Abnormal fatty acid composition and impaired oxygen supply in cystic fibrosis patients. Impaired oxygen supply and deteriorating health, in cystic fibrosis patients, correlates with abnormal changes in the fatty acid composition of blood lipids. As the proportion of oleates increases and that of linoleates decreases, erythrocyte membrane interference with the formation of intracellular oxyhemoglobin increases and arterial oxygen pressure decreases. The physical-chemical basis for these changes seems to be that oleic and linoleic acid differ in their ability to undergo reversible oxygenation in response to changes in oxygen pressure. The oxygen complex of linoleic acid dissociates at relatively high pressures, whereas that of oleic dissociates only at low pressures. Accordingly, excessive substitution of oleic for linoleic acid in membrane lipids would be expected to decrease the intracellular oxygen pressure to a level where hemoglobin oxygenation and any other oxygen-requiring processes would be impaired.


Computer-assisted newborn intensive care. A minicomputer has been programmed to aid in the intensive care of high-risk newborn babies. The computer provides 24-hour on-line access to physiologic and environmental data and controls the heating of infant incubators. The control algorithm limits fluctuations in the incubator chamber and protects the infant against escape from neutral thermal conditions. The mortality rate for 105 infants cared for using the computerized systems was significantly reduced when compared to that of 105 matched high-risk infants cared for using standard non-computer-assisted techniques in the same nursery setting.


Importance of radiant flux in the treatment of hyperbilirubinemia: failure of overhead phototherapy units in intensive care units. Prior to 1972, radiation used to treat neonatal hyperbilirubinemia was based upon the photometric unit, the foot-candle, a measure of light illumination. Measurements in terms of microwatts per square centimeter for selective wavelengths is more precise. We compared the effectiveness of phototherapy provided by overhead phototherapy units in intensive care modules vs. conventional phototherapy units. Forty-two infants were studied over a six-month period and divided into three groups based upon radiant flux measurements as follows: Group 1 (No. = 6), 1.0 muw to 1.9 muw/sq cm/nm; group 2 (No. = 15), 2.0 muw to 3.9 muw/sq cm/nm; group 3 (No. = 21), 4.0 muw to 6.0 muw/sq cm/nm. All flux determinations were made within the 400- to 500-nm range. All infants in group 1 were treated with overhead phototherapy units in the intensive care modules. Because of multiple factors known to increase the risk of kernicterus, evaluation of effectiveness of phototherapy at low radiant flux was limited in group 1. Significant changes in bilirubin were noted by 48 hours when comparing group 3 with groups 1 and 2. A minimum of 4.0 muw/sq cm/nm appears necessary for effective phototherapy. As designed, phototherapy units in intensive care modules are ineffective in delivering this therapeutic level of radiant flux.


Effects of phototherapy on platelet counts in low-birthweight infants and on platelet production and life span in rabbits. The effects of conventional phototherapy on platelets in vivo were studied in rabbits and in low-birthweight infants. Rabbits were divided into three groups and individually treated continuously for 96 hours, with blue light, daylight, or no phototherapy. Incorporation of selenomethionine Se75 was used to evaluate platelet production and life span. Platelet turnover was significantly increased in the blue-light phototherapy group, and was also increased in the daylight group but to a lesser degree. Daily platelet counts and hematocrits were performed in infants weighing less than 2,000 gm at birth randomized at 24 +/- 12 hours of life to receive daylight phototherapy continuously for 96 hours (31 infants) or no phototherapy (26 infants). In 12 treated infants (38.7%) platelet counts fell below 150,000/cu mm whereas this occurred in only 3 (11.5%) of the controls. These two lower platelet count subgroups differed significantly in mean gestational age and birthweight with the phototherapy group being the more mature. Pre-phototherapy, the mean platelet count of these 12 infants was lower than the mean of the entire control group, suggesting that these infants had borderline marrow reserve before phototherapy was given. These results suggest that phototherapy increases the rate of platelet turnover. When bone marrow compensation is inadequate, the platelet count may fall.


Compliance of chronic asthmatics with oral administration of theophylline as measured by serum and salivary levels. A group of ambulatory asthmatic children was studied with serum and salivary theophylline levels following a prescribed dose of a hydroalcoholic solution of theophylline to determine compliance. The gas chromatographic procedure used was both selective and sensitive for theophylline without the necessity of withholding coffee, tea, chocolate, or cocoa. In the first group of patients, only 11% achieved therapeutic levels, 65% had less than therapeutic levels, and 23% had no measurable drug in saliva. With more directive and supervised drug administration in a second group of patients, 42% achieved therapeutic levels, 51% were below therapeutic levels, and only 6% had no measurable drug. Monitoring patients with salivary theophylline levels proved an effective way of improving compliance and also alerted physicians to noncompliance as a possible explanation of "treatment failure". Salivary specimens are readily obtained and noninvasive so that the technique is readily adaptable for use in the office of clinic setting.


Theophylline secretion into breast milk. The infant of an asthmatic patient showed irritability associated with ingestion of breast milk only on days when the mother was taking theophylline. Pharmacokinetic studies in this woman and in four other subjects revealed that theophylline distributes well into breast milk. The average milk to serum concentration ratio of the drug was about 0.7 and milk concentrations paralleled the time-course of serum and saliva concentrations. On a relative body weight basis, a nursing infant would usually receive less than 10% of the mother's dose of theophylline which is normally an inconsequential amount.


Relationship of allergy, enuresis, and urinary infection in children 4 to 7 years of age. A group of 234 children, 4 to 7 years old, in a middle- to upper-middle-class Caucasian population, were divided into four groups and matched for age and sex. Group 1 consisted of 50 children previously treated for urinary infection: control group 1 contained 55 well children; group 2 consisted of 69 children treated for respiratory allergy; and control group 2 contained 60 well children. There was no statistical difference in persistent enuresis (night wetting every week), persistent day wetting (every week), allergy, or family history of enuresis, when group 1 and control group 1 were compared. A family history of urinary infection was higher (P less than .05) in group 1. There was no statistical difference in persistent enuresis, persistent day wetting, previous urinary infection, or family history of enuresis or urinary infection when group 2 and control group 2 were compared. This study suggests that there is no relationship between respiratory allergy, enuresis, and urinary infection.


Benign familial macrocephaly: report of a family and review of the literature. Five members in two generations of one family were found to have occipitofrontal head circumferences more than 2 SD above the mean. All five had normal intelligence and neurological examinations. Three of the five had ventricular dilatation by A-mode echoencephalography. The inheritance pattern of macrocephaly in this family appears to be autosomal dominant with incomplete penetrance. Possible causes of the macrocephaly in this family are discussed and the reported cases of macrocephaly with normal intelligence and no neurological deficits are reviewed.


Congenital multicystic kidney.

Congenital multicystic kidney. By employing the three basic diagnostic modalities of uroradiology--intravenous urography, retrograde pyelography, angiography--an accurate radiological diagnosis can be made. Since congenital multicystic disease by definition is a nonfunctioning dysplastic kidney with an atretic or absent ureter and absent renal vasculature, these diagnostic methods are tailored precisely to demonstrate the specific characteristic functional and pathological features of congenital multicystic kidney disease. We find no function on intravenous urography, hypoplastic atretic ureter on retrograde pyelography, and an absent or hypoplastic renal artery indicated on angiography.


Medullary sponge kidney.

Medullary sponge kidney. "Medullary sponge kidney" applies to pathologically dilated collecting tubules within one or more renal pyramids of one or both kidneys, almost always diagnosed radiographically, of uncertain etiology, and presenting a clinical spectrum varying from an asymptomatic, incidental finding to severely complicating calcareous-infective disease, renal insufficiency, and death. Recognition of the characteristic urographic pattern affords the patient presenting clinically with hematuria, ureteral colic, urinary tract infection, or nephrocalcinosis a prompt diagnosis with a frequently benign prognosis, and usually averts more extensive or invasive investigations.


Juvenile nephronophthisis and renal medullary cystic disease. In the past 30 years 238 cases have been published which describe the nephronophthisiscystic renal medulla complex. Of these, 110 are sufficiently adequate to permit detailed analyses. Both isolated and genetically transmitted cases are reported. The latter include the dominant and recessive modalities, both autosomal, and the former perhaps also X-linked. Renal disease also has been inherited as a recessive trait in association with retinal degeneration. Medullary cysts have been found in 73% of cases in which kidney tissue has been examined directly. Their presence seems to bear no relationship to the ability of involved kidneys to conserve sodium. Salt wasting is described in the presence and absence of medullary cysts. Techniques short of anatomic examination of the kidneys have rarely allowed cysts to be detected and diagnosis continues to rest on a high index of suspicion, aroused in turn by a positive family history for the disease. Arterial hypertension occurs in roughly one third of cases. Aminoaciduria is not a part of the syndrome. A defect in maximum urinary concentrating ability may be the best single early sign of involvement but data are scarce.


Extrarenal manifestations of cystic kidney disease. Cystic disorders of the kidney may manifest their presence not only through renal but also through systemic signs and symptoms. Extrarenal manifestations include cerebral aneurysms, hepatic cysts, hepatic fibrosis, polycythemia, and retinal changes. Awareness of such associations strengthens the likelihood that renal cystic disease will be detected in its earlier stages. Involvement of organs other than the kidneys takes on added significance as the lives of affected individuals are prolonged through dialysis and renal transplantation.


Normal development and experimental models of cystic renal disease. From a review of renal development and experimental cystic disease, the following observations can be made: 1. The previous theories developed to explain cystic renal disease (nonunion, failure of regression, and obstruction to urine flow) do not adequately fit with the numerous recent observations made in studies of most experimental models or in human renal cystic disease. 2. The most acceptable theory to date for most types of renal cystic abnormalities (except those due to known obstruction of urine flow) is that abnormalities of the tubular supporting wall occur, probably as a result of toxic or metabolic injury to the tubular cells of the wall and the related interstitial tissues, which are exposed to the highest concentrations of these compounds. This theory would also help explain the etiology of cystic renal diseases in man and should lead to attempts to isolate toxic factors or enzyme abnormalities in susceptible families and in early cases. 3. Induction of cystic abnormalities through a variety of experimental manipulations and drugs reveals impressive strain, sex, and species variability, and these differences should be more carefully examined. 4. The same chemical that induces a cystic change in the mature, fully developed kidney may cause changes which are quite different (location, severity, etc.) in both the fetal and newborn kidney, in which continual nephrogenesis is occurring. 5. Many of the previous explanations of cystic changes require careful reinterpretation of the findings (to reconcile certain differences), and confirmatory studies should be performed to help piece together some of the puzzling observations noted, such as the cystic changes seen with adrenocorticosteroids, and their relationship to potassium depletion.


