Effects of extradural block: comparison of the properties, circulatory effects and pharmacokinetics of etidocaine and bupivacaine. Five healthy, unmedicated male volunteers, aged 19-25 yr, participated in a double-blind, crossover study. Each subject received, on separate occasions and via a catheter placed at L2, 1.5% etiodocaine HCl20 ml with adrenaline 5 mug/ml, or 0.75% bupivacaine HCl 20 ml with adrenaline 5 mug/ml for extradural analgesia. In addition, in order to calculate the absorption rate of the local anaesthetic agent, each subject received on two further occasions etidocaine HCl 75 mg and bupivacaine HCl 75 mg respectively by i.v. infusion, over a period of 10 min. Spread of sensory analgesia to four segments above and below the site of injection was faster with etidocaine (13 +/- 3 min) (mean +/- SD) than with bupivacaine (22 +/- 8 min). Two-segment regression occurred later for bupivacaine (260 +/- 57 min) than for etidocaine (180 +/- 96 min). Caudal spread of analgesia was more extensive with etidocaine than with bupivacaine. The onset of motor blockade tended to be faster with etidocaine (5.8 +/- 3.0 min), than with bupivacaine (10.0 +/- 3.5 min); regression of motor blockade by one unit was longer with etidocaine (306 +/- 103 min) than bupivacaine (238 +/- 75 min). Sudomotor block occurred earlier with etidocaine (4.0 +/- 2.1 min) than bupivacaine (13.7 +/- 4.8 min). Significant changes in cardiac stroke work and stroke volume occurred. For etidocaine these measurements remained below control values for 120-210 min after injection. The mean maximum arterial plasma concentration of etidocaine was 1.52 +/- 0.64 mug/ml, at 14 +/- 2 min and of bupivacaine was 1.35 +/- 0.63 mug/ml, achieved at 20 +/- 4 min. The systemic absorption of both drugs occurred in a biphasic pattern with a fast and slow half-life of 0.3 and approximately 8 h respectively.


Influence of anaesthetic technique on postoperative pain. A comparison of anaesthetic supplementation with halothane and with phenoperidine. Fifty male patients undergoing elective surgery for duodenal ulcer received either phenoperidine or halothane 0.5% for the supplementation of anaesthesia. The patients in the phenoperidine group required the first postoperative dose of analgesic later and had lower pain scores in the first 2 h after operation. In the course of the 1st, 2nd and 3rd days, the two groups of patients showed a similar pattern after operation with regard to pain scores, vital capacity impairment and oxygen tension measurements.


Personality assessment and postoperative analgesia. A study in male patients undergoing elective gastric surgery. In 40 patients undergoing surgery for duodenal ulcer, personality was assessed by a PEN Inventory. After operation, the respiratory restoration factor (RRF) was used to indicate the pain relief from nitrous oxide (25%) and i.v. methadone (three doses of 2 mg). There was no correlation between the psychological factors and RRF. Twenty-five per cent nitrous oxide appeared to be equivalent to i.v. methadone 4 mg in terms of RRF. The degree of hypoxia after surgery correlated with vital capacity impairment and the improvement of oxygen tension after analgesia correlated with RRF after methadone 6 mg.


A useful tube for anaesthesia during laryngeal microsurgery. An endotracheal tube for use during anaesthesia for microsurgery of the larynx was made from a plastic endotracheal tube and an angiography connecting tube. It cannot be occluded, requires a minimum of space, and allows jet ventilation of the anaesthetized and paralysed patient. The value of a nitrous oxide-oxygen mixing valve in association with the tube is described.


Mechanisms of leucocyte migration inhibition by breast tumour cell fractions. Leucocyte migration inhibition by autologous breast tumour cell fractions was mediated by a soluble factor synthesized and released by mononuclear leucocytes and active against migrating granulocytes. This mechanism is similar to that previously described in respect to cell-mediated sensitivity to microbial antigens. Alternative mechanisms involving directly reactive granulocytes or cytophilic antibodies were rarely operative in the migration tests.


