacities (VC).sec-1 are relatively high for mammals, (4) isovolume pressure flow curves showed a clustering of flowrate plateaus from 40 to 80% VC, with a marked drop in the flow rate plateau at 20% VC, (5) the profile of flow-volume curves is unusually square shaped with flows remaining above 2 VC.sec-1 at a lung volume of 20% VC, (6) this feature is responsible for the short emptying time of less than 0.2 sec. It is concluded that cartilaginous airway reinforcement, which extends to the alveolar sac, is responsible for the unusual flow-volume properties. These porpoises have the capability of exchanging a large percent of their lung gas very rapidly during their brief pass through the air-water interface.


Carbon dioxide sensitivity of aortic chemoreceptors in the cat. Steady state CO2 sensitivity in the aortic chemoreceptors was variable. For 70.3% of the steady state response lines to increasing CO2 the slope was not significantly different from zero. For 24.3%, it was significantly positive and for 5.4% significantly negative. In contrast, in 86.7% of cases the oscillating response to alternate breaths of high and low CO2 suggested a transient response line which was significantly steeper than the steady state line. Removing CO2 from a high CO2 content inspirate for one breath caused a distinct drop in discharge on 83.3% of occasions. The significance of such transient CO2 sensitivity in the absence of clear steady state sensitivity is discussed.


Inspiratory-expiratory responses to alternate-breath oscillation of PACO2 and PAO2. Breath-by-breath respiratory responses of three healthy adults to imposed alternate-breath oscillation of end-tidal PCO2 (between +5 and +15 torr above the eupnoeic level) and/or PO2 (between 80 and 45 torr) were studied at rest and during mild cycle ergometer exercise. There was often alternation in inspiratory and expiratory tidal volumes and mean flows, and in expiratory duration, but not in inspiratory duration. The latency of responses, estimated by cross-correlation, corresponded closely to the lung-ear transport delay (measured by oximetry). There were two general patterns of response: in-phase, with inspiratory responses leading expiratory, and, more often, out-of-phase, with expiratory responses leading inspiratory. These patterns were associated with arrival of the onset of the alternating signal at the ear in inspiration and expiration, respectively. It is concluded that the timing of alternating humoral signals at the carotid bodies in relation to the phase of respiration determines the pattern of inspiratory-expiratory response, and that expiratory events can be independent of the previous inspiration.


Reflex influences from the extrathoracic trachea during airway occlusion. We have performed experiments in 26 dogs anesthetized with pentobarbital and fitted with an endotracheal tube. The inflatable cuff of this tube was positioned either at the level of the cricoid cartilage or at the thoracic inlet. In this latter situation the extrathoracic trachea (E.T.T.) is not subjected to any change in transmural pressure both during breathing and airway occlusion. We have compared the inspiratory output in term of the integrated phrenic discharge during airway occlusion at FRC with the tracheal tube positioned at either one of the two levels. In most of the experiments (16 out of 26) the inspiratory output during airway occlusion is significantly greater (157%) when the E.T.T. is not by-passed and this difference disappears after bilateral vagotomy. We interpret these results by the asymmetrical response of the tracheal stretch receptors to positive and negative transmural pressure (Pt); most of these receptors are active at FRC and decrease their activity at low negative Pt, as that attained in the first occluded breath. These results seem to suggest that the reflex influences from the extrathoracic tracheal receptors on the inspiratory output are similar to those originating from the intrathoracic airway stretch receptors.


Behavior of expiratory neurons in response to mechanical and chemical loading. The response of medullary expiratory neurons to added mechanical and chemical loads was studied in anesthetized cats. Alterations in burst characteristics and central timing were compared in the intact and bilaterally vagotomized cat. The following results were obtained: (1) Graded expiratory airflow resistances caused progressive increases in burst duration, spikes per burst and firing rate; similar effects were noted for end-inspiratory tracheal occlusions and continuous positive breathing; all facilitation was eliminated by vagotomy. (2) Graded inspiratory airflow resistances delayed the onset of an expiratory burst but did not change the overall burst characteristics. (3) Acute hypercapnia increased ventilation without noticeable changes in expiratory burst characteristics; acute hypoxia produced a reduction in burst duration concomitant with changes in ventilation. It is concluded that (1) expiratory neurons are responsive to vagally mediated volume information and (2) transient hypoxia and hypercapnia sufficient to increase ventilation does not increase the firing rate of expiratory neurons but exerts differential effects with respect to timing. It is suggested that expiratory duration is related to the time integral of expired volume and that the increase in FRC imposed by expiratory loads does not alter the central timing of the next inspiration.