The morphology of renal cystic disease.

The morphology of renal cystic disease. The morphologic criteria that are applied to make distinctions among the cystic diseases of the kidney involve not the cyst itself but include rather the size, number, and distribution of cysts within the kidney(s); the site(s) along the nephron from which cysts arise; and the presence or absence of involvement in other organs. There continues to be a great need to subject these diseases to the utmost morphologic scrutiny, using all available techniques.


A classification of renal cysts.

A classification of renal cysts. Renal cysts are a heterogeneous group comprising heritable, developmental, and acquired disorders. The classification presented here has been developed, as have several others in the past, to incorporate radiographic, functional, and genetic contributions in its clinicopathologic correlations. Its major categories are as follows: (1) dysplastic cysts arising in kidneys that have undergone abnormal morphogenesis and differentiation; (2) polycystic disease of autosomal recessive and autosomal dominant types; (3) heritable syndromes of multiple malformations with renal cysts resulting from presumed metabolic injury; (4) isolated cortical cysts of unknown pathogenesis; (5) medullary cysts of several types, including medullary sponge kidney and the progressive syndromes of medullary cystic disease, familial juvenile nephronophthisis, and renal-retinal dysplasia; (6) acquired parenchymal cysts of diverse origins; and (7) extraparenchymal cysts. This classification, which has been revised repeatedly over the years, is still tentative and undoubtedly will be revised again.


Genetics in cystic kidney disease.

Genetics in cystic kidney disease. It has become obvious that consideration of only pathological anatomy gives little insight into the pathogenesis of cystic kidney disease. Better markers are required before an adequate system of classification can be developed. Once nosologic separation has been effected, specific diseases can be studied in more detail and an attempt can be made to elucidate the fundamental molecular abnormality. Genetic factors may be extremely useful in defining discrete disease entities; unfortunately, they have been too frequently disregarded by workers in the field. If progress is to be made in the area of structural abnormalities of the kidney, the common efforts of nephrologists, pathologists, physiologists, and geneticists will be required.


Renal cystic disease: radiologic appearance. The great diversity of the various forms of renal cystic disease results in a formidable diagnostic challenge to the roentgenologist and clinician alike. Until recently, adequate diagnosis required surgical exploration or biopsy, or both, to establish benignity or to confirm the suspicion of a more esoteric form of renal cystic disease. Now, however, with refinements in excretory urography with tomography, bolus and infusion nephrotomography, selective renal arteriography, percutaneous aspiration of cysts, and sonography, the accuracy of a clinical diagnosis of cystic disease has approached that of surgical exploration and biopsy. In addition these noninvasive techniques eliminate the morbidity and mortality associated with surgical procedures.


Residues of organochlorines and heavy metals in ruddy ducks from the Delaware River, 1973. In December 1973, eight ruddy ducks killed in an oil spill on the Delaware River were collected to be analyzed for residues of environmental pollutants. Whole carcasses were analyzed for organochlorine pesticides and livers were examined for lead, cadmium, and mercury. Residues of polychlorinated biphenyls and DDT and/or its metabolites were present in all carcasses. Dieldrin and hexachlorobenzene were present in seven of the eight samples. All livers contained detectable levels of lead, cadmium, and mercury.


Chlorinated hydrocarbon pesticides and mercury in coastal young-of-the-year finfish, South Carolina and Georgia--1972-74. Pesticides and heavy metals were monitored in fish collected from 11 estuaries representing all the Atlantic drainage basins in Georgia and South Carolina. Part of the U.S. Environmental Protection Agency National Estuarine Monitoring Program, the semianual survey of young-of-the-year fishes, was conducted from 1972 to 1974. Data are intended to provide an initial base line for residue levels in the fish studied in these waters. Dieldrin was found in 2 percent of the samples, DDT and metabolites were in 33 percent, polychlorinated biphenyls were in 4 percent, and mercury was in 47 percent. Noticeably absent were any measurable residues of toxaphene even though there is a toxaphene manufacturing plant in Brunswick, Ga.


Nationwide residues of organochlorines in wings of adult mallards and black ducks, 1972-73. Organochlorine residues in wings of adult mallards and black ducks were monitored during the 1972-73 hunting season. DDE, DDT, DDD, dieldrin, and polychlorinated biphenyls (PCB's) were present in all samples. Mallard wings from Alabama contained the highest mean levels of DDE, DDT, DDD, dieldrin, and PCB's. Mallards and black ducks from the Atlantic Flyway and mallards from the Pacific Flyway contained significantly lower DDE residues than in 1969-70. Black ducks from the Atlantic Flyway contained significantly less dieldrin than in 1969-70, and mallards in the Central and Pacific Flyways contained significantly lower levels of PCB's. As in 1969-70, DDE residues were lowest in the Central Flyway and highest in the Atlantic Flyway. The average PCB level remained unchanged in the Atlantic Flyway but was higher in the Mississippi Flyway than in 1969-70, probably because of the unusually high levels in Alabama samples. All organochlorine residues in black ducks from the Atlantic Flyway significantly correlated. DDE concentrations in mallards from the Atlantic Flyway significantly correlated with those of DDT, DDD, and PCB's.


Seasonal concentrations of dieldrin in water, channel catfish, and catfish-food organisms, Des Moines River, Iowa--1971-73. Concentrations of dieldrin in aquatic insects, crayfish, minnows, and small carpsuckers, and muscle tissue of channel catfish (Ictalurus punctatus) were compared with the dieldrin content of Des Moines River water in 1971-73. Monthly mean concentrations of dieldrin in river water and most aquatic organisms were highest in June and July, soon after aldrin had been applied to corn land in the watershed. Several groups of aquatic organisms also exhibited high dieldrin levels in the fall when the dieldrin content of river water was seasonally low. The influence of temperature on metabolic rate and enzyme activity and the differences in body fat content were suggested as probable causes of variations observed in the dieldrin content of aquatic organisms.


[Gougerot-Sjögren syndrome in patients with sarcoidosis]. Three patients with eye and salivary dryness presenting the scintigraphic and histological features of Sjogren's syndrome and also suffering from sarcoïdosis, are reported. The authors stress the rarity of clinically indentifiable dry oculo-salivary syndromes whilst routine scintigraphy of the principle salivary glands using technetium 99 m often reveals altered salivary function. They consider that the primary feature in the development of this dry salivary syndrome consists of fibro-inflammatory lesions of the glandular interstitium, seen in specimens of the glands of the labial mucosae, which are sequelae of the initial sarcoid infiltration. They point out that Sjogren's syndrome occurring in relation with sarcoïdosis has certain special features. These include its appearance in relatively young subjects, the minimal symptoms, the non-essential presence of inflammatory signs and the absence of associated connective tissue disorder.


[Diagnostic value of closed thorax pericardial biopsy. 20 cases]. Twenty patients with sub-acute and chronic pericarditis under went closed thorax pericardial biopsy. In three cases the examination brought to light a diagnosis of tuberculosis and in one of a tumoural origin. In 16 cases in which the aetiology was that of a non-specific pericarditis, the value of this examination, integrated into the context, is discussed.


[Stimulation of testicular secretion by chorionic gonadotrophin. Results in normal men and in hypogonadic patients]. In normal adult male, the intra-muscular hCG-test (5000 I.U. X 3) results in a progressive rise of plasma testosterone and dihydrotestosterone, and in a sharp increase of plasma estradiol followed by a decrease although th hCG stimulation is maintained. In testicular dysgenesis, the testosterone and estradiol responses are variable. In adult male gonadotropin deficiency, basal testosterone is always very low, and rises strongly, under hCG-test, only when previous and recent (less than 10 years) exposure to endogenous or exogenous gonadotropin had induced virilization ; by contrast the defective response of estradiol in all cases provides a reliable estimate of the actual gonadotropin deficiency.


[Type IIb primary hyperlipoproteinemia. An homogenous series of 412 cases]. On the basis of a homogeneous series of 412 cases of type IIb primary hyperlipoproteinaemia, the authors compare their experience with findings in the literature. The prevalence of this type of hyperlipoproteinaemia in the general population has been underestimated at 3%. Biological diagnosis remains simple (identification of a double and distinct excess in beta and pre beta lipoproteins). Extravascular lipid deposits (gerontoxon, xanthelasma, tendon xanthomata) are not type specific. Hyperlipidaemic syndrome is rare. Above all, the importance of type IIb in atheromatous disease in the young subject now seems obvious. The mode of hereditary transmission of the familial anomaly is not certain but would appear to be often associated with a double heterozygote condition.


[The exercise electrocardiogram after the acute phase of myocardial infection. Analysis of 100 cases]. A study was made of the effort electrocardiogram (ECG) of 100 patients who had had a myocardial infarction and correlated in 46 cases with findings at coronography. Angina occurred in 38 cases. The ECG remained stable in 17 cases and showed changes in 83. In 60 patients, in those leads with pathological Q waves, isolated T wave changes (15 cases), ST elevation (43 cases) or ST depression were seen. In 17 cases there was isolated ST depression in leads free of any signs of infarction. In 6 cases alterations in rhythm or conduction were seen.


[Renal insufficiency and diabetes cured by removal of a villous tumor of the rectum]. A case of villous tumour of the rectum presenting in a misleading fashion : clinically, an apparent adrenal insufficiency and biologically renal insufficiency and diabetes. The abnormal glucose metabolism was attributed to potassium deficiency. The conditions and frequency of occurence of hydroelectrolytic problems in association with villous tumours and the various presenting features, some misleading, are discussed. The difficulties of diagnosis and treatment are emphasised.


