[Dissecting aneurysm of the anterior cerebral artery and Guillain-Barré-syndrome during pregnancy (author's transl)]. In the 8th month of her second pregnancy a young woman fell ill with polyradiculitis. She suddenly died because of a massive abdominal hemorrhage, the cause of which remained obscure. Autopsy revealed typical morphological findings of polyradiculoneuritis and a dissecting aneurysm of the anterior cerebral artery and the recurrent artery of Heubner. The importance of elastic tissue degneration in intracranial dissecting aneurysms is stressed and similar reports in the literature are referred.


Geography in multiple sclerosis.

Geography in multiple sclerosis. Both mortality and morbidity data indicate quite clearly that multiple sclerosis is a geographically-related disease, and thus MS can be thought of as an acquired environmental (exogenous) illness. High frequency parts of the world for MS are Europe between 65 degrees and 45 degrees north latitude, northern United States and southern Canada, New Zealand, and southern Australia. These regions are bounded by medium frequency MS regions: in Europe to the north, east, and south; in America for southern U.S.; and the remainder of Australia. Latin America, Asia and Africa are essentially of low frequency from present data. Latitude is not a sufficient criterion: at 40 degrees north latitude, MS is high in America, medium in Europe, and low in Asia. All high and medium risk areas therefore are in Europe or European colonies; thus MS is the white man's burden spread from western Europe. Within the U.S., MS is less common among Negroes, Japanese, and possibly Amerindians than in whites regardless of geography. Migration studies among risk areas indicate that migrants keep much of the risk of their birthplace, but also that overall the risk is decreased by high-to-low migration, and probably increased by low-to-high. For the former, it seems that adolescence is the age critical for retention of birthplace risk. Some preliminary data on a possible epidemic of MS are also presented. All the epidemiologic information would be most easily explained if MS were an infectious (viral) illness with prolonged latency. The proof of this though must come from the laboratory.


Biochemical findings in multiple sclerosis IV. Isoelectric focusing of the CSF gamma globulins in multiple sclerosis (262 cases) and other neurological diseases (272 cases). Despite enormous efforts to find a specific laboratory test for multiple sclerosis, agar gel electrophoresis of the CSF proteins has remained the next to the best one. This study presents evidence that thin layer polyacrylamide isoelectric focusing of the CSF gamma globulins is by far superior for this purpose. In effect, about 91% of the 262 multiple sclerosis patients studied had oligoclonal fractions present in the very alkaline region of the pH gradient. Of the same group of patients only 65% did show pathological results when studied by agar gel electrophoresis. Of the 272 CSF samples from patients suffering from other neurological diseases, only about 7% showed the presence of oligoclonal bands in the same region of the pH gradient, when submitted to isoelectric focusing.


Periodic synchronous and stereotyped myoclonus with postanoxic coma. 5 patients with cerebral anoxia of various etiology had postanoxic coma with the syndrome of periodic synchronous and sterotyped myoclonus first mentioned by Lance and Adams. These authors observed action myoclonus as a sequel to this syndrome which is rarely survived. Most reports have dealt mainly with its bad prognostic significance. Although the localization of action myoclonus has much been discussed, and is still controversial, little attention has been paid to the possible localizing significance of its acute precursor syndrome. Most patients with this type of myoclonus (all in our series) present a lower pontine/upper oblongata syndrome. The distribution patterns of the jerks are constant, do not represent topographic but functional relationships showing innervation patterns which are presumably integrated in the vestibular system and upper oblongata reticular formation. Interval histograms show that the jerks, unlike those in subacute sclerosing panencephalitis, are not repeated at regular intervals. Several rhythms might be intermingled, or a rhythmic (physiological?) pacemaker could be modified by proprioception of the jerks. The latter possibility is supported by the observation that EEG discharges in one patient became rhythmic when the jerks ceased. The only other instance of rhythmicity was in a very special observation of continuous seesaw alternations of slow jerks of m. levator palpebrae sup., and tonic contractions of m. corrugator glabellae. Rhythmicity in this case had a 1:2 relation to heart rate indicating the nucleus tractus solitarii region as a possible site of origin of the impulses. Our observations indicate an upper oblongata origin for this type of myoclonus. Autopsies in 3 of our cases revealed widespread severe anoxic damage but nothing to add to the pathological localization.


Two cases of giant intracerebral aneurysm simulating neoplasm on ct scan; one with coexistent chronic subdural hematoma. Two cases of giant intracerebral aneurysm are presented. Both exhibit increased absorption values in a circumferential configuration peripherally after the administration of contrast material. In addition, one case demonstrates a coexistent contralateral chronic subdural hematoma. No previous example of intracranial aneurysm exhibiting this configuration on computed tomography has been described in the literature. The operative, computed tomographic, radionuclide and angiographic findings are described and the differential diagnosis discussed.


[The "off-on" phenomenon during treatment of parkinson's disease with levodopa (author's transl)]. The fluctuation in daily performance of Parkinson patients on long-term L-dopa therapy is known as the so called "off-on" phenomenon. Cotzias et al. found that a low protein diet is able to control this phenomenon in patients taking L-dopa alone but not in those receiving a combination of L-dopa and decarboxylase inhibitor. The author's hypothesis was based on the competition between the alimentary aminoacids and L-dopa for transport to the brain ganglia. In our attempt to prove the findings of Cotzias group we tested the influence of a low protein diet on 23 Parkinson patients manifesting the "off-on" phenomenon. All had been pretreated with L-dopa for 5--8 years and taking dopa DI for a minimum of 3 years. The protein intake was limited to 25 g/day (which is less than 0.5 g/kg body weight) for 1--4 months. In 6 cases there was a marked improvment with reduction of the "off-on" effect, and in one it disappeared completely. A distinct improvment of general capability was seen in the other 5 cases, and an objective improvment of the symptoms was noted, except during the "off" period. No response could be observed in the remaining 12 cases. All cases with hyperkinesia showed an augmentation of this symptom during the use of the diet. The diet restriction was not found to be correlated with age, stage, duration of illness or duration of dopa treatment. The possible mechanism of the "off-on" phenomenon and some suggestions to influence it, are presented.


The mechanism of spinal cord cavitation follwing spinal cord transection. Part 2. Electron microscopic observations. The authors report their findings by electron microscopy after microsurgical subpial spinal cord transection in dogs. After cord transection, conspicuous myelin microcysts are formed in a background of otherwise intact cord tisue at a distance of 1 to 2 mm from the cut end of the cord, both proximal and distal to the transection, Seen through the electron microscope, the microcysts iss a myelin sac distended by fluid under pressure, containing a swollen axon filled with excessive axoplasmic organelles; that is, a terminal club. Later the microcysts and terminal clubs rupture. The large spaces within the microcysts are opened to heretofore small extracellular spaces and the spinal cord tissues are destroyed. Thus, microcysts are precursors of large cavitites seen at the ends of transcreted cord stumps. The formation of microcysts and their subsequent rupture, which leads to cord cavitation, is interpreted as an inherent response of cord tissue to injury, and the result of an abortive attempt at cord regeneration.


Developmental effects of prolonged pregnancy and the postmaturity syndrome. The development of 40 postterm, postmature infants was compared to that of 40 normal control infants during the first year of life. The postterm, postmature infants had more prenatal complications and received lower Brazelton interaction and motor scores at birth. At four months they scored lower on the Denver developmental scale and were rated "difficult" babies by their mothers. At eight months their Bayley motor scores were equivalent to those of the control infants, but their mental scores were lower. At this time their mothers reported a higher incidence of illnesses and of feeding and sleep disturbances.


Permeability studies on taenid metacestodes: I. Uptake of proteins by larval stages of Taenia taeniaeformis, T. crassiceps, and Echinococcus granulosus. Host immunoglobulins of several different classes were detected within the bladder fluids of Taenia taeniaeformis, T. crassiceps, and Echinococcus granulosus. Radioiodinated proteins were taken up in vitro by larvae of both T. taeniaeformis and T. crassiceps and were shown to retain their physicochemical and antigenic characteristics. Rates of uptake were similar in the 2 species and were not related to the molecular weight of the proteins. Immunoglobulins were taken up both in vitro and in vivo by larvae of T. taeniaeformis. Absorbed immunoglobulins were shown to retain both antigen binding capacity and biologic functions associated with the Fc portion of the molecules. Not all cysts of E. granulosus contained detectable host proteins. Uptake of 125I occurred when hydatid cysts were exposed to labeled proteins in vitro, but it appeared that rapid degradation of the labeled carrier led to the appearance of dialysable fragments. This may be attributable to proteolysis within the bladder fluid. We conclude that taeniid metacestodes are capable of absorbing a variety of proteins, and that these macromolecules can retain their structural and functional integrity following transport. This absorptive capacity accounts for the presence of host serum components within bladder fluids.


Dissociation of changes in enzymatic and immunoreactive rat serum dopamine bets-hydroxylase during growth and development. Dopamine beta-hydroxylase (DBH) activity was measured in the serum, heart and salivary glands of Sprague-Dawley rats from 1 day after birth to 90 days of age. Serum DBH activity in blood from newborn animals was 90 units, approximately 4.5 times higher than in blood from 60- to 90-day-old rats. The serum enzyme activity increased to 130 units at 15 days of age and then decreased rapidly to adult levels (20 units). This decrease was not due to changes in levels of circulating inhibitors or activators of the enzyme. Four different inbred strains of rats also demonstrated a striking decrease in serum DBH activity between 15 and 60 days of age. Cardiac DBH in Sprague-Dawley rats increased approximately 5-fold from birth to 15 days of age, but failed to decrease thereafter. Salivary gland DBH activity also increased with maturation and failed to decrease. Plasma concentrations of epinephrine and norepinephrine were no different in blood samples obtained from Sprague-Dawley rats 15 and 60 days of age. This finding makes it less likely that the decrease in serum DBH activity with maturation represents a decrease in the functional activity of sympathetic nerve terminals. Antibodies against DBH were used to measure immunoreactive DBH protein in serum from rats 15 and 60 days of age. These studies demonstrated a significantly higher enzymatic activity per unit of immunoreactive protein in blood from young rats than in blood from animals 60 days of age. The ratios of enzymatic activity to immunoreactive protein as measured by the quantity of antibody necessary to precipitate 50% of the endogenous serum DBH activity (AD50) were 21.18 +/- 1.04 and 3.83 +/- 0.40 (mean +/- S.E.M.) for blood from animals 15 and 60 days of age, respectively. Among the possible explanations for this observation are included a greater quantity of enzymatically inactive but immunoreactive DBH in blood of adult animals as compared with the blood of young rats, or the existence of a different form of serum DBH in blood of young animals.


