Ultrastructural differences during embryonic cell death in normal and peripherally deprived ciliary ganglia. Normally occurring neuron death and that brought about by prior removal of the peripheral target organ was studied ultrastructurally in embryonic chick ciliary ganglion in order to better understand the mechanism of cell death in this system. Before the period of cell death, all neurons in the normal ganglion developed a well-organized rough endoplasmic reticulum (RER) which coincided with peripheral synapse formation. None of the peripherally deprived neurons underwent this change, suggesting that some interaction with the periphery, possibly synapse formation, triggered them into the secretory state. Cell death in peripherally deprived neurons was signalled by nuclear changes followed by freeing of ribosomes from polysomes and RER and presumably cessation of protein synthesis. In contrast, normal cell death was brought about by dilation of the RER with eventual cytoplasmic disruption, nuclear changes appearing only secondarily. It is suggested that failure to form or maintain peripheral synapses could result in the accumulation of transmission-related proteins with consequent cisternal dilation, and eventual cell death.


Analysis of fatty acid and alcoholic components of sebaceous lipid types. Lipids were extracted from hair, scalp wipings, ovarian dermoid cysts, and vernix caseosa and submitted to alkaline hydrolysis. Alumina chromatography applied to the unsaponifiable portions allowed for the separation of hydrocarbons, alcohols, and sterols. The fatty acids from the saponifiable mixtures were converted to the methyl esters and analyzed by gas chromatography in conjunction with mass spectrometry. This technique permitted the identification of the even, odd, iso, and anteiso fatty acid levels of the various pools. Analysis of the alcohols was afforded by gas chromatography of the acetates. Ratios were determined among the acidic and alcoholic components of each lipid class and the alcoholic constituents of each pool appeared to be increased by two C2-fragments over the average carbon number of the corresponding acid fraction. Branched components ranged higher in all alcohol mixtures as compared to the respective acids and thus, indicative of a specificity for the synthesis of a specificity for the synthesis of alcohols.


A volumetric study of winter fungus prevalence in the air of midwestern homes. Volumetric recoveries of airborne, mesophilic microfungi were made during winter months at three specific points in 150 single-family dwellings in southeastern Michigan. Mean levels of total isolates/m3 comprised a range of from less than 10 to over 20,000, although concurrent outdoor levels never exceeded 230/m3. Form species of Penicillium, Aspergillus, Cladosporium, and Rhodotorula as well as non-pigmented yeasts were the types encountered most widely indoors. Certain homes showed high recoveries of other types, including Cephalosporium, Sporobolomyces, Verticillium, and Sporothrix form species. A positive association between indoor fungus prevalence and bedroom relative humidity was strongly suggested, and high levels were observed in well-humidified homes despite the presence of electrostatic air cleaners. The data indicate characteristic patterns of (winter) air spora in specific homes and suggest that humidifying devices may serve as dispersion sources in addition to their permissive role in facilitating fungus growth.


The dynamics of dietetics.

The dynamics of dietetics. The forces which have and are producing change in dietetics are recapitulated, as are developments in the profession which have evolved since 1972 when the Study Commission on Dietetics made its report. The coordinated undergraduate program in dietetics has gained much ground; in 1972, there were but seven such programs. Today there are forty-three. More than three hundred traineeships are currently preparing over five hundred trainees to take their places in the profession. Another facet of training involves programs for dietetic technicians and dietetic assistants, designed to open up the career ladder concept. Continuing education is of prime importance for those beyond the entry-level of competence. The dietitian's first responsibility is to society, preceding that for the profession-as has been plainly indicated in a number of A.D.A. Position Papers and the emphasis of the Association in its legislative thrust on the value of nutrition education in preventive health care. Concern of the Association about the competency of practicing dietitians has also been reflected in the early appointment of a Committee on Professional Standards Review. The Association, as a member of the National Nutrition Consortium, is an advocate for a "National Nutrition Policy" and must continue to work for recognition that nutritional care is basic to comprehensive health care.


Acceptability of three convenience chicken products. Three convenience products--frozen, precooked chicken apple fritters, chicken breast fillets, and chicken patties--provided by one processor were subjectively evaluated by two taste panels of older adults, ranging in age from the sixties to middle eighties. The panelists represented a middle-income group maintaining private homes and a low-income group living in public housing. Both panels rated each product above "good" (score=4) or "fair" (score=3) on four acceptability factors and the overall score. Although mean scores of the low-income taste panel on all factors were generally higher for all products, the only significant difference (P less than .01) pertained to the appearance factor. Both panels indicated willingness to buy all three products.


Ultraviolet-induced alterations of beat rate and electrical properties of embryonic chick heart cell aggregates. Embryonic heart cell aggregates were irradiated with ultraviolet light at wavelengths between 260 and 310 nm. Spontaneous beat rate was monitored with the aid of a closed-circuit TV camera and, in separate experiments, electrophysiological changes were assayed by intracellular recording. The characteristic response of 7-day aggregates was an increase in spontaneous beat rate to a maximum plateau level, followed by a rather abrupt cessation of beating. Intracellular recordings during irradiation showed a marked decline in the maximum rate of rise, overshoot, and repolarization phase of the action potential, and a significant change in threshold toward zero. The action spectrum for the termination of beating peaked between 290 and 295 nm; it fell off sharply at longer wavelengths and more slowly at shorter wavelengths. The maximum increase in beat rate was increasingly greater for shorter wavelengths and exhibited no peak in the wavelength range investigated. The sensitivity of aggregates to 295-nm light, as measured by the inverse of irradiation time required to terminate beating, decreased with increasing aggregate size and external potassium concentration, was relatively independent of temperature, and increased with embryonic age. The ultraviolet-induced increase in beat rate and termination of beating are attributed to separate complementary processes, a depolarization of the membrane, and a decline in "fast" sodium conductance.


Toxicity of poly(rI).poly(rC) for interferon-treated cells. An ultrastructural evaluation. The cytotoxic effect of poly(rI).poly(rC) for interferon-treated cells is preceded by discrete ultrastructural alterations in (1) the mitochondria: swelling of the cristae and increased density of their matrix, (2) the nucleus: disorganization of the structure, and (3) the endoplasmic reticulum: slight dilatation with disorganization and depletion of the filament bundles. Our results do not allow us to conclude whether any of these alterations is a primary effect of the treatment. Possibly they are secondary to some, as yet unknown, functional defect, and only reflect incipient cell death.


Viral factors required for interferon induction by Newcastle disease virus in mouse macrophages and chicken embryo cells. The triggering mechanism for interferon synthesis in mouse peritoneal macrophages and chick embryo (CE) cells by Newcastle disease virus (NDV) exposed to hydroxylamine or homologous antiserum was investigated in relation to the intracellular fate of these agents. Inactivation of NDV at 22 degrees C by I M-hydroxylamine proceeded with first-order kinetics, whereas the interferon-inducing capacity of hydroxylamine-treated virus in macrophages was unimpaired. In contrast to infective NDV, hydroxylamine-inactivated virus produced interferon in CE cells, and such a virus still had partial RNA-dependent RNA polymerase activity. Hydroxylamine-inactivated NDV was adsorbed to and uncoated in both normal and chloroquine diphosphate treated cells, but no viral double-stranded RNA was detected. Hydroxylamine treatment of virion-extracted RNA and neutralization of intact virions by antibody abolished the capacity of the virus to induce interferon. Infective as well as neutralized NDV interacted with macrophages to the same degree, but association between NDV and CE cells was prevented by antibody-coating. In macrophages, the RNA of neutralized NDV became more sensitive to RNase than RNA of infective NDV, but this process was inhibited in chloroquine diphosphate-treated cells. These results suggest that interferon induction by NDV involves components of the virion which are present up to the regular uncoating process.


Influence of diet, cortisol and insulin on the activity of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in the rat liver. The influence of nutritional factors, such as fasting (24, 48 and 72 hours), protein free and high protein diets, and endocrine factors (cortisol and insulin) on the activity of hepatic phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC) in adult rats was studied. The circadian rhythm in the activity of these enzymes was studied at two protein levels: 15% and 50%. Under all conditions which favored gluconeogenesis the activity of PEPCK increased. Cortisol did not further increase the activity of PEPCK in rats fed a high protein diet. Regardless of the protein content of the diet, insulin did not reduce PEPCK activity. Dietary protein level had no influence on the usual rhythm of activity of PEPCK. On the other hand, the high protein diet increased it threefold. Under all experimental conditions we observed no changes in PC activity. This is probably due to the fact that PC is a constitutive enzyme and therefore is not adaptative.


A possible essential role for dietary linolenic acid in the development of the young rat. Female rats were fed semi-purified diets containing 10% safflower oil or 10% soybean oil for six weeks prior to mating and through-out pregnancy and lactation. The progeny were weaned to the diet of the dam. Physical, neuromotor and reflex development was monitored in the progeny prior to weaning and learning ability of the mature progeny was assessed in a simple Y-maze test. Brain lipid analyses were conducted in the progeny at birth, 21 and 210 days of age. Inclusion of soybean oil in the diet resulted in higher levels of 22:6omega3 and lower levels of 22:5omega6 in the brain ethanolamine glycerophosphatides. The nature of the dietary fat exerted no effect on the physical development, onset of reflexologic responses or onset of neuromotor co-ordination in the pups. The soybean oil-fed animals spent more time in certain neuromotor activities possibly associated with explorative drive than did their safflower oil-fed counterparts. The performance of the mature soybean oil-fed progeny in the discrimination-learning test was superior to that of progeny fed safflower oil. The association of superior learning capacity with dietary soybean oil-induced incorporation of omega3 fatty acids into the brain glycerophosphatides is offered as support for an essential role for dietary linolenic acid for the young rat.


In vitro production of platelet-binding IgG in childhood idiopathic thrombocytopenic purpura. We studied two boys, 9 and 10 years old, respectively, who underwent splenectomy eight months and six weeks after initially presenting as "typical" cases of childhood ITP. Splenic leukocytes from each child were cultured and net synthesis rates of IgG determined. Splenic synthesis rates of IgG were five-and sevenfold greater, respectively, than in spleens of control subjects. A significant portion of the splenic culture-produced IgG from each patient demonstrated specificity for homologous and autologous platelets. Synthesis rates of IgG were determined on serial cultures of bone marrow cells from the 10-year-old boy who failed to respond to splenectomy. His initial marrow synthesis rate of IgG was five times greater than mean control values. His synthesis rate of IgG in marrow decreased to the control range in association with immunosuppressive therapy and intesive platelet transfusions. These data suggest that (1) the spleen was a production site of platelet-binding IgG in the two children, and (2) the bone marrow may have been an additional site of production in our second patient.


