Pharmacological content of hyperproteolytic states in blood by synthetic inhibitors of serine proteinases. Proteolytic enzymes participate extensively in coagulation, fibrinolysis, kininogenesis, and complement activity. Synthetic low molecular weight inhibitors of these enzymes which belong to the group of serine proteinases allow pharmacological control of these processes. The development of such inhibitors and their therapeutic importance are reported, especially on the pattern of benzamidine derivatives.


Chromogenic substrates for horseshoe crab clotting enzyme. Its application for the assay of bacterial endotoxins. An endotoxin-activated hemocyte lysate from the horseshoe crab (Tachypleus and Limulus) was found to hydrolyze Bz-Ile-Glu-(gamma-OR)-Gly-Arg-p-nitroanilide (PNA), Bz-Val-Gly-Arg-PNA, Boc-Val-Leu-Gly-Arg-PNA, and Boc-Leu-Gly-Arg-PNA, all of which have the COOH-terminal Gly-Arg sequence. This amidase activity was due to a clottting enzyme contained in the lysate. Furthermore, the amidase activity increased by increasing the concentration of bacterial endotoxin (E. coli, 0111-B4) added to the lysate. Therefore, the measurement of the endotoxin-induced amidase activity made it possible to determine the concentration of the endotoxin.


Designing of peptide substrates. Different approaches exemplified by new chromogenic substrates for kallikreins and urokinase. Chromogenic peptide substrates for serine proteases have been designed by using two approaches: (1) by using the natural substrate as a model and (2) by structure-activity correlations obtained through screening of a large number of tripeptides. Some recent examples, substrates for kallikreins and urokinase are given.


Changes in plasma levels of prekallikrein, kallikrein, high molecular weight kininogen and kallikrein inhibitors during lethal endotoxin shock in dogs. Plasma levels of prekallikrein, kallikrein, high molecular weight kininogen and kallikrein inhibitors were measured in samples from dogs infused with E. coli endotoxin. Markedly reduced levels of prekallikrein and high molecular weight kininogen were seen at circulatory collapse and free kallikrein was detected. Both 'fast-reacting' and 'time-dependent' inhibitors of plasma kallikrein were significantly reduced. Fractionation of pre-infusion and collapse samples by gel filtration together with immunological procedures indicated that both alpha2-macroglobin and alpha1-antitrypsin were the major kallikrein inhibitors in dog plasma, and that they were significantly reduced in the collapse samples.


New chromogenic peptide substrates for factor X. The factor Xa-sensitive substrate BZ-Ile-Glu-Gly-Arg-p-nitroanilide has been made more sensitive by making ester and amide derivatives of the gamma-carboxyl group of the glutamyl residue. The morpholinyl and piperidyl amides react 2.5 times more rapidly with factor Xa.


Rat coagulation factors V, VIII, XI, and XII: vitamin K dependent. When rats were given single or multiple doses of warfarin, the levels of prothrombin and factors VII, IX, and X were depressed, as expected. However, modest reductions of factors V, VIII, XI, and XII, but not of fibrinogen, also occurred. The levels of all eight factors promptly returned to normal when vitamin K1 was given. Warfarin-resistant rats had no depression of any of the eight factors. When vitamin K deficiency was induced by internal or external biliary fistula, factors II-VII-IX-X decreased sharply and factors V-VIII-XI-XII decreased modestly. Again, all depression were promptly reversed by vitamin K1. Isolated livers from warfarinized rats did not generate the classic vitamin K-dependent factors during 5 h of perfusion but did generate small amounts of factors V, XI, and XII, although less than normal. The isolated rat liver apparently does not generate factor VIII.


Automated antithrombin III assay with a centrifugal analyser. The factor Xa inactivating function of antithrombin III is measured automatically by an amidolytic method, adapted to a centrifugal analyser. Plasma is diluted in buffer with heparin. In stage I, diluted plasma is incubated with excess factor Xa. Heparin accelerates the saturation of antithrombin with factor Xa. In stage II, remaining factor Xa is determined with the chromogenic substrate Bz-Ile-Glu-Gly-Arg-pNA. The precision of the present assay compares favourably with that of the clotting assays and immunoassay. There is a close correlation (r = 0.82) between the results obtained with this assay and the immunoassay of antithrombin III.


The effect of trypsin and storage on aggregation and release of human gel-filtered platelets. Trypsin was studied as an aggregating and release-inducing agent with gel-filtered platelets (GFP) and was compared with ADP, epinephrine and collagen. GFP aggregated irreversibly with final concentrations of 0.5-4 microgram/ml trypsin, 1.6-3.2 micrometer ADP, 2.5-5 micrometer epinephrine and 40 microlite 1/ml soluble collagen. Addition of human fibrinogen to the Tyrode-suspending buffer was required for ADP and epinephrine, but was not necessary for trypsin or collagen. Release of (14C)5HT was obtained with trypsin and collagen using the same concentrations as used in aggregation. GFP stored at room temperature for 48 h were still responsive to trypsin and collagen, whereas aggregability and (14C)5HT release induced by ADP and epinephrine were already impaired 5 h after collection of blood. CP-CPK, an ADP-removing reagent, blocked aggregation and release induced by low trypsin concentrations, suggesting that ADP plays an intermediate role in the mechanism by which trypsin activates platelets. Trypsin appears to be a valuable reagent for studying platelet physiology, particulary following storage.


Uptake by blood components and by subcellular platelet fractions of 1-14C-acetylsalicylic acid. 1-14C-Acetylsalicylic acid was used to study the distribution and the kinetics of the acetyl group in blood components. Tests were carried out in 4 patients in vivo and on four blood samples in vitro. At various intervals after tagging, whole blood, plasma, platelets and platelet fractions were examined. In vitro, relative activity was found to be higher in platelets than in all other blood components. When platelet fractions were examined, the highest specific activity was found in membranes. In vivo, rapid disappearance of activity from circulation was observed. The decrease of activity was slower in platelets than in whole blood and in plasma. The highest specific acitivty was again found in platelet membranes. The half-life of the 14C tag was measured in all components. It was found to be longest in platelet membranes where it corresponded to the half-life of platelets in circulation. From the results obtained, the conclusion was drawn that irreversible acetylation of the platelet membrane must be considered to be one of the main causes of platelet dysfunction induced by acetylsalicylic acid.


Ultrastructural morphometric investigations on normal human platelets. Platelets from normal human volunteers were investigated by ultrastructural morphometry. Preparation of blood samples was done in two different ways in order to evaluate the possible influence of the preparative method on the size and shape of platelets and their organelles. No significant differences could be dmonstrated for any of the measured parameters. Relative volumes of specific granules, mitochondria and the open canalicular system were calculated according to the method of Weibel. Surface and numerical densities of some compartments were determined. Direct measurements of the long and short axes of the platelets were conducted to ascertain further information about their size and shape. Absolute data are in good agreement with the few reports in the literature.


Institutions and alternatives for older people. A major national priority for older people is the provision of systems of social and medical care that may be applied to individuals in an effort to extend residence in the community or avert institutionalization altogether. Data reviewed here suggest that goals must be modest in attemtping to deinstitutionalize or avert institutionalization.


Stop the action: a program for parents of severely disturbed children. Severely disordered children are frequently difficult to manage in an outpatient setting because of their disruptive actions. A brief period of hospitalization stops this action and allows professionals time to work with parents and correct dysfunctional family interactions.


Linkages among organizations: considerations and consequences. The continuing concern about integration and coordination of health care services can lead to intensive linkages that may have undesirable effects on the participating organizations. A case study of three neighborhood health centers in a large urban area demonstrates the potential stresses such linkages create for personnel. Research and administrative efforts toward mitigating such  problems are suggested.


Social work with epileptic patients.

Social work with epileptic patients. Although more than 4 million people in the United States have epilepsy, misconceptions about the disease are prevalent among the public. The author discusses some of the physical and psychosocial problems related to epilepsy and offers suggestions on how social workers can assist epileptic patients and their families.


A training program for interprofessional health care teams. Interprofessional approaches to practice have gained increased popularity. This paper describes a course in team training for professionals in health care. It is an overview of the course's content with a discussion of the problems and issues that arose as the course was designed and implemented. It concludes with a discussion of the outcomes and evaluations of the students' and faculty's experience.


Evaluating a social work department in psychiatric hospital. It has become increasingly important, as an administrative aid in assessing the functioning of hospital social work departments and improving their services, to determine and evaluate their activities. This article reports on a study conducted by the social work department in a Canadian university psychiatric hospital to determine the work load of social workers, aspects of the process of referring persons for social work services, and differences between hospitalized persons who do or do not receive social work services.


Psychiatric problems in emergency rooms. This study compared the diagnosis and referral of mental health problems in the emergency rooms of four hospitals located in communities of varying size. Although deficiencies were found in the recognition of psychiatric problems in all the hospitals, the effectiveness of emergency room service was related to the size of the community.


Cytological study of inhibitory effects of IAA on the root growth in the Pinus silvestris. It has been found that IAA at the concentrations 0.1--10.0 ppm retards the pine root growth and decreases mitotic activity. All the applied concentrations of this hormone cause a decrease of the 3H-thymidine incorporation index and inhibit endomitotic polyploidization in suprameristematic segments. The mean time of the cell cycle prolongs and the heterogeneity of cellular populations increases in parallel with the increase of IAA concentration. The template activity of DNA decreases under the influence of the applied concentrations of IAA; this effect is being particularly strong in the meristematic root segment. IAA exerts also an inhibitory influence on protein synthesis, especially reducing the synthesis of histones.


RNA synthesis and changes in template--DNA activity during the growth and differentiation of parenchyma cells of the primary cortex of roots of Zea mays and Tulipa kaufmanniana. In this study, changes in DNA transcription activity are presented during parenchymal cell differentiation of the primary cortex of roots of a species with elevated DNA content in which endomitotic polyploidization does not occur (Tulipa kaufmanniana), as well as a species with low content levels in which an increase in endomitotic polyploidization occurs during differentiation (Zea mays). Changes in the degree of histone acetylation during the cellular differentiation of both species were also studied. An autoradiographic method was employed using the following indicators: for transcription activity--3H-uridine; for potential activity of template DNA--3H-actinomycin D (3H-AMD); for histone acetylation--the intensity of labelled nuclei after incubation with 3H-sodium acetate, as well as decrease in nuclei radioactivity after extraction of the histone fractions. It was found that during cellular growth and differentiation in both Zea mays and Tulipa daufmanniana (and therefore, irrespective of the presence or absence of endomitotic polyploidization) a progressive decrease of DNA transcription activity occurs. At the same time, the possibility that the acetylation of arginine--rich histones plays a definite, yet undecisive, role in the regulation of DNA transcription activity cannot be excluded.