Cytotoxic antibodies to cultured melanoma cells in the sera of melanoma patients. By means of the complement-dependent microcytotoxicity test, cytotoxic antibodies to melanoma cells in long-term culture were detected in 34 of 90 sera from melanoma patients. The incidence of cytotoxic antibodies in melanoma patients was significantly greater than in subjects free of malignant disease but not significantly greater than in patients with other types of cancer. The sera were cytolytic to melanoma cells only in conjunction with rabbit complement, and they reacted with the pabel of melanoma cells in a distinct fashion. No association was found between presence of cytotoxic antibodies and the occurrence of metastasis.


Lysis of human normal and sarcoma cells in tissue culture by normal human serum: implications for experiments in human tumor immunology. Sera from 8 of 9 patients with osteogenic sarcoma equally lysed autologous tissue-cultured cells of both skin and osteosarcoma in the presence of complement. Of 155 normal human sera tested, 103 (66%) lysed allogeneic normal ksin in tissue culture. These antibodies appeared more prevalent in younger (96% in ages 11-20 yr) than older (33% in ages 41-50 yr) humans. The presence of these "natural" antibodies against normal and malignant cells growing in tissue culture was possibly directed against components adsorbed to the cells during tissue culture or to "new" cell-surface antigens expressed by these cells grown in tissue culture. These non-tumor-related neoantigens on normal and malignant cells in tissue culture represented a potential source of confusion in studies of the serologic response of humans to tumors.


Characterization of immune responses to spontaneous hamster lymphomas. Tumor resistance could be induced against the transplantation of cell lines derived from spontaneous lymphomas that occurred in the third of three lymphoma epizootics in a hamster colony. Immunization of normal hamsters with irradiated lymphoma cells promoted resistance to homologous lymphoma challenge and prevented the development of spontaneous lymphomas when immunized hamsters were exposed to the contaminated colony. This immunity could be transferred in an adoptive transfer assay. Resistance to direct challenge was not extended to simian virus 40(SV40)-induced sarcomas carrying SV40 tumor-specific transplantation antigen nor to herpesvirus-induced carcinoma cells, indicating specificity. The nature of the antigen(s) involved was discussed.


Serologic identification of multiple tumor-associated antigens on murine sarcomas. The humoral immune response to two transplanted chemically induced murine sarcomas (MCA-2 and MCA-3) was studied in C57BL/6N mice. These tumors were immunogenic as evidenced by tumor amputation and rechallenge experiments, and no cross-reactivity between them was observed in in vivo challenge experiments. Utilizing a complement-dependent microcytotoxicity assay, we detected antibody to both MCA-2 and MCA-3 in the sera of animals bearing MCA-3 as well as after tumor removal. The sera of animals hyperimmunized to MCA-3 (MCA-3HI) was also cytotoxic in high titer to both MCA-2 and MCA-3 (50% cytotoxicity titers of 1:80 and 1:320, respectively). Sequential absorptions of sera from animals bearing MCA-3 and MCA-3HI sera with fresh MCA-2 cells completely removed activity against MCA-2 but retained reactivity to MCA-3. Sequential absorptions with fresh MCA-3 cells produced stepwise reductions of activity against both tumors, whereas absorption with normal cells produced no loss of activity against either tumor. Thus both specific and cross-reactive antigens were expressed on the surfaces of MCA-3 cells. Only the specific tumor antigen appeared to be involved in in vivo protection against tumor challenge.


Effect of camptothecin and adriamycin on bleomycin-induced tritiated thymidine triphosphate incorporation in a rat nuclear system. We investigated the effect of camptothecin and adriamycin on [3H]TTP incorporation and bleomycin-stimulated [3H]TTP incorporation in host liver and hepatoma nuclei of rats. Camptothecin neither stimulated nor inhibited incorporation in the regular nuclear incorporating system. Bleomycin stimulated incorporation to a much greater extent in host liver nuclei and slow-growing hepatomas than it did in the fast-growing hepatoma 7777. Addition of camptothecin to bleomycin stimulated incorporation of [3H]TTP even further. This camptothecin stimulation was slightly greater in hepatoma nuclei than it was in host liver nuclei. Adriamycin inhibited [3H]TTP incorporation in the regular system as well as the bleomycin-induced incorporation. Hepatoma nuclei were more sensitive to this inhibition than were host liver nuclei. Sucrose density gradients indicated that camptothecin caused DNA strand scissions in addition to those produced by bleomycin. Camptothecin alone produced some single-strand but no double-strand scissions. The action of bleomycin was dependent on sulfhydryl-reducing agents. Camptothecin could partially substitute for this requirement. Adriamycin did not produce DNA breaks as determined by neutral or alkaline sucrose density gradients. Despite complete inhibition of bleomycin-induced [3H]TTP incorporation, adriamycin did not prevent bleomycin-induced DNA breaks. The inhibitory effect of adriamycin might have been on the repair system.


Antigenic changes of DBA/2J mastocytoma cells when grown in the BALB/c mouse. A 10-day growth period of the DBA/2J strain-specific P815-X2 mastocytoma in the BALB/c mouse altered the antigenicity of the tumor cell surface. The in vivo-modified mastocytoma cells differed from mastocytoma cells grown in the original DBA/2J mice in suspectibility to lysis by immune peritoneal exudate cells, in vitro antigenic recognition by cytotoxic T-cells, and immunizing capacity in allogeneic C57BL/6 mice. Propagation of the altered tumor cells in the original host or maintenance in tissue culture for 40 hours restored complete susceptibility to lymphocyte-mediated cytotoxicity.


Expression of Mason-Pfizer and simian type C viruses in the presence of 5-iododeoxyuridine and dexamethasone. Production of infectious Mason-Pfizer monkey virus (M-PMV) was enhanced after treatment of the CMMT cell line with 2.5 x 10(-5) M dexamethasone phosphate (DXM). The reverse transcriptase (RT) activity and infectivity titers of treated culture fluids were enhanced by five- and tenfold, respectively. Along with stimulation of M-PMV synthesis, a simian type C virus (SCV) was also detected by electron microscopic and RT analyses. The SCV was serologically related to the endogenous baboon type C virus. 5-iododeoxyuridine (IUDR) also activated the SCV in the CMMT cell line while significantly inhibiting the production of infectious M-PMV. The activation of endogenous SCV by IUDR or DXM was transitory, since removal of these compounds from the growth medium resulted in the disappearance of SCV buds and the related RT activity; however, low levels of specific viral structural proteins continued to be synthesized intracellularly. Similarly, the enhancement of M-PMV production seen with DXM was lost when the treated cells were subcultured for 2 weeks in the absence of the hormone.


Yolk sac carcinoma grown from rat egg cylinders. Eight-day rat egg cylinders transplanted in toto under the kidney capsules of adult histocompatible recipients gave rise to small nodules composed of parietal yolk sac cells surrounded by Reichert's membrane-like material. These yolk sac cells could grow and give rise to malignant, transplantable tumors identical to mouse yolk sac carcinomas derived from teratocarcinoma. The sera of rats with yolk sac tumors contained elevated concentrations of alpha1 fetoprotein.


[Prostatic adenomectomy with forced diuresis considerations based upon 100 cases (author's transl)]. The method of forced diuresis by furosedium after adenomectomy is an effective method which decreases the postoperative complications of such surgery (haemorrhage, infection, etc.) and reduces the time of hospitalisation.


New procedure for the direct analysis of in vitro reverse transcription of Rous sarcoma virus RNA. Based on the observation that in vitro transcription of Rous sarcoma virus (RSV) RNA by avian myeloblastosis virus DNA polymerase renders the RNA PROGRESSIVELY MORE SENSITIVE TO Escherichia coli RNase H digestion, a new procedure for the in situ analysis of this process has been developed. In vitro transcription products of 32P-labeled RSV RNA are first treated with RNase H, the resistant fraction is then digested to completion with RNase T1, and the oligonucleotides are analyzed by a fingerprint technique. By using the established order of these oligonucleotides along the RNA molecule, a comparison of the yields of each oligonucleotide, before and after transcription, allows qualitative and quantitative in situ analyses of the transcription process. Using this new procedure, we find that upon transcription of purified RSV RNA, DNA synthesis occurs mainly at three sites, one near the 5' end and two near the center of the subunit RNA molecule, and that most of these RNA molecules are competent templates for limited transcription at these specific sites. We also show that purified RSV 70S RNA contains a low-molecular-weight DNA hybridized to a nucleotide sequence near the center of the subunit molecule. Furthermore , we find that the low-molecular-weight nucleic acid fraction extracted from purified RSV virions contains DNA that can hybridize to RSV 70S RNA and that the virion DNA in such hybrids can function as a primer for an extensive in vitro reverse transcription.


RNA-dependent DNA polymerase associated with equine infectious anemia virus. Equine infectious anemia (EIAV) is shown to have an associated RNA-instructed DNA polymerase similar in its cofactor requirements and reaction conditions to the RNA tumor virus DNA polymerases. Demonstrating this DNA polymerase activity requires a critical concentration of a nonionic detergent, all four deoxyribonucleoside triphosphates, and a divalent metal ion. The reaction is sensitive to RNase, and a substantial fraction of the FNA synthesized is complementary to viral RNA. The detection of a complex of tritium-labeled polymerase product DNA-template RNA, which sedimented at 60S to 70S, provided evidence that EIAV contains high-molecular-weight RNA. These results, obtained with both virus propagated in cell culture and virus from the serum of an experimentally infected horse, indicate that EIAV may properly be considered a member of the family Retroviridae. They may also be pertinent to the mechanism(s) of viral persistence and periodic recrudescence of disease in chronically infected horses.