Pelviureteric obstruction in infancy.

Pelviureteric obstruction in infancy. Of 33 infants with pelviureteric obstruction, most presented in the first month of life with an abdominal mass and most were males. Half of these patients had bilateral renal pathology. The association between cystic dysplasia in the hydronephrotic kidney and contralateral cystic renal abnormality in patients with unilateral pelviureteric obstruction is noted. There were 34 pyeloureteroplasties performed on 27 patients, mostly with good results, even in patients with bilateral renal pathology.


Aporphines. 14 Dopaminergic and antinociceptive activity of aporphine derivatives. Synthesis of 10-hydroxyaporphines and 10-hydroxy-N-n-propylnoraporphine. The synthesis of racemic 10-hydroxyaporphine [(+/-)-2a] and 10-hydroxy-N-n-propylnoraporphine [(+/)-2b] is described. The method involved a Reissert alkylation-Pschorr cyclization route. The dopaminergic activity of (+/-)-2b was evaluated in comparison with L-Dopa, (-)-apomorphine (1a), (+/-)-N-n-propylnorapomorphine (NPA) (1b), and (+/-)-11-hydroxy-N-n-propylnoraporphine [(+/-)-11-OH-PNA] by the behavioral model of rotational behavior in animals after unilateral lesion of the ascending DA pathways. The dopaminergic activity of NPA and 11-OH-PNA is essentially equivalent to L-Dopa and (-)-apomorphine, and both are more active than (+/-)-2b. Furthermore, (+/-)-NPA (threshold doses, 5 mug/kg) appears to be even more potent that (-)-apomorphine (threshold doses, 25 mug/kg). The duration of action of NPA and 11-OH-PNA is considerably longer than that obtained with L-Dopa. The antinociceptive activity of (+/-)-2b was evaluated by the tail-flick procedure and compared with 1a, 2b, morphine, and L-Dopa. Weak but significant antinociceptive activity was shown by (+/-)-2b and by (+/-)-1b but not by (-)-apomorphine. This effect was not antagonized by naloxone. The finding that (+/-)-2b and particularly (+/-)-11-OH-PNA are active in doses from 500 to 50 mug/kg, respectively, in causing rotational behavior further supports previous studies indicating that N-n-propyl derivatives of monohydroxylated aporphines were more active than the corresponding parent N-methyl derivatives as DA receptor agonists and that a catechol system is not an absolute requirement for dopaminergic activity in such aporphines.


Non-seminomatous testis tumors: a plan of management based in 96 patients to improve survival in all stages by combine therapeutic modalities. To develop a plan of management based on the clinical and pathologic stage of the tumor the results of treatment of 96 consecutive patients with non-seminomatous testis tumors have been analyzed. There were no exclusions and all patients were treated, including 17 with advanced stage C disease. All patients underwent retroperitoneal lymph node dissection as primary treatment but the judicious use of adjuvant therapeutic modalities improved survival in all stages of disease. Chemotherapy was the most important adjuvant and postoperative radiation therapy was reserved for patients with extensive retroperitoneal metastatic disease. Results indicate that a modified unilateral thoracoabdominal retroperitoneal lymph node dissection can effectively remove the retroperitoneal nodes. Of 57 patients 50 with stage A or B tumor survived after lymph node dissection without radiation therapy. Compared to an operation alone prophylactic adjuvant chemotherapy improved survival from 82 to 93 per cent for patients with minimal disease (stage A or B1). Postoperative irradiation therapy combined with cyclic chemotherapy improved survival for patients with advanced retroperitoneal disease compared to an operation and radiation alone or an operation and chemotherapy alone. An aggressive approach that combined operation with chemotherapy, radiation therapy or both, has salvaged 8 of 17 patients with disseminated metastatic disease (stage C). The over-all survival rate for these 96 patients is 78 per cent. A plan of management has evolved, which is based on retroperitoneal lymph node dissection followed by the judicious use of adjuvant chemotherapy and radiation therapy as determined by pathologic findings.


Suppression of antitumor lymphocyte mediated cytotoxicity by human chorionic gonadotropins. The effect of human chorionic gonadotropin on the in vitro cytotoxicity of lymphocytes against human transitional cell carcinoma cells was studied in 9 patients using the microcytotoxicity assay. Lymphocytes from 6 patients were cytotoxic against transitional cell carcinoma cells. However, in the presence of human chorionic gonadotropin the cytotoxicity of these lymphocytes against transitional carcinoma cells was diminished. Human chorionic gonadotropin alone or in combination with non-cytotoxic lymphocytes did not change the growth of target cells and human chorionic gonadotropin did not have a direct toxic effect on lymphocytes alone. These results demonstrate that human chorionic gonadotropin can inhibit the cytotoxic action of lymphocytes against human tumor cells in vitro. Human chorionic gonadotropin may contribute to the poor prognosis associated with certain human chorionic gonadotropin-secreting human tumors.


New trial for fiberoptic cystourethroscopy: the use of metal sheath. To overcome the disadvantages of using the fiberscope to observe the lower urinary tract we devised a metal sheath, which is used in combination with the fiberoptic cystourethroscope. The metal sheath helps in a smooth introduction of the fiberscope through the urethra and also in a close approximation of the fiberscope to the lesion. Fiberoptic cystourethroscopes combined with the metal sheath are useful in observing the bladder neck, the pedicle of tumors, the inner surface of the diverticulum and the condition of the intestine anastomosed with the bladder, which the current rigid endoscopes cannot approach. Photographs of the lower urinary tract were easily taken with this metal sheath method. However, the fiberoptic cystourethroscopes have a much smaller field of view, lower resolution and mor obscurity in the view. These drawbacks should be improved in the future.


An operation for relief of severe left ventricular outflow tract obstruction. The case history of a 30-year-old man with severe mitral and aortic stenosis and slight aortic regurgitation who underwent replacement of both valves is presented. At the initial surgical procedure, because of the small-size annuli, a small Beall mitral prosthesis and a No. 19 Björk-Shiley aortic prosthesis were used. The subsequent recurrence of severe symptoms and findings of an 80 mm. Hg gradient across the Björk-Shiley aortic valve led to repeat exploration and corrective surgery. The operative procedure to relieve left ventricular outflow obstruction is described. It is felt that this procedure can be used not only for the relief of severe aortic annular stenosis but also for other forms of severe left ventricular outflow tract obstruction such as idiopathic hypertrophic subaortic stenosis and particularly in the patients who have experienced poor results with one of the known surgical procedures for this clinical entity.


Measuring the quality of medical care. A clinical method. We outline the implementation of a new method of measuring the quality of medical care that counts cases of unnecessary disease and disability and unnecessary untimely deaths. First of all, conditions are listed in which the occurrence of a single case of disease or disability or a single untimely death would justify asking, "Why did it happen?" Secondly, we have selected conditions in which critical increases in rates of disease, disability, or untimely death could serve as indexes of the quality of care. Finally, broad categories of illness are noted in which redefinition and intensive study might reveal characteristics that could serve as indexes of health. We describe how these inth of the general population and the effects of economic, political, and other environmental factors upon it, and to evaluate the quality of medical care provided both within and without the hospital to maintain health and to prevent and treat disease.


Spinal descent of cerebrospinal fluid in man. The descent of radiopharmaceuticals injected within the right lateral ventricle toward and into the spinal subarachnoidal spaces has been followed by scintiphotographic techniques and by computerized flow analysis in a group of "normal" patients. A substantial and rapid downward progression of the albumin-tagged tracer has been observed. This progression is faster than the subarachnoidal ascent toward the convexity of the brain.


Intention myoclonus: successful treatment with clonazepam. Clonazepam, a new benzodiazepine derivative, was used in the treatment of intention myoclonus with excellent results. Five patients, three with postanoxic encephalopathy and two with degenerative central nervous system disorders, all refractory to other therapy, responded with marked decrease in myoclonus. The effective dosage was 7 to 12 mg a day in divided doses. One patient has been treated for over 4 years with no toxicity or breakthrough of symptoms. Except for transient sedation, there have been no untoward side effects. Clonazepam is an important addition to the therapy of intention myoclonus.


Trichinosis: severe myopathic involvement with recovery. A case of clinically severe trichinosis following ingestion of commercially prepared pickled pigs' feet is reported. An unusual finding on muscle biopsy was a larval count of 4,046 per gram of muscle, the second highest density of muscle invasion recorded to date. Survival has not been reported previously in patients with greater than 1,000 trichinae per gram of muscle. Complete symptomatic recovery followed combined corticosteroid and thiabendazole administration.


Platelet-bound and free serotonin levels in jugular and forearm venous blood during migraine. The level of serotonin in platelets and free in plasma has been determined in jugular and forearm venous blood before and during migraine attacks in six women. A significant fall in platelet serotonin was observed in five subjects and was accompanied by a significant fall in plasma free serotonin in the four subjects for whom data concerning free serotonin levels were available. There was no significant difference between jugular and forearm blood in respect to either platelet-bound or free serotonin in the headache-free phase, and during migraine, the values for jugular and forearm blood were parallel. The significance of these findings in relationship to the serotonin theory of migraine is discussed.


Hypernatremia and chorea. A report of two cases. The appearance of transient, generalized chorea in conjunction with brief, symmetrical myoclonic movements is described in two adult patients with hypernatremia secondary to dehydration. The association of hypernatremia and chorea is rare, even in massive salt poisoning, and has not been described previously in adults. Since both patients recovered, no pathologic material was obtained; but a speculative commentary on the possible underlying pathophysiology is included.


Gamma hydroxybutyrate. Correlation of serum and cerebrospinal fluid levels with electroencephalographic and behavioral effects. Gamma hydroxybutyrate was administered to adult cats by intravenous infusion at varying dosages while an electroencephalogram (EEG) was recorded from electrodes placed stereotactically in the right and left hippocampus and thalamic intralaminar nucleus and from cortical electrodes. Blood cerebrospinal fluid samples were assayed for gamma hydroxybutyrate. The first EEG change, slowing was occasional spikes, was seen at serum levels of 75 mug per milliliter. Changes in the recordings progressed through a number of stages, culminating in bursts of poly spiking interspersed among periods of electrical silence first seen at 350 mug per milliliter. Behavior was characterized by a progressively deepening trancelike state punctuated at higher serum levels by spontaneous and stimulus-induced myoclonic jerks. These changes were correlated with serum levels and are more similar to petit mal stupor than any kind of natural sleep-like state previously used to describe them.