[Changes in anti-tetanus antibodies under sero-toxoid therapy. Study in 50 patients with tetanus]. A study concerning changes in anti-tetanus antibody (ATA) levels in 50 patients with tetanus following the injection of antitetanic serum of equine origin and of toxoid, the first dose of the latter being given 24 hours after the administration of serum and the others at intervals of 5 to 7, 15 and 30 days. Repeated estimation of ATA demonstrated, regardless of the toxoid dose protocol adopted, that levels did not reach 0.1 IU/ml on the 30th day and that they only rose late. By contrast, after a booster, the increase was the same as that seen in subjects who had not acquired tetanus. The various factors which may underly defective active immunisation during the acute phase of tetanus are discussed. Heterologue serum therapy, which has been held responsible, cannot be considered to be a responsible factor since patients who did not receive serum behaved in exactly the same way as those who had. By virtue of this "gap" in the acquisition of immunity, the use of heterologue serum is recommended to neutralise any remaining circulating toxin as rapidly as possible.


[Descriptive anatomical study of the major coronary trunks and the principal epicardial collaterals. 125 cases]. Abnormalities at the origin are rare and involve only the left coronary artery: absence of the trunk of this artery in 3 cases, as a result of separation of the origins of the anterior interventricular and the left circumflex. As far as course is concerned, the principal abnormality involves the anterior interventricular: presence in 17% of cases of an intraparietal segment, quite narrow and with a thin wall which is remarkably fixed and constant in its different characteristics: rapid reading of a film taken during selective injection may lead to a conclusion of stenosis or to that of a non-existent spasm. In 6% of cases, the posterior interventricular is short, joined to the middle part of the posterior interventricular sulcus by a collateral of the right coronary. Thus in the case of a long stenosis of the right coronary artery, right aorto-coronary by-pass, distal, provides no blood supply to the postero-inferior part of the septum and the posterior part of the apex. In more than one third of cases the left first diagonal and marginal arteries are of sufficient calibre to permit implantation of an aorto-coronary graft.


[XXYY chromosomal constitution recognised during the 1st year of life]. The authors report two cases of infants with an XXYY chromosomal constitution. The anomaly was suspected in the presence of a particular facies associated with abnormalities of development of the external genitalia. The diagnosis was confirmed rapidly and easily by immunofluorescent study of buccal scrapings and polynu clear cells. Early diagnosis is a value with regard to family counselling.


[Rheumatoid polyarthritis: should corticotherapy be interrupted in case of gastro-duodenal ulcer?]. The possibility of healing of a corticosteroid-induced ulcer depsite the continuation of the treatment, is now an established fact. It is thus reasonable to continue corticosteroids in those cases where interupption  severely compromises the prognosis. The chances of healing of the ulcer would appear to be great, especially when corticosteroids are being used in low dosage, but the exact frequency of healing remains unknown, just as the frequency of ulcers due to corticosteroid therapy has not been accurately established.


[Poland's syndrome. Clinical and genetic studies; physiopathologic considerations]. Study of malformations of the hand makes possible the definition of three forms of progressive severity in the Poland syndrome, in which there is unilateral symbrachydactylie associated with homolateral aplasia of the pectoralis major. The three forms share the predominance of involvement of the 2nd, 3rd and 4th fingers. The existence of alterations in palmar creases and dermatoglyphia of the involved side alone confirms the absence of any lesion, even infra-clinical, of the other hand. Genetic study favours a pluri-factorial inheritance. Topographical data and the comparative study of vascularisation suggest the possibility of hypoplasia of the proximal portion of the sub-clavian at the origin of this malformative association.


[Fulminating streptococcal cellulitis. Importance of hypovolemic shock]. The authors report three cases. Hemostasis abnormalities and lowering of complement fractions was observed. Severe shock was lethal in two cases associated with severe local lesions. The role of unadapted treatment like corticosteroids and the lack of early penicillino therapy is discussed to explain this evolution.


[Bacterial adjuvants in cell mediated immunity. Recent data]. Only some bacterial adjuvants are able to stimulate cell-mediated immunity. It has been shown recently that this property is due to a cell-wall component, the peptidoglycan. The relevance of these findings to tumor immunity has been discussed.


[Should all prosthetic valve patients be treated by platelet inhibitors?]. The number, volume and adhesive and aggregation activities of platelets were studied in 31 patients with artificial valves. The differences observed in comparison with a control population are due to stimulation of thrombocytopoiesis secondary to the destruction or concumption  of the platelets, it being impossible to be sure as to the dominant mechanism. Under these circumstances it would seem important in each patient to verify the therapeutic effectiveness of platelet inhibitors or of traditionnal anticoagulants by direct or indirect study of platelet life duration.


[Irapa type spondylo-epiphyso-metaphyseal osteochondrodysplasia. New type of dwarfism with short spine and metatarsals]. A new dwarfism of a spondyloepiphysometaphyseal dysplasia is described among Venezuelan Indians of the Yukpa (Irapa) tribe. Brachyrrhahia, brachymetatarsia and brachyrhyzomelia in upper limbs and manifestations in proximal epiphyses of femora and distal epiphyses of humera, with moderate to serious impairment of gait, but no significance deviations of the spine, are the main clinical findings. It is a well individualized type among a very heterogeneous and ill-defined group of chondrodystrophies. The inheritance is through an autosomal recessive or less probably an X-linked gene.


[12 years of medical treatment of Cushing's disease. Long-term use of Op, DDD in 46 cases]. The authors report the results of the medical treatment in 46 cases of Cushing's disease. Long-term Op,DDD therapy apparently results in a drug-induced total adrenal suppression in 28 cases. In 12 cases it reduces the adrenal secretion down to the normal level. In only 6 cases of this series was the treatment unsuccessful. Accordingly the authors think that long-term medical treatment with Op,DDD deserves to be considered as a major total tool within the therapy of Cushing's disease. However regular and precise monitoring under therapy is necessary. The schema of the method used is described.


[Acute purulent meningitis of traumatic origin. 16 cases]. The current frequency of road accidents leads to the necessity to seek a possible head injury in the past history of patients suffereing from acute purulent meningitis. This investigation must be all the more assiduous in the presence of a meningitis which is pneumococcal in origin and recurrent. Rhinorrhoea is a sign of primary importance. Tomography of the frontal and sagittal views of the skul remains of value. Radio-isotope studies of the CSF happile make up for the deficiencies of radiological examination, without providing an infallible means for the detection of osteomeningitis defects. The authors report their findings and therapeutic results in 16 patients collected in a series of 162 cases of acute purulent meningitis.


[The role of pericardial pathology in internal medicine]. In the multiple pathology of a non-specialised patient group in internal medicine, 1,2% presented with a pericardial disorder. The true occurrence rate of pericarditis is in fact much higher since if the cases where pericarditis is found only at autopsy are taken into consideration, pericardial involvement is found in almost 10% (this figure is higher, for obvious aetiological reasons, than that for non-fatal peridarditis). The improvement in obtaining a positive diagnosis of pericarditis is obvious when a study carried out ten years ago is reviewed. Finally, comparison of the aetiological types in our study with those seen in cardiology services shows important differences and takes account of the special nature of pericardial pathology in general medicine and the interest of its study.


[Serum antibodies in urinary infection in children. Significance and relation to pyelonephritis]. Serum antibodies were measured repeatedly in 176 cases of urinary tract infections in children. The method used, passive haemagglutination with the bacterial antigen of the patient's urinary infection, gives a positive reading from 1/160. Antibodies were found in 139 cases and the lower limit compatible with a diagnosis of pyelonephritis was 1/2560. The result may, however, be negative in infants of less than one year. As in the first publication, the authors describe three types of curves of progression. Analysis confirms the relationship between persistent antibodies and evolutive pyelonephritis. Experimental results and a comparison of clinical and pathological findings are discussed and support the notion of the value of a persistent high antibody level in the diagnosis of chronic pyelonephritis.


[HL-A antigens in patients with psoriatic rheumatism]. The authors studied HLA tissue groups for 28 specificities in 70 patients with psoriatic arthropathy (44 with pure peripheral arthropathy and 26 with axial involvement, 19 of whom also had peripheral lesions). Four antigens of this system were found with a significantly increased frequency in 70 patients in comparison with a control group of 152 normal subjects. For antigen HLA-B27, the frequency seemed very significantly increased in patients with axial involvement as compared with those without axial troubles (pc less than or equal to 0.0001) and with the controls (pc less than or equal to 0.0001). For antigen HLA-B13, the frequency was significantly increased in patients with axial involvement as compared with the controls (pc less than 0.05). Antigen HLA-Bw17 was present with significantly increased frequency as compared with the controls in the patients with peripheral involvement (pc less than 0.001). For antigen HLA-Bw38 (W16.1), the frequency in patients with or without axial involvement was significantly increased in comparison with the controls (pc less than 0.001). The interpretation of these results is discussed and the association of antigen HLA-B27 with sacro-iliac involvement once again stressed.


[Ultrasonic echocardiography in the normal newborn infant. Application to the diagnosis of congenital cardiopathies]. Ultrasound echocardiography is automatic easy to carry out even in children in a precarious condition. The authors show the value of echocardiography in the neonatal period in a preliminary study involving 50 normal newborn infants. They discuss the cardiac abnormalities which may be diagnosed using this technique.


[Degenerative spondylolisthesis. Clinical manifestations and treatment apropos of 26 operated cases]. The authors report 26 cases of surgically treated degenerative spondylolisthesis. Twelve patients complained of permanent uni or bilateral sciatica. All the others had a syndrome of intermittent claudication with pain and paresthaesia. The authors stress once again the highly evocative nature of this syndrome which reflects involvement of the nerve roots in the stenosed lumbar canal. Treatment consisted of lamino-arthrectomy which resulted in the disappearance of symptoms in most of cases. In four cases, vertebral slipping worsened during the post-operative cowise with, in three cases a recurrence of symptoms necessitating a complementary arthrodesis. This risk of increased slipping is a result of the instability created by the arthrectomy, especially when it is bilateral, and has led the authors to widen their indications for routine complementary postero-lateral arthrodesis.