On the distribution of succinic dehydrogenase in the segmental ganglia of Poecilobdella granulosa. Studies on the distribution of SDH in the segmental ganglia of leech have revealed the presence of light and dark cells. The enzyme has been seen mainly around the nucleus. The neuronal periphery, cytoplasm and axons of almost all the cells have also manifested positive activity. The neuropile depicts predominantly granular reaction. The metabolic significance and the possible role of SDH at various localisations have been discussed.


Membranolytic activity of detergents as studied with cell viability tests. The membranolytic activity of 12 chosen detergents upon Ehrlich ascites tumour and Chinese hamster lung cells were studied with the fluorescein diacetate and the dye exclusion tests of cell viability. It was found that all these tests give reproducible and concordant results when non-ionic detergents are used but for ionic detergents only the fluorescein diacetate test can be applied. Membranolytic activity of the detergents appeared to be uncorrelated with their capacity of membrane solubilization. Digitonin and aescin, the horse-chestnut saponin, were found to be much more toxic than sodium dodecylsulphate or Triton X-100. When the detergents with aliphatic hydrophobic residues were compared, a cationic detergent cethylmethylammonium bromide (CTAB) was more toxic than non-ionic or anionic detergents. A hydrophobic part of the aescin molecule, that is its aglycone appeared responsible for the membranolytic activity of this saponin. When the lytic activity of the tested detergents for the two tested types of cells was compared it was found that the horse-chestnut saponin substances show different toxicity for various cells. It is suggested that in the future some of the detergents can be applied for detection and quantitative monitoring of species and tissue specific differences in plasma membrane properties of animal cells.


Degradation and inactivation of ceruloplasmin and haptoglobin by rat liver lysosomes and some other proteinases. Lysosomal fraction was isolated from rat liver by density gradient centrifugation after pervious loading of lysosomes in vivo with Triton WR-1339. Tritosome preparations were incubated at 37 degrees C and pH 5 for 24 hr with purified human ceruloplasmin or haptoglobin. After this period approximately 20% of total alpha amino nitrogen was released from ceruloplasmin and over 40% from haptoglobin. This was accompanied by loss of peroxidase activity of haptoglobin (in complex with haemoglobin), while enzymatic activity of ceruloplasmin remained unaltered. Removal of sialic acid by neuraminidase had no effect on digestion of ceruloplasmin by rat liver tritosomes. Both glycoproteins were resistant to horse leucocyte proteinases and pancreatic eleastase but were easily inactivated by trypsin and chymotrypsin.


Interaction between cholinotropic and adrenotropic drugs on the histofluorescence of the central catecholamine structures in the rat. Male Wistar rats were given phentolamine or phenoxybenzamine in the lateral ventricles in doses of 1 mg/kg. After 30 minutes they received in the same way atropine in doses of 1 mg/kg or carbachol in doses of 0.05 mg/kg. The control group was given physiological saline. The animals were decapitated 30 minutes after drug administration. The Falck and Hillarp histofluorescence method was applied. The areas of DA (nigrostriatal and meso-limbic) and NA systems were examined. It was found, that atropine increased the intensity of fluorescence in comparison with the control group, in all areas of DA structures. The action of carbachol was more differentiated. In the substantia nigra (A8 and A9) respectively in the globus pallidus and the nucleus arcuatus (A12) its effect was the same as that of atropine. In other areas it caused weakening of fluorescence or showed no effect. In the NA system atropine weakened the fluorescence considerably while carbachol increased it in five out of eleven areas. The interaction of cholinotropic and adrenotropic drugs is disscused.


[Effect of estrone on rat uterine contraction induced by prostaglandin (author's transl)]. Influence of estrone on uterine contraction and increase of internal pressure of uterus induced by PG were studied in the rat. The sensitivity of the uterus to PG was increased after estrone injection, the maximum effect being observed 72 hours after the administration. Regarding uterine contraction and increase of internal pressure induced by PGE2 or PGF2alpha, the amplitude was enlarged but the frequency was decreased with estrone injection. Contraction and increase of internal pressure induced by PG were well correlated in the rat uterus treated with estrone. Progesterone inhibited the stimulatory action of estrone on uterine contraction induced by PG. These results suggest that estrone may play an important role in action of PG in rat uterus.


[Pharmacological studies of loperamide, an anti-diarrheal agent. III. Interaction between loperamide and various agonists in the guinea pig intestine (author's transl)]. To clarify the mode of action of loperamide, the interaction with various agonists was investigated in guinea pig intestines. The following results were obtained. Prostaglandin E1 (0.1 microgram) or acetylcholine (1 approximately 3 microgram) injection into the mesenteric artery at 10 min intervals caused a constant rise of intraluminal pressure of the intestinal loop in situ. Loperamide (0.01 approximately 0.1 mg/kg i.v.) markedly suppressed the response induced by prostaglandin E1. Morphine (0.1 approximately 1.0 mg/kg i.v.) and atropine (0.01 mg/kg i.v.) also suppressed the response. The intestinal response induced by acetylcholine was inhibited markedly by atropine and slightly by loperamide (0.1 mg/kg i.v.) but not by morphine. Contractions of the isolated ileum induced by coaxial stimulation, BaCl2, nicotine and serotonin were suppressed by loperamide (10(-9) approximately 2 X 10(-7) g/ml). Morphine, methadone and codeine showed the same effect as loperamide but the activity was weaker than that of loperamide. Contractions of isolated ileum induced by acetylcholine, histamine and bradykinin, and Ca-contraction in the depolarized taenia coli were inhibited by relatively high concentrations of loperamide (2 X 10(-7) g/ml or above). These results suggest that loperamide suppresses the function of cholinergic neurons in the intestines.


[Changes in the response to drugs of the rat stomach after a chronic vagotomy and a sympathectomy (author's transl)]. Effects of cholinergic agonists and serotonin were examined on the chronically denervated stomach fundus. We developed a new method of adrenergic denervation (sympathectomy), which was confirmed chemically, histochemically and functionally. Vagotomy was performed by the usual method. The sensitivity of the longitudinal muscle of the fundus to cholinergic agonists and serotonin was not modified by chronic sympathectomy or vagotomy when determined from the ED50 of the dose-response curve. The maximum contractile response of vagotomized fundus to each cholinergic agonist and to serotonin was significantly decreased, whereas only a slight decrease was observed in sympathectomized fundus. Ca2+-contracture in Ca2+-free isotonic K+ Ringer's solution was markedly decreased in chronically vagotomized or sympathectomized fundus. Efflux of 45Ca in Ca2+-free isotonic K+ Ringer's solution was significantly lowered by vagotomy but only slightly by sympathectomy. No significant change in ATP content was observed in the vagotomized or sympathectomized fundus.


[Pharmacological study on diuretic action of 2-methyl-3-(o-tolyl)-6-sulfamyl-7-chloro-1, 2, 3, 4-tetrahydro-4-quinazolinone (metolazone) (author's transl)]. Renal effects of metolazone (MET), a new diuretic agent, were compared with those of hydrochlorothiazide (HCT) in rats. MET in an oral dose of 0.01 approximately 0.5 mg/kg resulted in a dose-related increase in urine flow, sodium excretion and osmolal clearance in male rats. The natriuretic action of MET was not enhanced by administration of an increased dosage (1 approximately 5 mg/kg). Urinary excretion of potassium was significantly increased after MET, but was less than that of sodium. Therefore, the ratio of urinary concentration of sodium to potassium was markedly increased. Similar results were obtained when MET was intraperitoneally administered. In female rats, MET also proved to be an effective natriuretic. The diuretic effects of HCT were qualitatively similar to those of MET, but MET was 10--20 times as potent as HCT on a basis of minimal effective dose. In the renal clearance experiments, MET did not influence the renal plasma flow and glomerular filtration rate. From these findings, it is concluded that MET exerts a diuretic effect by inhibiting the reabsorption of electrolytes in the renal tubules.


[Biological activity of 1alpha-hydroxycholecalciferol (1). Effect on intestine and bone in rats (author's transl)]. Biological activity of 1alpha-hydroxycholecalciferol was studied in rats. 1alpha-Hydroxycholecalciferol was found to be more potent and rapidly active than vitamin D in stimulating intestinal calcium transport and calcium mobilization from bone both in normal and vitamin D deficient rats. 1alpha-Hydroxycholecalciferol was also active in nephrectomized and/or thyroparathyroidectomized rats both in intestine and bone. Although it is well known that 1alpha-hydroxycholecalciferol is metabolized to 1alpha, 25-dihydroxycholecalciferol in the liver, there is the possibility that the former is active without further metabolism. In rats in which hepatitis was induced by CCl4, 1alpha-hydroxycholecalciferol was active both in the intestine and in the bone, while it was inactive in hepatectomized rats. These data clearly demonstrate that 1alpha-hydroxycholecalciferol is not active by itself and must be metabolized in the liver. This idea also shows the lag time in response of rats to 1alpha-hydroxycholecalciferol has more potent antirachitic activity than vitamin D and does not lose its activity with chronic oral administration. In view of these findings, 1alpha-hydroxycholecalciferol appears to have a good potential for clinical application in cases of renal failure and metabolic bone diseases.


[Inhibitory effect of cholesterol on changes in membrane permeability and potential induced with lysolecithin in red blood cells (author's transl)]. Membrane stabilizing effects of cholesterol on the permeability of K+ and change in membrane potential induced with lysolecithin were investigated. Cholesterol inhibited K+ release from rabbit red blood cells treated with lysolecithin. 3.3 X 10(-6)M of cholesterol was the optimum concentration required to inhibit K+ release from rabbit red blood cells treated with lysolecithin (1.25 microgram/ml) at the level of 100 percent. Change in membrane potential was evident with lysolecithin by the method of fluorescent dye and, cholesterol inhibited the change which was dose dependent. These inhibitory effects of cholesterol on the K+ release and changes in membrane potential served as the membrane stabilizing action on red blood cell membrane. It is assumed that cholesterol acts as an inhibitor to increase membrane fluidity and permeability of malignant transformed cells such as tumor and lymphoid cells.