Antigens of Pichinde virus I. Relationship of soluble antigens derived from infected BHK-21 cells to the structural components of the virion. Antigens detected by the complement-fixation (CF) test were prepared from BHK-21 cells infected with Pichinde virus. The preparations contained two antigens demonstrable by immunodiffusion. The antigen present in abundance was heat stable, Pronase resistant, and had a molecular weight of 20,000 to 30,000 as estimated by gel filtration. Polyacrylamide gel electrophoresis of purified antigen demonstrated two low-molecular-weight polypeptides. An identical antigenic determinant was found by disrupting purified virus with Nonidet P-40; however, none of the viral polypeptides co-migrated with the polypeptides derived from purified CF antigen. Pronase digestion of disrupted virus did not alter antigenicity but degraded the viral peptides to sizes similar to those associated with the major CF antigen. These observations suggest that the major CF antigen of Pichnide virus is a cleavage product of the structural proteins of the virus.


RNase H and RNA-directed DNA polymerase: associated enzymatic activities of murine mammary tumor virus. The RNA-directed DNA polymerase of murine mammary tumor virus, a type B RNA tumor virus, was purified sequentially through DEAE-cellulose, phosphocellulose (step gradient), and phosphocellulose (linear salt gradient) chromatography followed by glycerol sedimentation centrifugation. During all stages of purification, coincident peaks of RNA-directed DNA polymerase activity, templated by polyribocytidylate-oligodeoxyguanidylate, and RNase H digestion of [3H]polyriboadenylate-polydeoxythymidylate were observed, and both enzymatic activities displayed a cation preference for magnesium. Under conditions that removed adventitiously associated nucleases, RNase H activity was found to co-purify with polymerase. The specificity of this nuclease was assayed with various prepared substrates, which indicated that the polymerase-associated RNase H activity was directed only against the RNA strand of an RNA-DNA hybrid. It is highly probable that RNase H (RNA-DNA hybrid: ribonucleotide-hydrolase, EC 3.1.4..34) and RNA-directed DNA polymerase of type B viruses are associated enzymatic activities analogous to those observed for avian and mammalian type C RNA tumor viruses.


Specific inhibition of DNA polymerase-associated RNase H by DNA. The RNase H activity associated with several RNA-directed DNA polymerases is inhibited by the addition of DNA, in contrast to RNase H activity from enzymes devoid of polymerizing activity. Kinetic investigations of the inhibitory effect of DNA, using purified Rauscher leukemia virus DNA polymerase as a test enzyme, revealed that the addition of DNA to an ongoing RNase H reaction causes an immediate cessation of RNase H activity. Concomitant initiation of DNA synthesis by inhibitory DNA can occur, provided that appropriate substrate and primer is available. Thus, in addition to providing a simple test for the distinction between polymerase-associated and polymerase-independent RNase H activity, this study strongly supports the concepts that (i) RNase H activity expressed by several mammalian oncoviral reverse transcriptases is an integral part of that molecule, and (ii) that the catalytic site of RNase H activity is also involuved in template-primer binding.


Viral proteins expressed on the surface of murine leukemia cells. Leukemic cells of AKR mice contain as constituents of their membranes the murine leukemia virus envelope protein gp70 and the precursor polyprotein of the viral internal (core) structural proteins. Both gp70 and the core polyprotein are represented on the cell surface as glycoproteins, as evidenced by incorporation of [3H]glucosamine into their structure and the binding of these proteins to lectins. The glycosylated core polyprotein exists in at least two serologically distinguishable forms: the 95,000-dalton polyprotein reacts with antisera prepared against the viral proteins p30, p12, and p10, whereas the 85,000-dalton polyprotein reacts with antisera prepared against the viral proteins p30 and p12, but not p10. Additional heterogeneity in these cell surface polyproteins has been observed wtih leukemias induced by exogenous leukemia viruses. Spontaneous leukemia cells of AKR mice invariably express gp70 and the core polyprotein on their cell surface; normal thymocytes of young AKR mice express gp70, but not the core polyprotein on their surface.


In vitro transcription of theavian oncornavirus genome by the RNA-directed DNA polymerase: analysis of DNA transcripts synthesized in reconstructed enzymatic reactions. We have analyzed the DNA products synthesized in vitro in reconstructed reactions containing purified avian oncornavirus genome RNA and RNA-directed DNA polymerase. The results of these studies indicate that: (i) the initial DNA product synthesized on either 70S RNA or reconstituted 35S RNA-tRNAtrp template - primer complexes in the presence of low concentrations of deoxynucleoside triphosphates consists of several discrete size classes, none of which exceed 200 nucleotides in length; (ii) large DNA transcripts (about 2,000 nucleotides) can be synthesized on both 70S RNA and the 35S RNA - tRNAtrp complex by increasing the deoxynucleoside triphosphate concentration; and (iii) DNA synthesized by detergent-disrupted virus is considerably longer than DNA synthesized in reconstructed reactions.


The diagnosis of bladder tumors by concentration of epithelial cells in the urine and by the help of the fluorescence property of tetracycline. Positive results were obtained in epithelial concentrations when tetracycline was given to 50 patients with bladder tumors. The diagnosis of bladder tumors with epithelial concentration is especially helpful in patients with hematuria and pyuria. With this technique many epithelial cells radiate a bright yellow fluorescence.


Some endocrine aspects of the thymus gland. In studies of the mouse thymus, lymphocyte mitoses are seen to be most frequent in the thymus cortex. There is evidence from thymic grafts that a hypothetical factor, thymopoietin, may stimulate mitosis of thymic lymphocytes. It is a factor which is postulated to act in conjunction with the PAS-positive mesenchymal reticular cells and epithelial reticular cells of the cortex. The thymus medulla is necessary for the integrity of thymic grafts, and may also elaborate a secretion for maintaining the cellular functions of the gland. Thymectomy has been used as a gauge for judging normal thymic function and results, in the mouse, in lymphopenia, degeneration of spleen and lymph nodes, delayed rejection of skin allografts, reduced ability of spleen cells to mount the graft versus host reaction, and reduced primary immune response to certain antigens. Correction of these deficiencies offers a means of evaluating various thymic extracts and grafts. Lymphocytosis-stimulating hormone (LSH) is known to maintain the peripheral lymphoid organs and cause lymphocytosis in the thymectomized animal. Diffusion chamber studies of thymic grafts also show restored lymphoid tissue by a cell-free factor (CIF). These two factors may be the same and probably represent the basis of the highly purified lymphocyte-stimulating proteins, LSHr and LSHh, which restore the L/P ratio in thymectomized animals and may stimulate lymphopoiesis in spleen and lymph nodes. LSHr, unlike LSHh, increases the total lymphocyte count. LSHr has been found to increase the humoral antibody response in neonatal mice both by the PFC technique and by direct hemolysis of sheep erythrocytes. Homeostatic thymic hormone (HTH) is a thymic extract of small molecular weight and contains nucleic acid. In the thymectomized guinea pig it has been found to maintain normal levels of lymphocytes in the blood, spleen and lymph nodes, to restore antibody titers to typhoid H antigen and to restore the toxic allergic reaction. Thymic humoral factor (THF) is of smaller molecular weight (less than 1,000) and probably is not a protein. It also enhances lymphoid proliferation in neonatally thymectomized mice. There is evidence that THF participates in humoral antibody formation because it stimulates PFC formation from neonatally thymectomized mice after inoculation with sheep erythrocytes. Its effects on cell-mediated immunity are seen from findings that injection of THF restores the ability of thymectomized mice to reject skin allografts. THF enables spleen cells from thymectomized or neonatal animals to mount the graft versus host reaction, and causes maturation of bone marrow cells and spleen or lymph node cells so that they can participate in the graft versus host reaction. It has been reported to stimulate lymphocytes to kill isogeneic tumor cells in vitro. Thymosin is protein extracted from the thymus. It has been found to alleviate leukopenia slightly and provide some improvement in lymphoid histology in thymectomized mice...


[Comparison of antiarrhythmic and chronotropic effect of obsidan and isoptine in extrasystole]. The rhythmographic technique was used to study the antiarrthythmic and chromotropic effect of intravenous injections of 10 mg of Obsidan (105 patients), of 10 mg of Isoptine (105 patients), and of oral administrations of 120 mg/day of Obsidan (160 patients) and Isoptine (128 patients). All patients demonstrated persistent extrasystole of different genesis against the background of the sinus rhythm. With intravenous injections the antiarrhythmic effect of Obsidan at rest did not differ from that of Isoptine. Under physical exercises Obsidan tended to display a more powerful negative bathmotropic effect. With the oral route of administration Obsidan was more effective both at rest, and under exercises. It produced a distinct negative chromotropic effect, while Isoptine displayed a biphasic effect. The results of automatic detection of the classes of the antiarrhythmic effect of Obsidan as judged by the dynamics of the sinus rhythm characteristics permit to suggest the possibility of using the later for an individual selection of the therapeutic means for extrasystole.


[Incidence and characteristics of cardiac rhythm disorders after myocardial infarct]. In the course of 1 year 130 patients were examined who had survived myocardial infarction and were alive 2 months after the onset of the disease and were included into the Myocardial Infarction Registry. After 2,3,6,9 and 12 months ECG of various duration was recorded. The prolongation of ECG recording permits to give a more precise characteristics of the incidence and nature of the rhythm disorders observed in chronic ischaemic heart disease patients. Repeated heart rhythm examinations at rest during 1 hour, or during physical exercises (bicycle test) permitted to reveal rhythm disorders in 72.2--66.7% of the patients, and among them ventricular extrasystole in 62.6--66.7% of those examined, respectively. The appearance of ventricular extrasystoles correlates with the state of the patients surviving myocardial infarction A higher incidence of ventricular extrasystoles is observed in pateints with distinct tecg changes, with angina pectoris and elevated blood pressure (larger than or equal to140/90mm Hg).