Monocytosis associated with the growth of transplanted syngeneic rat sarcomata differing in immunogenicity. The effect of the growth of two syngeneic transplanted sarcomata of widely differing biological properties on the number of monocytes in the blood of rats was measured (1) by binding of a specific antimacrophage serum to leucocytes, and (2) by sedimenting in a density gradient rosettes between mononuclear cells and antibody-coated sheep red cells under conditions in which B-cells are not brought down. For the 4 syngeneic sarcomata studied there was a progressive increase in the number of monocytes with tumour growth and the values returned to normal a few days after their surgical removal. The extent of monocytosis was related to the immunogenicity of the tumour and was most pronounced for the HSBPA sarcoma, which is highly immunogenic, has a low rate of spontaneous metastasis and contains many macrophages, and least for the MC-3 sarcoma which is essentially non-immunogenic, invariably gives rise to distant metastases and contains only about 8% macrophages. The growth of sarcomata had previously been found to reduce the number of monocytes which enter inflammatory lesions, both non-specific and due to a delayed hypersensitivity reaction. This "anti-inflammatory" action of sarcomata which is related to their immunogenicity cannot be ascribed to the preferential uptake of monocytes by the tumours and it is concluded that the monocytes in the blood of tumour-bearers, though increased in number, are modified so that they do not enter sites of inflammation.


Stem cell characterization of neutropenia: velocity sedimentation and mass culture analysis. Human bone marrow obtained from patients with neutropenia contains a cell population which is absent or diminished in normal marrow. The abnormal population is composed of cells of volume 200-300 mum3 which sediment at 5-5 to 8-5 mm/h. Normal marrow contains one cell class giving rise to increased numbers of grnaulocyte colonies after mass culture, while marrow obtained from neutropenic patients, or from patients with marrow regeneration, shows two such populations; one of these cell classes corresponds to the abnormally large cells demonstrated on velocity sedimentation analysis. This population of large cells may represent a group of either self-renewing cells related to the committed granulocyte progenitors or the pluripotent stem cell.


Rubidazone vs adriamycin: an evaluation of their differential toxicity in the spleen colony assay system. Rubidazone, the new semi-synthetic benzol hydrazone hydrochloride derivative of dauorubicin, has proved on a molecular weight basis to be less toxic than adriamycin and similar to daunorubicin in cardiac toxicity studies in the hamster as well as in other in vivo and in vitro test systems. It has proven effectiveness against several animal tumours and human acute leukaemias. We have compared the inhibitory effect of rubidazone to that of adriamycin on P388 leukaemia and normal bone marrow colony-forming units (CFU) using the spleen colony assay system in male DBA2 mice. The efficacy ratios (i.e., the ratio of the slopes of the normal bone marrow CFU to leukaemic CFU dose-survival curves) in the spleen colony assay system for rubidazone and adriamycin were 7-8 and 7-5 respectively. This near identity of efficacy ratios fro rubidazone and adriamycin correlated with the results of median survival time studies in the leukaemic mice. Their dose-median survival time curves were almost parallel, having nearly identical slopes. Rubidazone's equal therapeutic index as compared to adriamycin in the spleen colony assay system together with its known decreased toxicity to cardiac muscle cells makes it an extremely promising new anthracycline derivative to study in comparison to adriamycin in human malignancies.


Methods of classifying and ascertaining children's tumours. Several methods of ascertaining and classifying childhood neoplasms for epidemiological study have been evaluated using material from the University of Manchester Children's Tumour Registry (CTR), which includes data from several sources on children with neoplasms first seen in the period 1954-73 who were under 15 years old and living in the Manchester Regional Hospital Board area at the time. Two systems of classification-the International Classification of Diseases (ICD) and the Morphology Section of the Manual of Tumor Nomenclature and Coding (MOTNAC; Percy, Berg and Thomas, 1968)-were tested. No major problems arose with the Morphology Section of MOTNAC, and we recommend that the revised version of this section, in the proposed "International Classification of Diseases for Oncology", should be used in epidemiological reports on children's tumours whenever possible. The ICD discriminates less well between the commoner types of childhood neoplasms, but must be retained as a supplementary classification to facilitate international comparisons. A comparison of the completeness of ascertainment achieved in recent years by each source of data showed that more than 98% of the serious cases (neoplasms that were malignant and/or lay within the craniovertebral canal) could have been identified using a combination of Hospital Activity Analysis (HAA) and cancer registration records, and more than 95% using HAA and death records. But in an analysis of 2 years' HAA returns and 6 years' cancer registrations of serious cases, nearly one quarter of the former and one fifth of the latter were shown to record diagnoses which differed from those finally assigned at the CTR. It is concluded that, in epedimiological studies based on routine records, the diagnoses given should always be checked centrally, by experts, in the light of all the available clinical and pathological material (including histological preparations).