Patterns of food sharing among mother and infant chimpanzees at Gombe National Park, Tanzania. The patterns of food sharing among mother and infant chimpanzees at the Gombe National Park, Tanzania, are primarily influenced by the infants' ability to procure and process foods independently. Foods infants could find and process on their own were not shared by mothers as frequently as foods infants could not obtain independently. Temporal changes were observed in the patterns of interactions as infants matured. It is suggested that food sharing may be considered a behavioral strategy which facilitates the infant's transition from dependent suckling to independent foraging.


Skeletal differences between pygmy (Pan paniscus) and common chimpanzees (Pan troglodytes). Skeletal dimensions of pygmy (Pan paniscus) and common (Pan troglodytes) chimpanzees were compared. Significant differences were found in the clavicles, scapulae, pelvises, and in the humerus/femur and femur head/length ratios. No significant differences were observed in long bone lengths or talar breadths. There is extensive overlap in body weights, so that the observed differences cannot be accounted for by body size alone. We conclude that pygmy and common chimpanzees are morphologically distinct. Implications for hominoid evolution are discussed.


Pathological changes of peripheral nerve and muscle of patients with hemiatrophy. Peripheral nerve and muscle of patients with hemiatrophy were biopsied and examined by means of light and electron microscope. The unmyelinated nerve fibers decreased in number and remaining fibers were atrophic with irregular shape and high electron density, while myelinated nerve fibers slightly decreased in number. The Schwann cells enveloping nerve fibers were also atrophic with high electron density. The muscles contained numerous glycogen granules in the myofilaments and between the myofilaments. The mitochondria in the muscles showed atrophy with high electron density. Some parts of severe atrophy showed honeycomb-like structure forming large vacuoles in the muscle fibers. From the findings mentioned above, it is speculated that primary change was nerve fibers, especially unmyelinated nerve fibers.


Neuropathology of secondary generalized epilepsy--(Lennox-Gastaut syndrome)--a case report. Neuropathological considerations were performed on a case, who went into Lennox syndrome after an acute encephalopathy at the infantile period, and moreover who fell into an akinetic-mute state derived from brain damage by herniation caused by a head injury and subsequent status epilepticus. Neuropahtological background in the present case of Lennox syndrome is thought to be based on the widespread unilateral cerebral lesions and the basal ganglional, especially thalamic, degenerations derived secondarily from the diffuse cerebral damage. The patient revealed akinetic mutism with the disappearance of the epileptic seizures and the desynchronization of the EEG's, when the brain lesions formed at the adult period spread over the opposite hemispheric limbic system and the brain stem tectum.


Chronic alcoholism: report of an autopsy case and comparison with pseudoulegyric type of hepatocerebral degeneration. An autopsy case diagnosed as chronic alcoholism was reported. He clinically showed progressive neurological illness. His CNS lesions were composed of disseminated necrotic foci in the cerebral cortices with many Alzheimer type II astrocytes, pachymeningitis hemorrhagica interna, and lesions similar to pellagra and Wernicke encephalopathy. Some clinical and pathological analogous features between chronic alcoholism and pseudoulegyric type of hepatocerebral degeneration were discussed.


Effects of thyroid deficiency at birth on deoxyribonucleic acid synthesis and deoxythymidine kinase activity in the developing rat brain. In thyroid deficiency at birth, the endogenous pool sizes of cellular dTTP did not change much in the cerebellum, cerebrum and brain stem at the whole ages studied, but the specific radioactivities of dTTP, at 2 hours after the subcutaneous injection of [3H]-thymidine, apparently increased only in the cerebellum on the 14th and 21st days as compared with the normal controls. The highest rate of DNA synthesis in vivo, expressed in terms of the specific radioactivity ratio of DNA to dTTP, was observed at the four-day-old normal rat cerebellum, and in the thyroid deficiency it appeared to shift between seven and 14 days of age. On the other hand, no apparent effects of thyroid deprivation on the rates of both the cerebrum and brain stem were found. The results suggest that a temporal alteration of DNA synthesis as well as thymidine metabolism occurred by thyroid deficiency was confined to the cerebellum in the early postnatal development of rats. Indeed, cerebellar thymidine kinase activity, related to DNA synthesis, also displayed a concomitant delay in thyroid deficiency to the characteristic age-dependence of DNA synthesis. No significant difference between normal and thyroidectomized rats was revealed in this respect on both the cerebrum and brain stem throughout the experimental periods.


"Syndrome malin"-like symptoms probably due to interaction between neuroleptica and oral antidiabetic agents. In two cases of chronic schizophrenia complicated by diabetes mellitus, the concomitant use of the neuroleptica and oral antidiabetics was attended by the appearance of symptoms simulative of syndrome malin, i.e. hyperpyrexia, tachycardia, blood pressure instability, disturbances of consciousness, muscle rigidity, tremor, dysphagia, salivation and urinary incontinence. In one of these cases, the patient, a 47-year-old man, died 10 days later. In the other case, a 62-year-old woman, almost all the symptoms subsided after 14 days, and oral dyskinesia persisted for only one additional month. In both cases, hypoglycemia due to oral antidiabetics was not seen. In Case 2, a combined regimen of oral antidiabetics and neuroleptica was later resumed. Again, a similar set of symptoms as seen initially were noted, along with an elevation of the serum CPK level. Parenterally administered biperiden proved to be highly effective in the control of the symptoms. The pathogenetic mechanism of these symptoms might possibly be explained as potentiation of the action of the neuroleptica by oral antidiabetics.


On early and mid-adolescent schizophrenia. Part 1: Phenomenological aspects. One hundred and seventy-three early and mid-adolescent schizophrenic patients were investigated during the 18-year period from April 1958 to March 1976 and the results concerning phenomenological aspects were reported here along with some considerations. 1. Hereditary predispositions were found in 43 cases among 161 patients. Male patients seemed to be more predisposed than female patients. The incidence of schizophrenia was the highest among other mental disorders, while it was most frequently observed in mothers and siblings among other kinships. 2. Precipitative factors were recognized in 45 cases. Among them, primary social factors and physical conditions seemed to play a rather important role. These factors seemed more frequent in males than in females. 3. As to birth order, the incidence of adolescent schizophrenia seemed to be higher in the last half of sibships than in the first half but the difference was significant at a five-percent level when the sibship sizes were 5--9. From the comparison of our results with the national statistics of the birth order in general population, the incidence of adolescent schizophrenia seemed to be lowest in the sublings of the second birth. 4. We divided the onset into three types; acute, intermediate and insidious. We were impressed that the acute onset seemed gradually to increase in mid-adolescence and the insidious onset vice versa. In addition, the insidious onset was found chiefly in cases with hebephrenic pictures except hebe-paranoid. 5. Hebephrenic form and simple form were frequently observed but catatonic form was relatively few. Genuine paranoid form was not found in our materials. Hebephrenic and catatonic forms were more frequently seen in males, while hebe-paranoid form was more frequent in females. 6. Main symptoms at the onset were discussed. Delusional activities, still vague and fragmentary, were observed in about half of our materials, being mostly persecutory. It seemed that they were strongly influenced by the state of mood of patients. Hallucinations, mostly auditory of verbal nature, were observed in more than one-fourth of our patients. On the contrary, the cases with visual and bodily hallucinations were a few in number. Autistic tendency and refusal of scholastic activities were more frequently seen in early adolescence, while suicidal attempts or self-injuring tendency, manic or depressive tinge, "gemachte Erlebnisse", "Eigengeruchsparanoia" were rather prevalent or first observed in mid-adolescence. Various symptoms, in general, seemed to become gradually more prominent along with the progression of ages. 7. EEG findings and treatment were reported at the same time. But the course and the problem of defect will be discussed in another paper. 8. Finally, the summaries of sex differences and of the comparison between early and mid-adolescence were supplemented.


Changes of behavior, fear and thought in the treatment by response prevention--a case study of obsessive compulsive disorder. A 15-year-old boy with compulsive hand washing and fear of contamination was treated by response prevention. Each series of the response prevention was experimentally divided into four periods: total response prevention, partial response prevention, free hand washing under noticed observation, and free from prevention and free from observation periods. After nine repeats of the series he became free of the symptoms. Temporal increase of fear and appearance of "freezing" phenomenon were observed in the total response prevention periods. Besides decrease in fear and hand washing, there was observed a change of his thought on symptoms with progress of the treatment. Based on these observations and results, the mechanism of treatment of response prevention was discussed.


Changes in sleep pattern after sleep deprivation. Total sleep deprivation (TSD) was performed for one night with 11 healthy male students and three-consecutive-recovery night-sleep was recorded. Special attention was paid to the analysis of the individual difference in SWS(min, %) on the baseline and recovery nights. The total sleep time increased on the first recovery night compared to the baseline, but it decreased significantly on the second and third recovery nights. Stage 1(%) decreased significantly on the first and second recovery nights. Stage SWS(min) showed a significant increase on the first recovery night, while SWS(%) increased significantly on the first and second recovery nights. As for Stage REM(%), there was no significant difference between the baseline and the recovery nights. There was a positive correlation between SWS(min) on the baseline and that on the recovery nights. SWS(%) also showed the same results as those obtained with SWS(min). Between SWS(min) in the baseline and the increase rate of SWS(min) on the first recovery night, there was a significant inverse correlation, while there was a tendency to inverse correlation on the second and third recovery nights. As to SWS(%), there was a significant inverse correlation between SWS(%) in the baseline and the increase rate of SWS(%) on the first and third recovery nights.


Indefinite storage of dried Gm and Km (Inv) antigens: (examination of bloodstains 33 years old). We confirm the great stability of the A and B antigens in dried blood, and the markedly lesser stability of antigen H. We demonstrate that it is possible to determine the immunoglobulin groups Gm(1), Gm(10) and Km(1)--formerly Inv(1)--in bloodstains 29 to 33 years old.