[Myocardial infarct repair in the light of clinico-biochemical and morphological studies]. To develop intravital criteria of the reperative processes following myocardial infarction, clinical, biochemical and morphological parallels were traced in 62 patients dying of myocardial infarction after different periods following the onset of the disease. It was demonstrated that a set of laboratory techniques (examinations of haptoglobin, chloridesoluble mucoprotein, of heterogeneity of mucoprotein, v2-macroglobulin) helps in the evaluation of the severity of the inflammatory and macrophagel reactions in the paranecrotic zone. A useful intravital sign of the formation of a postinfarction scar is provided by the examination of collagen metabolites--oxyproline bound with collagen-like plasma protein and free serum oxyproline and urine excretion of total oxyproline. The obtained data can be used for the development of a rehabilitation programme, differentiated therapy in various groups of patients.


[Localization of plasma proteins and beta-lipoproteins in the walls of arteriosclerotic coronary arteries]. Immunofluorescent analysis was used to study the topography of plasma proteins and beta-lipoproteins in the wall of human coronary arteries in cases of atherosclerosis. The dynamics of protein fractions deposits is not uniform in the process of the formation of the disease. Along with the progress of atherosclerosis, the infiltration of proteins, lipoproteins and lipids is increasing. A regular combination of beta-lipoproteins and gamma-globulin localizations was established. The role of the examined components in the wall of the coronary arteries and their participation in the formation of atherosclerotic plaques is discussed.


[Indices of lipid metabolism, thyroid gland and adrenal cortical function in prolonged stress of the central nervous system in chronic stimulation of the adrenals]. The experiments were conducted in 14 male rabbits dynamically on the 5th, 10th, 20th, 30th, 40th, 60th and 80th day of the central nervous system tension or at rest, including the studies of lipid metabolism (total cholesterol and beta-lipoproteins content), the function of the thyroid gland (protein bound iodine content) and the function of the adrenal cortex (11-OCS content). Such lasting stimulation of the adrenal cortex was found to be accompanied by hypercholesterolemia, hyper-beta-lipoproteinemia, elevated 11-OCS level and lack of thyroid function changes. A lasting tension of the central nervous system against the background of chronic stimulation of the adrenals delays the development of hypercholesterolemia and hyper-beta-lipoproteinemia, reduces the function of the thyroid gland, and increases the function of the adrenal cortex. The observed shifts in the lipid metabolism may be of atherogenic importance. The obtained data may be useful for the study of the pathogenesis of hormonal shifts in atherosclerosis.


[Accelerated idioventricular rhythm in acute myocardial infarct]. A continuous (for 24 hours) ECG recording on a magnetic tape with its subsequent decodification on a special analyser was performed in 31 patients with acute myocardial infarction during the 1st day of the onset of the disease in order to reveal an accelerated idioventricular rhythm and ventricular tachycardia. An accelerated idioventricular rhythm was found to occur within the 1st and early during the 2nd day of the disease in 29% of the patients. The importance of some factors, that of the sinus rhythm rate in particular, was studied with reference to the development of an accelerated idioventricular rhythm. The causes of its development are discussed, as well as those of its disappearance, interrelationship with ventricular tachycardia, and the prognostic importance of the accelerated idioventricular rhythm recorded throughout a 3-month observation and its place in the differential diagnosis in acute myocardial infarction.


A communication system for the severely dysarthric speaker with an intact language system. Two severely dysarthric speakers who had previously spelled entire messages on an alphabet board were taught a system in which they pointed to the first letter of each word as they spoke. Rate and intelligibility of speech produced with (aided) and without (unaided) the communication system were judged by observers who viewed videotaped samples. The rate of aided and unaided speech was markedly faster than spelling the entire message. Aided speech was slower but more intelligible than unaided speech. Further analysis revealed that intelligibility was influenced by at least two factors: (1) rate and (2) information provided by the identification of the first letter of each word. For one speaker both factors contributed to increased intelligibility, while for the other speaker only initial letter information appeared to influence intelligibility.


A relative change index in evaluating alcoholism treatment outcome. A technique for computing a relative change index for evaluating an alcoholic's progress is presented and contrasted with less satisfactory methods of comparing data from patient intake and follow-up interviews. Applicability of the index to other treatment groups is discussed.


1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. 1-Deamino-8-d-arginine vasopressin (D.D.A.V.P.) infusion causes a marked increase in factor-VIII (antihaemophilic-factor)-related properties in patients with moderate and mild haemophilia and von Willebrand's disease (vWd). The possibility was therefore evaluated that such an autologous factor-VII response might be haemostatically effective, allowing patients to undergo surgery without plasma concentrates. 0.3 microng/kg of D.D.A.V.P. given before dental surgery and repeated in the early postoperative period was followed by a two to three fold rise in factor-VIII coagulant activity (VII C.A.) in four patients with moderate and mild haemophilia. In two, there was no abnormal bleeding after dental extraction, whereas plasma concentrates were necessary to control oozing from the sockets in the remaining two patients. A higher D.D.A.V.P. dosage (0.4-0.5 microng/kg) in patients with higherstarting VII C.A. (9% or more) was followed by a more marked response (four to six fold). VII C.A. levels up to 100% of average normal were achieved and dental extraction and major surgery (such as cholecystectomy, thoracotomy, and two tonsillectomies) were carried out successfullly in six patients with mild haemophilis and in two with vWd. The mean half-life of autologous VII C.A. was 9.4 h (range 7.5-11.6). Plasma and urine osmolality showed no consistent variation after drug administration. Thus D.D.A.V.P. appears a promision pharmacological alternative to plasma concentrates in the management of some patients with haemophilis and vWd.


Ultrasonography in the management of haemophilia. Ultrasonography was used to demonstrate retroperitioneal haemorrhages and intramuscular haematoma in three patients with antibodies to factor VIII and one with von Willebrand's disease in whom major bleeding episodes occurred. Scans were useful in demonstrating the presence, location, size and regression of haemorrhages.


Influence of previous blood-transfusion on incidence of pre-eclampsia. The incidence of pre-eclampsia in 125 primigravidas who had previously received blood-transfusions was significantly less than in a matched series of controls--i.e., 12.8% compared with 23.2%. This suggests that immunological factors may be involved in the aetiology of pre-eclampsia.


Clonal priming of human lymphocytes: Specificity and cross-reactivity of cellular immune reactions. Clonal priming in response to chemical and microbial antigens which defines the specificity of cellular immune reactions, was demonstrated by culture techniques. Human leucocyte cultures stimulated with specific antigens typically show peak levels of D.N.A. synthesis after 5 to 7 days in culture. Such primary leucocyte cultures were incubated for 10-20 days, then the cells were gently centrifuged and resuspended in fresh RPMI 1640 with 20% plasma. These secondary or primed cultures typically showed less than 1000 c.p.m. after 48 hours. However, if the original antigenic stimulant was added, specific accelerated responses were seen by 48 hours in the secondary cultures. Lymphocyte clones in these sceondary cultures primed with dinitrophenylated (D.N.P.) antigens (from subjects sensitised to dinitrochlorobenzene) showed enhanced D.N.A. sythesis in response to the same dinitrophenylated antigens and showed varible accelerated responses to related chemically modified antigens. However, D.N.P.-activated clones in these secondary cultures did not show enhanced responses to microbial antigens even though the lymphocytes had been highly responsive to tetanus toxoid and other microbial antigens in primary cultures. The specificity of this clonal activation was further demonstrated by the enhanced response of secondary cultures of tetanus-toxoid-activated clones to tetanus toxoid but not to dinitrophenylated antigens. The abiltty to detect specificity and cross-reactivity of cellular immune reaction has broad implications for investigations of cellular immunity as well as many potential applications in the diagnosis and understanding the patogenesis of inflammatory and neoplastic diseases in which cellular immune discrimination may be involved.


Aspects of coma after severe head injury. Features of coma during the first week after sever head injury  were analysed in 700 patients. Coma is best defined as inability to obey commands, to speak, or to open the eyes. If eye opening is omitted from the definition then some less severly affected patients will be included in the early stages, the duration of coma will be overestimated, and in the later stages the distiction between coma and other unresponsive states may be blurred. Other features which correlate with responsiveness (as judged by motor response, speech, and eye opening) are pupil reactions and eye movements; respiratory abnormalities are less common and less closely related to other aspects of severity. A rigorous fefinition of coma is necessary for valid commparisons between individual patients and between different series of patients with head injury. This is essential for the assessment of alternative management regimens and for establishing predictive criteria.


Serum thyroglobulin and recurrent thyroid cancer. Many thyroid malignancies are sufficiently differentiated to produce thyroglobulin both in situ and in perpipheral blood. Since patients who have undergone total thyroidectomy for malegnancy should not have normally circulating thyroglobulin, their serum thyroglobulin may provide a simple and specific tumour marker for recurrent disease. Of 30 such athyroid patients who were studied, all of the 20 patients who were disease-free ten years  after thyroidectomy had minimal (less than15 ng/ml) serum-thyroglobulin levels while all of 10 patients with recurrences had raised levels (greater than 90 ng/ml). Controls ranged from 0 to 60 ng/ml. This assay should prove valuable in following patients who have undergone total thyroidectomy for recurrent thyroid malignancy.


Coxsackie virus infection in acute myocardial infarction. Of 38 patients with a clinical diagnosis of acute myocardial infarction 10 had serologial evidence of recent Coxsackie B virus infection.


Effect of feeding habit on weight in infancy. A population study of 758 infants born at the same hospital showed that weight at the ages of six week and six months was not significantly related to breast or bottle feeding, the early introduction of solids, or the sodium content of bottle feeds. Weight at six weeks was related to the volume and energy content of the feeds which were examined in those bobies that were bottle-fed alone. Although analysis of a single feed showed that mothers mixed feeds incorrectly, there was no evidence that mixing of overstrength feeds leads to obesity.


Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases. Data from 30 fatal cases of dextropropoxphene poisoning occurring in Northern Ireland over three years have been studied. All the victims had ingested more than therapeutic amounts, and many had also taken alcohol or other drugs. Most of the deaths were probably suicides. Death occurred very rapidly suggesting that the narcotic effects of dextropropoxyphene predominated, and this may explain the scarcity of clinical reports, It is suggested that many doctors are unaware of the danger of dextropropoxyphene in overdosage and that the problem of dextropropoxyphene poisoning in the United Kingdom has not been fully appreciated. This supposition, if correct, highlights the absence of a satisfactory early-warning system for serious drug effects including death.


Aetiology of acute epididymitis.