Viruslike particles in muscle from a patient with amyotrophic lateral sclerosis. An electron microscopic study of muscle and central nervous tissue from a case of amyotrophic lateral sclerosis showed crystalline arrays of 20 to 24 nm viruslike particles in muscle. The particles were located between the myofibrils, adjacent to the Z bands, and near the perinuclear region, but were never seen within the nucleus. Cell cultures from the same muscle specimens showed no such particles. Central nervous system tissues and cultures also failed to show viruslike particles. The cultures were negative by the indirect fluorescent antibody technique with serums from patients with amyotrophic lateral sclerosis. The nature of these particles or their relationship to amyotrophic lateral sclerosis is unknown.


Effects of glycerol administration on experimental brain edema. The effects of glycerol on brain water and solute distribution in cerebral edema are not well known. In brail edema induced in dogs by focal freezing, tissue underlying the necrotic lesion had an elevated water content but the remainder of the brain was unaltered. Administration of glycerol to maintain plasma glycerol at about 35 mM dehydrated normal white matter, but water and solute contents of the edematous white matter were not changed. During the initial 3 hours of glycerol infusion, CSF pressure fell, but when the infusion was continued for 6 hours or more, a gradual rise in CSF pressure was observed. In three animals, the final CSF pressure was higher than preinfusion values. At this time, brain water content was significantly less than normal, but both CSF osmolality and glycerol concentration were higher than plasma. The data show that glycerol infusion can decrease intracranial volume towards normal by dehydration of normal, but not damaged, brain tissue. The rebound rise in CSF pressure observed during the continuous administration of glycerol cannot be explained by rehydration of brain tissue but may be related to alterations in CSF dynamics.


A heat-stable blocking factor in the plasma of patients with subacute sclerosing panencephalitis. The possible role of a defective cell-mediated immune response in the pathogenesis of subacute sclerosing panencephalitis remains unclear. Cell-mediated immunity has been investigated in nine patients with this disorder. In eight patients, a heat-stable blocking factor in the plasma inhibited normal lymphocyte transformation to phytohemagglutinin and mixed lymphocyte cultures. The degree of blocking increased as the disease progressed. The nature of the blocking factor is unknown and is currently under investigation. A heat-stable blocking factor has not been described previously in subacute sclerosing panencephalitis, althouth a heat-labile blocking factor has been reported in a total of five patients.


Nonkitotoc hyperosmolar hyperglycemia during glycerol therapy for cerebral edema. Glycerol, an effective cerebral dehydrating agent, also has gluconeogenic properties, and can thereby elevate serum glucose to dangerously high levels in predisposed patients treated for cerebral edema. The nonketotic hyperosmolar hyperglycemic state usually occurs in cases of maturity onset diabetes or prediabetes, as in the two elderly patients discussed in this paper. The pathogenesis usually evolves through a constant diabetogenic stress that causes persistent hyperglycemia resulting in the exhaustion of ordinarily adequate insulin stores, ultimately allowing hyperglycemia to progress unchecked to metabolic coma. Precautions to recognize this development should be taken in appropriate patients.


Multiple central nervous system infections in progressive multifocal leukoencephalopathy. Clinical, pathologic, and immunologic features of two patients with progressive multifocal leukoencephalopathy and multiple coexisting central nervous system infections are presented. Both showed impaired cell-mediated immunity whereas immunoglobulins were normal, suggesting that defective cellular rather than humoral immunity predisposes to progressive multifocal leukoencephalopathy. Continued neurologic deterioration might be due not only to progression of the condition but also to simultaneous opportunistic bacterial and fungal infections that may be amenable to treatment. Unusual features in case 1 included striking neurologic remission for 8 months and a positive brain scan corresponding to a large demyelinated lesion in the frontal lobe.


Permeability of human chorion laeve to diazepam and meperidine. In vitro placental permeability to diazepam (Valium) and meperidine (Demerol) in excess of that measured for antipyrine, suggest that these compounds will diffuse across placental tissue in vivo at a maximal or perfusion-limited rate. Such findings correspond to the high fetal blood levels reported for these substances following maternal administration and indicate that these lipid-soluble analgesics cross this tissue by transcellular as well as extracellular pathways.


The occupational health audit.

The occupational health audit. The final report contains no magic or proprietary secrets. It is simply a logical review of what exists with an orderly recommendation of what should be done. To repeat -- many times the hardest part of any job is getting started. The purpose of this exercise is to provide a plan and a way to get started. This may seem like something so obvious that it is not needed. But a review of existing occupational health programs dispels that view. Five years after the enactment of the Occupational Safety and Health Act of 1970, hundreds of thousands of physical examinations are still being performed in a total vacuum; examinations whose contents bear little relationship to the hazards encountered. Countless laboratory determinations are being provided to personnel officers and plant managers who have absolutely no background in interpreting the meaning of those results. Millions of records are being meticulously kept with no goal in mind as to what purpose they should serve nor consideration for the privacy of individuals. In short, untold millions of dollars are being wasted while the things that should be done are left undone because, to quote, "the cost is too high." Often health professionals are employed by an organization because health crises have developed which force expert handling. The health professional enters chaos and is kept so busy answering fire-calls that there is no time for the orderly evaluation of needs and the development of operating routines required to prevent new crises from developing. Today's crises are being addressed while tomorrow's crises are developing out of routine situations. The health professional is not at fault; rather, executive management has failed to provide the necessary systems to meet its responsibilities. So long as this situation prevails, there is a need for someone to take the time to develop an orderly approach to occupational health surveillance. When such a condition exists, it is time to call in an independent auditor to provide an objective evaluation of what needs to be done. It is to provide a "handle" for getting hold of such situations that we developed our Occupational health Audit. It offers one way to get the job started.


Substrate-induced acceleration of lactase synthesis in fetal rat intestine. Twenty milligrams of lactose were injected into the amniotic sacs of fetuses in one uterine horn and 20 mg glucose were injected into the amniotic sacs of fetuses in the opposite uterine horn of six rats on days 17-19 of pregnancy. Two or 3 days later the pregnant animals were killed and segments of jejunum obtained from their fetuses were homogenized in water. Assays for lactase and protein determinations were performed on these homogenates. Lactase values were significantly higher in the lactose-injected group than in fetuses receiving glucose (Table 2), P less than 0.0005. Thus, fetal intestinal lactase activity can be increased by exposure to the substrate lactose during late fetal life.


Object orientedness: the person or the thing. Infant observation indicated that there is an individual variation in development characterized by orientedness either toward the animate or toward the inanimate world. These variants, which are manifest as early as the second month of life, influence the surrounds, the continuing developmental processes, and certain aspects of character formation. Each variation in orientedness evokes a preferred way of processing percepts and situations.


Metaphase chromosome anomaly: association with drug resistance and cell-specific products. Large, homogeneously staining chromosome regions which lack the longitudinal differentiation ordinarily revealed by cytogenetic "banding" methods have been found in antifolate-resistant Chinese hamster cells and also in human neuroblastoma cells established in vitro. The drug-resistant cells are characterized by excessive production of the target enzyme, dihydrofolate reducatase, while the human neuroblastoma cells have phenotypes of normal neuronal cells. The homogeneously staining region appears to represent a novel metaphase chromosome anaomaly which may have functional significance in cells with specialized properties.


Nucleus suprachiasmaticus: the biological clock in the hamster? Destruction of the suprachiasmatic nuclei in the golden hamster by bilateral radiofrequency lesions abolishes three well-documented circadian rhythms--locomotor activity, estrous cyclicity, and photoperiodic photosensitivity. Entrainment of these rhythms by light cycles fails in lesioned hamsters; females become persistently estrous; in both sexes locomotor activity becomes sporadic, confined primarily to the light instead of darkness, and is totally arrhythmic when lesioned animals are exposed to continuous darkness; the photoperiodic gonadal response (gonadal regression induced by short day lengths) is abolished; lesioned animals remain reproductively mature irrespective of photoperiodic treatment.


Selective brain dopamine depletion in developing rats: an experimental model of minimal brain dysfunction. Administration of 6-hydroxydopamine to neonatal rats produces a rapid and profound depletion of brain dopamine. Total activity of treated animals is significantly greater than that of controls between 12 and 22 days of age, but then declines, an activity pattern similar to that seen in affected children. This suggests a functional deficiency of brain dopamine in the pathogenesis of minimal brain dysfunction.


Polydipsia-induced alcohol dependency in rats: a reexamination. Seven Holtzman rats were kept on a polydipsia-induced schedule of alcohol consumption for 3 months in a replication of a 1972 study by Falk and colleagues. Contrary to their results, there was no evidence of alcoholism.


Angiosarcoma of the breast: a report of two cases and a review of the literature. Angiosarcoma of the breast, a rare tumor with very poor prognosis and insidious early manifestations, frequently is far advanced when first detected clinically. The clinical and pathologic changes in two women with primary, unilateral angiosarcoma of the breast are reviewed and the results are compared with 46 cases already published in the literature. Both patients were middle aged with symptoms for approximately 6 months prior to operation. Both frozen section reports were benign and only called malignant on permanent section. Microscopically the tumors were composed of varying sized, tortuous, elongated vascular channels. The operation varied--a modified radical and a simple mastectomy--and both patients are free from disease 4 and 2 years following operation. It is considered that, in view of the proclivity of this tumor for hematogenous metastases, an axillary dissection may not be justified.


Duodenogastric reflux of lysolecithin in the pathogenesis of experimental porcine stress ulceration. The role of duodenogastric reflux of lysolecithin, a normal constituent of duodenal juice, in the pathogenesis of gastric stress ulcerations was investigated with a swine shock-ulcer model. Twenty-seven piglets, weighing 8 to 12 kilograms, were used. In an intact animal, the average concentration of intragastric lysolecithin before shock was 138 mug per milliliter (median, N = 6). At the end of the shock period, the average concentration of lysolecithin was 540 mug per milliliter and the over-all amount in the gastric juice was 14.3 mg. (median, N = 6). Following hemorrhagic shock (3 hours duration; mean arterial pressure, 40 mm. Hg), all six control animals with normal gastroduodenal continuity got gastric ulcerations. Interruption of duodenogastric reflux by duodenal exclusion and gastrojejunostomy completely abolished the development of these ulcerations in six test animals. When the interrupted duodenogastric reflux was replaced artificially by intragastric instillation of lysolecithin (500 mug per milliliter; 25 ml.), all six animals developed lesions. Intragastric lysolecithin without shock had no effect. The results provide further support to the concept that regurgitation of duodenal juice into the stomach is an essential factor in the pathogenesis of gastric stress ulceration. The results also suggest that, in this respect, one of the active components in duodenal juice is lysolecithin.