Influence of the temperature on the detection of fluorescent Y-bodies in blood stains. An investigation on the significance of the temperature when examining the presence of Y-bodies in cells from blood stains was performed. Stains on cotton cloth were placed at 53 degrees C and 5 degrees C respectively, and the results were compared with those of an earlier report on stains stored at room temperature. There proved to be a much more rapid decline of the male count, and false negative results appeared earlier. This was most pronounced for the "cold" stains. No false positives were found. Twenty-five fresh blood smears from one male were examined in order to get an impression of the accidental variation. It was found that even in the case of a male with a rather low count (mean: 28%) the chance of accidentally getting a false negative result (less than 10%) was less than 2%.


Matrix proteins of human hair as a tool for identification of individuals. A rapid, simple, reproducible and relatively inexpensive electrophoretic technique for displaying the structural proteins of hair is described. Hairs from a large number of individuals were examined and a number of distinct differences are presented. The possibility of using these individual differences as a means of individual identification is discussed.


Further study on spectrophotometric determination of CO--Hb in post-mortem blood. The method for spectrophotometric determination of CO--Hb in blood on the basis of difference in absorbancies of deoxy- and carboxy-hemoglobin reported previously [1] was further improved. The total blood hemoglobin content was determined by the azide-methemoglobin method instead of the well-known cyanmethemoglobin method. This method was found to be useful even if applied to old or putrefied blood samples.


Electron microscopic study of the effects of thallium poisoning on the rat cerebellum. Rats were given thallium acetate (5 mg elemental thallium/kg body weight) intra-peritoneally daily for 7 days. The brain was fixed by perfusion-fixation and small pieces of the cerebellum were processed for electron microscopy. Variegated mitochondrial profiles, increased incidence of electron--dense bodies and proliferation of Golgi zones were observed in the thallium--poisoned rat cerebellum. Multilamellar cytoplasmic bodies were discernible in the cerebellar cortex of the thallium-treated rats.


[The hepatic porphyrias].

[The hepatic porphyrias]. Among the different types of hepatic porphyrias, acute intermittent porphyria (AIP) and the group of chronic hepatic porphyrias (CHP) are most frequently seen in Europe. Both diseases are supposed to be inherited, but clinical manifestation mostly occurs following endogenous and especially exogenous stimulation. While recurrent attacks of abdominal and neuropsychiatric symptoms in AIP are frequently precipitated by therapeutic doses of commonly used drugs, the gradual development of porphyria cutanea tarda (PCT) from a clinically non-apparent type of CHP seems to be most commonly due to excessive and prolonged intake of alcohol. The characteristic and with regard to the laboratory findings important pathobiochemical features, the clinical symptoms, and the present therapeutic concepts of both disorders of hepatic porphyrin metabolism are discussed. The prognosis of hepatic porphyrias will be determined above all by early diagnosis of the metabolic disorder as well as by a profound medical information of the patient to avoid strictly all well-known exogenous factors which may initiate or exacerbate the disease.


Bromine in human tissue.

Bromine in human tissue. The normal levels of bromine in human tissue are given and their use in the interpretation of levels found when over-exposure is a possibility is described. Bromine is "normally" distributed in human tissue as are essential trace elements. This allows a bromine (microgram) to chlorine (mg) ratio to be established (3.2) above which bromine exposure must be considered. The bromine concentrations in sections of hair can be used to establish the time of administration even when small amounts are ingested, but owing to the long half-life (about 15 days) found in human tissue interpretation after multiple doses may be difficult.


[Effect of normal and leukemic leukocytes on blood coagulation and fibrinolysis]. Lysates of leukocytes of healthy persons and of patients with acute and chronic leukemias possess a weak tissue factor activity. This procoagulant activity is increased greatly when leukocytes are stimulated by endotoxin. The tissue factor is derived almost exclusively from the monocytes and not from lymphocytes and granulocytes. Monocytes are stimulated to the same extent by adherence to plastic surfaces. The fibrinolytic activity of lysates of mixed leukocytes is due to a nonspecific protease and a plasminogen activator. Only granulocytes can cause fibrinolyses. Endotoxin stimulation enhances the plasminogen activator but not the protease. Normal leukocytes and leukocytes of patients with chronic leukemias also exert an antithrombin activity.


Phosphoglucomutase1 (PGM1) and 6-phosphogluconate dehydrogenase (PGD) types in the human hairbulb. Phosphoglucomutase1 and 6-phosphogluconate dehydrogenase types present in human red cells were also found in human hairbulbs. These phenotypes were detectable up to 2 weeks following extraction of the hair. The results are useful in medicolegal individualization of the human hair.


[Replacement of the choledochus with autologous vascularized gallbladder]. Multiple experiments to replace the extrahepatic bile duct by autologous or homologous and alloplasty failed until now. The possibility to employ autologous gall bladder as replacement for the common bile duct has been examined in animal experiments. With the supposition of primary vascularization and the adaptation of the luminal proportion of the transplant to the common bile duct, it could be demonstrated that a flapped, tubular gall bladder interposition kept its epithelium and, by this way, showed no shrinkage or stenosis. The functionaal performance of this method has been confirmed by clinical, laboratory, radiological, and bacteriological, as well as micro- and macropathological experiments.


[The anti-hypertensive effect of the diuretic etozolin. Results of a double-blind test]. In a double-blind study under strict, standardized hospital conditions, the antihypertensive effect of etozolin was evalulated in 100 patients with hypertension. 50 patients received the drug, 50 placebo. The study was carried out over 22 days (5 days without medication, 12 days therapy, 5 days follow-up). A significantly better reduction of systolic and diastolic blood pressure in the supine and upright positions was observed with etozolin as compared to the pre-period and the placebo group. There were only minor side-effects; in 4 patients, therapy had to be interrupted because of orthostatic complaints.


Scuba diving accidents in Sweden 1960--1976. Thirty "scuba" diving accidents (29 of them fatal) which occurred in Sweden during 1960--76 are listed. Nine of these are described in some detail. The probable causes of these accidents are evaluated, and suggestions for prophylactic measures are made.


[Doppler sonography in venous diseases of the legs]. The Doppler ultrasound is a proper method to diagnose pathologic venous flow in the pelvic and and femoral regions. It is possible to differentiate deep vein thrombosis and chronic venous insufficiency of the typical kind of disturbance. This method permits only functional but not morphological findings; it offers the chance of preselection to other invasive methods.


[Effect of naproxen on the thrombocyte bleeding time and on the anticoagulant treatment with phenprocoumon]. With a dose of 250 mg b.i.d. naproxen causes a slight, apparently clinically not relevant alteration of the primary bleeding pattern. Against phenprocoumon, naproxen has a transient hypoprothrombinemic effect which is followed by a short phase of increased tolerance. A further influence on anticoagulant therapy is not shown.


[Telethermography in the diagnosis of breast neoplasms. Report on the experience with 5198 studies]. Four-year experiences made in the course of 5198 examinations of the female breast with the help of telethermography are reported. Altogether 40 mamma carcinomas were found, 29 of them being cases in women over 50 years. Consequently, the participation of women older than 50 years in cancer screening must be considerably increased. Taking all diagnostic possibilities and their rates of failure into consideration, any sound method of early diagnosis of breast cancer, including telethermography, should be integrated into the available screening methods.


[Sex education and education for family life in adolescents]. A program of education of college girls and boys between 14--18 years of age for sexual and family life is going on in the Hungarian secondary school. There are 20 lectures within 4 years. The goal and the subjects of the lectures specially designed for each semester are outlined by the author.


[Studies on the estimation of the postmortem interval. 4. Spontaneous opening and closing of the eyelids after death (author's transl)]. The authors have investigated the findings of 410 cadavers which were subjected to medicolegal autopsies in our laboratory as to whether their eyelids were open or closed at the time of autopsy and have come to the following conclusions. 1) It has been found that the eyelids of cadavers may open or close spontaneously as a cadaveric phenomenon. In about 27 per cent of cadavers dead from 6 to 12 hours the eyelids were open and thereafter they were closed gradually and all of them were closed from 36 hours to 4 days. After 4 days the eyelids of some cadavers were open again. The mechanism of this cadaveric phenomenon has been discussed. 2) Concerning the opening or closing of the eyelids, neither seasonal variation nor variation by age except newborn infants has been found. In death from exsanguination many were open and in death from drowning and carbon monoxide poisoning all were closed. 3) The findings whether the eyelids of cadavers are closed or open may be utilized as a criterion for estimating the postmortem interval; the cadavers with open eyelids are estimated to have been dead less than 36 hours or over 4 days.


[Role of hypothalamic somatostatin in the regulation of growth hormone secretion in the rat (author's transl)]. Series of studies were performed to elucidate the role of hypothalamic somatostatin in the regulation of growth hormone (GH) release in rats. Somatostatin was determined by a specific radioimmunoassay. In the first series of experiments, the effects of hypophysectomy, thyroidectomy, the administration of hGH and thyroxine on the hypothalamic somatostatin content were examined. Among these treatments, only hypophysectomy resulted in a significant reduction in somatostatin content and none of the rest of treatments altered somatostatin content. These results suggest that somatostatin content in the hypothalamus did rarely change in response to various endocrine treatments when anatomical connections between hypothalamus and pituitary gland were intact. In the second series of experiments, the effects of dopamine, high (K+) and Ca++ on the release of somatostatin from isolated hypothalamic synaptosomes were studied. Dopamine and high (K+) in the media stimulated the release of somatostatin and the latter effect was completely abolished by the removal of Ca++ from the media. The results suggest that dopamine has a role in modulating the release of somatostatin. In the third series, the effects of hypothalamic deafferentation on plasma GH levels and responses to ether stress were examined. Somatostatin content in the hypothalamus was reduced to about 50% in both anterior (AC) and complete deafferented (CC) rats as compared to their respective controls. The mean plasma GH levels were elevated in AC rats and the levels in CC rats were significantly higher than the control. Plasma GH levels 15 min after ether stress reduced significantly in both AC and CC rats, similarly to their respective controls. These findings suggest that the major portion of hypothalamic somatostatin was provided by other regions of the brain, which did not play a role in mediating stress-induced plasma GH reductions, but appeared to be responsible for maintaining basal GH levels.