Properties of inspiratory termination by superior laryngeal and vagal stimulation. Electrical stimulation of two respiratory afferent nerves, the vagus and the internal branch of the superior laryngeal, was used to terminate inspiration. The short latency responses of phrenic motoneurones to these stimuli were studied to determine if inspiratory termination was preceded by a characteristic phrenic motoneurone discharge pattern, reflecting changes in brainstem inspiratory neurone discharge and inspiratory terminating mechanisms. Stimulus trains of sufficient intensity delivered to the superior laryngeal nerve terminated inspiration within 50 ms and were preceded by a stereotyped pattern of phrenic motoneurone discharge. This consisted of a short latency (disynaptic), predominantly contralateral excitation in response to the first shock of the train, followed by a marked and long lasting inhibition. In contrast, vagal stimulation typically terminated inspiration hundreds of milliseconds after the onset of the stimulus train and was not preceded by a stereotyped pattern of phrenic motoneurone responses to single shocks. Transient short latency responses were obtained but were extremely small, requiring considerable excitation followed by a moderate bilateral depression of activity. Inspiration could be terminated with or without the presence of these short latency responses. These results indicate that superior laryngeal and vagal (presumably pulmonary stretch receptor) afferents have different projections to brainstem inspiratory neurones and may exert their effects on inspiratory duration through different, but as yet undefined, neural mechanisms.


Respiratory stimulation by angiotensin II. The changes in breathing accompanying increases in arterial pressure caused by intravenous injections of angiotensin II were examined in dogs anaesthetized with chloralose, and in unanaesthetized rabbits. They were compared with the effects on breathing caused when the alpha-adrenergic vasoconstrictor, phenylephrine, or inflation of an aortic balloon were used to raise blood pressure to comparable levels. Phenylephrine and balloon inflation always depressed breathing: this depression was secondary to the increase in arterial pressure and was abolished by denervation of the arterial baroreceptors. In every animal ventilation was greater with angiotensin II than it was at a comparable blood pressure achieved with phenylephrine or balloon inflation. When compared with control levels of ventilation, however, angiotensin II sometimes caused an increase in breathing, sometimes a reduction, and sometimes had little effect. When both carotid sinus and vagus nerves were cut, angiotensin II consistently stimulated breathing. This shows that angiotensin II has an independent stimulating effect on ventilation which cannot be attributed to inhibition of any baroreceptor-mediated respiratory restraint nor to stimulation of either arterial chemoreceptors or intrathoracic receptors which run to the CNS through the vagus.


Acclimatization of newborn rats and guinea pigs to 3000 to 5000 m simulated altitudes. Two species of newborn rodents (guinea pigs and rats) were acclimatized to simulated altitudes of 3000 to 6000 m during 2 to 8 weeks after birth. Body weight increase was significantly retarded in both species at altitudes of 5000 m and higher. Heart weight relative to body weight increased by 50% at 3000 m and 300% at 5000 m (after 7 weeks) in rats but was only 17% increased even at 5000 (6 weeks) in guinea pigs. Relative lung weights increased by 40% at 3000 m in rats and 5000 m in guinea pigs; at 5000 m rats showed a 130% increase. Hb-concentration increase (20%) was not significantly different in rats at 3000 m and 5000 m, respectively, in guinea pigs it was below 10% at 3000 m and around 40% at 5000 m. Half saturation pressures of blood (P50) increased in rats significantly compared to controls but not in guinea pigs. The results suggest that relative maturity and high blood oxygen affinity in newborn guinea pigs favor high altitude acclimatization. Immaturity of newborn rats, their low blood oxygen affinity and immature enzyme patterns are considered as reasons for the smaller resistance against high altitude stress compared to guinea pigs.


Long-term studies on therapy and tolerance of ketoprofen. The therapeutic value of non-steroid anti-inflammatory agents for therapy of rheumatoid arthritis is discussed and a long-term study is described which was carried out for up to 12 monts on tolerance of ketoprofen compared with indomethacin. Objective laboratory data were used as criteria for possible influence on organ function. No abnormalities in renal and liver function were observed.


Prospective chromosomal study of 30 patients undergoing 90Y synovectomy. Chromosome studies were performed on 30 patients undergoing 90Y synovectomy before and after therapy. It was observed that overall there was a small but significant rise from 0.33% to 0.87% in the frequency of cells with specific chromosome aberrations following treatment. These findings agree well with those of other surveys. Analysis of individual results show that, of the 30 patients, only 10 showed chromosome damage that could be attributed unequivocally to the 90Y therapy.


Social implications of rheumatoid arthritis in young mothers. A brief survey of the difficulties facing a mother of pre-school children has been made. The time from 1 to 2 1/2 years is probably most demanding of the mother's patience and energy. Much can be done to support the family by adequate control of the disease, splinting and sparing of involved joints and provision of an easily maintained home, children's clothes and attention to environmental design. Domestic help, education of the husband, playgroup for the child and correct family spacing are all helpful.