Leydig cell tumor in identical twin.

Leydig cell tumor in identical twin. A case is presented of an identical twin who had an interstitial cell tumor of the testis removed, and comparison is made with his identical brother over an ensuing six-year period. The dramatic effects of the interstitial cell tumor are clearly shown in the comparison of the two males over this six-year period. To our knowledge this is the only such case in the world literature.


Cross-sectional echocardiographic localization of sites of left ventricular outflow tract obstruction. Real time two-dimensional echocardiographic studies of left ventricular outflow tract cross-sectional anatomy were obtained by the multicrystal echocardiographic method (Bom system) in 35 patients with various types of outflow obstruction as delineated by clinical, hemodynamic and angiographic studies. In each patient the noninvasive test allowed prediction of the site of obstruction. In valvular aortic stenosis, echocardiographic diagnostic findings included poststenotic dilatation of the ascending aorta, thickened aortic cusp tissue and increased superior-inferior cusp excursion (doming). The site of supravalvular aortic stenosis was readily observed although echocardiographic findings often underestimated the degree of obstruction recorded at cardiac catheterization. In patients with discrete subvalvular aortic stenosis, the major finding was a localized thickening of the septum and anterior mitral anulus producing a narrowing of the left ventricular outflow tract that was present in diastole and persisted throughout the cardiac cycle.


Microvascular structure of the human epididymis. The microvascular anatomy of the human epididymal duct system from rete testis to vas deferens was studied using microangiography and histology. Various segments of the duct system show significant differences in the density and arrangement of the small blood vessels. The rete testis is poorly vascularized while the first lobulated segment of the epididymis, which is formed by the efferent ducts is provided with a dense subepithelial capillary bed. The more distal segments of the epididymis have less dense capillarization surrounding the epididymal duct. In the vas deferens the blood vessels form a double capillary network. The outer capillary network surrounds the smooth muscle layers and the inner is located immediately beneath the duct epithelium. The organization of blood capillaries in the human epidymis and the differences seen in different portions of the excurrent duct system follow basically the general pattern seen in some experimental animals.


Gonadoblastoma with tubal pregnancy.

Gonadoblastoma with tubal pregnancy. A case of unilateral gonadoblastoma in association with a ruptured ectopic tubal pregnancy is presented. The patient had normal menstrual history prior to a missed period followed by abdominal pain and the passage of clots. The surgical specimens, in addition to the ruptured tubal pregnancy, showed nodular foci of typical gonadoblastoma in the right ovary, the remainder of the ovarian tissue being normal. The left ovary was subsequently removed and examination revealed normal constituents without evidence of tumor. Cytogenetic evaluation of peripheral leukocytes showed cells with a normal female sex chromatin complement, 46-XX, as well as cells with 45 chromosomes in which one of the X chromosomes was missing.


Immunization schedules for the new human diploid cell vaccine against rabies. Clinical and antibody responses of human volunteers to four different serial production lots of human diploid cell vaccine (HDCV) each with a different antigenic value are described. Three to four doses of HDCV administered over a period of 14 days produced high levels of virus neutralizing antibodies with an average titer up to 20 times higher than the titer elicited by four doses of duck embryo vaccine. Antibodies were still present one year after completion of vaccination. Only minimal differences in antibody response could be observed between groups receiving vaccines of different antigenic values. Untoward reactions to the vaccine were few. The possibility of using the vaccine as part of postexposure human prophylaxis against rabies is discussed.


Estriol in pregnancy. IV. Normal concentrations, diurnal and/or episodic variations, and day-to-day changes of unconjugated and total estriol in late pregnancy plasma. Normal values of unconjugated, total, and immunoreactive (measured without extraction) plasma estriol (E3) have been determined from radioimmunoassay data obtained in 217 uncomplicated third-trimester pregnancies. Small but significant diurnal variations in unconjugated and total plasma E3 have been observed in a study comprising 12 women who were hospitalized during late pregnancy for diabetes, toxemia, or placenta previa. The late morning decreases in unconjugated and the afternoon/evening decreases in total plasma E3 concentrations, averaging some 10 to 15 per cent, were overshadowed by considerable episodic fluctuations and may thus be clinically irrelevant. Day-to day changes of unconjugated and total plasma E3 concentrations in late pregnancy were similar and smaller than changes in urinary E3 measurements. The urinary E3/creatinine ratio, however, reducing inadequacies of 24 hour urine collections, varied less than unconjugated or total plasma E3. The data suggest that a decrease in unconjugated or total plasma E3 must exceed 40 to 45 per cent of the mean of the three preceeding determinations if it is to be considered a signal of fetal distress.


Genetic basis of hair medulla by twin study. Data on the incidence of medulla of human head hair based on 9,600 strands examined from 48 pairs of zygosity--determined German twins were quantified as medullary ratio and subjected to variance analysis to give information about genetic significance of the character concerned. The results of F test and heritability estimate yielded significant values indicating the presence of a strong genetic component of variability in the incidence of medulla of human head hair. Sex influence upon the character is found to be absent.


Peer review and PSRO: an update.

Peer review and PSRO: an update. The author provides a summary of developments in peer review and Professional Standards Review Organizations (PSROs) within APA, the federal government, and the American Medical Association between June 1974 and June 1975. He discusses the reaction of the medical profession to the interim guidelines from the U.S. Department of Health, Education, and Welfare and the problems of financing PSROs. He concludes that the key issues for PSROs and peer review in general are the availability and effectiveness of local review components, and that lack of involvement on the part of psychiatry will only ensure that nonpsychiatrists will design the review procedures.


Three-dimensional organization of testicular interstitial tissue and lymphatic space in the rat. Rat testes fixed by vascular perfusion were examined by scanning and transmission electron microscopy. This revealed a complex organization of the interstitial tissue and an extensive "testicular lymphatic space" composed of continuous "peritubular lymphatic sinusoids." No cellular connections exist between the interstitium and the tubules. Each sinusoid completely surrounds an individual seminiferous tubule, and adjacent sinusoids communicate freely through fenestrae in the interstitium. Thus, material must enter the lymph to gain access to the tubules. The sinusoids are delimited by separate endothelial cell layers over the tubules and interstitium. The layer over the interstitium is discontinuous in specific areas according to the geometry of the tubule packing. Interstitial tissue located in the flattened biconcave interstices between two adjacent tubules is consistently covered with endothelial cells, while that located in the open, triangular interstices between three or more tubules consistently lacks an endothelium. Most of the Leydig cells are located in the "open interstitium" and are directly exposed to the lymph. Physiological implications of the "testicular lymphatic space" and additional features of the interstitium are discussed.


Contributions to an analysis of the avian vitelline membrane's potential to promote outgrowth of the yolk sac-serosal membrane. Explanted blastoderms of freshly laid chicken eggs expand their area during the first 44-45 hours of incubation by a factor of at least 11 if they are placed with the epiblast on the inner surface of explanted fresh chick vitelline membrane and provided with chick egg extract. This expansion is due essentially to the spreading of the yolk sac-serosal membrane. On turkey and duck membrane the expansion factor is about 6 and 3.8 respectively under otherwise identical conditions, but 1.9 only on a semisolid nutrient agar plate. Only the inner surface of the vitelline membrane has this growth-promoting potential, which markedly and progressively declines during incubation in ovo because of systemic factors rather than because of a direct influence by the outgrowing yolk sac-serosal membrane. Trypsinization of fresh chick vitelline membrane (1% trypsin 3 hours) reduces the growth-promoting potential to about 40% of its normal strength. The outgrowth of the extraembryonic tissues on vitelline membrane is better supported in the presence of a species' own egg extract than by extract from another species.


Propranolol and surgical anesthesia.

Propranolol and surgical anesthesia. The potential danger of anesthetizing a patient on beta-adrenergic blockade therapy has long been recognized. The cases of 73 patients taking propranolol and anesthetized for non-cardiac operations were reviewed with regard to preoperative administration of propranolol and intraoperative and postoperative complications. Of these patients, 72 percent took propranolol to within 24 hours of operation and 85 percent took it to within 48 hours. The mean dose of propranolol was 77 mg/day (range, 10 to 320 mg/day). Anesthetic technics and agents included enflurane, halothane, N2O-narcotic-relaxant, and spinal anesthesia. There were only three episodes of hypotension, all of which responded to a decreased depth of general anesthesia, IV fluid administration, and, in one patient, a small dose of a vasopressor. There were no intraoperative or postoperative deaths. It is concluded that if propranolol is indicated for medical control of the patient's symptoms, it need not be discontinued before surgical anesthesia.


Absence of autoregulation of cerebral blood flow during halothane and enflurane anesthesia. The effects of halothane and enflurane anesthesia under conditions of normo-, hyper-, and hypocarbia on the autoregulation of cerebral blood flow (CBF) in the goat were evaluated. The goat was selected because of its unique arterial blood supply to the head and the development of a method by which CBF may be continuously measured. The study revealed that 1 MAC of halothane or enflurane anesthesia at normocarbia abolished cerebral autoregulation, CBF increasing or decreasing with increasing or decreasing peripheral blood pressure. Reduction of anesthesia to 0.5 MAC partially restored cerebral autoregulatory capability. The effect of 1 MAC and 0.5 MAC anesthesia on cerebral autoregulation of blood flow was potentiated by hypercarbia and antagonized by hypocarbia, indicating that the vascular response to blood CO2 fluctuations remained intact.


Cardiac failure associated with hypocalcemia. Rapid transfusion of citrated whole blood was associated with acute hypotension and a rising central venous pressure in a patient undergoing pelvic exenteration and hemipelvectomy. Evidence of cardiac failure was accompanied by a precipitous decrease in serum ionized calcium (Ca++) concentration. When the rate of blood transfusion was slowed, arterial blood pressure returned to the control level and serum Ca++ increased.