Geographic correlation between mortality from primary hepatic carcinoma and prevalence of hepatitis B surface antigen in Greece. Average annual age-adjusted mortality rates per 100,000 from primary hepatic carcinoma (PHC) among males for 1971-1973 in the urban and rural areas of the 9 geographical regions of Greece were estimated. Hepatitis-B surface antigen (HBsAg) prevalence by region and area was evaluated in a sample of 22,844 Greek Air Force recruits from all parts of the country. Mortality from PHC was found significantly higher in urban areas (28-30 vs. 18-81) whereas prevalence of HBsAg was higher in rural areas (5-3% vs. 3-90%). Nevertheless further statistical analysis showed that there is a strong correlation between HBsAg prevalence and mortality from PHC, which is higher in rural (r = + 0-88) than in urban (+ 0-57) areas. The latter findings indicate that hepatitis B infection and PHC may be causally related.


Selection of skin tests in childhood asthma. Skin tests have been applied to 161 asthmatic children seen consecutively at a paediatric respiratory clinic. To demonstrate whether a child's asthma is associated with a positive skin test it is suggested that only four extracts need be applied: house dust, house dust mite (D. farinae), grass pollens and a control.


Thoracoabdominal aortic aneurysm presenting as a solitary pulmonary nodule. Bronchogenic carcinoma was suspected in an elderly male smoker who had lost weight and presented with a large solitary pulmonary nodule on the radiograph. On thoracotomy a thoracoabdominal aortic aneurysm was found. The diographic findings in this case and the characteristics of thoracoabdominal aneurysms in general are briefly discussed.


Eosinophilic granuloma of the lung.

Eosinophilic granuloma of the lung. Pulmonary eosinophilic granuloma diagnosed by lung biopsy is described; the case demonstrates the remission and relapse that may occur.


Sarcoidosis and thyrotoxicosis: A study of five patients. Five patients with sarcoidosis and thyrotoxicosis have been studied. Autoimmunity resulting from loss of thymus-derived lymphocyte control is suggested as a cause common to both.


Sleeping ventilatory patterns in patients with severe chronic airflow obstruction causing respiratory failure. During sleep some patients with airways obstruction and hypoxaemia developed tachypnoea. This could not be explained by the severity of their abnormality of lung function, their CO2 responsiveness, the nature of their lung disease or their personality. This nocturnal tachypnoea correlated best with a raised resting arterial blood PCO2, and was not seen hypoxaemic patients with a normal PCO2 who showed the usual fall in respiratory rate when asleep. We suggest that in patients with both hypoxaemia and hypercapnia sleep removes a cortical inhibitory mechanism which slows breathing durigng waking hours, and is linked to the arterial blood PCO2.


The prevalence of asthma and wheezing in children. The prevalence of asthma and wheezing in children in Birmingham in 1974-5 was compared with the previous studies in 1968-9 and 1956-7. The frequency of asthma increased over the 20-year period, although the rate of increase had slowed. Asthma was commoner in boys than in girls. Children of the same racial group were more prone to asthma, and probably to other atopic diseases, if born in England than if born in poor tropical countries. Environmental factors in early life profoundly influence the prevalence of asthma in childhood.


Drug-induced proteolysis: a correlation with oedema-reducing ability. A very strong correlation has been shown to exist between acid and neutral protease activity levels in the skin, the acid protease activity level of the oedema fluid, and the oedema-reducing ability of the benzo-pyrones and related drugs. Macrophages, which are believed to be the main cells affected by the drugs, are very common in thermally injured tissues. Their lysosomal enzymes work at an acid pH. Since the main acid protease is cathepsin D, the overall acid protease levels are representative of changes in cathepsin D levels. Elevated levels are concomitant with more complete and rapid digestion of accumulated protein. The resulting fragments then can rapidly leave the injured tissues, freeing the oedema fluid. This form of proteolysis is very much different from that which is used by pharmacologists as a measure of inflammation. Normal proteolysis in inflammation represents an estimate of tissue derangement, but the proteolysis induced by drugs such as the benzo-pyrones represents a means of lessening some of the more injurious effects of this derangement. The results presented here strongly confirm this.