The metabolic and structural changes of the liver in experimental animals after administration of isoprenaline. Application to rats and rabbits of higher doses of isoprenaline (IP) results in derangement of glycid metabolism, manifested by the decrease of free glycogen (free-GL), and in an even more significant impairment of lipid metabolism, evidenced by an earlier increase of non-esterified fatty acids (NEFA) followed by an increase of esterified fatty acids (EFA) and a concomitant development of fatty infiltration, all indicators of marked lipomobilization. Histograms obtained from hypersensitive individuals show besides fatty infiltrations also necrobiotic processes and structural changes, seen as distinctly marked liver cell membranes. It is perhaps relevant to draw attention to the fact that there are both individual and species differences in the metabolic changes ensuing on application of IP.


Pharmacobotanical investigations on some species of the Scrophulariaceae family. Part V. Chemical constitutents in Lathraea squamaria L. From the Lathraea squamaria L. aucuboside and D-mannitol have been isolated and the presence of glucose, fructose and the ester of aucuboside stated. In the fraction after hydrolysis the presence of 6 phenolic acids has been found. The glucosides of the aucuboside group have been considered as elements of chemotaxonomical meaning.


Studies on the synergism of some hypotensive drugs with ethanol. Synergism of some hypotensive drugs with ethanol was studied for its influence on the central nervous system. A very strong central action of the drugs and ethanol administered simultaneously in subthreshold doses was observed. Intensity of synergism was calculated by comparing the results with the effective doses of each drug administered seperately.


The influence of cholinomimetics on bioelectric activity of rabbit's limbic system and behaviour. The influence of acetylcholine, physostigmine, and carbachole administered systemically in aqueous solutions and the volume of 2 or 3 mul to dorsal hippocampus (DH) or basal amygdaloid nucleus (BA) on rabbit's EEG and behaviour in chronic experiment was examined. EEGs were recorded from anterior cingular gyrus, DH, BA and medial hypothalamus. The excitation or attack activities after the administered compounds and of the receptors sensitive to acetylcholine in DH and BA were stated. Moreover, a strong functional connection of DH and BA was observed.


On the choice of so-called placebo solution for the intranigral microinjection in the rat. Rats moving freely in their cages were injected into substantia nigra with bidistilled water, with NaCl solutions of various concentrations or with a multionic Merle's solution. The solutions were administered uni- or bilaterally at volumes of 1-5 mul through chronically implanted chemitrodes. The behavior of animals and the EEG of frontal cortex, hippocampus, caudate nucleus and substantia nigra were observed. A part of the usual EEG record analysis two channels of EEG were evaluated with amplitude integrators. The main goal of the experiment was to find the optimal solvent for microinjection into the substantia nigra. So-called physiological saline solution (0-9% NaCl) was found to be most toxic and the multionic Merle's solution most suitable among the control fluids tested. The influence of "pressing effect", of pH as well as the influence of ionic concentrations of solutions tested are discussed.


The effect of neuroleptics on the development of gastric ulcers in rats exposed to restraint-cold stress. Gastric ulcer development and changes in the contents of glucose, free fatty acids (FFA), and K and Ca ions in the blood were studied in rats subjected to a graded stress of immobilisation and cold. During stress the volume of secretion and the output of HCl, decreased although the concentration rose slightly. Chlorpromazine (CPZ), thioridazine (TRZ), spiroperidol (SPI), and fluphenazine (FLU) inhibited to various degrees ulcer formation during stress. SPI reduced stress-induced mucosal damages in 94%, but FLU even in doses 100 times smaller than those of the other drugs counteracted ulcer formation. CPZ, TRZ and SPI in preventive doses increased proportionally the blood glucose level both in control rats and in those subject to stress. FLU in effective doses produced no hyperglycemia either in control rats or in those exposed to stress. We conclude that the prevention of gastric ulcer development by neuroleptics may be the result of their antisecretory action and counteracting of breakdown of sympathetic activity during severe stress.


Synthesis of 2,4-disubstituted 5-aminopyrimidine-6-carboxylic acids derivatives part I. 5-Benzoyloaminoorotic acid in a reaction with POCl3 forms 2,4-dichloro-5-benzylo-aminopyrimidine-6-carboxylic acid lactam 3, which heated with aliphatic and aromatic amines gives corresponding amides 6-11. These compounds don't show any antiinflammatory or antivirus activity.


Kinetics of drug decomposition. Part 37. Kinetics of autoxidation of narcotine in aqueous solutions. The overall apparent first-order rate constants for the reaction of autoxidation of Narcotine (NC) - k1 and Cotarnine (CT) - k2 and the rate constants for autoxidation of the protonated (ks) and undissociated (kb) forms have been determined. The kinetic equation for the reaction of autoxidation at constant concentration of NC, CT and the atmospheric oxygen depending on the pH of the reaction medium has been established as: k1 = ks([H+]/([H+]+K'a))+kb(K'a/([H+]+K'a), k2=(ks[H+]+K'a))+kb (K'a/([H+]+K'a) (1+1+1/kt+1K)). The following thermodynamic parameters for the rate constants ks and kb have been calculated: deltaH not equal to, log A and deltaS not equal to.


Derivatives of the L-lysine-peptides with antibacterial activity. A number of derivatives of the L-lysine peptides has been obtained and their antibacterial properties were evaluated and compared with those of the ethyl ester of Nalpha-palmitoyl-L-lysyl-L-lysine dihydrochloride. Some correlations have been found between the chemical structure and antibacterial activity of the compounds.


The search for new drugs in the group of xanthine derivatives. Part XL. 7-Aminoxyalkyltheophyllines. 7-Aminoxyalkyltheophyllines 4-6 were obtained in good yield by acidolysis or hydrazinolysis of 7-phtalimidoxyalkyltheophyllines 1-3. The structure of obtained compounds was confirmed on chemical routs by preparing typical derivatives (acyl, and oximes) and by UV, IR and NMR spectra.


Transient ischemic attacks: Pathophysiology and medical management. There is substantial evidence to support the concept that most transient ischemic attacks (TIAs) are caused by microemboli that originate in areas of atherosclerosis in the blood vessels of the neck. TIA's are important risk factors in the development of stroke. The most common clinical features of TIAs caused by carotid insufficiency are hemianesthesia and hemiparesis; other symptoms in these cases include headache, dysphasia, and visual field distrubance. By far the most common clinical manifestation of vertebrobasilar insufficiency is vertigo.


Radiologic examination of patients with stroke. The reasons for radiologic evaluation of patients with cerebrovascular accidents, or strokes, and transient ischemic attacks are (1) to demonstrate surgically correctable vascular lesions and intracerebral masses due to hematomas and (2) when necessary, to confirm a diagnosis of atherosclerotic brain disease and rule out the presence of such conditions as subdural hematoma, aneurysm, arteriovenous malformation, or tumor. The radiologic techniques available include plain skull radiography, ultrasound, radionuclide scanning, computerized transaxial tomography (CTT), and cerebral angiography.


The role of surgery in ischemic stroke.

The role of surgery in ischemic stroke. Surgery in the management of stroke is useful primarily as a stroke-preventive measure for patients with extracranial carotid artery occlusive disease. Ideally, lesions that are potential sources of ischemia are removed before a fixed neurologic deficit can occur. Patients with transient ischemic attacks and no deficit or only minor neurologic deficit comprise the largest group of surgical candidates. Diagnostic angiography must be carried out before endarterectomy and should include aortic arch studies of both extracranial and intracranial carotid arteries. Placement of an intra-arterial catheter at the beginning of surgery provides the best method of monitoring arterial pressure. A postoperative angiogram allows visual confirmation of the patency of reconstructed vessels. Such confirmation is particularly important if patients have severely stenotic bilateral carotid artery disease. The surgical mortality for all patients with TIAs is between 1% and 2% in those clinics in which this type of operation is commonly done.


Rehabilitating patients with stroke.

Rehabilitating patients with stroke. Experience at the Burke Rehabilitation Center indicates that a rehabilitation program established early and giving proper attention to both personal and medical aspects can make it possible for 80% of stroke victims to return home and to function with reasonable adequacy. Rehabilitation efforts should begin as soon as possible after a stroke and can be effectively carried out in community hospitals.


Traumatic injuries: office treatment of minor burns. While minor burns are not life threatening, they may result in significant morbidity, such as loss of function, prolonged healing time, and scarring. Proper office care is mandatory if such complications are to be prevented.


Community medicine: screening for rubella on a university campus. Today's college-age students have not benefited from the mass immunization of children that followed the introduction of live attenuated rubella vaccine in 1969. Speculation on one university campus as to the number of young women who were susceptible to rubella led to a pilot program of rubella screening and a follow-up program of immunization and provided valuable data on the need for such a project.


Dealing with possible rabies exposure.

Dealing with possible rabies exposure. When a patient has come in contact with a domestic or wild animal that may be rabid, the physician must decide whether postexposure rabies prophylaxis is warranted. Among the factors that must be weighed are the animal species involved, the epizootiology of rabies, and the circumstances surrounding the exposure.


Selecting chemotherapy for metastatic breast cancer. When cytotoxic chemotherapy is indicated in metastatic breast cancer, usually a combination of an alkylating agent and an antimetabolite, with or without doxorubicin, is used. The combinations including doxorubicin appear to give the best response rate.


Diuretic agents. Mechanisms of action and clinical uses. Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Furosemide (Lasix), ethacrynic acid (Edecrin), and possibly organomercurial agents are effective in the ascending limb of Henle's loop. Thiazides are the major agents acting in the early distal tubule. In the late distal tubule and collecting duct, spironolactone (Aldactone) and triamterene (Dyrenium) are useful, especially in combination with diuretics which act more proximally. In treating edematous states, initial therapy with thiazides is effective in most patients who do not exhibit moderate or severe renal insufficiency, severe hyperaldosteronism with excessive distal reabsorption of sodium in exchange for potassium, or excessive sodium reabsorption in the proximal tubule or ascending limb. Nonedematous states in which diuretic therapy is useful include hypertension, hypercalcemia, hypercalciuria, diabetes insipidus, and acute renal failure.