Hypnosis for monitoring intraoperative spinal cord function. In such procedures as the Harrington operation for idiopathic scoliosis, evaluation of spinal cord function is advisable immediately after the back is straightened. The authors have used hypnosis for this procedure, as an adjunct to anesthetic management. Patients are awakened on the table, given lower extremity tests, and are then reanesthetized. The incidence of postoperative pain and other discomfort is also reduced by hypnosis.


Effect of mechanical ventilation with end-inspiratory pause on blood-gas exchange. The effects of end-inspiratory pause (EIP) on gas exchange were measured in 10 adult patients with acute respiratory insufficiency while maintained on mechanical ventilation. Four inspiratory patterns were studied with a constant tidal volume (10 to 15 ml/kg body weight), respiratory rate (9 to 12 breaths/min), FIO2 (0.5) and end-expiratory pressure. Inspiratory flow rate (V insp) and EIP time were varied to produce a control pattern (V insp = 60 L/min, EIP = 0), 2 EIP patterns of 0.6 and 1.2 seconds with a similar V insp and a "slow" flow pattern (V insp = 30 L/min) without EIP. The control pattern was applied before and after each study period. Arterial oxygenation was unchanged with both EIP and "slow" flow patterns when compared to control. Dead-space ventilation (VD/VT) and Paco2 were significantly decreased (p less than 0.01) as EIP was increased from 0 to 1.2 seconds, but remained unchanged with slow inspiratory flow. Thus, EIP improved the efficiency of ventilation with no apparent improvement in oxygenation in patients with acute respiratory insufficiency.


Hemodynamic effects of morphine during and early after cardiac operations. Hemodynamics and blood gases were measured before and 15 minutes after small (10 mg/70 kg) doses of intravenously administered morphine in two groups of patients having open heart surgery. In one group, the study was undertaken after median sternotomy but before perfusion. The other group had been in the intensive care unit for approximately 1 hour. No changes were found in either group in cardiac index, atrial pressures, arterial pressure, or blood gas variables. However, mean systemic vascular resistance decreased from 41.5 to 35.4 after morphine was given postoperatively. Hence, hemodynamically, morphine is a safe drug if given in small doses for pain relief and sedation early after open heart surgery.


A one-year survey of mold growth inside twelve homes. A survey was performed of the mold flora in the air and on the surfaces inside twelve homes throughout four seasons. There were significant variations of the mold flora in homes associated with the outdoor spore count, various rooms, carpeting, central air-conditioning and pets. We conclude that homes may be a source of perennial mold exposure.


The pulmonary absorption-excretion volume effect. An in-vitro experiment demonstrated the concentration effect of N2O (3% versus 75%) during elimination and during uptake. Other pulmonary absorption-excretion phenomena also occur simultaneously, as paired events during uptake and then during elimination:diffusion hyperoxia and diffusion anoxia; alveolar concentration of CO2, and alveolar dilution of CO2. These clinical phenomena, as well as the second gas effect, are all related, and the pulmonary absorption-excretion volume is found to depend in part on the type of ventilation:volume controlled, pressure controlled, or spontaneous respiration.


Laryngeal stenosis in acromegaly: a possible cause of airway difficulties associated with anesthesia. After difficult intubation in an acromegalic patient was encountered, 7 additional acromegalic patients were studied by measuring the cricoid width and anteroposterior diameter. Cricoid width and anteroposterior diameter were generally found to be narrower than in a group of normal patients. Such narrowing may explain airway problems encountered in acromegalic surgical patients.


Caudal analgesia for quadruplet delivery. During the period January 1969 to November 1974, in a total of 39,800 deliveries, there were two sets of quadruplets. Both parturients had been taking ovulation-inducing drugs. Maternal problems were distended abdomen and heavy uterus, causing supine hypotension and lordosis; toxemia of pregnancy; increased possibility of hemorrhage before, during and/or after delivery; edema of the back; mental depression. The fetal problems were prematurity; intrauterine growth retardation; increased possibility of transfusion syndrome and prolapsed cord; increased obstetric manipulation. An adequate number of obstetricians, pediatricians, anesthesiologists, and nurses, necessary equipment, and blood and blood components should be available. Early  hospitalization is necessary. Close observation of the patient before, during, and after delivery is essential. The patient should stay on her side throughout the labor. General anesthesia may add to fetal depression and increase the possibility of uterine atony. Spinal or lumbar epidural anesthesia may be difficult because of the associated lordosis and back edema. Caudal block allowed intrauterine manipulation; provided adequate analgesia, permitted high FIO2 administration, and did not interfere with voluntary bearing down when required.


Changes in calves and rats consuming milk from cows fed chronic lethal doses of Senecio jacobaea (tansy ragwort). Chronic lethal doses of Senecio jacobaea, which contains 6 pyrrolizidine alkaloids, were fed to 6 cows close to parturition. Their calves were allowed to suckle for 40 to 126 days to determine whether pyrrolizidine alkaloids or their toxic metabolites had been passed into the cow's milk. Histopathologic changes were not detected in the calves consuming the milk; however, clinical chemical tests suggested the presence of hepatic biochemical lesions. Rats gavaged daily for 30 days with milk from Senecio-fed cows were not grossly or histopathologically affected.


Familial renal disease in Norwegian Elkhound dogs: physiologic and biochemical examinations. Renal disease was detected in 21 of 56 progeny from a specific line of inbred Norwegian Elkhound (NE) dogs. Results of hematologic and clinical chemistry examinations revealed that minor differences existed between affected and nonaffected NE dogs. Of 21 NE dogs with renal disease, 3 had persistent glucosuria without hyperglycemia. The 21 affected dogs had impaired ability to concentrate urine. According to renal function tests, glomerular filtration rate of normal NE dogs was less than that of normal mixed breed dogs. Although a few affected NE dogs excreted large amounts of amino acids in urine, statistically significant differences did not exist between normal and affected NE dogs with regard to alpha-amino acid nitrogen content of their plasma or urine. By paper chromatographic separation techniques, free amino acids of plasma, urine, and extracts of liver and kidney were not qualitatively different for mixed breed dogs, normal NE, and NE with renal disease. Statistically significant differences were not detected between serum calcium concentrations of normal and affected NE dogs. In NE dogs with renal disease, there was significant hypercalciuria, but a few normal dogs excreted more than did some dogs with disease. Blood pressure values of normal mixed breed dogs and affected NE dogs were similar. It was concluded that hematologic and blood chemical abnormalities, derangement of amino acid or calcium metabolism, and hypertension were not associated with renal disease in these NE dogs.


Focal chorioretinitis and iridocyclitis associated with scleroderma. A case of chorioretinitis and iridocyclitis in a patient with progressive systemic sclerosis is reported and the literature on the ocular manifestations of the disease is briefly reviewed.


Low-dose intramuscular ketamine for pediatric radiotherapy: a case report. Ketamine in low IM doses was found to produce satisfactory anesthesia for radiotherapy in a pediatric patient in a series of extended treatments. Change in anesthesiologists may have been a factor in increasing apprehension and anesthetic dosage in later treatments.


Circulatory changes during anesthetic induction: impact of d-tubocurarine pretreatment, thiamylal, succinylcholine, laryngoscopy, and tracheal lidocaine. Circulatory changes after IV d-tubocurarine (3 mg), thiamylal (4 mg/kg) plus succinylcholine (2 mg/kg) and followed by direct laryngoscopy with or without intratracheal lidocaine spray (2 mg/kg) just before endotracheal intubation (EI), were measured in 40 adult patients. Pretreatment with d-tubocurarine did not alter mean arterial pressure (MAP), heart rate (HR), or central venous pressure (CVP). One minute after thiamylal-succinylcholine and just before laryngoscopy, MAP was 15 torr less than the awake value (p less than 0.05) and HR was 13 beats/min greater than the awake value (p less than 0.05). Laryngoscopy and EI elevated MAP above awake levels and further increased HR in all patients. The magnitude of these responses immediately following EI was not altered by tracheal lidocaine. However, the pressor and HR changes following EI were more transient when tracheal lidocaine was used (20 patients) and these patients were more likely to tolerate the tracheal tube without immediate additional anesthesia. The incidence of ventricular dysrhythmias was not altered by tracheal lidocaine. Compared with awake values, the cardiac index did not change significantly following intubation but stroke volume was decreased (p less than 0.05), with or without tracheal lidocaine.


Extended use of intra-aortic balloon pumping in peripartum cardiomyopathy. A patient with perinatal cardiomyopathy was greatly benefited physiologically by 7 weeks of intra-aortic balloon pumping. This experience documented that extended pumping can be carried out with only manageable complications. Although the patient survived the hospitalization, she died shortly thereafter of intractable congestive failure. Perinatal cardiomyopathy is a potentially reversible condition. Ventricular assistance by intra-aortic balloon pumping may be sustaining during continued systemic treatment of this entity. Further evaluation for longevity of more advanced congestive heart failure from cardiomyopathies needs further clinical trial.


Lower extremity ischemia after femoral arteriovenous bovine shunts. Use of bovine carotid artery grafts for femoral arteriovenous fistulas is now an accepted method of circulatory access for patients who require chronic hemodialysis. A serious but infrequently mentioned complication of this technique is lower extremity ischemia secondary to an arterial steal phenomenon. Three cases of this syndrome are presented and specific recommendations made for preoperative and intraoperative evaluation in order to avoid this complication. A possible surgical technique for correction of this syndrome is also discussed.


Corticosteroid treatment of experimental smoke inhalation. The effect of four corticosteroid analogs was evaluated in the treatment of smoke inhalation injury. Rats were exposed to white pine smoke for 15 minutes at 25 C, in a specially designed smoke apparatus. Methylprednisolone, 10 mg bid x 2d, starting one hour post exposure, was most effective in reducing expectant mortality (22.6%). A single injection of methylprednisolone, 20 mg, at one hour, resulted in a 76.7% reduction. There was no significant difference between the single injection of methylprednisolone and dexamethasone, 4 mg, but the administration of analogs with primarily mineralocorticoid activity, cortisone and hydrocortisone, actually increased mortality. In the control rats, marked interstitial edema occurred by 24 hours, the absence of which following treatment correlated closely with the results of the mortality study. This suggests that post exposure death due to white pine smoke is a result of direct lung injury, with increased endothelial and alveolar membrane permeability and edema, and that administration of glucosteroids in massive doses was effective in reducing this permeability and resultant edema.