Aetiology of acute epididymitis. 24 patients with acute epididymitis were examined and underwent urethral and urine cultures for Neisseria gonorrhoeae, Ureaplasma urealyticum, herpes-simplex virus, Chlamydia trachomatis, cytomegalovirus, and gram-negative aerobic bacteria. The results suggest that in young men the sexually transmitted organisms which cause urethritis (N. gonorrhoeae, C. trachomatis, and possibly U. urealyticum) may also lead to acute epididymitis, whereas in older men coliforms and Pseudomonas are the predominant causes of epididymitis.


Platelet activation in acute cerebral ischaemia. Serial measurements of platelet function in cerebrovascular disease. Circulating platelet aggregates formed in vivo were serially measured, and platelet-aggregation thresholds were determined in vitro in 82 patients with acute cerebral ischaemia. The percentage of aggregated platelets was increased in 53 patients with completed stroke (30.9% +/- 2.0) and in 29 patients with transient ischaemic attacks (34.1% +/- 2.3), all studied within 10 days of the acute event. These values were higher (P less than 0.001) than levels of aggregated platelets in 30 patients with non-vascular neurological disease (16.8% +/- 2.3). The percentage of aggregated platelets returned to normal 10 days to 6 wk after acute cerebral ischaemia. Aspirin and dipyridamole did not affect either the increase in or subsequent normalisation of circulating-platelet-aggregate levels in these patients. Platelet-aggregation sensitivity to adenosine diphosphate and adrenaline was also increased in patients with acute cerebral ischaemia, but this abnormally resolved during convalescence. Platelet activation is abnormal in acute cerebral ischaemia but usually returns to normal with or without anti-platelet therapy. This activation of platelets may contribute to the clinical manifestations of occlusive vascular disease.


Antiarrhythmic action of lignocaine in early myocardial infarction. Plasma levels after combined intramuscular and intravenous administration. In an attempt to find a regimen suitable for pre-hospital prevention of arrhythmias following myocardial infarction, the antiarrhythmic and pharmacokinetic effects of combining intravenous and intramuscular lignocaine have been studied. In nine patients with acute myocardial infarction, 100 mg of lignocaine was administered intravenously and 300 mg into the deltoid muscle. The antiarrhythmic effect was observed by continuous tape monitoring of the patients' rhythm before and after treatment. Plasma levels above 2 microng/ml were achieved within 1 min and maintained for 1 h in all patients; in seven this level was maintained for 2 h. A marked reduction in the occurrence of ventricular ectopic beats was observed in the first 15 min after treatment and was maintained for 90 min, but a significant effect was still present at 3 h. No serious side-effects were noted.


Serum-25-hydroxyvitamin-D concentrations in adolescent boys. In March, 1976, vitamin-D status was investigated in 256 thirteen-year-old school boys of Asian, West Indian, andEuropean origin in Birmingham. Serum-25-hydroxyvitamin-D3 (25-OHD3) concentrations in 78% of the 124 Asian boys resembled those found in rickets and osteomalacia. Serum-25-OHD3 concentrations were also low in a few West Indian and European children. Dietary intake of vitamin D and exposure to sunlight were similar in each group. Serum-parathormone concentrations were increased in many children with low serum-25-OHD3. Reinvestigation in October, 1976, of a group of children whose serum-25-OHD, concentration had been less than 8 microng/l in March, 1976, showed pronounced improvement in all, but some still had concentrations which indicated a possible deficiency. It is suggested that the high frequency of vitamin-D deficiency in Asian adolescents would be much reduced if 1 mg of vitamin D3 was given orally each school term during adolescence.


Ocular involvement in leukaemia. Report of three cases. Three patients with treated acute lymphoblastic leukaemia acquired visual symptoms believed to be caused by ocular infiltration by malignant cells. All three patients had other evidence of systemic disease including bone-marrow involvement at the time. One patient had a previous history of meningeal leukaemia and none had received "prophylactic" cranial irradiation. The ophthalmoscopic appearances were similar in each case and were thought to have been caused by obstruction of axoplasmic flow associated with infiltration of the optic nerve by neoplastic cells. The three patients were treated by local irradiation and two also received intrathecal chemotherapy. Response to treatment was variable but the use of radiotherapy combined with intrathecal cytoxic drugs is probably the best available approach.


A controlled trial of D-penicillamine therapy in primary biliary cirrhosis. D-penicillamine, 900 mg daily, was used in a randomised controlled trial for treatment of patients with primary biliary cirrhosis. 19 patients received D-penicillamine and 13 received placebo. The two groups were similar in age, duration of illness, liver function tests, and liver histology. Before entry into the trial liver-copper concentration was raised in 25 of the 27 patients in whom it was measured. After three months patients taking D-penicillamine showed a significant reduction in serum-aspartate-transaminase concentrations compared with the placebo group, and this reduction seemed to be sustained. In the 4 patients on D-penicillamine for a year, a second liver biopsy showed that mean liver-copper concentration fell from 310 +/- 128 (S.E.M.) to 84 +/- 36 microng/g dry liver, compared with a reduction from 511 +/- 169 to 454 +/- 128 in the 7 patients in the placebo group in whom serial liver-copper measurements were available. Liver histology demonstrated a comparative improvement in cholestasis in patients on penicillamine, but the degree of inflammation, necrosis, and the histological stage of disease remained similar in both groups. In 5 of the 19 patients in the D-penicillamine group the drug was discontinued because of side-effects. D-penicillamine seems to be a promising treatment for patients with primary biliary cirrhosis. It may produce its effect by reducing liver-copper concentration.


Depressed lymphocyte function after bereavement. During 1975 twenty-six bereaved spouses took part in a detailed prospective investigation of the effects of severe stress on the immune system. T and B cell numbers and function, and hormone concentrations were studied approximately 2 weeks after bereavement and 6 weeks thereafter. The response to phytohaemagglutinin was significantly depressed in the bereaved group on the second occasion, as was the response to concanavalin A at 6 weeks. There was no difference in T and B cell numbers, protein concentrations, the presence of autoantibodies and delayed hypersensitivity, and in cortisol, prolactin, growth hormone, and thyroid hormone assays between the bereaved group and the controls. This is the first time severe psychological stress has been shown to produce a measurable abnormality in immune function which is not obviously caused by hormonal changes.


Day-case surgery for hernias and haemorrhoids. A clinical, social, and economic evaluation. Patients with inguinal hernia or haemorrhoids were randomly allocated to an experimental group expected to stay in hospital for only eight hours after surgery or a control group scheduled for discharge on the fifth or sixth day. There was no difference in clinical outcome between the two groups of hernia patients. However, complications were twice as common in haemorrhoid day-patients as in long-stay haemorhoid patients. The standard postoperative regimen for haemorrhoids has since been changed and the change has been accompanied by a fall in the complication-rate. Day-case surgery appears to have similar social effects on the patient and his family as traditional hospital care. There was no significant difference in either the additional expenditure incurred or patients' perceptions of the disruption associated with their operation and convalescence. In the hospital under study, day-case surgery was saving between 20 pounds and 29 pounds per patient. However, this conclusion should not be extrapolated to the N.H.S. as a whole without taking into account the use to which the resources released by day-case surgery will be put.


Short-stay surgery for inguinal hernia. Clinical outcome of the Shouldice operation. In 1970 a general surgical team on Teesside adopted the Shouldice operation for inguinal hernia together with a policy of short-stay surgery. Careful follow-up has established that repairs using the suture material of choice--stainless-steel wire--have an estimated 6-year recurrence-rate of 0.8%, statistically indistinguishable from that achieved by the highly specialised Shouldice Clinic. However, the recurrence-rate 2 years after suturing with an alternative polyester-based material is estimated at 8.1%--a figure much more in keeping with rates reported by general surgeons using traditional methods.


Morphology of rapidly adhering amniotic-fluid cells as an aid to the diagnosis of neural-tube defects. In 20 amniotic-fluid samples taken in the second trimester from pregnancies in which the fetus had a neural-tube defect, the proportion of the total viable cell which adhered to glass surfaces after 20 hours in culture ranged from 9 to 100%. In 92 normal amniotic fluids this proportion was less than 6%. Furthermore, the morphology of the rapidly adhering cells was characteristic in spina bifida (8 cases) and anencephaly (12 cases) and distinct from the epithelioid-like cell seen in normal amniotic fluids, including many which were grossly blood-stained. A sample of amniotic fluid from fetal exomphalos and one from a pregnancy in which the placenta had been repeatedly traversed during amniocentesis had proportions of adherent cells in the pathological range, but the morphologies were very different from those seen in neural-tube defects. It is suggested that the techniques described here will be useful adjuncts to amniotic-fluid alpha-fetoprotein determination in the early diagnosis of fetal abnormality, particularly in blood-stained samples.


Importance of abnormal glucose tolerance (hypoglycaemia and hyperglycaemia) in the aetiology of pre-eclampsia. In a series of 794 patients who had glucose tolerance tests done before the onset of pre-eclampsia, both hypoglycaemia (less than 5th percentile) and hyperglycaemia (P less than 95th percentile) had a significant association with early-onset severe pre-eclampsia ( less than 0.05). In the total series of 794 patients, hypoglycaemia had a significant association with low oestriol excretion (p less than 0.01), fetal growth retardation (p less than 0-05), low Apgar score (p less than 0.05), and perinatal mortality (p less than 0.05). These data indicate that, in patients with pre-eclampsia, hypoglycaemia is directly related to the cause of perinatal death.


Kidney transplantatability across a positive cross-match. Cross-match assays and distribution of B lymphocytes in donor tissues. Lymphocyte subpopulations were determined in peripheral blood, abdominal lymph-nodes, and spleens from renal allograft donors. Percentages of B lymphocytes were low in peripheral blood (mean +/- S.E., 10-0 +/- 1-0%), variable in lymph-nodes (28-8 +/- 3-8), and high in spleens (41-4 +/- 2-1). Microlym-phocytotoxicity cross-match assays in which sera with B-cell-specific antibody were used were invariably negative with peripheral-blood lymphocytes but positive with lymph-node or spleen preparations. Four renal allografts were transplanted when the standard cross-match was positive with spleen or lymph-node but negative with blood. No hyperacute or accelerated rejection was observed. Potential recipients are often denied allografts because of a positive cross-match with either lymph-node or splenic preparations, and this could be avoided in some cases if cross-matches were performed on peripheral blood or B-lymphocyte-depleted splenic or lymph-node preparations. These results accord with those of other workers who found that B-cell pre-sensitisation is not a contraindication to transplantation.