Stinging insect allergy: changing concepts. Immunologic advances promise changes in the approach to diagnosis and treatment of Hymenoptera stings. Results of skin tests with venom show good correlation with those of in vitro tests (histamine release and radio-allergosorbent test [RAST]). Similar comparisons of whole-body extract (WBE) skin tests with in vitro tests show poor correlation. Treatment emphasis must currently be placed on sting prevention and on medical treatment. The only material now available commercially for immunotherapy is WBE. Circumstantial evidence suggests some benefit from immunotherapy with WBE, but immunologic data do not support this observation.


Managing obesity: why diet is not enough. When the many biologic and societal factors predisposing persons to obesity are considered, it is understandable why traditional therapy so often fails. To be effective, a program of therapy for obesity must include necessary changes in behavior, attitude, and life-style; dieting is not enough. As a first step, the determinants of past and present behaviors contributing to high energy intake, low energy expenditure, or both are identified. Once this is done, therapy is directed toward altering exposure, susceptibility, or response to these determinants.


Recognizing alcoholism early by physical signs. It is hoped that by being alert to clues easily seen on simple inspection, physicians will be more confident in uncovering hidden alcoholism or at least will pursue further any indications in the patient's behavior or history that might lead to early diagnosis and hence to treatment.


Assessing drinking problems by history.

Assessing drinking problems by history. Patients with alcohol problems can be categorized as either medical alcoholics, who have medical problems caused by high levels of alcohol consumption, or behavioral alcoholics, whose drinking results in adverse changes in their behavior. Behavioral alcoholics pose a diagnostic problem to the physician because of their highly developed denial systems. A detailed, accurate drinking history is necessary for diagnostic assessment, and the physician must employ several key strategies in order to circumvent the denial system and elicit relevant information. Additional information can be obtained from a member of the problem drinker's family. Family members should also be involved in the treatment process.


Diuretics. Use and misuse.

Diuretics. Use and misuse. It is apparent that the large number of diuretics available today enables the clinician to mobilize edema fluid from patients with heart failure or other fluid retention states, to control blood pressure effectively in many patients with hypertension, and to manage many nonedematous states more successfully. The potency of some of these agents and their varied effects on renal tubular transport necessitate a cautious approach based on an understanding of their mechanisms of action. By selectively choosing different diuretics or diuretic combinations, the clinician can achieve the desired diuretic effect and prevent many of the electrolyte and acid-base derangements that accompany diuretic therapy. Selectivity of usage based on knowledge of the practical clinical pharmacology of these agents will also minimize the occurrence of side effects and avoid undesirable drug interactions.


Antiarrhythmic drugs for ischemic heart disease. Therapy with antiarrhythmic drugs may offer the best immediate hope for reducing the large number of deaths due to arrhythmias among patients with ischemic heart disease (IHD). For the prevention of sudden death from ventricular fibrillation, chronic use of these drugs is reasonable in high-risk ambulatory IHD patients, in any patient in whom acute myocardial infarction (MI) is suspected, and in some patients hospitalized for acute MI. However, the effectiveness and possible risks of administering antiarrhythmic drugs in these settings remain essentially unknown. The selection of IHD patients who will benefit most from prophylactic antiarrhythmic drug therapy, the best times for starting and stopping this therapy, and the choice of drug cannot yet be guided by controlled clinical experience. Carefully controlled prospective studies of the beneficial and untoward effects of different drugs in IHD patients are urgently required to provide better guidelines for the clinical use of these potentially life-saving drugs.


Why the angry adolescent?

Why the angry adolescent? The angry behavior of youth today is not a phenomenon but one that is becoming more widespread. The reasons behind it are many and varied. Government commissions formed to review the circumstances and prospects of children in America have repeatedly pointed out the needs of youth, but their recommendations have largely been ignored. That "we get what we give" is particularly true in regard to the behavior of our youth. A national commitment must be made to fulfill the basic needs and rights of all young people. They must be given responsibility for their own acts, and the transition from adolescence to adulthood must be facilitated by concerned, caring adults.


Traumatic injuries: office treatment of lacerations. Every laceration should be explored to its depth to locate foreign bodies and damage to tissues. Debridement should be thorough except on the face, where conservation of skin is important. Deep lacerations are closed in layers, using different sutures for each layer; if tissue has been lost, plastic tecnhiques of closure are necessary. Lacerations that are carefully repaired rarely become infected, and tetanus prophylaxis is the only required safeguard against infection.


Psychiatry: unresolved grief. Clinical considerations. Unresolved grief refers either to the absence or to the prolongation of normal grief. It is identified by (1) painful response to recall of the deceased, (2) realization of not having accepted the loss or of not being able to grieve, and (3) unaccountable depression, emergence of medical symptoms on the anniversary of the loss, or both. Three clinical syndromes can be defined in relation to the stage at which the grief process has been arrested. Treatment involves encouraging patients to talk about the deceased and guiding them through a normal grief reaction. Psychiatric evaluation should be considered when suicidal ideation is present.


An investigation of the incidence of cardiac murmurs in young health women. Healthy women students who asked for oral contraceptives were carefully examined to ascertain whether they had a cardiac murmur. Over 52 per cent of the 509 women examined had such a murmur and of these murmurs 3-4 per cent were thought to have an organic origin.


Rubella antibody tests in family planning clinics. Women attending for family planning advice at area health authority and general practitioner clinics were offered a test of rubella antibody status. The acceptance rate was approximately 50 per cent. Of the 100 women tested, 15 were not immune and 8 of these were subsequently vaccinated. In this study, the cost of the service was estimated to be 1-50 pounds per woman, or approximately 5000 pounds to prevent one case of congenital rubella. On this basis the assessment of rubella immunity in women using reliable contraception is considered to be feasible and could prove even more worthwhile on a cost-benefit basis if applied to an entirely nulliparous group.


Samuel Hyde lecture. Polypharmacy in rheumatoid arthritis--help or hindrance? The use of multiple drugs in treating rheumatoid arthritis is based on the assumption that their effects are additive. Sometimes the results are unexpected or the added drug may confer no additional benefit to the patient whilst leaving him more liable to undesirable side-effects. Some form of polypharmacy may be necessitated by the different pharmacological properties of our drugs. Certain drugs have been judged on their steroid-sparing effects allowing lower doses to be used and thereby reducing the toxicity of corticosteroids. It is likely that some potential areas of danger from interacting drugs have been over-emphasized, being based on speculative rather than real data or purely on animal experiments using non-clinical doses. The patient with active RA with a low serum albumin would be unusually susceptible to changes induced by combinations of strongly bound anti-inflammatory drugs. He would also be highly susceptible to side-effects, as has been shown with prednisone. Side-effects here are doubled when the patients serum albumin is below 2.5g/100ml(lewis et al.1971). I believe we should continue to ask ourselves whether by subtracting one or more drugs from the patients cocktail we may not produce a most welcome benefit for both patient and doctor and, I suppose we could even add, the hard-pressed tax payer.


Lipoprotein lipase activity in the bovine corpus luteum during the estrous cycle and early pregnancy. Lipolytic activity measured at pH 8.6 in bovine corpora lutea exhibited classical properties of lipoprotein lipase (LPL) in terms of serum and heparin stimulation and NaCl inhibition. LPL activity was measured in 23 corpora lutea collected at different stages of the estrous cycle and early pregnancy. The LPL activity in cyclic corpora lutea (mumole FA released/hr/100 mg acetone powder) was low at Days 4-8 of the estrous cycle (3.1 +/- 1.5: mean +/- SE) and at Days 19-20 (1.6 +/- 0.6). However, high activity of the enzyme was found at Days 12-15 of the cycle (11.8 +/- 1.8); these concentrations were significantly (P less than 0.01) elevated over those found at Days 4-8 and 19-20. The enzyme activity began to decline at Days 16-18 of the estrous cycle (5.1 +/- 1.7). Low enzyme activity was found in the corpora lutea removed from two cows at Day 22 of pregnancy. Progesterone concentrations were measured in 16 of the 23 corpora lutea and a good correlation (r = 0.75, P less than 0.01) was found between lipoprotein lipase and progesterone concentrations of the tissue. The data suggest that LPL may be involved in controlling the transfer of fatty acids, including arachidonic, from plasma lipoproteins to luteal tissue.


Comparison of dy and dy2J, two alleles expressing forms of muscular dystrophy in the mouse. The muscular dystrophies caused by dy and dy2J on a C57BL/6J genetic background are similar in quality. At 1 month, slight differences occur in distribution of the muscle lesions, diffuse and focal, respectively, but at 3 months little, if any, differences exist. The dy dystrophy appears the same histologically on either the C57BL/6J or original 129/ReJ and 129B6F backgrounds.


Differences in survival among germfree mice following transfer to a conventional colony. Sex and strain differences in survival were studied in 7-9 month old germfree mice following transfer to a conventional colony. One outbred and three inbred strains were observed. All outbred CD-1 mice survived transfer and in 4 months increased their weight by 50%. The majority of inbred mice survived 7 months after transfer. Sex differences in survival were evident throughout the experimental period and were most marked 7 months after transfer. An unexpected new finding was the viability of the male sex in germfree mice after transfer. Possible explanations are considered.


Reduction of experimental myocardial infarct size with hyperosmolar mannitol. Hypertonic mannitol previously has been shown to improve cardiac function, increase collateral flow, and decrease epicardial ST segment elevation following coronary occlusion in anesthetized or awake dogs. The present study quantitates by morphologic techniques, the effect of hypertonic mannitol on infarct size. Ischemic injury was produced by proximal occlusion of the circumflex artery for 40 min and necrosis was assessed after 48 hr of reflow. One group of dogs was given isotonic saline and the other hypertonic mannitol beginning the infusions just prior to, during, and for a short period after the release of the circumflex coronary artery occlusion. Serum osmolality increased by approximately 40 mOsm in the mannitol group. The administration of hypertonic mannitol was associated with a 40-50% reduction in infarct size ventricular fibrillation during occlusion and following release of the circumflex coronary artery occlusion was greater in mannitol-treated dogs although the difference was not statistically significant. Thus, the data obtained in this study extend previous observations and provide direct evidence that hypertonic mannitol can reduce infarct size in dogs with temporary circumflex artery occlusion and reflow.