The modified bovine heterograft in vascular access for chronic hemodialysis. The results of 100 modified bovine heterografts constructed in 93 patients for subcutaneous arteriovenous fistulas for chronic hemodialysis have been reviewed. Fifty-seven patients had the bovine heterograft inserted as the primary method of vascular access. Twenty-eight patients had complications consisting of graft thrombosis and stenosis, graft infection, and hemorrhage that required additional surgical procedures. Three patients with diabetes mellitus developed ischemia of the hand. Fourteen patients have died but none of the deaths could be attributable to the use of the bovine heterograft. In our experience the modified bovine heterograft has enjoyed a higher patient acceptance as compared to other methods of vascular access for hemodialysis. The chief advantage of the bovine graft has been the ability to use the graft in any patient as a means of immediate dialysis.


Idiopathic thrombocytopenic purpura complicating chronic lymphocytic leukemia. Three patients had severe, symptomatic idiopathic thrombocytopenic purpura (ITP) complicating chronic lymphocytic leukemia (CLL) that was refractory to prednisone treatment but that responded to splenectomy alone or in addition to immunosuppressive-cytotoxic treatment. Evidence of high titer of an antiplatelet factor, most likely an antibody, was corroborated in one case by the 14C-platelet serotonin release assay. This experience suggests that the treatment of ITP complicating CLL is similar to that of ITP not associated with lymphoproliferative disorders.


Argon laser application to the angle structures in the glaucomas. The argon laser beams' effect on angle structures was studied in 20 uncontrolled glaucomatous eyes. Nineteen eyes became hypotensive quickly, but in 15, the elevated tension returned during the 20 to 40 day follow-up period. Four eyes sustained low pressures throughout the ten-month follow-up period. Two were of babies with congenital glaucoma, one had simple glaucoma following an unsuccessful filtering operation, and one was aphakic following congenital cataract extraction. Ten eyes were medically controlled postoperatively, and six were failures that had to undergo further surgery. Outflow facility measurements revealed an increase in C values during the hypotensive period. The C values were reduced later, with the decrease corresponding to the increase in intraocular pressures. The hypotensive effect together with the increase in outflow facility was probably related to laser-induced openings in the angle structures. The varying results at the later stages depended on whether or not these openings remained opened, or became partially or completely closed during healing.


Chemical modification of carboxypeptidase A crystals. Nitration of tyrosine-248. Nitration of bovine carboxypeptidase A crystals with tetranitromethane increases esterase activity, decreases peptidase activity, and modifies about one tyrosyl residue. Modification of enzyme crystals avoids the polymerization that occurs when the enzyme is nitrated in solution. Two procedures have been employed to identify the tyrosyl residues nitrated. The first involves cyanogen bromide cleavage and isolation of the fragment containing residues 104-301. After solubilization by succinylation, this fragment is digested with chymotrypsin, the peptides are fractionated by gel filtration, and the nitrotyrosyl peptides are purified by affinity chromatography on an antinitrotyrosyl antibody-Sepharose conjugate followed by ion-exchange chromatography. In the second, the nitroenzyme is heat denatured, digested by chymotrypsin, and fractionated on the affinity and ion-exchange columns. By both methods, the major mitropeptides, representing between 60 and 80% of the nitrotyrosyl label, are uniquely compatible with that segment of the sequence of carboxypeptidase containing Tyr-248. A nearby cation, either the active site zinc ion or Arg-145, would seem to be an important factor in determining the selective nitration of this residue.


The role of lysine in the action of bovine pancreatic ribonuclease A. The involvement of lysine residues in the active site of pancreatic ribonuclease has been investigated by assessing (a) the degree of substrate and substrate analogue protection of individual lysine residues against acetylation, and (b) the individual contribution of remaining unacetylated lysine residues to the total catalytic activity of the enzyme. Different substrate analogues (RNA digest, CMP, ATP, and pyrophosphate) were found to give different degrees of protection against acetylation with acetic anhydride. Instead of the expected specific protection of active site lysine residues such as lysine-7 and lysine-41, however, a general decrease in reactivity of all the lysines was observed when the substrate analogues were present during the acetylation. The fraction of enzymatic activity remaining in the protected samples was consistently greater than the fraction of any one lysine remaining unacetylated, and was found to correspond fairly well with the sum of the fractions of unacetylated lysine-7, lysine-41, and a third residue, tentatively assigned as lysine-66. This is consistent with other observations of ribonuclease which suggest that while no lysine residue interacts with substrate and substrate analogues in the formation of the Michaelis-Menten complex, a lysine amino group is required for catalysis. It is proposed that this lysine amino group can be supplied by any one of two or three lysine residues (7, 41, and 66) located close to the substrate binding site.


Influence of electric dichroism on the temperature-jump relaxation study of proflavine-DNA complexes. The temperature-jump relaxation kinetics of proflavine-DNA complexes has been reinvestigated with a standard apparatus equipped for absorption detection of plane-polarized light in order to discriminate between chemical relaxation and transient orientation effects. Under low ionic strength conditions (0.015 M Na+), these effects may represent the major contribution to the signal when the T-jump apparatus is used without a polarizer. They have been improperly assigned to chemical relaxation in previous work. The actual relaxation times are smaller than 30 musec at 10 degrees C. Under medium ionic strength conditions (0.2 M Na+) it is shown that: (i) the "instantaneous" change of transmission reported in earlier work (Li, H. J., and Crothers, D. M. (1969), J. Mol. Biol. 39, 461-477; Schmechel, D. E. V., and Crothers, D. M. (1971), Biopolymers 10, 465-480) is due to orientation effects; (ii) an intermediate exists whose absorption spectrum resembles somewhat that of proflavine aggregates on a linear polyanion; (iii) the rate constants for outside binding may be significantly larger than previously reported. The new kinetic data are consistent with a modified mechanism derived from equilibrium studies (Ramstein, J., Hogrel, J. F., Dourlent, M., Leng, M., an Hélène, C. 1973), in Dynamic Aspects of Conformation Changes in Biological Macromolecules, Sadron, C., Ed., Dordrecht, Holland, Reidel Publisher, pp 333-347; Dourlent, M., and Hogrel, J. F. (1976), Biopolymers (in press)), but, however, do not unambiguously prove it. From these studies, it is inferred that orientation effects can perturb relaxation data on systems containing linear polymers in many cases.


Polynucleotide displacement reactions: detection by interferon induction. A large variety of displacement reactions between homopolynucleotides and complexes thereof has been demonstrated by interferon induction data obtained in primary rabbit kidney cell cultures superinduced with metabolic inhibitors. The polymers involved in these helix-coil displacement studies were: poly(adenylic acid), poly(inosinic acid), poly(cytidylic acid), poly(uridylic acid), poly(ribothymidylic acid), polylaurusin, poly(7-deazaadenylic acid), poly(7-deazainosinic acid), poly(5-bromocytidylic acid), and poly(5-bromouridylic acid). As monitored by ultraviolet absorbance-temperature profiles, all displacement reactions were directed toward the formation of the helix with the higher thermal stability. Concomitantly, the resulting helix was invariably more active as interferon inducer than the reactant helix, except for some reactions in which poly(7-deazaadenylic acid) was involved. For the latter reactions both the reactant and resultant helices were inactive as interferon inducer. The interferon induction data revealed that all displacement reactions proceeded to completion within 1 h even at temperatures well below the Tm of the reactant helix. The helix-coil displacement reaction could also be monitored by sucrose velocity gradient analysis, and, as evidenced for poly(A)-2poly(I) + 2poly(C) leads to 2poly(I)-poly(C) + poly(A), readily occurred at the cellular level, presumably at the cell surface.


Triple-helical polynucleotides. Mixed triplexes of the poly(uridylic acid)-poly(adenylic acid)-poly(uridylic acid) class. By the techniques of interferon induction in primary rabbit kidney cells "superinduced" with metabolic inhibitors, ultraviolet absorbance-temperature profiles, sensitivity to pancreatic ribonuclease A, and sucrose velocity gradient ultracentrifugation, a number of reactions between double-helical RNA and single-stranded RNA or DNA homopolymers were investigated. The polymers involved in these studies were poly(adenylic acid), poly(uridylic acid), poly(ribothymidylic acid), poly(5-bromouridylic acid), poly(deoxythymidylic acid), poly(deoxyuridylic acid), poly(3-methyluridylic acid), poly(2'-O-methyluridylic acid), and poly(2'-azido-2'-deoxyuridylic acid). Two different reaction courses, both leading to the formation of triple helices, were noted: (1) poly(Ux)-poly(A) + poly(Uy) leads to poly(Ux)-poly(A)-poly(Uy) if the Tm of poly(Ux)-poly(A) was higher than the Tm of poly(Uy)-poly(A); (2) poly(Ux)-poly(A) + poly(Uy) leads to poly(Uy)-poly(A)-poly(Ux) if the Tm of poly(Ux)-poly(A) was lower than the Tm of poly(Uy)-poly(A). In these equations, the homopolymer written to the left of poly(A) implies Watson-Crick hydrogen bonding whereas the polymer to the right of poly(A) is involved in Hoogsteen hydrogen bonding.


Structure of wye (Yt base) and wyosine (Yt) from Torulopsis utilis phenylalanine transfer ribonucleic acid. A fluorescent base wye (Yt base) was isolated from Torulopsis utilis tRNAPhe. The structure was established as 4,9-dihydro-4,6-dimethyl-9-oxo-1H-imidazo[1,2-alpha]purine based on ultraviolet (uv), nuclear magnetic resonance (NMR), and mass spectra, and by direct comparison with synthetic material. The nucleoside, wyosine (Yt), was isolated from purified tRNAPhe by enzymatic degradations followed by column and thin-layer chromatographies. The structure of wyosine is proposed as 3-ribofuranosyl-4,9-dihydro-4,6-dimethyl-9-oxo-1H-imidazol[1,2-alpha]purine (the ribosyl group is attached to the N-9 position of guanine nucleus) on the basis of comparison with model compounds.