[Nasal route flexible broncho-fiberscopy, as a tool of mass examination for hilar type lung cancer (author's transl)]. Early detection of lung cancer is mandatory problem in the medical field. Although, chest x-p examination is a strong armament for detection of peripheral type of lung cancer, the method has rather weak point in detection of hilar type of bronchogenic carcinoma. Bronchoscopy is essential method for diagnosis of bronchial changes of this disease. It is, however, not popular method yet, because of its troublesome technique, such as insertion of tracheal tube, eventhough new instrument of flexible fiber bronchoscopy makes us very much easy way to use, compared with old-fashioned rigid bronchoscopy. For mass examination of high risk group of bronchogenic carcinoma (chromate workers), we are using nasal route flexible fiberbronchoscopy. Comparing of this method with previously used trans-oral route, both easiness of the technique on doctor's side, and comfort during the examination on the patients's side revealed favorable results for nasal method.


[Studies on the estimation of the postmortem interval. 5. The turbidity of the cornea (author's transl)]. The authors have investigated the relationship between the postmortem interval and the turbidity of the cornea of 410 persons who had died at known times and had been subjected to medico-legal autopsies in our laboratory. The conclusions are as follows: 1) Differences due to the states of the eyelids of cadavers, either open or closed, gave rise to slight variations of the turbidity of the cornea only within 12 hours after death. Slight variations due to age and sex were seen only from 12 to 24 hours after death and only in the age group of 0 to 19 years. Seasonal variation was not seen on the cadavers which had remained indoors at the Hokkaido districts. 2) In death from exsanguination none became a state of the strong turbidity. In death from intracranial injuries and asphyxia the strong turbidity developed earlier than in the other types of death. 3) When the cornea is transparent, the time which has elapsed since death is less than 36 hours, with few exceptions, with eyelids either open or closed. On the cadavers with closed eyelids, the week turbidity of the cornea is seen between 6 hours and 3 days, the moderate turbidity between 12 hours and 2 weeks and the strong turbidity over 18 hours.


The effect of medial preoptic area lesions on sexually stimulated hormone release in the male rat. Male rats were subjected to bilateral electrolytic lesions in the medial preoptic area (mPOA). These lesions disrupted sexual behavior without affecting basal levels of luteinizing hormone (LH), prolactin (PRL), or testosterone (T). During exposure to an estrous female, intact and sham-operated rats mated; these rats showed elevations in LH, PRL, and T levels. Lesioned rats, which did not mate, showed elevations in LH but not PRL or T levels. These results demonstrate that the mPOA is not required for sexually stimulated LH release. The failure of lesioned rats to release PRL and T may be secondary to their failure to mate. Alternatively, the mPOA may participate in sexually stimulated PRL release, while T release may depend on prior elevations in both LH and PRL levels. LH release may be related to arousal, and PRL release to consummation, providing a hormonal analogy for the dual mechanism theory of sexual behavior.


Prenatal endogenous androgenic influences on masculine sexual behavior and genital morphology in male and female rats. Female rats located near a male during uterine development showed increased frequencies of male-like behavior as adults and virilization of genital morphology. These changes in behavior and morphology were blocked by prenatal treatment with the anti-androgen, Flutamide.


Behavioral characteristics of freemartins administered estradiol, estrone, testosterone, and dihydrotestosterone. Eighteen genetic females born co-twin with males and diagnosed as being sterile intersexes (freemartins) were studied from birth to 79 weeks of age. Testosterone (T) and estrone (EI) were administered in Silastic capsules of two groups from birth to 50 weeks of age and other animals were left untreated. At 50 weeks the two treated groups had larger implants installed and the untreated animals were assigned to a new estrone (EII) and estradiol (E2) treatment. Later a dihydrotestosterone (DHT) group was formed in comparison with new E2 and testosterone propionate-enanthate (TP-TE) groups, plus untreated controls. Vulvar interest, Flehmen lip curl, mounting, and agonistic behavior were recorded daily for 30 min while animals were allowed social interaction. Agonistic behavior, interest in the genital area, and mounting were induced or stimulated by T, TP-TE, and E2, but not by DHT or estrone (EI or EII). Also, only animals in the T, TP-TE, and E2 groups induced to mount displayed the standing type of behavioral estrus. Flehmen lip curl was stimulated only by T or TP-TE. The evidence is interpreted to indicate that T, per se, evokes the lip curl, but it probably stimulates other responses at the neural level by conversion to E2. Also, the freemartin response, the response of castrates to steroid hormones, and current knowledge of circulating steroid hormones in male and female cattle could be interpreted to indicate that the neural tissue responsible for sexual behavior in both sexes of this species may respond similarly in several respects.


The effects of photoperiod on androgen-induced reproductive behavior in male ring doves, Streptopelia risoria. The effect of photoperiod on reproductive behavior in male ring doves (Streptopelia risoria) was studied in androgen-injected castrates maintained under long (16L:8D) or short (86:16D) photoperiods. Behavioral recordings were made over a 2-week period during which each male was paired with a female for 6.5 hr/day. There was some indication that males held on long days display higher levels of courtship activity during the initial period following pairing, but the evidence was not conclusive. Day length had no effect upon copulatory behavior. Long-day males exhibited consistently higher levels of nest building than short-day males, indicating that photoperiod affects building through some mechanism other than changes in endogenous androgen levels.


Nonhospital alternatives for acute psychiatric care in California. In California multiple social forces and financial constraints are leading to the rapid development of local alternatives not only to state hospitals but to general hospital psychiatric units as well. Two dissimilar patterns of acute-care services are emerging: the use of skilled nursing facilities with additional staff to provide mental health services and the development of a wide range of primarily nonmedical facilities under the licensing category of "residential care facility." The author summarizes characteristics of both kinds of programs and describes how they draw on all available sources of revenue before using state and county mental health funds. He also describes Santa Clara County's plan for local acute-care services in which a 54-bed residential building and a 15-bed psychiatric unit in a county hospital will replace two county-hospital psychiatric wards.


Competency evaluations in Connecticut.

Competency evaluations in Connecticut. New procedures for conducting competency evaluations were adopted in Connecticut in 1975 as a result of a change in the state law. The accused person is now evaluated in the setting in which he finds himself by virtue of his conflict with the criminal justice system, rather than automatically being remanded to the state hospital for evaluation. The criteria used are legal rather than medical-psychiatric, and the evaluations are conducted by a mental health team consisting of a psychiatric social worker, a psychiatrist, and a psychologist. The authors describe the procedures and discuss the benefits deriving from them, as well as some of the real and potential problems.


A review board for determining the dangerousness of mentally ill offenders. Partly as the result of legislative changes made in 1975 and 1977, Texas has a workable system for dealing with mentally abnormal offenders and assessing the dangerousness of committed offenders. The author summarizes provisions of the law related to pretrial evaluation, competency to stand trial, dispositions after a ruling of incompetency, and the insanity defense. He describes the activities, during the first two years, of multidisciplinary review boards for manifest dangerousness; the boards met monthly to assess the dangerousness of patients committed to a state hospital's maximum-security unit after rulings of incompetency (without the probability of attaining competency in a foreseeable period) or of not guilty by reason of insanity. During the two years, the boards declared 171 of 364 patients to be not manifestly dangerous and thus ready for transfer or release, but they became more conservative in making judgments of not dangerous as time passed.


Public perceptions of the criminally insane. The authors interviewed 413 residents of New York State in a study of public perceptions of the criminally insane. They found that the criminally insane are generally considered dangerous, harmful, and violent, and as a class they are feared and rejected by society far more than are than are the mentally ill. However, none of the individuals identified by study respondents as criminally insane were legally classified as such. The authors believe the public confusion about who is criminally insane arises from the media's emphasis on prior history of mental treatment of individuals committing violent and bizarre crimes, and from misunderstanding of the role of mental health professionals in criminal proceedings.


Managing the violent patient in a community mental health center. Staff ofcommunity mental health centers are finding that they must deal with increasing numbers of imminently or potentially violent patients. Some of the author's suggestions for handling such patients include assigning two therapists, one man and one woman; holding the interviews in special offices that have two exits and are in view of staff but out of view of other patients; and notifying the center director and other staff that a potentially violent patient is in the center. The author also reviews some of the literature on correlates of violent behavior. The most obvious correlate is a previous history of repeated severely violent behavior.


Equipment selection for inhouse laundry demands careful planning. Laundry equipment has become increasingly sophisticated in recent years, and, as a result, equipment selection decisions have become extremely complex. Whether installing an in-house laundry or modernizing an existing one, equipment selection demands knowledgeable consideration of several key factors.


Hospitalwide inventory turnover gives hospitals positive results. This article describes the problems involved in reaching a rational inventory investment and describes a hospitalwide inventory turnover program that can be used as an aid in reaching this decision. The article illustrates a hospitalwide inventory program at one hospital. The systematic program entails the collection of data, review of the data to develop a program for reducing inventories, and monitoring of the results.


Improving the operations of the emergency department. Review of the operations of 20 Washington, DC, area hospitals' emergency departments raised some important questions about the care of the emergency patient. This article answers some of those questions and outlines methods for improving the operations of the emergency department.


Informed, involved employees aid hospital's cost control program. A community hospital's two-part program emphasizes employees' responsibilities and participation in cost control. First, department managers were made more aware of and knowledgeable about costs and techniques for control through use of an AHA educational program. Second, an employee committee studies cost problems and recommends solutions that have effected substantial savings.


Cost improvement program generates major savings. The rationale and components of a model for containing and reducing costs are described in this article. The project-oriented program, which uses cross-functional teams as well as individual participants, encourages employees to be aware of the need for cost effective performance.


Pharmacists voice their concern over patient package inserts. The annual meetings of the America Pharmaceutical Association and the American Society of Hospital Pharmacists are a time for discussion of issues that currently affect the profession. Two major issues discussed at this year's meetings were the distribution of patient package inserts and the increased numbers of pharmacists graduating from college each year. This report highlights discussion about these two issues and presents excerpts from the inaugural addresses of the incoming presidents.


Calling Nurse Blaze: tailoring programs to fit human behavior. Researchers conducted a study to analyze hospital fire safety procedures and training, with a particular emphasis on verbal alarm systems. Their findings are presented, along with recommendations for fire safety training and a suggestion from a verbal fire alarm message.


P.L. 93--641:a recipe for action.

P.L. 93--641:a recipe for action. Reduced to its plainest terms, health planning is a means to facilitate genuine coordination and cooperation among the many components of the American health care system. The health planning law should give local community providers and consumers a better opportunity to make health planning work, but its success will depend on the willingness of the community to effect change through local decision making.