Persistent infection of cells in culture by respiratory syncytial virus. The virus-cell relationship of RS virus and the HEp-2 cell line has been examined. The production of cytopathic effect (c.p.e.) on HEp-2 cells has been found to be dependent upon the passage level  of the cell line. Cells at lower passage levels exhibit c.p.e. in the form of syncytium formation, while those at higher passage levels no longer exhibit this effect. Cells infected at higher passage levels are covertly infected and continue to produce large amounts of infectious virus which remains cell-associated. On continued passage, these cells remain infected with virus but show no c.p.e. and release little if any infectious virus into the medium. Examination of the RNA species present in infected cells revealed that similar species are present in both the overtly and covertly infected cells.


Comparison of effects of prolactin and growth hormone on adrenal 5alpha-reductase in hypophysectomized rats. Adrenal 5alpha-reductase activity was measured in female rats 0, 2, 5, and 6 days after hypophysectomy. Enzyme activity increased progressively exhibing a 35-fold elevation at 6 days. The effects of high (250 mug/100 g of body wt), intermediate (25 mug/100 g of body wt), and low (2.5 mug/100 of body wt) daily doses of bovine prolactin and bovine growth hormone were compared at 2 and 5 days posthypophysectomy. At 2 days, enzyme activity was partially inhibited by the high and intermediate doses of prolactin and not affected by growth hormone. At 5 days all doses of prolactin were inhibitory, whereas enzyme activity was suppressed only by the high dose of growth hormone. With a given dose of hormone, the amount of suppression of enzyme activity is greater at 5 days than at 2 days posthypophysectomy. In 5-day hypophysectomized rats the inhibitory effects of prolactin and growth hormone were additive. It is concluded that: (i) hormonal sensitivity  and responsiveness of the adrenal reductase pathway increases with duration of pituitary ablation; (ii) the reductive pathway is more sensitive to the effects of prolactin than growth hormone; and (iii) the effects of growth hormone and prolactin on reductase activity are mediated via different mechanisms, as suggested by the additive effects of individual hormones.


Effect of vitamin B12 and folate on biosynthesis of methionine from homocysteine in the nematode Caenorhabditis briggsae. (i) Omission of L-methionine from the medium resulted in an 80% population reduction. Substitution of D,L-homocysteine corrected methionine deficiency in C. briggsae in the presence of supraoptimal vitamin B12 and folic acid. (ii) An absolute vitamin B12 requirement in C. briggsae developed in the medium containing homocysteine at the second subculture. Concentration of 6 ng/ml of vitamin B12 (at 100 ng/ml of folic acid) was sufficient to support maximum growth of C. briggsae in the medium containing homocysteine. (iii) It was found that either supraoptimal folic acid (2000 ng/ml) or supraoptimal vitamin B12 (3750 ng/ml), with homocysteine, supported very little population growth of C. briggsae. However, supraoptimal folic acid and supraoptimal vitamin B12 together supported a maximum population growth. Therefore, it was concluded that both vitamin B12 and folic acid were required for the biosynthesis of methionine from homocysteine. Studies also showed that the two vitamins spared each other for population growth in the medium containing homocysteine.


Evaluation of (14C)aminopyrine clearance for determination of gastric mucosal blood flow. This study has demonstrated high correlation between the radiometric and spectrophotometric determinations of gastric mucosal aminopyrine clearance. The radiometric method is technically easier, allows a larger number of samples to be determined and is safer to the subject. The clearance of small amounts of [14C]aminopyrine was unaffected by large doses of unlabeled aminopyrine showing that mucosal extraction is not concentration limited. Small amounts of [14C]aminopyrine may provide an excellent tool for examining the role of mucosal blood flow in the pathogenesis of gastric disease in man.


Levamisole augmentation of lymphocyte hyporesponsiveness to phytohaemagglutinin in patients with pulmonary tuberculosis. Levamisole has been shown to augment the in vitro responsiveness of lymphocytes to PHA stimulation. The response of lymphocytes of 14 (42%) of 33 patients with pulmonary tuberculosis was augmented by levamisole. Augmentation was observed in 9 (64%) of 14 PHA hyporesponsives lymphocytes and in 5 (26%) of 19 normo-responsive lymphocytes.


Peripheral plasma progesterone during egg transport in the rabbit. Peripheral plasma progesterone concentrations were measured in New Zealand rabbits every 6 hr beginning 12 hr before and continuing until 96 hr after either natural mating, hCG injection, or saline injection. The number of ovulation points in naturally mated animals (9.3 +/- 0.6, mean +/- SE) was not significantly different from that in hCG-injected animals (8.6 +/- 1.5). There was a surge in progesterone secretion following both mating and hCG injection. Plasma progesterone concentrations reached a peak prior to ovulation and then fell to basal levels at the time of ovulation. Beginning at approximately 30 hr after the ovulation-inducing stimulus, there was a progressive, significant (P less than 0.001) increase in plasma progesterone concentration, which continued for the duration of the sampling period. The initiation of the postovulatory increase in progesterone secretion corresponds temporally with the movement of eggs from the ampullary-isthmic junction into the isthmus. The progressive increase in plasma progesterone between 30 and 72 hr after the induction of ovulation corresponds with the gradual movement of eggs through the isthmus into the uterus. The data suggest that movement of eggs through the oviductal isthmus is influenced by the postovulatory secretion of progesterone.


The effect of detergent treatment of the gastric mucosa on drug transport. The effect of detergent treatment of the canine gastric mucosa on transport of drugs from blood to gastric juice was studied using a chamber technique, in vivo. Detergent treatment was found to increase antipyrine and aminopyrine transport. Facilitation of drug transport was associated with disruption of the gastric mucosal barrier and an increase of aminopyrine clearance.


Effect of sodium intake on gentamicin nephrotoxicity in the rat. Gentamicin nephrotoxicity was examined in rats on normal, high, and low sodium diets. Low sodium diet markedly potentiated nephrotoxic effects of the drug as evidenced by animal mortality, renal failure, pathological changes, and increased renal cortical concentration of the drug. High sodium intake reduced the cortical concentration of gentamicin but renal function and ultrastructure were similar to normally fed rats given in the same dose.


Antigenicity of licensed whole virion and subvirion influenza vaccines in "high risk" persons. The frequency and magnitude of serum antibody response to type A and B influenza virus induced by whole virion and subvirion vaccines were essentially comparable. Immunization was followed in vaccinated individuals by an antihemagglutinin antibody response to the common antigenic determinant shared by the type A H3N2 viruses. Relatively few individuals developed antibody to the type-specific determinant.


Changes in the composition of canine respiratory cells obtained by bronchial lavage following irradiation or drug immunosuppression. Canine respiratory cells, obtained by bronchial lavage, and blood leukocytes were monitored to observe cellular changes following acute and chronic immunosuppression. Irradiation (350 R) produced bone marrow suppression and prompt peripheral blood leukopenia, but did not affect recovery of pulmonary alveolar macrophages or lymphocytes for 12 days after. Treatment for 6 weeks with daily methylprednisolone (1 mg/kg) caused  a progressive decrease in the number of recoverable respiratory lymphocytes, whereas alternate day methylprednisolone (2 mg/kg) had less effect. Cyclophosphamide in  combination with steroids generally augmented the progressive loss of blood and respiratiory lymphocytes. Recovery of alveolar macrophages was not changed appreciably. Thus, the population of lung macrophages, sampled by pulmonary lavage, withstood acute and chronic forms of immunosuppression very well. In contrast, canine lymphocytes seem more susceptible to injury, especially to drug regimens containing steroids.


Vitamin E supplementation and glutathione peroxidase activity. Both excess dietary vitamin E and vitamin E deficiency in rats can significantly depress the activity of GSH peroxidase in liver and plasma of rats. Of all the six levels of vitamin E tested in this study, the dietary level of vitamin E found to maintain the maximum activity of GSH peroxidase in tissues of rats was somewhere between 25 and 250 IU/kg diet. This study conclusively indicates that the excess dietary vitamin E represses GSH peroxidase activity.


Transferrin function in zinc absorption and transport. Blood was drawn from the portal vein of rats immediately after the insertion of 65Zn into the duodenal lumen. Analysis of the plasma from the portal blood demonstrated that the major portion of absorbed 65Zn was bound to transferrin. When apotransferrin was incubated with 65Zn-labeled basolateral plasma membranes, 60% of the isotope was removed from the membrane. Zinc-free albumin prepared with histidine removed 25% of the 65Zn from labeled membranes and histidine had no effect. These results demonstrate that transferrin functions in the absorption and transport of zinc.


Effect of diuretics on intestinal transport of electrolytes, glucose, and amino acid. The jejunal mucosal membrane of albino mice was used to study the electrical properties and ion transport. The membrane was bathed in Krebs-Ringer solution with or without glucose. When ethacrynic acid (EA), furosemide, or amiloride was added to the bathing fluid of both sides, a transient increase followed by a decrease of both potential difference (PD) and short circuit current (Isc) were observed. In glucose-containing bathing medium, EA inhibited both net Na and Cl flux and residual flux; however, EA had little effect on both Na and Cl flux in glucose-free bathing medium. Studies using everted intestinal sac technique showed that EA inhibited both glucose and L-tyrosine across the mucosal membrane against concentration gradients. Furosemide and amiloride were less potent than EA in inhibiting the Na and Cl flux when the bathing solution contained glucose. But these two compounds had no effect on glucose and L-tyrosine transport across the intestinal mucosa. Furthermore, they did inhibit Cl flux even in the condition of glucose-free bathing medium. It is postulated that all three diuretics act on the brush-border membrane of the intestine. EA probably inhibits the Na-glucose cotransporting system; furosemide and amiloride inhibit the simple diffusion process of Na entry of Cl exit by decreasing the conductance of the membrane.