SS-interchanged and oxidized isomers of bovine serum albumin separated by isoelectric focusing. Column isoelectric focusing separates commercial bovine serum albumin in 5 fractions with isoionic points in the vicinity of that of mercaptalbumin (pI 5.24). About 20% of the bovine albumin have isoionic points higher than mercaptalbumin and are split into two fractions, both recognized as SS-interchanges isomers: (1) pI 5.39 is the "aged" albumin described by Nikkel and Foster (1971, Biochemistry 10, 4479); (2) pI 5.45 represents a further degree of SS-interchange, catalyzed by small amounts of cysteine in the solution ('cysteine-aged' albumin). In 6 M urea the "cysteine-aged" albumin is electrofocused to the same pH value as mercaptalbumin. In 6 M urea 40% of commercial albumin focuses in 3 fractions with isoionic points lower than mercaptalbumin. This percentage will increase during incubation at oxidizing conditions ("oxidized" albumin). Electrofocused in water the oxidized fractions have isoionic points at pI 5.28, 5.18 and 5.12, respectively. The shifts in isoionic point of the "oxidized" albumins are caused by irreversible changes in the primary structure. Although the free SH group of albumin is oxidized during the oxidation reaction, the observed changes in isoionic points are caused by modifications of some other amino acid residues. Both "cysteine-ageing" and "oxidation" are inhibited by alkylation of the SH group. "Cysteine-ageing" is furthermore inhibited when the bovine albumin is "oxidized".


Further studies on the blue and near ultraviolet reversible photoreaction with an intracellular particulate fraction of the fungus, Alternaria tomato. Further studies have been made on the blue and near ultraviolet-reversible photoreaction in a cell-free system of the fungus Alternaria tomato, prepared by two-layer sucrose density gradient centrifugation. A light-minus-dark difference spectrum of the supernatant fraction showed a dip in the near ultraviolet region, mainly at 280 nm, when irradiated with near ultraviolet light which could not be reversed by following the initial irradiation with blue light. The difference spectrum of the dialyzed particulate fraction, located in the 68% sucrose band, showed a peak absorbance in the blue region, mainly at 400 nm, when irradiated with near ultraviolet light, and also could not be reversed by blue light. When the particulate fraction plus the supernatant fraction was irradiated with near ultraviolet light, the increment rate of peak absorbance in the  blue region increased compared to that of the particulate fraction lacking the supernatant, and both peak absorbance in the blue region and the  dip in the near ultraviolet region were reversed by irradiation with blue light following the application of near ultraviolet light. Thus, it was concluded that two photoresponsive systems are involved in blue and near ultraviolet reversible photoreaction on an intracellular particulate fraction.


The interaction of pyridoxal phosphate with aspartate apoaminotransferase. The rate of biniding of pyridoxal phosphate to the apoenzyme of pig heart cytoplasmic aspartate aminotransferase (L-aspartate: 2-oxoglutarate aminotransferase, EC 2.6.1.1) was measured by adsorption spectroscopy and by formation of active enzyme. At pH 5.1 and 8.3 the binding of coenzyme follows saturation kinetics. The binding process thus involves at least two steps. The rate of pyridoxal phosphate binding to the apoenzyme is dependent on the anion present in the pH 8.3 triethanolamine buffer. Chloride activates somewhat at very low concentrations. Phosphate and its methyl, ethyl, and phenyl esters are very effective inhibitors of the recombination in that 0.2--0.4  mM inhibit the rate of coenzyme binding by 50%. This is below the physiological concentration of phosphate. Sulfate also inhibits the rate of binding, but nitrate and acetate have little effect.


Effect of lipid composition on sensitivity of lipid membranes to Triton X-100. The effect of lipid composition on the sensitivity of liposomes (multilamellar liposomes) and sonicated liposomes, which were composed mostly of single-compartment liposomes, toward Triton X-100, a detergent, was examined. Monomeric molecules of Triton X-100 seem to penetrate into liposomal bilayers, since Triton X-100 could modify the permeability of liposomes at concentrations below its critical micellar concentration. Cholesterol incorporation into egg lecithin liposomes had a negligible effect on the sensitivity to Triton X-100. On the other hand, cholesterol incorporation drastically reduced the Triton-induced permeability change of multi-lamellar liposomes prepared with dipalmitoyl and dimyristoyl phosphatidylcholines. Liposomes prepared with dipalmitoyl phosphatidylcholine or dimyristolyl phosphatidylcholine showed a strong resistance to the action of the detergent when prepared with 50 mol% of cholesterol, releasing at most 10% of trapped glucose. Ultrasonicated liposomes of dipalmitoyl phosphatidylcholine were, however, still sensitive to Triton X-100, releasing almost 100% of the trapped glucose even when 50 mol% of cholesterol was incorporated. This fact indicates that only the outermost bilayers in multilamellar liposomes composed of dipalmitoyl phosphatidylcholine and cholesterol may be sensitive to the Triton X-100. In cases of multilamellar liposomes with less than 33 mol% of cholesterol, sensitivities of liposomes to the detergent decreased in the following order; dipalmitoyl phosphatidylcholine, dimyristoyl phosphatidylcholine, egg lecithin and rat liver phosphatidylcholine liposomes. The same order of sensitivity to Triton was also observed in the system of sonicated liposomes. Membranes in the gel state are most sensitive to the detergent, followed by membranes around the phase transition. Egg and rat liver phosphatidycholine membranes, both of which are liquid-crystalline, were the least sensitive to the detergent.


Acetylcholinesterase and butyrylcholinesterase of developing human brain. Acetylcholinesterase (AchE) and butyrylcholinesterase (BuchE) activities were studied in 20,000 g supernatant (S) and pellet (P) fractions of cerebrum1, caudate nucleus and cerebellum regions of human brain between the gestational ages of 20 and 40 weeks. On a per gram wet tissue basis, cerebrum and cerebellum had 60% and caudate nucleus had 80% of AchE activity present at 20-22 weeks as compared to 38-40 weeks of gestation. Specific activity (SA) of AchE did not change appreciably with gestational age in any of the P fractions. In S fractions of cerebrum and cerebullum there was about a 1.5-fold increase during this period. BuchE SA and activity per gram tissue in P and S fractions of cerebrum and cerebellum increased by 1.5- to 3-fold and decreased by about the same order of magnitude in caudate nucleus, during 20-40 weeks of gestation.


Interaction of nucleic acids with electrically charged surfaces. II. Conformational changes in double-helical polynucleotides. The influence of adsorption of double-stranded (ds) DNA, ds RNA and homopolymeric pairs at a mercury electrode on conformation of these polynucleotides was studied. Changes in the polarographic reducibility of polynucleotides, which were followed by means of normal pulse polarography and linear sweep peak voltammetry at the dropping mercury electrode were exploited to indicate conformational changes. It was found that, as a consequence of adsorption of ds polynuclotides on the negatively charged electrode conformational changes similar to denaturation take place in a narrow potential region around -1.2 V (the region U). After sufficiently long time of the contact with the electrode (under our conditions about 10 s) these changes reach limiting values, which can approach total denaturation. Upon adsorption of ds polynucleotides on the electrode charged to more positive potentials than the region U either (1) no conformational changes occur or (2) only a small part of the polynucleotide (probably labile regions of the ds molecule) is very quickly denatured - the remainder of the molecule preserves its ds structure. Conformational changes of adsorbed ds polynucleotides are influenced by factors which change the stability of ds polynucleotides in solution. It is supposed that denaturation of ds polynucleotides in the region U might result from the strains connected with the repulsion of certain segments of the molecule anchored on the electrode from the negatively charged surface.


[The role of prolonged emotional stress in the genesis of hypercholesterolemia and hypertension]. Stable endogenous hypercholesterolemia and a slight, but stable hypertension developed under conditions of unrestricted behaviour in rabbits subjected for 4 months to daily prolonged (2-hour) interrupted stimulation of negative emotional zones of the hypothalamus through the implanted electrodes. Changes in cholesterol content were more noticable in case the stimulation was continued against the background of daily feeding of these rabbits with small doses of methylthiouracil.


[Reversible suppression of cellular aggregation by cytochalasin B and kolkhamin]. Aggregation of normal mouse fibroblast-like cells plated on the surface of millipore filter was studied quantitatively. It was shown that addition of 10 mug/ml of cytochalasin B (a drug which blocked active cell locomotion) or 0.1 mug/ml of colcemid (a drug which destroyed polarization processes in the cells and therefore interfered with the oriented cell movement) completely inhibited such aggregation. This inhibition was reversible: after the drugs were washed off the cells did aggregate. It was concluded that cell aggregation in this experimental system required active cell movement and cell polarization.


[Proliferative activity of stromal cells--bone marrow precursors possessing clonogenic properties]. Proliferative activity of bone marrow clonogenic stromal precursor cells was studied by using the thymidine "suicide" method in vitro. Crude bone marrow stromal clonogenic cells failed to proliferate in vivo. But 24 hours after the explantation they entered the S-period and formed colonies of fibroblasts in monolayer cultures. 39+/-4% of these clonogenic cells were subject to thymidine "suicide". It follows that, in difference from cells-precursors in the crude bone marrow, clonogenic stromal cells were actively proliferating in monolayer cultures.


[The effect of uncouplers of oxidative phosphorylation on granule precipitation of neutral red in normal and tumor cells]. A study of the effect of uncouplers of the oxidative phosphorylation on the interaction on neutral red with the normal mouse fibroblast and tumour L-cells showed the former to retain the capacity for the dye granule formation in the presence of 1x10 4 M 2,4-dinitrophenol (DNP). Another uncoupler of the oxidative phosphorylation - n-trifluoromethoxycarbonycyanidephenylhydrazone (FCCP) depressed the granule formation both in the tumour L-cells and in the mouse normal fibroblasts. The dye uptake in the normal fibroblasts and in the tumour L-cells was inhibited by both the DNP and the FCCR in the concentration which uncoupled the oxidative phosphorylation.


Originalarbeiten.

Originalarbeiten. In 5 cases of polycythaemia vera and 2 cases with other myeloproliferative disorders accompanied by thrombocythaemia (megakaryocytic myelosis), the megakaryocytes were differentiated and studied by use of the combined application of cytophotometric determination of the DNA content and autoradiography with tritiated thymidine (3H-TdR) in vitro. A shift to the right of the megakaryocyte series, occurence of high polyploidy cells at 64c and a decrease of the 3H-TdR-labeling indices were observed. The data suggest a disturbance of the rhythmical polyploidization of the megakaryocytes, consisting of an elevated proportion of rest cells at the different ploidy stages. The maturation capacity of megakaryocytes may be related more to the resting than to the DNA synthesizing cells.