Program expedites reporting, resolving medical incidents. Given the current seismic wave of malpractice and liability litigation, hospitals must implement programs to effectively manage loss caused by injury within their institutions. A risk management program at Halifax Hospital Medical Center effects prevention of medical incidents, identifies and investigates incidents, and administratively deals with incidents entailing risk of financial loss.


In-house television news: focus on employees boosts morale. A medical center is using a monthly videotaped television news program to effectively inform its departments and personnel about one another, to provide them with special recognition, and to help nurture their esprit de corps. For these reasons, staff participation, especially by nonsupervisory personnel, both in producing and in appearing on the program is emphasized.


Diagnostic testing as a cost factor in teaching hospitals. The interpretation of laboratory tests by resident physicians is an integral part of the process of medical education. Therefore, the resident's awareness of the validity, reliability, and usefulness of laboratory tests and their alternatives, coupled with an analytical dialog between the supervising attending physician and the resident can help limit the ordering of diagnostic tests to what is logically and scientifically appropriate. Such a dialog may partially address the issue of teaching cost-effectiveness within the graduate medical education curriculum.


From "Humanae Vitae" to "Human Sexuality": new directions? Ten years after Humanae Vitae, Human Sexuality, a study commissioned by the Catholic Theological Society of America, is being widely discussed. The four propositions that served as the study's theoretical base are examined in an attempt to "better appreciate and evaluate the present significance of Humanae Vitae for Catholics in general and for Catholic health care professionals in particular."


After "Humanae Vitae": a decade of "lively debate.". In the decade since Humanae Vitae, dissenting Catholic moral theologians have objected to treating the biological structure of the marital act as normative. Pluralism both in ethical methodologies and in specific teachings is developing. This article discusses one example of this trend in Human Sexuality, a study commissioned by the Catholic Theological Society of America, which posits creative growth toward integration as the principle from which values and norms are to be derived.


Long range planning in the church and in CHA. The Fathers of the Second Vatican Council designed objectives for the contemporary Church in accord with the signs of the times and based on the Church's ultimate goal as defined by the Council. These Church objectives suggest a set of CHA objectives, or functions, couched here in the language of long range planning so that they might lend themselves to strategy making.


Echocardiography as an index of cardiac performance. Ultrasound imaging of the heart provides a noninvasive technique for assessing cardiac performance and diagnosing a wide range of disorders. Recent improvements in two-dimensional, planar instrumentation promise to make echocardiography even more versatile, permitting more comprehensive views of left ventricular function, valve orifice areas, and the spatial relationships of the great vessels and ventricular chambers.


Asthma in adults: the ambulatory patient. Heterogeneity is the hallmark of adult asthma, and patients thus need individualized therapeutic programs. But there are unifying underlying mechanisms, understanding of which makes it easier to design the clinical stategy appropriate to each case.


Aging: biologic or pathologic?

Aging: biologic or pathologic? If disease is only case casually related to aging, the prevailing strategy of dealing with each disease category is appropriate; if they are linked causally, the current strategy may not only be inappropriate but prove futile. The extent to which optimal gerontologic care can delay the onset of biologic deterioration, together with the use of short-lived animal models for research, may eventually resolve this issue.


Lyme arthritis: a new clinical entity.

Lyme arthritis: a new clinical entity. Named for the Connecticut town where the first identified cases occurred in 1972, this disorder has since been found elsewhere and may be caused by a virus transmitted by ticks. Attacks are often preceded by erythema chronicum migrans and are seldom prolonged, though they may recur. Symptomatic treatment only is advised, except in the rare instances of severe neurologic complications or myocardial conduction abnormality.


Surgical treatment of hydrocephalus in infancy. Correction of hydrocephalus by means of a ventriculoperitoneal shunt incorporating a pericranial reservoir is demonstrated in a five-day-old infant. The reservoir affords access to the ventricle and shunt for pressure determinations and for administration of antibiotics should infection occur. The initial shunt is revised at about one year of age to permit intraventricular pressure to rise to adult levels and to provide for growth.


Recruitment and the manpower crunch.

Recruitment and the manpower crunch. In summary, the signals are clear that current trends indicate a scarcity of pathologists not too many years hence. Recruiting efforts must be mounted now to bring to the attention of the appropriate medical students that pathology is a demanding, rewarding clinical discipline whose importance and satisfaction reach beyond basic science and the physical confines of the clinical laboratory.


Malignant mesothelioma with minimal asbestos exposure. The association of malignant mesothelioma and asbestos fibers is well established. The minimal exposure that may produce the tumor is not known. The present report documents the minimal exposure by thorough examination of occupational history and personal hobbies, and counting of the number of asbestos fibers in the lungs. The evidence for the elemental composition of asbestos fibers by electron probe (EDAX) is also presented.


The 13C/12C ratio in black pulmonary pigment: a mass spectrometric study. Ratios of the two stable isotopes of carbon, 13C and 12C, were measured in black pulmonary pigment and in several endogenous tissues removed during 20 autopsies on Long Island, New York. The mass spectrometer used for carbon isotope ratio analyses has a precision of +/- 1 13C atom per million carbon atoms. The 13C/12C ratio was found to be distinctly lower in black pulmonary pigment than in endogenous tissues, the mean difference amounting to 65 13C atoms per million carbon atoms. The results demonstrate that the elemental carbon fraction of black pulmonary pigment is exogenous and constitutes roughly 30 per cent of the weight of the pigmented material. It was also observed that 13C/12C ratios in endogenous tissues from individual autopsy cases were not quite identical, tending to be slightly greater in corpus callosum than in liver or peripheral lung.


An unusual fibro-osseous component in intracranial lesions. An unusual fibro-osseous component has been identified in intracranial lesions. Ultrastructurally this component appears to represent stages of membranous bone formation, but of an atypical and incomplete sort. The fibroosseous component may be an aberrant type of bony metaplasia and is seen in several lesions all of which probably do not share the same etiology although in each case meningeal or choroid plexus stroma appears to be involved.


Hibernoma: a possible model of brown fat histogenesis. Hibernomas are composed of cells remarkably similar to those observed in brown adipose tissue. A surgically resected hibernoma was observed to contain cells at all stages of maturation from immature, relatively lipid free cells to multiloculated and finally uniloculated adipocytes. The ultrastructural features of adipocytes contained in the hibernoma were compared to previously reported features of differentiating preadipocytes and lipid depleted mature adipocytes derived from human white adipose tissue. This comparison confirmed the existence of distinct mitochondrial and cytoplasmic membrane component differences at all developmental stages and suggests that brown and white adipose tissue are two unique histologic types.


Peliosis: a morphologic curiosity becomes an iatrogenic problem. Peliosis is a morphologic entity describing a condition of blood filled spaces, most frequently occurring in the liver. In recent years it has evolved from an anatomic curiosity seen at autopsy to a potential clinical problem in view of its association with the administration of anabolic steroid hormones. The pathogenesis and predilection of peliosis for the liver remain unexplained. This article reports five patients with peliosis, four with splenic involvement, all but one of whom received an anabolic steroid preparation. One patient died as a result of rupture of the splenic peliotic spaces. The diagnosis in three cases was established on the basis of surgical material, i.e., liver biopsy or splenectomy. An increased awareness of peliosis in patients at risk, as well as an appreciation for the histopathologic changes in less advanced cases, may become an important issue for the surgical pathologist.


Mucoepidermoid carcinoma of the esophagus: a case report. The eighth reported case of mucoepidermoid carcinoma of the esophagus is described by light microscopic and ultrastructural examination. The reason of such a paucity of reports, the probable origin, and the natural history of this neoplasm are examined through our observations and reference to the literature.


Plasma cell granuloma of the stomach.

Plasma cell granuloma of the stomach. A case of plasma cell granuloma of the stomach is described, only one similar case having been previously recorded. Differentiation from a neoplastic plasmacytoma was achieved by demonstrating the polyclonal nature of the plasma cells using an immunoperoxidase technique.


Lithopedion: case report and ultrastructural study of the skeletal muscle. A case of lithopedion (lythokelyphopedion) is reported in a 69 year old woman who had carried a nearly full term dead fetus for at least 20 years. The fine structure of the skeletal muscle was in an astonishingly good state of preservation with contractile elements and myosin molecules identifiable. The conditions and modifying factors that may play a role in the development of a lithopedion are discussed, and x-ray, histologic, and electron microscopic studies are described.


Lymphomatoid granulomatosis: report of a case without pulmonary lesions and with ischemic colitis, probably a sequel to granulomatosis. This article describes a case of lymphomatoid granulomatosis without active pulmonary involvement of stigmata of healed granulomatous lesions in the lungs. The patient had ischemic segmental colitis due to mesenteric arterial intimal fibrosis, which we interpreted as spontaneously regressed granulomatous involvement of the mesentery. The report deals with the lack of pulmonary involvement and regression of lesions in lymphomatoid granulomatosis.


The sero-anthropology of the Rhodesian Lemba. 122 Rhodesian Lemba were blood grouped to establish whether there was any serological evidence to support their claim to be immigrants into central and southern Africa; and whether their endogamous practices had resulted in blood group frequencies different from those of their present neighbours. Our results are typical of those found in central Africa, and show no similarity to the blood group frequencies of populations outside sub-Saharan Africa.


The detection of genetical influences on human family size. The genetics of human family size is not readily susceptible to analysis. Some of the problems in its investigation are discussed, together with methods for overcoming them. In particular, the problem of obtaining a satisfactory model which will account for both the low heritability of family size and its over-dispersed distribution is examined in detail.


ABO blood groups and serum proteins in thromboangiitis obliterans (Buerger's disease). In Madhya Pradesh, India, 43 patients with thromboangiitis obliterans showed a decrease in total serum proteins and in the albumin fraction, an increase in a1-and a2-globulin fractions, and decrease in the albumin/globulin ratio. In the ABO blood groups, patients show a significant excess of group B individuals. It is possible that the disease may be more severe in individuals with the B blood group substance.