Age and sex differences in the response of lymph node post-capillary venules in mice infected with Toxoplasma gondii. Groups of male and female mice of varying ages were infected with a low-virulence strain of Toxoplasma gondii and killed 3 weeks and 6 weeks after infection. The lymph nodes of the female group showed a greater prominence of the endothelial cells of the post-capillary venules. This difference was most marked at the age of 15 weeks and least at 30 or more weeks. The same sex difference was demonstrated in control mice although to a lesser extent. The possible role is discussed of the effect of female sex hormones on vascular endothelium in modifying the development of an immune response and in explaining the observed female preponderance in human cases of auto-immune disease.


Biochemical effects of asbestiform minerals on lung fibroblast cultures. The ability of different types of asbestiform minerals to enhance or suppress the levels of fibrous collagen in cultures of lung fibroblasts was tested. All commercially important asbestos dusts produced both effects, a lower dose favouring a fibrogenic response whereas a higher dose favoured an opposite effect.


DNA content of cultured mammalian cells exposed to smoke and smoke fractions from cigarettes containing tobacco or NSM, a tobacco substitute. The effects of smoke and smoke fractions from tobacco and a substitute smoking material (NSM) on the DNA content of mammaliam cells in culture were measured. Tobacco smoke caused significant (P less than 0.001) changes in the DNA content of all the mammalian cells exposed compared with controls. NSM smoke did not have a significant effect on the DNA content of the exposed cells (P less than 0.95). Smoke from blends of NSM and tobacco caused changes in DNA content in proportion to the amount of tobacco in the mixtures. Condensate from cigarettes containing tobacco or blends of tobacco and NSM caused significant (P less than 0.001) changes in DNA content of mammalian cell populations in culture, whereas equal weights of condensate from NSM alone or NSM containing nicotine did not cause significant changes (P less than 0.05). NSM produces 28% of the weight of condensate per cigarette in comparison with tabacco and would, therefore, be expected to be far less biologically active than tobacco. Filtered smoke from cigarettes containing tobacco caused significant (P less than 0.001) changes in the DNA content of mammalian cells in culture. These changes were quantitatively similar to those caused by whole smoke suggesting that the gas phase of cigarette smoke is biologically more reactive than the particulate phase. The filtered smoke from the substitute smoking material NSM did not cause significant (P less than 0.95) changes in DNA content of cultured mammalian cells. Filtered smoke from blends of NSM and tobacco caused changes in DNA content in proportion to the amount of tobacco in the mixture.


Pathogenesis and pathology of respiratory tularaemia in the rabbit. The development of pathological lesions in the organs of rabbits was examined at intervals from 1 h to 4 days after aerosol infection with Francisella tularensis. The earliest change, accumulation of polymorphonuclear leucocytes (PMN) in ulmonary alveolar ducts, occurred at 19 h. From the 2nd day multiple foci of necrosis and PMN infiltration were present in large airways and alveoli throughout the lungs and progressively increased in size. Pulmonary arteritis was a prominent feature of the infection. Areas of necrosis were present in the nasal mucosa, pharynz and trachea, and pyogranolomatous lesions consistently developed in the liver, spleen, and lymph nodes.


Excision repair of DNA in some photodermatoses. Excision repair of DNA was measured in a number of photosensitive subjects by estimating unscheduled DNA synthesis in cultured fibroblasts after ultraviolet radiation. The amount of unscheduled DNA synthesis and the action spectrum for this process were estimated in each subject and compared with seven normal subjects. Two subjects with polymorphic light eruption and three with actinic reticuloid exhibited normal levels of DNA repair and normal action spectra. In one subject with classical xeroderma pigmentosum no excision repair could be demonstrated whilst in another the amount of repair was lower than normal. The finding of normal DNA excision repair in polymorphic light eruption does not support an earlier claim that this repair process is abnormal in this common photodermatosis.


A follow-up study of patients with recurrent urticaria and hypersensitivity to aspirin, benzoates and azo dyes. We have studied seventy-five patients with recurrent urticaria and angio-oedema of more than 4 months duration and with positive provocation tests to aspirin, azo dyes, and/or benzoates. Cross-reactions between the test compounds were common. The patients were recommended to be on a diet free from salicylates, benzoates, and azo dyes. They were then followed for 6-24 months. At the follow-up, 24% were free from symptoms, 57% considered themselves much better and 19% stated that they were slightly better or unchanged. All patients had followed the diet for at least 1-3 months. Most of those who became totally free of symptoms did not continue with the diet, while most of the patients who considered themselves much better found that it was necessary to continue on the recommended diet. They usually developed symptoms as soon as they ingested something containing azo dyes or benzoates. To be able to maintain such a diet, it is important that the content of additives in food and drugs be properly declared.