Sex-related difference in antral and serum gastrin levels in the rat. Antral and serum gastrin concentrations were found to be significantly lower in female than in male rats. Following ovariectomy, serum gastrin concentration significantly increased to male levels; tissue gastrin also increased, but not significantly. Daily injections of estradiol benzoate (2 mug/day) abolished the rise in gastrin levels after ovariectomy. Antral and serum gastrin concentrations were significantly higher in lactating rats than in any other group tested. The possible relationships among sex-dependent changes in food intake, gastrin concentration, and gastric secretion are discussed.


Capillary density of skeletal muscle in Andean dogs. High capillary density and small muscle fiber diameters were found in the sternothyroid muscle of dogs native to 4350 m. The number of capillaries per square millimeter was three times greater while the diameter was less than half of those obtained in the same muscle of normoxic dogs. These findings suggest that tissular adaptative mechanisms are important in the process of acclimatization to hypoxia, contributing to the maintenance of adequate levels of PO2 in the tissue in the presence of hypoxemia.


Thyroxine and triiodothyronine influence cultured throid cells: alterations of morphology and mucosubstances. Further experimentation with the steer thyroid cell line indicates that the formation of "follicles" is enhanced by exposure to 8.9 X 10(-7) M thyroxine (T4) or triiodothyronine (T3) for 96 hr. The production of mucosubstances by the cultured thyroid cells is also increased by treating with T4 or T3, effects demonstrable after staining with PAS-alcian blue at pH 2.5. It is suggested that these in vitro effects bear on morphological organization and synthetic activity of the thyroid gland as well as on autoregulation and intraglandular homeostasis that may occur in situ.


Failure of ovalbumin associated with allogeneic spleen ceels to stimulate proliferation of lymph node cells of immune mice. Ovalbumin-pulsed spleen cells were found to stimulate thymidine uptake of lymph node cells of syngeneic mice immunized with ovalbumin in complete Freund's adjuvant after treatment of spleen cells with Mitomycin C but not after heating the spleen cells at 56degrees for 30 min. Ovalbumin-pulsed spleen cells of allogeneic mice failed to stimulate the immune lymph node cells more than unpulsed cells, although a net increase in the thymidine uptake above the allogeneic stimulation was observed when free ovalbumin was added to the mixed culture. To eliminate the high background of the mixed lymphocyte reaction, F1 mice were made chimeric with bone marrow of one of the parental strains. Using lymph node cells of the immunized chimeras, the stimulation by pulsed spleen cells was much greater when antigen was presented on cells of the parental strain used for bone marrow injection than when presented on cells of the other parental strain.


Decreased venous compliance in dogs with chronic renal hypertension. Femoral vein (FV) pressure-volume relationships were measured in vitro in 14 dogs with chronic (more than 4 weeks), one-kidney perinephritic hypertension and in 13 unilaterally nephrectomized normotensive control dogs. Segments of FV were also examined histologically and analyzed for their water and electrolyte contents. Compared to controls: (I) the FV pressure-volume curves of hypertensive dogs were shifted toward the pressure axis (P is less than 0.05); (ii) calcaulated vagous compliance in the pressure range of 0-15 mm Hg was decreased (P is less than 0.05); and (iii) the water and sodium contents of vwins from hypertensive dogs were increased (P is less than 0.05). Histological examination of the FV from hypertensive and control dogs did not reveal significant differences. The findings indicate that the decreases in venous compliance that we have previously observed in the early stages (less than 4 weeks) of perinephritic hypertension in dogs persist into the chronic stage of hypertension. Venous wall "edema" may account for the decreased venous compliance in this form of hypertension.


Inhibition of cholera toxin-stimulated intestinal epithelial cell adenylate cyclase by adenosine analogs. The ability of various adenosine analogs to inhibit cholera toxin activation of the intestinal epithelial cell adenylate cyclase-cyclic AMP system was investigated. After incubation of cells with cholera toxin for 6 hr, large increases in cellular cyclic AMP content were observed. Addition of 2', 5'-dideoxyadenosine during the last 30 min of this 6-hr incubation resulted in 70% reduction in elevated cyclic AMP content. Other analogs were not effective inhibitors. 2', 5'-Dideoxyadenosine was also a potent inhibitor of cholera toxin-activated intestinal cell adenylate cyclase activity with half-maximal inhibition occuring at 16 muM. NaF-stimulated cyclase was less susceptible to inhibition. The data suggest that inhibition by 2', 5'-dideoxyadenosine is due at least in part to direct inhibition of the cholera toxin-activated intestinal adenylate cyclase activity.


Pleural fluid lysozyme in human disease. A prospective study was conducted to define the content, significance, and source of lysozyme present in the pleural fluid in human diseases. The pleural fluid lysozyme activity is similar in various malignant and nonmalignant transudates and exudates, and is of limited diagnostic value. The pleural fluid activity correlated well with that of paired serum samples but it had poor correlation with the disease state, the pleural fluid granulocyte counts, and total white blood cell counts. The data suggest that the pleural fluid lysozyme may be derived primarily from the blood and that it is not the product of inflammatory or neoplastic cells in the fluid itself.


Actin associated with membranes of monoamine storage organelles. A histo-immunofluorescence technique using anti-actin antibodies has been applied to various subcellular fractions of bovine adrenal medulla and rabbit blood platelets. In the adrenal medulla only the membranes of the chromaffin granules, but not the fractions containing other subcellular particles (microsomes, mitochondria) showed marked immunofluorescence was present in the membranes of the 5-hydroxy-tryptamine organelles as well as in other subcellular particles. It is concluded that in the adrenal medulla, actin is specifically associated with the membranes of the amine storage organelles, whereas in platelets the protein shows a rather general subcellular distribution.


Glucose tolerance, insulin and catecholamine levels in germfree rats. Glucose was administered intravenously to 50- and 100-day-old GF and CV rats. Fasting blood glucose levels in GF and CV rats were found to be comparable. Glucose tolerance tests showed that GF and CV rats clear glucose from the blood at a similar rate. Although insulin concentrations in 100-day-old GF rats tended to be somewhat lower than in CV rats, the percentage increase during the 30-min period after glucose administration was similar, and matched the increase in blood glucose. Levels of plasma catecholamines were analyzed fluorometrically and were found to be comparable in 100-day-old GF and CV rats. It was concluded that insulin insufficiency plays no role in the syndrome of metabolic anomalies demonstrated by the germfree rat.


Variations in elastaselike esterase activities in human leucocytes during cell maturation. Granules of human peripheral blood leucocytes contain four well-characterized elastase isozymes and one or two slow-moving elastaselike esterases (SE) which have not been as well characterized. SE are capable of hydrolyzing typical elastase synthetic sybstrates such as N-acetyl-dl-alanine-alpha-naphthyl ester (Ac-DL-Ala-1-ONap) and N-t-butyloxycarbonyl-L-alanine-p-nitrophenyl ester (Boc-Ala-ONp), but unlike the highly basic elastase isozymes, SE barely migrate into 13% acrylamide gels during cationic electrophoresis at pH 4.3. Hydrolysis of Ac-DL-Ala-1-ONap by SE requires the presence of Triton in the gel, and hydrolysis of Boc-Ala-ONp by the same enzyme(s) is also enhanced in the presence of the detergent. Triton is not required for these activities, in the case of the elastase isozymes. Diisopropylfluorophosphate (Dip-F) inactivates both SE and the elastase isozymes, whereas Ac-(Ala)2-Pro-AlaCH2Cl (a powerful inactivator of the leucocyte elastase isozymes at 10-4 M concentration) does not inactivate SE at the same concentration. Immunochemical studies revealed antigenic cross-reaction between the rapidly migrating leucocyte elastase isozymes and SE. Two preparations of leucocyte granules from nonleukemic bone marrow cells showed no activity of the rapidly migrating elastase isozymes, but did contain SE activity. SE may be a precursor or zymogen form of the elastase isozymes, present in immature cells and partly retained through later stages of development.


Correlation of plasma lysosomal enzyme levels with hepatic reticuloendothelial function after trauma. Plasma lysosomal enzyme levels and hepatic phagocytosis were determined following Noble-Collip drum trauma in the rat. Circulating cathepsin and acid phosphatase activity increased after sublethal trauma (300 rev), reaching maximal levels at 1-3 hr and returning to pretrauma levels at 24 hr after trauma. Hepatic phagocytosis was decreased maximally at 1 hr and recovered to control levels at 24 hr after sublethal trauma. Increasing trauma intensity (100-500 rev) resulted in a progressive failure in hepatic Kupffer cell phagocytosis and a progressive increase in plasma lysosomal enzyme levels when tested at 60-min post-trauma. A significant inverse correlation was found between the plasma lysosomal enzyme levels and Kupffer cell phagocytosis after trauma. The functional significance of the relationship between these two parameters and its importance in shock survival remain to be determined.


Effect of fasting and insulin on the glucagon-induced orthophosphate incorporation to the isolated perfused rat liver. Isolated perfused fed rat livers spontaneously liberated glucose and orthophosphate to the medium; 24-hr fasted rat livers did not exhibit these phenomena. In perfused fed rat livers, glucagon (2 mug) increased glucose output and promoted orthophosphate incorporation. In perfused fed rat livers, insulin (250 or 500 mU) inhibited the spontaneous liberation of glucose and orthophosphate. Comparable doses of insulin significantly reduced the glucagon (2 mug)-induced increase in glucose output from perfused fed rat liver, but did not affect orthophosphate uptake by the organ.


O2 extraction of right and left ventricles. O2 extraction was measured simultaneously in right and left ventricles of dogs. Extraction was about 2.5 vol% higher in left ventricle. This figure, together with flow measurements of others (1-3), indicates that VO2/100g is at least twice as great in left ventricle as in right.