C3 polymorphism in a Danish cystic fibrosis population and its possible association with antibody response. The C3 types of human serum are reported for a material of 113 Danish cystic fibrosis patients, age 0-30 years. The frequency of the C3F gene was 0.2832 which was significantly higher (p less than 0.0005) than the frequency found in a control group of 224 healthy babies (C3F = 0.1585). It also differed significantly (p less than 0.01) from the C3F gene frequency of 0.1780 found in 177 blood donors, age 20-24 years. A significant association between any of the C3 phenotypes and the most serious infection in cystic fibrosis, chronic mucoid P. aeruginosa infection, or the antibody response against these bacteria was not found.


Complex segregation analysis of tongue pigmentation. A search for residual family resemblance. Complex segregation analysis of tongue pigmentation in 493 nuclear families fails to indicate significant evidence for incomplete recessivity, polygenic variation, or an effect of sibship environment, thus establishing simple Mendelian inheritance for the trait.


[Treatment of rheumatoid arthritis with 90yttrium. Follow up studies (author's transl)]. 90Yttrium-silicate was injected into 131 knee-joints from patients with rheumatoid arthritis with stadium II-IV according to Steinbrocker. The observation period lasted until two years. After three months about 80% and after 24 months still more than 50% of the patients treated showed complete or partial remission. Side-effects as formerly observed with 198-goldpreparations did not occur. Therefore the treatment with 90Yttrium-silicate offers an alternative to surgical synovectomy.


[Solid-phase radioimmunoassay for class specific immunoglobulins against tick-borne encephalitis virus (author's transl)]. By adsorbing purified Tick-borne encephalitis (TBE) virus antigen onto beads of polystyrene, a solid-phase radioimmunoassay (RIA) for specific antibodies of the IgM- and IgG-class in untreated and nonfractionated human sera could be developed. The antibodies were measured by antihuman-gamma and antihuman-mu globulin labelled with 125 I. The RIA was about 20 times as sensitive as the hemagglutination-inhibition test. About 10% more cases of TBE could be diagnosed with the RIA than with the 2-mercaptoethanol test.


Lymphocyte cytotoxicity in the X-irradiation induced rat small bowel adenocarcinoma. II. Presence of cytotoxic lymphocytes in irradiated animals. Cytotoxic peripheral blood lymphoid cells were demonstrated in both Holtzman and Lewis Brown-Norway rats which had received 2000R of local X-irradiation to the temporarily hypoxic, exteriorized, ileum and jejunum regardless of whether a small bowel adenocarcinoma subsequently developed. The cytotoxic response, which was detectable at two days, was quite evident by day 5 post-irradiation. No evidence of cross-reacting tumor antigens was obtained when similarly processed effector cells from Holtzman rats bearing a spontaneous mammary carcinoma were incubated with cell cultures derived from the small bowel adenocarcinoma. These findings indicate X-irradiation of the small bowel initiates lymphocyte sensitization that is manifested as in vitro cytotoxicity against cell cultures of the adenocarcinoma.


Levels of total haemolytic complement activity in paired dairy cow-newborn calf sera. Total haemolytic complement (CH50) activities of sera obtained from newborn dairy calves and their corresponding dams were compared. The differences between the mean maternal and neonatal CH50 concentrations were significant (P less than or equal 0.001). The concentration of CH50 units/ml in sera from 16 calves was 52.0 +/- 21.4, whereas, for the cows it was 195.8 +/- 24.0. The ratio of cow: calf serum CH50 values averaged 4.24 with a range from 1.77 to 8.00. A positive rank correlation of 0.479 (P less than 0.05) was found between the CH50 titres in calves and their dams. Anticomplementary substances were not detected in calf sera. The possible relationships betweeen deficient CH50 levels in newborn calves and their susceptibility to infectious agents is discussed.


Cellular changes in the lymphoreticular tissues of C57L/J mice infected with Echinococcus multilocularis cysts. The pathology of the spleen, lymph nodes and thymus of C57L/J mice, infected intraperitoneally with 20 and 100 cysts of Echinococcus multilocularis is described at 2, 4, 8 and 12 weeks postinfection (p.i.). For the first 8 weeks, growth of the larval cyst mass (LCM) was slow and blastogenesis in T-dependent areas of both spleen and lymph nodes was moderate whereas in B-cell compartments it was intense. A rapid growth of the LCM between 8 and 12 weeks p.i., 15-20 times greater than for the first 8 weeks, was associated with depletion of lymphocytes in thymus dependent area (TDA) of both spleen and lymph nodes, gross expansion of the red pulp with extramedullary haemopoiesis, partial atrophy of spleen follicles, but not those of the lymph node, and involution of the thymus. At 12 weeks p.i. the TDA had mainly plasma cells and histiocytes among occasional lymphocytes and blast cells; germinal centre activity and plasmacytosis persisted in B-cell areas. Morphological aspects of these changes are discussed in relation to the invasiveness and proliferation of the LCM during the course of infection.


Simultaneous stimulation and suppression of two different indicators of the cell-mediated immune response by the immunoregulator dextran sulphate. The effect of high mol. wt dextran sulphate (DS) on two different indicators of the cell-mediated immune response was studied simultaneously in the same animal. The two indicators of the cell-meidated immune response chosen for this study were the footpad swelling response to sheep red blood cells (SRBC) and skin allograft rejection. Mice receiving DS and SRBC showed a significant increase in the delayed-type footpad swelling response over the controls at 24 and 48 h after challenge, while in addition, the same mice showed a significant suppression of the delayed-type response to allograft antigens as indicated by a significant delay in rejection time of allografts. The results presented here show that DS is capable of simultaneously stimulating and suppressing two indicators of the cell-mediated immune response in the same animal.


Metabolism of homologous and heterologous serum proteins in garter snakes (Thamnophis ordinoides). The half life (T1/2) of serum immunoglobulin (Ig) and albumin from snakes and mammals were determined in both garter snakes (Thamnophis ordinoides) and mice (Mus musculus). Metabolism of serum proteins in snakes was similar to mammalian protein metabolism in that homologous serum albumin had shorter T1/2 (16 days) than IgG (38 days). Also, reptilian and mammalian serum proteins had a relatively longer T1/2 when injected into closely related species. Thus mammalian serum Ig (rabbit gamma globulin (RGG)) had a shorter T1/2 (6.3 days) in snake than did homologous snake IgG (38 days), whereas in mice, RGG had a longer T1/2 (3.8 days) than snake Ig (0.9 days). Differences between metabolism of homologous and heterologous albumins were apparent only in snakes in which the T1/2 of homologous albumin was approximately 8-fold greater than mammalian albumin. These results indicate that metabolism of both Ig and albumin in snakes is regulated by specific receptors whereas albumin receptors have been difficult to demonstrate in mammals. The results of this study suggest that one of the factors determining the metabolism of a protein is its foreignness to the host perhaps because of receptor cross reactions.


The role of IgA immunoglobulins in the passive transfer of protection to Taenia taeniaeformis in the mouse. Normal mice were protected against infection with metacestodes of Taenia taeniaeformis when administered intestinal, colostral or serum immunoglobulins obtained from adult mice previously orally infected with the parasitie. The protective capacity of these preparations was found to be associated mainly with IgA of colostrum and intestinal secretions and IgG of serum. The removal of IgA and IgG from immune colostrum and serum, respectively, abolished the protective effect. Neonatal mice were protected against infection with T. taeniaeformis when fed purified colostral IgA and serum IgG from immune donors. The intraduodenal injection of intestinal IgA from immune donors into 4-week-old mice passively protected the recipients against infection with T. taeniaeformis, but intestinal IgG from immune donors had no protective effect when given in this manner. The protective capacity of IgA and IgG was largely eliminated by prior absorption with T. taeniaeformis antigen or hatched, activated oncospheres of T. taeniaeformis.


Histamine in nasal secretions.

Histamine in nasal secretions. The histamine content of secretions collected by small-volume nasal washes was assayed by a spectrophotofluorometric method. A wide range of histamine concentrations (less than 5-1,519 ng/ml) was found. The mean concentration in secretions from normal individuals (91 ng/ml) was not significantly different from that found in allergic individuals (51 ng/ml). Females had significantly lower concentrations than did males. Sequential sampling in normals and allergics showed a great deal of daily variation in histamine content. This technically simple method may prove useful in examining the epidemiology and pathophysiology of allergic rhinitis.


The effect of transfer factor on lymphocyte transformation. Comparison of augmentation by dialysates of leucocytes and lymphoid and non-lymphoid organs. In this paper we describe experiments to determine whether dialysable extracts of non-lymphoid and lymphoid organs augment lymphocyte transformation in vitro in a manner similar to the augmenting activity of leucocyte dialysates. Human peripheral blood leucocytes were cultured with tuberculin PPD or leucoagglutinin, and dose-related effects of the dialysable extracts on lymphocyte transformation were studied by 125IUdR incorporation. Augmentation of lymphocyte transformation was obtained not only with leucocyte dialysates but also with dialysable extracts of lymphoid and non-lymphoid organs (e.g. spleen, liver, kidney, brain). It is concluded that the agent or agents present in dialysable leucocyte transfer factor preparations, which augment lymphoid transformation in vitro, are widely distributed throughout mammalian tissues.


The H, HI, I and i blood group antigens in butanol extracts of rabbit tissues. Aqueous and butanol phase extracts of rabbit erythrocytes and the tissues gastric mucosa, liver, lung and kidney were examined by inhibition of agglutination for the presence of H, HI, I and i blood group substances. Of the four specificities, only I substance was recovered from erythrocytes and only in the aqueous phase extracts. Both aqueous and butanol extracts of gastric mucosae contained H substance, but HI and I were present only in the aqueous extracts of this tissue. Extracts of rabbit lungs only had H and I activity and only in the aqueous phase. No H, HI, I or i substance was detected in any of the extracts of liver and kidney. Reduced levels of H substance were found in aqueous extracts of gastric mucosae of 'A-like' rabbits. Three H specificities were demonstrated in the butanol phase extracts of gastric mucosae of rabbits. These specificities were similar to those previously shown in extracts of gastric mucosae and erythrocytes of humans.