Necropsy and ultrastructural findings in histiocytic medullary reticulosis. In a case of histiocytic medullary reticulosis with protracted course and necrotic skin lesions, histological study revealed infiltration of the fat tissue by atypical reticulohistiocytic cells, areas of associated fat necrosis and vascular lesions. Autophagocytosis (phagocytosis of erythrocytes, erythroblasts, platelets, lymphoid cells, and nuclear debris) was found in biopsy specimens of the subcutaneous infiltrates, lymph nodes, and bone marrow, and in necropsy specimens of skin, iliac mesenteric lymph nodes, bone marrow, liver, spleen, and suprarenal glands. Electron microscopy of various viscera showed abnormal histiocytic cells containing multiple phagocytosed erythrocytes and other blood cells in different stages of destruction and digestion. Multi-membranous bodies also were present. Defective lysosomal degradation of intracytoplasmatic ceroids in this condition is postulated.


Hypersensitivity of scleroderma cutaneous vascular smooth muscle to 5-hydroxytryptamine. Vascular smooth muscle strips from subcutaneous wrist vessels of patients with scleroderma (systemic sclerosis) were studied in an isolated system. No difference between catecholamine response of scleroderma or control vessel strips was observed. Three of four patients demonstrated significant hypersensitivity to 5-hydroxytryptamine as compared to control values. Serotonin hypersensitivity may play a role in the evolution of Raynaud's phenomenon and vascular scleroderma.


The prognosis of systemic sclerosis.

The prognosis of systemic sclerosis. Eighty-four patients with systemic sclerosis have been investigated and observed at intervals for up to 15 years. The prognosis is worse in males than in females although in any individual case the clinical course is unpredictable. Those patients with the combination of calcinosis, Raynaud's phenomenon, sclerodactyly and telangiectasia have the same degree of systemic involvement and the same prognosis as other patients with systemic sclerosis, and the term 'CRST syndrome' should be abandoned.


An auto-antibody profile in alopecia totalis and diffuse alopecia. Thirty-one patients suffering from alopecia totalis and fourteen patients with idiopathic diffuse alopecia were examined for evidence of an endocrinopathy and their sera screened for organ-specific auto-antibodies. The results were compared with matched control groups of dermatological patients and a random group of dermatological patients. There was no statistically significant difference in the groups and the results were similar to those found in the general population.


Immunological demonstration of multiple esterases in human eccrine sweat. Eccrine sweat collected from the human skin surface contains at least five different esterases. One of them  is a cholinesterase. A non-specific carboxylesterase with the electrophoretic mobility of an alpha-globulin appears to be a serum protein. Besides this, there are two isoenzymes of human origin migrating with the same electrophoretic mobility as gamma-globulins. These two isoenzymes are immunologically identical with a non-specific carboxylesterase occurring in numerous organs and body fluids. Lipase activity could not be demonstrated.


Septrin in the treatment of dermatitis cruris pustulosa et atrophicans. The results of treatment of 30 Nigerian patients suffering from dermatitis cruris pustulosa et atrophicans by a 7-week course of Septrin are described. Septrin was effective in twenty-three of twenty-four patients who completed the study. The best therapeutic effects were observed in the early, pustular phase of the disease.


The treatment of psoriatic nail dystrophy with intradermal steroid injections. Thirty-seven patients with psoriatic nail dystrophy were treated with intradermal nail-fold injections of either triamcinolone acetonide or triamcinolone hexacetonide, using the Port-O-Jet needleless injector. Mild nail-matrix changes showed a very good response to treatment, whilst nail-bed and/or hyponychial changes causing onycholysis and the more severe types of dystrophy usually showed little improvement. Although in occasional cases this may be a useful form of treatment, we would not recommend its general use in patients with psoriatic nail dystrophy.


High dose dapsone toxicity.

High dose dapsone toxicity. A description of the clinical and biochemical course is given for a patient who developed haemolysis and methaemoglobinaemia following dapsone therapy in high dosage for 2 weeks.


Prurigo nodularis and gluten enteropathy. Two cases of prurigo nodularis are described. Each is considered to have a gluten sensitive enteropathy. This association may be one facet of prurigo nodularis.


Carbohydrate metabolism in lichen planus. A study of forty patients with active lichen planus and a negative family history for diabetes showed that 42% had unequivocally abnormal oral glucose tolerance. The pattern of insulin response to glucose is similar to that seen in typical mild maturity-onset diabetes. There was no association between the presence of glucose intolerance and the duration or type of lesions. None of the patients with glucose intolerance had demonstrable islet-cell antibodies.