Surface immunoglobulins and receptor sites for aggregated IgG on leukemic reticuloendotheliosis cells. On blood lymph nodes and spleen cells of 4 patients with leukemic reticuloendotheliosis (LR) the binding of 125-J-labelled IgG aggregates as well as binding of 125J-labeled anti immunoglobulin sera was studied. Moreover the capacity to form spontaneous rosettes with sheep red blood cells to bind immune complement complexes as well as the proliferative response in the presence of PHA were investigated. On the surface of hairy cells a variety of immunoglobulins were demonstrable. IgG of both types was found to be the predominant surface bound immunoglobulin and evidence was obtained, that these antibodies were adsorbed from the serum via Fc-receptors. In all LR-cases the percentages of T-cell rosettes as well as the PHA responses were decreased when compared with the normal controls. The numbers of immune complement complex binding cells were in the range of the normal controls. Results are discussed with respect to the origin of hairy cells in LR.


IgA deficiency in one of identical twins. A disease resembling childhood coeliac disease occurred in one of identical twins. When the twins were investigated at the age of 23 the initial diagnosis could not be substantiated but the twin who had been ill had selective IgA deficiency. Differences dating from early infancy may have been a result of the discordance for IgA deficiency. Thus in some patients environmental influences may be important in either the initiation or the perpetuation of the deficiency.


Effects of ceramide analogs on myelinating organ cultures. Analogs of ceramide which inhibit galactocerebrosidase also demyelinate or inhibit myelination in organ cultures of rat cerebellum. The potency of the analogs in culture correlated with their effectiveness as inhibitors of cerebrosidase, but not with their effectiveness as inhibitors of galactosyl transferase. The most effective compound was the decanoyl amide of 3-phenyl-2-amino-1,3-propanediol with erythroconformation. Stimulators of cerebrosidase also demyelinated cultures. With both groups of compounds, myelin sheaths became distorted, then broke into lipid droplets. Axons were preserved, but neurons showed some nuclear changes and granularity. Metabolic studies with the most effective inhibitor showed that glucose incorporation into cerebroside and other alkali-stable lipids was initially depressed compared to proteins and total lipids.


[Shock-induced aggression and reactivity following raphe lesion in rats. Effects of physostigmine (author's transl)]. Shock-induced fighting behavior, flinch-jump thresholds and locomotor open-field activity were studied following dorsal and medial raphe lesions in rats. Attack scores were raised for low-intensity shocks (1 mA) only, whereas they remained unchanged for shocks of higher intensity (2 mA), as compared to controls. The jump threshold is decreased in raphe lesioned animals, but the flinch threshold is unchanged. Physostigmine (0,2-0,5 mg/kg) reduces the lesion-induced hyperreactivity: locomotor open-field activity is reduced to a greater extent than in the controls, and habituation to the open-field situation is restored. Doses of physostigmine (e.g. 0,2 mg/kg), that do not modify shock-induced aggression in controls, reduce aggression in lesioned animals to the level shown by controls for low-intensity shocks. In conclusion, shock-induced aggression is not directly dependent on a serotonergic brain mechanism. The behavioral changes observed are related to the hyperreactivity induced by raphe lesions. This hyperreactivity presumably results from a reduced activity of cholinergic brain mechanisms.


Effects of intraventricular 6-hydroxydopamine injections on serum prolactin and LH levels: absence of stress-induced pituitary prolactin release. The drug 6-hydroxydopamine (6-OHDA) has been reported to reduce hypothalamic norepinephrine (NE) content after administration into the lateral ventricle without altering the dopamine content of tubero-infundibular neurons. Serum prolactin levels in male rats injected with 2 X 250 mug 6-OHDA were significantly higher than in untreated control rats. Intraventricular injection of male rats with artificial cerebrospinal fluid resulted in elevated mean prolactin levels similar to those observed in 6-OHDA-treated animals. Further experimentation on animals decapitated at different times after removal from the animal quarters, indicates that prolcatin levels in 6-OHDA-treated rats are continuously elevated whereas they rise from basal levels to extremely high levels in CSF-treated rats, thus resulting in similar mean values. The CSF-treated controls ate hypersensitive to the stress of being removed from their normal environment. Such an effect was not observed in 6-OHDA-treated nor in untreated, and thus stress-inexperienced rats. In a long term study, serum prolactin and luteinizing hormone (LH) levels were followed over a period of 71 days after 6-OHDA treatment. Prolactin levels increased within one day after treatment and stayed at a high level for 15 days. Subnormal prolactin values were measured 37 days after 6-OHDA treatment. Serum LH levels were below normal 3 h and one day and were increased 37 and 71 days after 6-OHDA treatment. These results suggest that NE is important in the transmission of stressful stimuli to hypothalamic prolactin regulating centers. They further suggest functional recovery of LH and prolactin regulating mechanisms after 6-OHDA treatment.


Clinical and morphologic features of hepatic angiosarcoma in vinyl chloride workers. Fifteen male workers exposed to vinyl chloride developed angiosarcoma of the liver. Thirteen died of disease and two are currently living for short periods after diagnosis. Their ages ranged from 36 to 58 years (average 47.5 years). Their exposure time ranged from 4 to 27.8 years (average 16.9 years). The most common presenting symptoms were fatigue, weight loss, and abdominal pain. Hepatomegaly followed by splenomegaly were the most common physical findings. Biochemical profiles yielded variable results and proved to be of little value in the detection or diagnosis. Of eight patients autopsied, distant organ involvement was present in two cases, duodenal involvement in one, and direct extension of tumor to adjacent organs or tissues in four additional ones. The remainder, diagnosed by open liver biopsy, revealed no tumor extension. The gross features of the tumors were hemorrhagic necrosis, cystic degeneration, fibrosis, and apparent multicentricity. The histologic features were those of the typical angiosarcoma found in a variety of sites with a wide range of cellular differentiation. The histologic diagnosis was often impaired by the extensive tumor necrosis. Elsewhere in the liver subcapsular fibrosis, a distinct type of portal fibrosis, and endothelial cell hyperplasia with or without sinusoidal dilatation were noted. The reduction of industrial chemical exposure has already been achieved and will hopefully eliminate this chemically related tumor in the future. There is, however, a significant group of previously exposed workers who will require careful monitoring to detect functional abnormalities of the liver and possible early neoplastic changes.


Current status of lymphography in patients with cancer. In the early 1960's lymphography was received enthusiastically. Expectations were high that a very accurate diagnostic method for the detection of metastases had been found. This enthusiasm subsided after it became apparent that small lesions could not be discerned and that the images demonstrated were frequently nonspecific. Better correlation was achieved with advanced stages of cancer but because the presence of metastases was usually already known, it was questionable if the lymphogram contributed much to the management of the patient. In recent years, after the examination was placed in its proper prospective, the value and status of lymphography in patients with cancer were reassessed. The radiographic findings were divided into direct, or actual demonstration of metastastases, and indirect changes--those changes resulting from replacement of lymph nodes or blockage of the vessels by metastases. Lymphography proved particularly valuable in the diagnosis and staging of patients with pelvic cancer arising from such organs as cervix, uterus, vulva, ovary, and from tumors arising from the prostate, testicles, and penis. It also proved valuable in the assessment of extension of disease in melanomas of the extremities. The value of the positive lymphogram is easy to assess. However, when one encounters a "normal" lymphogram, one must realize that this does not exclude the presence of metastatic disease; it merely demonstrates that the the time of the study no lesions were recognized in visualized lymph nodes. Therefore, the negative lymphogram should not result in any modification of treatment which would have been prescribed under the same clinical circumstances if one did not have the lymphogram at hand.


The current status of angiography in the evaluation of cancer patients. Angiography has maintained a central role in the preoperative evaluation of patients with both benign and malignant tumors. A great deal of experience has accumulated with the method and the angiographic appearance of most tumors is well established. Although most cancer patients are first evaluated by less invasive techniques,angiography remains the most accurate method for the diagnosis of tumors of the liver and pancreas. In those patients in whom excision of a malignancy is considered, angiograms should be used preoperatively to assess both the resectability and curability of the lesion. In patients with carcinoma of the lung or esophagus invading the azygos vein or in patients with pancreatic carcinoma invading the visceral veins, needless radical operative procedures can be avoided. Finally, as angiographers are becoming more therapy-oriented, the palliative effects of selective arterial embolization with radioactive and infarcting materials are being evaluated.


Cycling aggregation patterns of cytoplasmic F-actin coordinated with oscillating tension force generation. Isometric contracting protoplasmic veins of Physarum polycephalum show cycling patterns of cytoplasmic F-actin, dependent on their oscillating contraction behaviour (minute rhythms). The process of fibrillogenesis represents a parallel arrangement of F-actin chains ("plasma filaments, microfilaments") during the isometric contraction phase. A part of the results of the present work corroborates previous results on stretch-activated veins which showed that the fibrillar form of F-actin reflects the isometric contracted state. During isometric relaxation phase, a disaggregation of the fibrillar pattern takes place and is accompanied by a deparallelisation of F-actin chains. Therefore, the isometric relaxed state of cytoplasmic actomyosin is non-fibrillar in nature. Thus, the morphologically detectable fibrillar form of cytoplasmic actomyosin, according to physiological interpretation, is solely representative of the isometric contracted state. The question whether assembly-disassembly processes, e.g. G equilibrium F-actin-transformation, play a role in the contraction-relaxation cycle is discussed.


The presence of transverse and axial tubules in the ventricular myocardium of embryonic and neonatal guinea pigs. Developing transverse (T) tubules are found in embryonic guinea pig ventricular myocardium after approximately eight weeks of gestation. By the time of birth (nine weeks total gestation); longitudinally-oriented axial tubules connected to the T tubules also have formed, and the majority of cells closely resemble those of the adult. The form taken by the developing T and axial tubules suggests that they are generated in a manner similar to that for T tubules in chick and rat skeletal muscle, namely by repeated formation of caveolae.


Preferential inhibition of the synthesis of 45S ribosomal rna precursor by N-acetoxyacetylaminofluorene in rat liver epithelial cultures. After exposing a line of rat liver epithelial cells to a single dose of the carcinogen N-acetoxy-2-acetylaminofluorene (N-acetoxy-AAF), a dose-dependent decrease in (3H) uridine incorporation into total cellular RNA was found. Approx. 50% inhibition occurred with 0.5 mug/ml of the compound. The kinetics of the response, the effects of actinomycin D, and the fractionation of the newly synthesized RNA by polyacrylamide gel electrophoresis indicated preferential inhibition of the synthesis of 45S ribosomal RNA precursor and relative sparing of the synthesis of heterogeneous nuclear RNA.