Secretin-induced histamine release in duodenal-ulcer patients. Because a majority of duodenal-ulcer patients responded locally to intradermal secretin, skin samples from 7 patients with duodenal ulceration and 6 patients with goitre or cholelithiasis were incubated with "tris" buffer alone and with tris buffer containing 20 C.U./ml synthetic secretin or 100 microng/ml compound 48/80. Skin from duodenal-ulcer patients released significantly more histamine than did that of controls (p less 0-01). Histological examination of skin samples from these patients showed that the number of histamine-containing mast-cells averaged 5-7 per field and dropped to 1-2 per field after incubation with secretin. It is concluded that in a certain type of duodenal ulceration intradermal secretin releases histamine from mast-cells and thus induces a local anaphylactic reaction. This might prove suitable for preclinical ulcer diagnosis and/or for detection of patients at risk of acquiring that disease.


On the cause of raised serum-amylase in diabetic ketoacidosis. 7 of 13 patients with diabetic ketoacidosis had raised serum-amylase concentrations. Isoenzymes analysis by polyacrylamide-gel electrophoresis showed that salivary-type amylases and not pancreatic-type amylases were responsible for the rise in 6 or the 7 cases. This demonstrates that the pancreas is usually not the origin of the increase in serum-amylase. Since salivary-type amylases are widely distributed in glandular epithelium, it is suggested that hyperamylasaemia in diabetic ketoacidosis is most often caused by systemic derangement of carbohydrate metabolism.


Does Gilbert's disease exist?

Does Gilbert's disease exist? 18 454 men and 5471 women attending a screening centre had serum-bilirubin concentrations measured. 2.0% of men and 0.6% of women had concentrations of 25 micronmol/1 (1-5 MG/DL) or above. Both sexes showed skewed distributions for bilirubin concentration, but analysis of the data showed no evidence of bimodality for either sex. This suggests that people who are now diagnosed as having Gilbert's disease may constitute upper end of the normal range rather than a disease state. The term "constitutional hyperbilirubinaemia" is preferable, and its use can be coupled with reassurance to the patient that the condition causes no symptoms.


Raised urinary fibrin-degradation products, complement, and IgG during an influenza-like illness. Urine from eight normal controls in whom an influenza-like illness developed contained high concentrations of fibrin-degradation products (F.D.P.), IgG, and C3. The study was carried out when influenza A was prevalent in the community. However, a wide range of serological investigations revealed no evidence for influenza A or other viruses. The infection may have been caused by other viruses which produce upper-respiratory-tract infections and which are not readily diagnosed by serology. Urinary fibrin-degradation products are a well-known marker of glomerulonephritic activity and viral antigens may have induced an immune-complex glomerulonephritis in the 8 controls in whom an influenza-like disease developed. A larger normal population should be investigated during a virus epidemic.


Schizophrenia as a prostaglandin deficiency disease. Evidence that schizophrenia may be a prostaglandin deficiency disease comes from three main sources: (1) all effective antischizophrenic drugs stimulate prolactin secretion and prolactin is a potent stimulator of prostaglandin synthesis; (2) schizophrenics are resistant to pain and inflammation and are free of rheumatoid arthritis and there is increasing evidence that prostaglandins play important roles in pain, inflammation, and rheumatoid arthritis; (3) high doses of drugs recently shown to be prostaglandin antagonists cause schizophrenia-like syndromes. The hypothesis is not necessarily inconsistent with current transmitter theories of schizophrenia since prostaglandins modify transmitter secretion and action. It does indicate radically new approaches to investigation, treatment, and drug design not suggested by the transmitter concepts.


Juvenile diabetics growing up.

Juvenile diabetics growing up. Investigation of the present state of 45 diabetic children diagnosed in South Warwickshire between 1950 and 1965 disclosed an unexpectedly high mortality and morbidity in this group.


The Tromsø heart-study. High-density lipoprotein and coronary heart-disease: a prospective case-control study. The relationship of future clinical coronary heart-disease (C.H.D.) to the plasma-high-density-lipoprotein (H.D.L.)-cholesterol concentration has been examined in a 2-year case-control follow-up study of 6595 men aged 20-49 years living in the municipality of Tromsø, Norway. Measurements were also made of the cholesterol concentration in lower-density (i.e., density less than 1-603 g/ml) lipoproteins, plasma-triglycerides, systolic and diastolic blood-pressures, relative body-weight, and cigarette consumption. Discriminant-function analysis showed that coronary risk was inversely related to H.D.L.-cholesterol concentration and directly related to density less than 1-063 cholesterol. These relationships were independent of each other and of the other measured variables, which showed no significant differences between the cases and controls. H.D.L. cholesterol made a three-fold greater contribution to the prediction of future C.H.D. than did density less than 1-063 cholesterol in this cohort of young men. These findings support the proposal that a low H.D.L. concentration is a common antecedent of clinical C.H.D. and is important in accelerating the progression of coronary atherosclerosis.


High-density-lipoprotein cholesterol and other serum lipids in a New Zealand biracial adolescent sample. The Wairoa College survey. Among New Zealand adolescents, Maoris have lower serum high-density-lipoprotein cholesterol levels and higher serum triglyceride levels than non-Maoris. Boys have lower high-density-lipoprotein cholesterol and triglyceride levels than girls. Low-density-lipoprotein cholesterol levels do not show sex/race differences. These findings are reflected in an excess of hyperlipidaemia type IV in Maori girls. There may be a relation between these lipid distributions and the excess Maori mortality, especially among females, from ischaemic heart-disease.


Changes in haemostatic system after application of a tourniquet. In 35 patients undergoing routine orthopaedic operations in which occlusive tourniquets were used there was a pronounced rise in fibrinolytic activity in the systemic circulation which lasted for at least 15 minutes after the release of the tourniquet; this response was seen after operations on both arms and legs. In contrast there was no increase in fibrinolytic activity in the systemic circulation associated with venous occlusion. Neither the application of a tourniquet nor venous occlusion resulted in changes in factors V or VIII, fibrinogen, or platelet-count. The application of a completely occlusive tourniquet might be a simple form of prophylaxis against deep-vein thrombosis and would avoid the disadvantages of using heparin.


Enkephalin-like immunoreactivity in the human gastrointestinal tract. Morphine has powerful actions on brain and gut. Peptides with opiate-like actions (endorphins, enkephalins) are known to be normal constituents of the brain and now enkephalin-like immunoreactivity has been shown in the gut. Enkephalin-like immunoreactivity was present in all areas of the gut with particularly high concentration in the antrum and significant amounts in the upper small intestine. Immunocytochemistry on 1 micronm serial sections revealed enkephalin-like immunoreactivity in numerous cells of the antral mucosa, in a few cells of the duodenal mucosa and pancreas, and in the myenteric plexus of the gallbladder, cystic ducts, bileduct, and other areas of the lower intestine. Gastrointestinal physiology appears to be partly regulated by locally acting hormones and enkephalin may be one of these. The established effects of morphine on the alimentary tract provide a clue to the possible physiological role of enkephalin.


Intrathecal antitetanus serum (horse) in the treatment of tetanus. In a two-year study of 322 conservatively treated, consecutive cases of tetanus in a rural hospital (all over twelve months old), intrathecal administration of 200 units of antitetanus serum (A.T.S.) (horse) reduced the overall mortality of 4-5% (5/110) compared with 14-5% (16/111) in the control series. 200 units intrathecal A.T.S. (horse) gave better results than 1500 units A.T.S. (horse). The results with lumbar and cisternal administration did not differ. It is suggested that tetanus is a polysystemic condition requiring polysystemic therapy. A regimen in which intrathecal A.T.S. is given as an adjunct to low-dosage systemic A.T.S., high levels of systemic betamethasone and diazepam, and careful nursing gave results which compare favourably with those of centres with more elaborate equipment and specialised staff.


Effect of dose, time, and ascorbate on iron excretion after subcutaneous desferrioxamine. The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. 750 mg D.F. given over a 12 h period, gave a mean total (30 h) iron excretion of 17-5 mg, which was not statistically different from the mean iron excretion of 21-5 mg when the same dose was delivered over 24 h. 1500 mg D.F. gave a mean urinary iron excretion of 28-1 mg with a 12 h infusion, which was significantly less than the mean iron excretion of 39-6 mg with 24 h infusion. The 1500 mg dose gave a significant increase in iron excretion compared with the 750 mg dose when given by either 12 h or 24 h infusion. 7 of 8 patients, given D.F. over a 12 h period, had increased iron excretion when the dose was increased from 750 to 2000 mg. When the dose was increased to 4000 mg, however, the effect on iron excretion was variable. On the other hand, ascorbic-acid therapy was invariably associated with increased iron excretion after subcutaneous D.F. In twelve studies at different dose levels of D.F., ascorbate therapy was associated with increased iron excretion ranging from 24 to 245%. It is concluded that in most patients with transfusional iron overload subcutaneous D.F over a 12 h period, at a dose ranging from 2 to 4 g daily with ascorbic-acid saturation, is at present the most satisfactory method of removing excess iron.


Seasonal variation in serum-25-hydroxyvitamin-D in the elderly in Britain. In a group of thirty-six non-housebound normal people aged 70 to 88 years living independently in their homes, mean serum-25-hydroxyvitamin-D (+/- 1 S.D.) was 8-62 +/- 3-08 ng/ml in midwinter and had risen to 14-13 +/- 4-90 ng/ml the following September. These values were lower and the seasonal variation was less than previously found in healthy young British adults.