A study of the permeability barrier in epidermis and oral epithelium using horseradish peroxidase as a tracer in vitro. Small biopsies of skin, and of keratinized and non-keratinized oral mucosa were incubated with horseradish peroxidase, fixed and reacted to demonstrate peroxidase activity at the light and electron microscope level. In all tissues peroxidase extended through the intercellular spaces of the epithelium up to, but not into, the stratum corneum of keratinized, or the superficial layer of non-keratinized, tissue. This distribution corresponds to that seen in studies using the tracer in vivo where the presence of an intercellular permeability barrier has been demonstrated in the upper cell layers. It is suggested that the method is a useful way of investigating the permeability of normal and pathological human epithelial tissues.


Sociological implications of an epidemiological study of eczema in the City of Birmingham. An epidemiological study has been made of 4696 cases of eczematous dermatitis referred to hospital outpatient clinics in the City of Birmingham over a 3-year period. Some sociological implications of the investigation are discussed. The need for further sociological accounts of skin disease is stressed.


Complement component profiles in urticaria, dermatitis herpetiformis, and alopecia areata. Insignificant variation was noted in the mean levels of the complement components CIQ, C4, C2, C3, C5 and C3PA between various groups of sera from patients with urticaria, angio-oedema, dermatitis herpetiformis, alopecia areata, or hay fever. No deficiencies were found. Elevated C9 levels in chronic urticaria and angio-oedema reflected its nature as an acute phase protein. The assessment of C components in single or sequential serum samples revealed only marginal variations. Similar results were recorded for plasminogen the immunoglobulins, G, A and M. Some evidence is provided for the primary involvement of the kallikrein-kinin system in urticaria.


Erythropoietic protoporphyria. Hepatic implications. The terminal stages of erythropoietic protoporphyria are recorded. The observations are related to the site of the fundamental lesion and the nature of the biochemical defect. The possibly ominous prognosis in this usually mild condition is emphasized. Apart from congenital porphyria, the porphyrias do not usually confer severe cutaneous lesions. These diseases present to dermatologists because of moderate photosensitivity and are not usually regarded as a risk to life. Dangerous central nervous system involvement may occur, however, in acute intermittent, variegate and hereditary coproporphyrias, while in acquired symptomatic porphyria severe underlying liver dysfunction may occur. Probably the most common familial photosensitizing porphyria is erythropoietic protoporphyria. Recently some deaths from severe liver involvement have been reported in this disease.


HL-A antigens in patients with guttate psoriasis. Tissue typing was performed on lymphocytes of sixty-two patients with guttate psoriasis, in forty-four of whom this was the first manifestations of the disease. In 84% of cases, the guttate psoriasis was preceded by a clinical infection. A highly significant excess of antigen W17 (HLA-BW17) was found in patients when compared with healthy population. In common with some other studies antigens HL-A13 (HLA-B13), W15 (HLA-BW15) and W21 (HLA-BW21) were found in excess but these became non-significant after correction for the number of antigens studied. 68% of patients who had guttate psoriasis de novo, subsequently developed persistent plaque psoriasis.


HL-A antigens in lichen planus.

HL-A antigens in lichen planus. A study of fifty-seven patients with lichen planus showed a significant increase in the frequency of HL-A3 (54% compared with 29.7% in a control population). It is likely that there is a gene in the HL-A chromosomal region increasing the susceptibility to lichen planus. No correlation was found between HL-A3 and age of onset, sex, and presence or absence of mucosal lesions.


HL-A antigens and vitiligo.

HL-A antigens and vitiligo. HL-A antigens were found with similar frequency in ninety vitiligo patients and in 341 healthy controls. However there was a significant correlation between HL-A13 and vitiligo with antithyroid antibodies. This supports the concept that vitiligo is a syndrome rather than a disease.


Erythema multiforme in children. Response to treatment with systemic corticosteroids. It is generally accepted that the correct treatment for patients with severe erythema multiforme is systemic corticosteroids. This paper is a review of thirty-two paediatric patients with severe erythema multiforme (Stevens-Johnson syndrome) who were treated with either large doses of systemic corticosteroids or supportive care only. Those patients treated with steroids did not recover sooner than those treated in other fashions and the steroid treated group had a significant incidence of medical complications. This retrospective study proves nothing but it does suggest that treatment of patients with the Stevens-Johnson syndrome with systemic corticosteroids may be associated with significant side effects and prolonged recovery.