Crossed immunoelectrophoretic and crossed radioimmunoelectrophoretic studies employing a model allergen from codfish. A standard reference pattern in crossed immunoelectrophoresis (CIE) of the parvalbumin fraction of a cod white muscle extract was established. Crossed line immunoelectrophoresis (CLIE), tandem CIE and crossed radioimmunoelectrophoresis (CRIE) were used to identify the major allergens, thereby establishing a basis for future work employing quantitative immunoelectrophoretic techniques in the study of codfish allergens. Rocket immunoelectrophoresis and rocket-line immunoelectrophoresis were used to demonstrate antigenic determinants on polypeptide fragments of the major allergen, Allergen M. The results show the usefulness of these techniques in studies of antigenic determinants on non-precipitating polypeptides. CRIE with 8 patients's sera showed radiostaining indicating IgE binding corresponding to at least 7 precipitates in the crude extract CIE preparations. The purified DS 22 fraction was shown to contain 2 CRIE-positive (IgE-binding) precipitates. When using Allergen M, these precipitates were also demonstrated, one of them in trace amounts only.


Inhibition of human complement components by Loxosceles reclusa venom. Venom from the brown recluse spider, Loxosceles reclusa, was capable of inactivation human C1-C7 in vitro. This inactivation occurred if venom was added to fresh adult human serum, human cord serum, or functionally pure specific human components. Optimal incubation conditions for the inactivation of each component were determined and were found generally to be in the range of 25 or 37 degrees C for 30-60 min. The alternative complement pathway did not appear to be involved, since C1, C4, and C2 were readily inactivated, and inactivation took place in sera depleted of factor B of the properdin system. Venom-induced inactivation appeared to require few, if any, serum cofactors, because, with the possible exception of C2, functionally pure components, as well as those in sera, were readily inactivated.


Plasma prostaglandin concentrations in allergic bronchial asthma. Prostaglandin (PG) E plasma levels, measured by radioimmunoassay using anti-PGB1 antibody, were higher in asthmatic patients than in normal subjects. PGF levels measured with anti-PGF2alpha antibody, were not significantly different between normals and asthmatics. Plasma PGE/F ratios were elevated in the asthmatic patients. The results fail to support the hypothesis of decreased PGE or increased PGF production as an etiological factor in asthma.


Immunosuppressive effect of Staphylococcus aureus peptidoglycan on antibody response in mice. Immunosuppressive effect of an adjuvant, Staphylococcus aureus peptidoglycan, on the primary IgM antibody response in mice was studied with application of the hemolytic plaque assay. Peptidoglycan suppressed the IgM response to thymus-dependent sheep erythrocyte antigen when given intravenously before immunization. The effect of peptidoglycan and erythrocytes was both time and dose dependent. For the suppression, both the delay in the antibody response and overall decreased response were responsible. Peptidoglycan did not influence background counts of antibody-forming cells. Priming with subthreshold dose of erythrocytes did not overcome the suppression, although higher responses compared to unprimed animals were observed. Peptidoglycan did not suppress antibody response to thymus-independent antigens-lipopolysaccharide or high dose of erythrocytes. It is suggested that peptidoglycan-induced immunosuppression is mediated by a presently unidentified population of helper cells-macrophages or T lymphocytes.


Site of respiratory reaction in allergic rats challenged via the airways. Rats systemically sensitized to DNP-ovalbumin show a characteristic respiratory response to antigen challenge delivered via the airway. The slowing of expiratory air flow which occurs on aerosol challenge still occurs when the antigen is injected via a tracheostomy but not when it is delivered solely to the upper airways. Disodium cromoglycate administered via the tracheostomy 1 min before intratracheal antigen challenge reduces the respiratory response.


Immunological partial identity and in vitro inhibitory effect of two major timothy pollen allergens to whole pollen extract of four grasses. Crossed immunoelectrophoresis in various modifications has directly revealed the immunological partial identity between isolated major allergens of timothy pollen (antigens 19 and 25) and the corresponding pollen allergens of false oat, orchard and rye grass, using rabbit antibodies raised against all four grasses. The inhibitory effects of antigens 19 and 25 relative to those of whole pollen extracts have been determined by means of RAST, inhibiting serum pools from selected grass-pollen-allergic patients and using insolubilized whole pollen extracts from the four grasses as allergosorbents. The inhibitory effects of antigens 19 and 25 were determined to be 97, 91, 92 and 73% of those of whole extracts of timothy, false oat, orchard and rye grass, respectively.


In vitro generation of cytotoxicity against autologous human tumour biopsy cells. Blood lymphocytes from 22 cancer patients were examined for cytotoxicity against autologous tumour cells in a short-term 51Cr release assay. Only three showed reactivity. In an attempt to increase cytotoxic potential in these and induce reactivity in non-reactive cases, the lymphocytes were cultured alone or with autologous tumour cells for 6 days. Upon subsequent testing against frozen, stored targets, nine samples reacted, including two of those with primary reactivity. In seven cases augmented cytotoxicity was evident in mixed cultures compared with lymphocytes cultured alone. Two of 10 cases showed cytotoxicity against the K562 cell line after culture and, in two of 13 tests in which allogeneic tumour biopsy targets were used, weak reactivity was bound. Cytotoxicity for autologous tumour biopsy cells was uniformly accompanied by positive blastogenesis in MLTI assays. In four cases blastogenesis occurred without the induction of cytotoxicity.


Heterogeneity among human lymphocyte effector cells mediating spontaneous lymphocyte-mediated cytotoxicity. The spontaneous lymphocyte-mediated cytotoxicity (SLMC) of lymphocytes from normal individuals was studied using the lymphocyte titration assay. Various techniques were used to study selectively several lymphocyte subpopulations. The activity of these subpopulations was tested in both the antibody-dependent cellular cytotoxicity (ADCC) and lymphocyte titration assays. Surface marker studies were performed on each lymphocyte subpopulation. The results from these studies indicate that effector cells mediating SLMC are a heterogeneous lymphocyte population composed of Fc-receptor-positive lymphocytes both with and without C3 receptors that consistently segregate with cells that do not form rosettes with sheep red blood cells. Our data suggest that, in many respects, the effector cells in SLMC and ADCC are identical. However, the mechanism appears to be different.


Failure to relate the anti-tumour action of cyclophosphamide with the immunogenicity of two murine fibrosarcomas. A single intraperitoneal injection of cyclophosphamide (CY) had a stronger anti-tumour effect upon two syngeneic mouse fibrosarcomas when given within a few days of tumour implantation than when given 7-20 days after. CY was more active against the fast-growing, relatively non-immunogenic CBA fibrosarcoma, FS13, inducing a higher proportion and permanent regressions, than the slower-growing, highly immunogenic C57BL fibrosarcoma, FS6, at all comparable stages of tumour growth. Whole-body irradiation, which suppressed concomitant immunity in FS6-tumour-bearing mice, had no effect on the anti-tumour action of CY. A study of the cellular composition of the tumour masses over a 4-day period immediately after CY injection showed that there was a decrease in total cell yields, involving mainly a decrease in neoplastic cells, although normal cells, Fc-receptor-positive and -negative, were also affected to a lesser degree. The overall findings indicated a lack of correlation between the anti-tumour effects of CY and tumour immunogenicity. Moreover, it was apparent that the anti-tumour action of CY was mediated by a direct effect of its metabolites on neoplastic cells rather than by host anti-tumour effector mechanisms.


Genetic control of sensitivity to Moloney-virus-induced leukemias in mice. I. Demonstration of multigenic control. The appearance of hematopoietic malignancies and the level of viremia were studied in mice of different inbred strains and their F1 or F2 hybrids inoculated with the Moloney leukemia virus (MLV). The viremia was regularly measured in individual mice by radioimmunoassay of the major internal virion component p30. A complex genetic control was found. (1) The level of circulating virus was controlled by at least two genes. An H-2 linked gene, tentatively called Rmv-1, displayed a dominant sensitivity. Alleles for resistance existed in H2b and H-2r haplotypes and alleles for sensitivity in H-2a, H-2d and H-2f. Another gene with dominant resistance mapped outside the H-2 complex and probably interacted with Rmv-1. (2) A good correlation existed between viremia and the appearance of leukemias, the most viremic strains being also the most leukemic. (3) Nevertheless, additional genes which were not involved in the viremia control could be determinant in the induction of malignancies. One of them with a resistant allele in DBA/2 mice seemed to inhibit the appearance of leukemia despite a high level of viremia. Another gene controlled the spleen involvement resulting in generalized leukemias in sensitive lines contrasting with mainly thymus-localized tumors in resistant animals.


Cutaneous manifestation of internal malignancies (I). Acanthosis nigricans. Skin changes may be the first clue to a neoplastic process at a stage when it still is treatable (Such as the development of Acanthosis Nigrican (AN) in an otherwise healthy adult). Ninety percent of the neoplasm responsible for the development of AN originate in the abdomen. The tumor, even in a subclinical state, seems to possess unidentified properties that activate the dermatosis.


Hereditary sclerosing poikiloderma.

Hereditary sclerosing poikiloderma. Three persons with hereditary sclerosing poikiloderma were studied to find any clue to explain the mechanism involved in producing the cutaneous lesions which are so striking clinically and also evident histologically. Investigational studies included a blood chemistry screen, chromosome analyses, and skin biopsies evaluated by routine stains as well as by electron microscopy and direct immunofluorescence. No mechanism for the production of the clinical and histological changes in the dominantly inherited disorder was found.


The pattern of diseases of the skin in the Nigerian guinea savanna. Eight thousand and thirteen patients were seen in dermatological clinics at Kaduna and Zaria in the Northern guinea savanna of Nigeria. Fungal infections were found in 1,224 cases and scabies in 923 cases, of which 765 patients had secondary infections. Similar results were found in other surveys from Sub-Saharan Africa.


Oculo-auriculo-vertebral syndrome (Goldenhar's syndrome). Oculo-auriculo-vertebral syndrome (Goldenhar's syndrome) was found in a 10-month-old boy who had epibulbar dermoids, colobomata, pre-auricular skin tags, and hypomandibulosis.


Six years' experience in treatment of chromomycosis with 5-fluorocytosine,. Twenty-three patients with chromomycosis were treated with oral 5-fluorocytosine for periods ranging from 2 to 67 months. Sixteen were considered cured, after 3 consecutive monthly controls showing healing of the lesions and absence of fungi in mycologic and histopathologic examinations of biopsy specimens. Seven, in spite of initial clinical improvement, showed resistance to treatment. Associated treatment with amphotericin B, calciferol or thiabendazole failed to help patients resistant to 5-fluorocytosine. Resistance seems to occur especially in those with long-standing lesions or widespread involvement.