A possible association between house pets and multiple sclerosis. 29 patients with multiple sclerosis (M.S.) from families in New Jersey believed to have more than 1 member with this disease and 29 controls matched for age, sex, neighbourhood, and socio-economic status were questioned about their ownership of pets. No difference in ownership of cats or dogs was found. Exposure to small indoor pets (cats or dogs), however, was significantly higher in the M.S. group (P less than 0-001). Exposure to small indoor pets was particularly striking during the ten years before onset of initial symptoms of M.S. when the M.S. group was compared to the control group (P less than 0.01). 33 of 49 M.S. patients in these families had a cat or dog in the house within one year before onset of the first neurological symptom. 3 families had more than 1 member in whom initial symptoms of M.S. developed in the same year despite wide age ranges. These results suggest that exposure to house pets may sometimes be associated with subsequent M.S. Our findings should be interpreted with caution until they are confirmed by others.


Mortality, morbidity, and resource allocation. The correlation between age and sex standardised mortality-rates, and morbidity-rates from the General Household Survey (G.H.S.) similarly standarised, were examined for the 10 standard statistical regions for 1972 and 1973 combined. The correlations between mortality and acute sickness and between mortality and bed sickness were not significant. A significant correlation was found between mortality and chronic sickness, but not between mortality and work or school absence due to illness or injury in males. It is concluded that, on present evidence, there is some doubt whether mortality can be considered to be a valid indicator of morbidity in a population. Serious consideration should therefore be given to the removal of standarised mortality ratios (S.M.R.S.) from the formula for the distribution of revenue as recommended by the Resource Allocation Working Party (RAWP).


Diagnosis of alcohol ingestion in mild head injuries. 42 per cent of a consecutive series of patients with mild head injuries with concussion were found to have positive blood-alcohol tests. There were errors in the clinical diagnosis of alcohol ingestion among patients with both positive and negative blood-alcohols. Medicolegal questions have so dominated the problems of diagnosing alcohol ingestion as to prevent doctors considering its clinical importance. The value of a laboratory test giving an immediate reading is emphasised.


Seasonal variation of cardiac failure in northern Nigeria. The number of patients with cardiac failure admitted to hospital in Zaria, Nigeria, month by month during 1972-75 differed highly significantly between the cooler dry months and the hot wet months. The reasons are uncertain, but seasonal changes in blood-pressure and the effects of heat on the circulation and of humidity on the efficiency of sweating may be responsible.


Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. 20 out of 179 diabetics treated with oral hypoglycaemic agents (O.H.A.) within 3 mo of diagnosis had pancreatic-islet-cell antibodies (ICAb) in their sera at diagnosis or later. 13 of these 20, compared with only 14 of the remaining 159, subsequently required insulin at a mean follow-up of 2 yr 10 mo and 4 yr 11 mo, respectively (p less than 10(-7)). 5 of the 7 ICAb-positive diabetics still continuing on O.H.A. therapy after a mean follow-up of 4 yr 6 mo required maximum or near-maximum combined oral therapy, while only 34 of the 145 ICAb-negative diabetics continuing on O.H.A. did so at a mean follow-up of 5 yr 4 mo (p less than 0.02). In addition, 81 diabetics treated initially with diet for a mean time of 4 yr 7 mo before going on to O.H.A. therapy were studied. All were ICAb-negative when tested at a mean interval of 6 yr 10 mo from diagnosis. By the end of the mean follow-up period of 10 yr 3 mo, 27 were on combined oral therapy and 3 had been transferred to insulin treatment. ICAb-positive diabetics on O.H.A. had a high prevalence of a personal history of organ-specific autoimmune disease, thyrogastric antibodies, a family history of insulin-dependent diabetes and possibly of HLA-B8 comparable to that in insulin-dependent diabetes and higher than that expected in a control population or in diabetics controlled by diet alone. We believe that ICAb-positive diabetes controlled by O.H.A. is an earlier stage in the same disease process (type-I diabetes) that culminates in insulin-dependency.


Triiodothyronine, T.S.H., and prolactin in obese women. Basal levels of thyroid-stimulating hormone and prolactin and their response to thyrotrophin-releasing hormone are normal in obese women. Serum thyroxine and triiodothyronine are also normal and do not correlate with body-weight in healthy non-dieting women. After jejunoileal bypass, serum-triio-dothyronine levels fall, and this fall appears to depend more on the reduction in calorie intake after the operation than on the reduction in body-weight per se.


Isolation of amyloid P component (protein AP) from normal serum as a calcium-dependent binding protein. The P component of amyloid (protein AP, pentagonal unit) has been isolated from normal serum by using its hitherto undescribed calcium-dependent affinity for agarose. The presence of P component in all forms of amyloid may be due to this calcium-dependent binding to certain polyanions.


Alpha-beta thalassaemia.

Alpha-beta thalassaemia. In a Greek Cypriot family in which genes for both alpha and beta thalassaemias were expressed, haematological and biosynthetic investigations indicated that one family member was homozygous for beta thalassaemia and had alpha-thalassaemia1 trait. The concurrent inheritance of an alpha-thalassaemia gene in the beta-thalassaemia homozygote seemed to have modified his degree of chain imbalance and to have reduced the clinical severity of the disease.


Migraine and the blood-brain barrier.

Migraine and the blood-brain barrier. The prodromal (cerebral) symptoms of migraine are associated with a fall in cerebral blood-flow (C.B.F.). The suggestion that various circulating vasoactive agents might be the cause of this fall in C.B.F. ignores the contradictory findings that the cerebral vascular bed is normally unresponsive to such agents; but if the blood-barrier is disrupted, systemically administered monoamines and prostaglandins elicit pronounced changes in cerebral-tissue perfusion and metabolism. A defect in the blood-brain barrier of migraine patients (particularly those in whom an item of diet may trigger an attack) would make the cerebral circulation vulnerable to variations in circulating levels of vasoactive substances. Alternatively, the barrier could be intact in non-dietary patients, but release of monoamines or prostaglandins from the brain itself could account for the observed changes in the cerebral circulation.


Hospital outbreak of clostridium perfringens food-poisoning. An outbreak of Clostridium perfringens (C.welchii) food-poisoning affected a third of the patients in a large hospital, and one frail patient died. C.perfringens type A, serotype 1, was isolated from 46 (61 per cent) of 76 patients examined and from food, and a new serotype (61) was isolated from 16. The attack-rate among patients who ate a minced-ham dish was 78 per cent. The cooking and storage of this mince was faulty: cuts of meat were much too large, they were kept at room temperature too long before refrigeration, and after cooking they were put into mincers used also for raw meat. C.perfringens type A, serotype 1, was isolated from meat scraps in a mincer. Final reheating was inadequate to destroy even vegetative bacteria, and multiplication may have occurred during slow distribution to the wards. Outbreaks of C.perfringens fool-poisoning are common in hospitals, and some underlying problems are discussed. A plea is made for the Food Hygiene Regulations to apply to National Health Service premises and for simple but effective reforms in institutional catering management.


[Carcinoma of the anus - clinical signs and symptoms, therapy and prognosis (author's transl)]. Case reports are given of 37 patients treated between 1964 and 1976 because of carcinoma of the anus, and clinical signs and symptoms, therapy and prognosis are discussed. Most of the patients were 50-70 years old, women being more often afficted then men. Often the carcinoma was misdiagnosed as a benign disease. Hemorrhage and pain were the presenting symptoms in most of the case. Therapy depends upon the localization and the stage of the tumor. Carcinoma localizad distally of the linea dentata were excised locally; infiltrating carcinomas received radiotherapy postoperatively. Abdominal amputation of the rectum was performed if the linea dentata or regional lymph-nodes were involved. Bilateral dissection of inguinal lymph-nodes was performed only if inguinal metastases were suspected. No patients surviving 5 years were observed in the group with lymph-node metastases. On the contrary all patients survived, if carcinoma was localized distally to the linea dentata and had been excised locally. Recurrent malignancy was found only in 3 of these cases. On the basis of these findings it can be concluded that local excision is the therapy of choice in selected cases.


Biosynthesis of thyroid hormone: basic and clinical aspects. Thyroid hormone formation requires the coincident presence of peroxidase, H2O2, iodide, and acceptor protein at one anatomic locus in the cell. The peroxidase enzyme appears to be a protoporphyrin lX containing heme protein, with binding sites for both iodide and tyrosine. It is probable that both iodide and tyrosine are oxidized to free radical forms which unite to form iodotyrosine. The peroxidase is also involved through an uncertain mechanism in iodotyrosine coupling and probably in oxidation of sulfhydryl bonds in thyroglobulin. H2O2 may be supplied by microsomal NADPH-cytochrome c reductase or NADH-cytochrome b5 reductase. Other possible intracellular H2OI generating systems include monoamine oxidase and xanthine oxidase. The usual acceptor for iodide is thyroglobulin, which is currently believed to be iodinated within  apical secretory vesicles at the cell border just prior to liberation into the colloid, or possibly after liberation into the colloid. Other soluble an insoluble proteins are also iodinated within the gland. The peroxidase is present in numerous cellular structures, but iodination activity occurs primarily, if not only, at the apical cell border. The controls of iodination are imperfectly known. Thyrotrophin modulation of iodide uptake, H2O2 generation, thyroglobulin synthesis, and peroxidase enzyme level obviously are the main regulations. Many of these actions are thought to involve mediation of adenyl cyclase and subsequent activation of intracellular phosphokinases. Antithyroid drugs of the thiocarbamide group are competitive inhibitors of iodination under some circumstances, but if much iodide is present, they react with the oxidized iodine intermediate and are irreversibly inactivated themselves. Clinical problems involving defective peroxidase function are among the most frequent hereditary defects of thyroid hormone formation. Recognized abnormalities include deficient peroxidase, abnormality in binding of the peroxidase apoprotein to its prosthetic group, and other less well-identified abnormalities in peroxidase structure and function. Peroxidase is typically elevated in thyroid tissue from patients with hyperthyroidism sometimes deficient in cold thyroid nodules, and frequently diminished in tissue from patients with Hashimoto's thyroiditis.


Identification of lipids for intestinal absorption studies in resin-embedded tissue. The use of the dye p-phenylene diamine according to Korneliussen is described for the identification of lipids in tissues embedded in resins.


Modification of Cunningham's method for the detection of proteases in tissue sections. A modification of Cunningham's method to show the protease activity in fresh tissue sections on gelatin film is proposed. The diazotization of the gelatin film in two successive baths of Fast blue B salt sharply increases the colour intensity of the film, improving the contrast between the intact zones and the enzymatic lysis zones of the substrate. The various washings of the stained film have been simplified. After incubation, the histological staining of the sections by solid nuclear red is an improvement over the much more tricky Feulgen reaction, combined with PAS, used by Cunningham.