Progesterone synthesis by luteal mitochondria in vitro. Mitochondria were prepared from bovine corpora lutea by differential centrifugation and were purified by isopycnic zonal centrifugation. A marked increase in specific cytochrome oxidase activity and a marked decrease in specific DNA and RNA content indicate that the procedure resulted in a highly purified preparation of mitochondria. These organelles had a higher rate of conversion of [4-14C] cholesterol to [4-14C] progesterone than did mitochondria separated only by differential centrifugation, suggesting that luteal mitochondria contain the enzyme systems required for progesterone synthesis.


Effect of intrarenal arterial infusion of magnesium on renin release in dogs. Magnesium chloride was infused into the renal artery of anesthetized dogs in order to determine its effect on renal function. Natriuresis and diuresis were observed during MgCl2 infusion, but there appeared to be no effect on glomerular filtration rate (GFR), or plasma sodium or potassium concentrations. Although mean arterial blood pressure and renal plasma flow (RPF) decreased throughout the experiment, the fall was not significant until after stopping MgCl2 infusion. A significant stimulation of renin secretion occurred during magnesium administration.


Ammonia formation from glutamine isomers by nonacidotic and acidotic perfused rat kidneys. The following points summarize these findings: (i) there are 2 glutamine utilizing enzyme systems in the rat kidney; (ii) the cytoplasmic glutamyltransferase system hydrolyzes either glutamine isomer while the mitochondrial localized glutaminase 1 is specific for the L-isomer; (iii) the cytoplasmic pathway contributes 70% of the total renal ammonia production in the normal kidney; (iv) chronic metabolic acidosis results in a 20-fold activation of the mitochondrial glutaminase 1 pathway.


Release into culture medium of membrane-associated, tumor-specific antigen by B-16 melanoma cells. Serum-free supernatant fluids from monolayer cultures of B-16 mouse melanoma cells were found to contain a soluble membrane associated tumor-specific antigen. The 100,000 g supernatant of the culture fluid induced an antibody response to the B-16 cells both in rabbits and in the mouse strain of origin (C57Bl/6J). Similar supernatant fluids derived from an unrelated cell line (L-929) or from normal C57Bl/6 fibroblasts did not contain the B-16 specific material. Preliminary results indicate that the B-16 specific material is a protein of low molecular weight which is released into the culture fluid chiefly by living cells and, to a lesser extent, by autolysing cells.


Fluctuations of unbound whole blood polyamine levels during the menstrual cycle. Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine  and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.


Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin. Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion.


Evidence for hormonal participation in the natriuretic and kaliuretic responses to intraventricular hypertonic saline and norepinephrine. To examine if hypothalamic or pituitary hormones are involved in the induction of the natriuresis which follows the injection of hypertonic saline or norepinephrine into the third ventricle, lesions were placed in the median eminence and the responses to intraventricular norepinephrine or hypertonic saline were evaluated. Sham lesions in which the electrode was lowered into the brain but stopped short of the hypothalamic region did not interfere with the natriuresis, kaliuresis, and antidiuresis induced by the third ventricular injection of either hypertonic sodium chloride or norepinephrine. Lesions in the median eminence which induced diabetes insipidus as evidenced by an increase in water consumption to approximately four times normal completely abolished the natriuresis and kaliuresis in response to intraventricular hypertonic saline or norepinephrine and diminished the antidiuresis. The observations suggest the possibility that a natriuretic hormone(s) is involved in the induction of central natriuresis.


Alpha-adrenergic regulation of the secretion of an anticomplementary factor in mouse saliva. Mouse saliva contains a potent inhibitor of complement activity. The secretion of this inhibitor appears to be regulated by action on alpha-adrenergic receptors for two reasons. First, an alpha-agonist (norepinephrine) elicited saliva with a 260-fold higher specific activity of the inhibitor than that obtained with a cholinergic agent (pilocarpine). Second, the alpha-agonist elicited saliva having 43-foldgreater specific activity than that obtained following administration of a beta-adrenergic agonist (isoproterenol). This anticomplementary factor probably proteolytically degrades one or more of the complement components since it is inhibited by several protease inhibitors. The salivary anticomplementary factor is more potent than trypsin, chymotrypsin, thrombin, or Kallikrein. The anticomplementary factor has a pattern of inhibition like that of Kallikrein but unlike those of trypsin or chymotrypsin.


Role of stimulus locale on strain differences in active avoidance after scopolamine of D-amphetamine treatment. Three strains of mice were trained in a shuttle avoidance task following treatment with scopolamine (2.0 mg/kg) or d-amphetamine (3.0 mg/kg). When required to run towards light (CS) to avoid shock, A/J mice acquired the response more readily than DBA/2J or C57BL/6J mice. However, when required to run away from the light, the strain differences were eliminated. Under both testing conditions scopolamine and d-amphetamine augmented the performance of A/J mice, but had no effect of even disrupted performance of C57BL/6J. In DBA/2J mice d-amphetamine augmented performance only in the toward condition. Results were interpreted to support the hypothesis that scopolamine and d-amphetamine improve performance by response-disinhibition and response excitation, respectively. The presence of associative difficulties limit the effects of these agents.


Inhibition of cerebral protein synthesis: performance at different times after passive avoidance training. Inhibition of cerebral protein synthesis impairs long-term memory in a variety of species and tasks. Recently it was reported that subcutaneous injection of the protein synthesis inhibitor cycloheximide impaired short-term retention, measured 10 min after training in a passive avoidance task. To examine the possibility that inhibition of cerebral protein synthesis may sometimes disrupt short-term memory, mice were injected subcutaneously with cycloheximide (120 mg/kg) or anisomycin (150 mg/kg), or bitemporally with cycloheximide or anisomycin (100 mug/side) and given one training trial in a passive avoidance box. Subcutaneously injected cycloheximide reduced step-through latencies 10 min after training as reported previously, but anisomycin or bitemporally injected cycloheximide did not. All 4 drug groups exhibited impaired long-term memory. Since the results obtained at short intervals after training varied depending on the drug and route of injection, the impairment produced by subcutaneous cycloheximide at 10 min after training cannot be attributed to inhibition of cerebral protein synthesis. It is suggested that performance at short intervals after training reflects drug side effects on step-through behavior. By contrast, the impairment obtained at long intervals after training is consistent with the hypothesis that cerebral protein synthesis is required for formation of long-term memory.


Chronic delta-9-tetrahydrocannabinol. Transient and lasting effects on avoidance behavior. Delta-9-Tetrahydrocannabinol (THC) was administered to albino rats with extensive experience in free-operant (Sidman) lever-press shock avoidance. Dosing (30 mg/kg intragastrically) continued once daily, 3 hr before testing, for 1 to 6 weeks. Significant changes were noted in the response rates of several animals, but both the magnitude and direction of these were highly variable. However, shock rates were reliably elevated by THC, but complete tolerance was observed within 6 sessions. In several rats this was followed by sessions with significantly lower shock rates than the predrug baseline. These rats continued to perform at this level of proficiency until THC was discontinued, at which point the baseline was reacquired. These data emphasize that an important determinant of tolerance to a drug effect is the consequence of the effect for the organism.


Analgesia and hyperractivity following morphine microinjection into mouse brain. Analgesia and a paradoxical hyperreactivity to stimuli of sudden onset have recently been reported following the microinjection of morphine into the periacqueductal gray matter of rats. These effects have not been systematically investigated in other species. In the present study, both analgesia and hyperreactivity were observed as dose dependent effects of morphine microinjection into the periacqueductal gray matter of several strains of mice. Analgesia alone was produced by low doses of morphine while at higher doses analgesia was accompanied by hyperreactivity. Strain differences were noted with B6D2F1 mice being more susceptible to the hyperreactivity following morphine than BALB/c mice.


Myocardial sensitivity to catecholamines following exposure of rats to irregular, signalled footshock. Emotional stress is associated with an increased activity of both the pituitary-adrenal cortical system and the sympathetic-adrenal medullary systems resulting in raised plasma levels of glucocorticoids and catecholamines. There is evidence to suggest that prolonged stress induced adrenergic hyperactivity initiated myocardial pathogenesis and that this may relate to a corticosteroid catecholamine interaction. In the present study driven atrial strips removed from stressed male CSF rats were found to exhibit an enhanced sensitivity to both norepinephrine and epinephrine. These animals had previously been subjected to irregular foot shock associated with a warning signal; a situation producing a high plasma steroid level. The enhanced myocardial sensitivity to both catecholamines was observed in naive animals subjected to a single period, and persisted unchanged in animals stressed daily over a 28 day period. The hypersensitivity of the myocardium observed immediately after stress was maintained for at least 24 hr, whereas the circulating steroid level had returned to control values within 3 hr. In animals subjected to regular stress without a warning signal, a situation producing a much lower steroid level, no enhanced myocardial sensitivity was observed. While the aetiology of the phenomenon of enhanced myocardial sensitivity to catecholamines is not entirely understood, the evidence presented suggests that it may be related to the extreme elevation of circulating glucocorticoids. The sensitivity of the vas deferens however, was unaltered even though the animals were subjected to the stressor producing a high plasma steroid level. This apparent specifcity of the stress induced sensitivity change is discussed on the basis of receptor differences.


Endogenous levels of catecholamines in the rat myocardium following exposure to stress. Following exposure of male rats to irregular signalled footshock from which they could escape, the endogenous level of norepinephrine in the myocardium was significantly reduced. In atria the depletion of endogenous norepinephrine was significant following 1 day of stress. This significant depletion was maintained following 4 days of stress but began to return towards control levels by Day 10. A similar, but less pronounced pattern was seen with the ventricles. Little if any epinephrine was detected in both control and stress atria and ventricles. From the results presented it is postulated that irregular signalled footshock results in an inhibition of neuronal uptake.


Effect of stress on the uptake of 3H-norepinephrine into rat myocardium. Spontaneously beating atria from rats previously exposed to irregular, signalled footshock were incubated with 3H-norepinephrine. A significant reduction in the uptake and retention of radioactivity was found in the atria from stressed animals compared with unstressed controls. A kinetic study of the uptake process in both the stressed and control groups showed a similar Km value but a significantly different Vmax. It was concluded that the enhanced myocardial sensitivity to catecholamines previously reported can be explained in part, on the basis of an inhibition of neuronal uptake.