Methylene blue-azure B-eosin as a substitute for May-Grünwald-Giemsa and Jenner-Giemsa stains. The Romanowsky-type stain of Marshall et al. [J. clin. Pathol. 28, 920--923 (1975)] is described. It possesses several advantages over the widely used May-Grünwald-Giemsa and Jenner-Giemsa stains. These include ease and speed of preparation, a shorter staining time and reproducibility of results.


The development of a computer assisted instruction and assessment system in pharmacology. We describe the construction of a computer based system for instruction and assessment in pharmacology, utilizing a large bank of multiple choice questions. Items were collected from many sources, edited and coded for student suitability, topic, taxonomy and difficulty and text references. Students reserve a time during the day, specify the type of test desired and questions are presented randomly from the subset satisfying their criteria. Answers are scored after each question and a summary given at the end of every test; details on item performance are recorded automatically. The biggest hurdle in implementation was the assembly, review, classification and editing of items, while the programming was relatively straight-forward. A number of modifications had to be made to the initial plans and changes will undoubtedly continue with further experience. When fully operational the system will possess a  number of advantages including: elimination of test preparation, editing and marking; facilitated item review opportunities; increased objectivity, feedback, flexibility and descreased anxiety in students.


Communication in medicine: a study of how family doctors obtain information on recent advances in the treatment of rheumatic diseases. The results of a questionnaire on how 131 family doctors in Glasgow and the West of Scotland obtain information regarding recent advances in rheumatology are described. The results show that medical journals and formal lectures and symposia are still popular. Tape/slide and television presentations were not considered of much value.


[Relationship between culture and conditions, the qualitative composition of a culture of Bacillus brevis and its formation of gramicidin C]. Qualitative composition of the population of Bacillus brevis was found to depend on growth conditions. Under optimum aeration conditions for growth of the culture and biosynthesis of gramicidin C, the population was polymorphous and contained cells and spores of different age. No spores and prospores were found in the culture in conditions of weak and strong aeration. The population consisted only of young, intensively coloured cells with homogeneous or weakly differentiated content in conditions of strong aeration. Cells with the differentiated protoplasm containing large, distinctly seen vacuoles were found in conditions of weak aeration. Gramicidin C was synthesized by young cells with basophilic homogeneous or weakly differentiated protoplasm.


[Changes in the X-ray picture in Sudeckdistrophy after treatment with interferent current (author's transl)]. Treatment with interferent current has been applied to 150 patients having Sudeck dystrophy (in 133 cases developed after bone fractures,in 12 cases after distortion and luxation and in 5 cases after phlegmon etc.). It has been established that the normalization of the X-ray in Sudeck distrophy of the first degree takes about 30 days, in the second degree it goes in parallel with the clinical recovery and in the third degree it takes two to four months at an average. A great advantage of the interferent current treatment is that it can be applied as a dispensary treatment in delayed callus-formation and metal osteosynthesis.


Effect of acute disease and ACTH on serum zinc proteins. The effect of acute disease and ACTH infusion on serum zinc proteins was studied in serums from 156 healthy and diseased subjects. The mean (+/-2 S.D.) zinc content of 20 normal serums was 96 +/- 20 microng per 100 ml. In 87 serums from acutely ill patients the zinc ranged from 92 to 40 microng per 100 ml. The mean values for nearly all categories of disease studied were lower than normal (P is less than 0.001). Chromatography of normal serum on Sephadex G-100 separates two protein fractions, I and II, containing 37.8+/-8.8 and 76+/-10 microng of zinc per 100 ml, respectively. In serum from diseased patients the zinc in fraction I is unaltered whereas that in fraction II decreases to 29.8+/-7.5 microng per 100 ml (P is less than 0.001). ACTH administration reduces secrum zinc from 10 to 60 microng per 100 ml, the decrements being due to changes in the zinc content of fraction II. Thus, ACTH may have an important role in the reduction of zinc content associated with pathologic states.


[Contamination of the environment with hexachlorobenzene]. The causes of hexachlorobenzene (HCB) contamination of the environment are of complex nature. Besides the microbial metabolism of lindane to HCB, the pyrolysis of pentachlorophenol (wood impregnation), the chlorine treatment of lignin-containing lyes and possible contaminations with active agents which are industrially synthetized from polychlorbenzenes must be regarded as causes being in part still hypothetical.


Recent studies on the assessment of cell-mediated cytotoxicity in vitro. Experiments employing two new methods for the in vitro assessment of cell-mediated immunity against neoplastic target cells are indicated. Both methods offer the advantage of rapid and quantifiable determination of very early events in cell-cell confrontations. One technique measures the incorporation of precursors of proteins, RNA, and DNA synthesis by neoplastic cells incubated with effector cells during the first hours of contact. It was found that exposure of BALB/c plasmacytoma (PCT) cells to splenocytes from PCT-sensitized donors failed to bring about inactivation of the target cells or their release of 51Cr during several hours of interaction. However, inhibition of 3H-thymidine incorporation was almost instantaneous and pronounced. This observation suggests that cytostatic events may transpire in cell-cell interactions in the absence, or before the onset, of lethal changes. The second method assays the specific adherence of 51Cr-labeled lymphoid cells from Rous sarcoma (RS)-bearing chickens to RS target cells. This immunoadherence test revealed perferential, specific reactivity in autochthonous as compared with allogeneic interactions, which indicated recognition of individual-specific tumor-associated antigens against a background of strongly expressed group antigenicities.


[Subdural hematoma and anticoagulant therapy]. The authors report a series of 22 cases of subdural hematomas in patients submitted to anticoagulant therapy. A review of the literature finds 150 cases. Subdural hematomas occurs in about one third of the patients presenting hemorrhage of central nervous system related to anticoagulant therapy. Among subdural hematomas of any cause, the possible role of a previous anticoagulant therapy is stressed in 4,8 to 14% of cases. In most cases, long term anticoagulants were indicated for arterial or heart (ischemic) lesions (16/22 cases). In 6 cases, anticoagulants were indicated for prevention or treatment of pulmonary embolies. In 18 cases, anticoagulant drug is from the group of dicoumarol or phenylindanedione. In 3 cases, the only anticoagulant given to patient was heparin. Pathogenic study suggests that hypocoagulability might not always be the only factor of bleeding: high blood pressure, other drugs and head trauma (10 cases) are often associated. Clinical features, in our series, are similar to those encountered in cases of subdural hematoma of any cause. According to the existence of a cranial injury and to the chronology of anticoagulant therapy, the authors divide their 22 patients into 3 groups. The use of protamin sulfate or human plasma fraction PPSB provides in few minutes a normal coagulability. Neurosurgical treatment in all our cases evacuated in 11 patients a chronic subdural hematoma, in 2 cases an acute, and in 9 cases a subacute hematoma. Results were fair in 19 patients with no sequelae. 3 patients died during the immediate post-operative period. The authors conclude by stressing several preventive measures.


[Aseptic meningitis after isotope cisternography. 2 Cases]. In these two patients, as in 13 others described in the literature, a typical meningitic syndrome with excitement, confusion and a fever of 104degrees F (40degrees C) appeared 4-6 hours following the intra-thecal injection. Subsequent lumbar puncture usually reveals a cloudy C.S.F. under increased pressure. The polymorphs and proteins are increased but the glucose remains normal. There are no bacteria either on direct examination or after culture. All the patients receive antibiotics. After a course of three days, the symptoms and the fever have disappeared and the C.S.F. became normal. Bacterial contamination can be ruled out. The relative roles of iodine, radio-acitivity itself, albumine and of the radio-active element which are only used for this radiotracer are discussed. The tracer contains neither stabilizer nor pH buffer. One must presume that the syndrome is due to a direct toxic action rather than to an immunological or allergic reaction. Furthermore, it is of interest that similar reactions, without infection, are seen after spinal anaesthesia and intra-thecal injection of such differing substances such as iodine contrast media, gamma globulins, other isotopes or toxic substances (Lysol) (111In-DTPA).


[Bronchial reactivity in asthma. Immunopharmacological data]. Some aspects of bronchomotricity in bronchial asthma, with special emphasis on pharmacological and immunological data, are presented. Personal results on beta-adrenergic blockade and stimulation on simultaneous administration of histamine and beta-blocking and stimulating drugs and on the correlation between immunological factors as immunoglobulin IgE concentration, histamine binding power and alpha-1-antitrypsine deficiency and bronchial asthma are presented and discussed.


Response to experimental implantation of autologous iris tissue and to iris injuries. Autoimmune disease has been suspected in some cases of human uveitis. The initiating event has been thought to be injury and/or infection. To investigate the effect of injury on the uvea and on the immune apparatus rabbits and guinea pigs were subjected to various repeated iris insults, including implantation of autologous iris tissue into the anterior chamber of the contralateral eye. Of the procedures employed only iridectomy and insertion of iris produced some anterior chamber clouding, which was only slightly increased on repetition of the procedure; 76% of these animals failed to produce circulating CF antibodies. No local CF antibodies in the anterior chamber fluid nor increases in fluorescent antibodes in sections of the eyes could be detected. None of the animals tested developed skin hypersensitivity to homologous uveal antigen. None of the other traumatic procedures, which included repeated insertions of plastic into the anterior chamber, produced uveitis manifested clinically or by histological examination, circulating or local humoral antibodies, nor increases in fluorescent antibodies in the tissues of the eye. Introduction of antiuveal antibody into the anterior chamber also failed to produce uveitis. It can be concluded from these experiments that simple, repeated injury to the iris is not sufficient to elicit an autoimmune response under the conditions tested.


Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).


[Morphological diagnosis of Pneumocystis carinii]. Pneumocystis carinii pneumonia can only be diagnosed once the microorganism is demonstrated. The authors review and illustrate various staining technics, and discuss for each of them specific advantages. All samples must by systematically examined both by phase contrast microscopy and by light microscopy after Gomori-Grocott and Gram-Weigert stains. This morphological study is completed by ultrastructural photographs.