Studies on the effect of salicylic acid on normal skin. This investigation was prompted by our ignorance of the way in which salicyclic acid aids desquamation. Salicyclic acid in aqueous cream or white soft paraffin and in concentrations of 2-12% was applied to normal skin of twenty-three subjects while the vehicle alone was applied to the contralateral sites. Biopsies and skin surface biopsies were taken from the test and control sites after 1 week. Histological examination showed that there was less horny layer on the test specimens but that there were no qualitative or quantitative differences in the structure of the viable epidermis. Portions of the biopsies were incubated in the presence of tritiated precursor compounds and subsequent autoradiographic examination showed no difference in the incorporation of thymidine, cytidine or histidine between test and control preparations. Scanning electron microscopy of skin surface biopsies showed some changes in all specimens--presumably due to hydration--but also showed striking differences between test and control sites and were especially marked with higher concentrations of salicylic acid. It is suggested that salicylic acid causes desquamation by dissolution of intercellular cement material.


Mudi-childhood on the pinnae.

Mudi-childhood on the pinnae. A case of Mudi-childhood on the pinnae in a young girl is reported.


Multiple pigmented naevi in an albino.

Multiple pigmented naevi in an albino. A case of pigmented naevi arising in an albino is described. The histological appearance of a naevus is described in the nature of the pigment discussed.


Leg ulcers in a family with both beta thalassaemia and glucose-6-phosphate dehydrogenase deficiency. A family is presented in which the proposita, affected with thalassaemia major, developed a chronic leg ulcer at the age of 14 years. Her eldest brother, not affected with thalassaemia, had a transient leg ulcer at the age of 18 years and a second brother, affected with thalassaemia minor, developed leg ulcers when aged 15 years. Al three siblings were glucose-6-phosphate dehydrogenase deficient.


Glaucoma following the application of corticosteroid to the skin of the eyelids. A case is reported of intractable glaucoma presumed to be associated with the long-term use of a corticosteroid-containing dermatological preparation on the skin of the eyelids for the control of eczema.


Christmas disease (haemophilia B) in a girl with deletion of the short arm of one X-chromosome (functional Turner syndrome). A I-year-old girl with severe Christmas disease and a factor IX content less than I% of normal is described. The family history was negative and coagulation studies on her relatives were normal. Genetic investigation showed an XXp-karyotype with deletion of the short arm of one X-chromosome, a cytogenetic variant of Turner syndrome. The transmission pathway of the haemophilia gene is discussed.


Evidence that colagen releases human platelet constituents by two different mechanisms. Collagen is believed to be involved in the initial events in haemostasis and has been shown by others to cause platelet aggregation and release, and also to initiate the intrinsic pathway of coagulation. The present experiments provide evidence whihc suggests how these many effects of collagen may be involved in haemostasis. It is shown here that collagen releases platelet constituents by two different pathways. Collagen causes platelets washed free of loosely adsorbed coagulation factors to release constituents. This activity, is therefore, independent of the intrinsic pathway of coagulation, and is not inhibited by heparin or hirudin. Collagen also releases platelet constituents by an alternative pathway which is inhibited by heparin and hirudin and is independent of factor XII, but is dependent on factor XI, subsequent factors in the intrinsic pathway of coagulation and calcium. These results suggest that collagen-induced release of platelet constituents is in part due to a direct effect on the platelet, and , in part, to an indirect effect involving coagulation factors and mediated by thrombin. The present results suggest that irreversible aggregation by collagen is also mediated by thrombin. The possible significance of this dual action of collagen in the haemostatic process is shown in Fig 7.


Another example of an antibody reacting optimally with p red cells. An antibody is described that reacted strongly with red cells of the p(Tj(a-)) phenotype and moderately to strongly with cord red cells of the P2 phenotype. The antibody failed to react, or reacted very weakly, with red cells of the P1k and phenotypes and with the red cells of five children of a p individual, ahd reacted weakly with occasional red cell samples from adults of the P2 phenotype. These results suggest that the antibody does not detect a product of the p gene but instead detects a P system precursor substance. In p individuals this P system precursor substance is not altered by the p genes. In individuals of the P1 or P2 phenocursor substance is not altered by the p genes. In individuals of the P1 or P2 phenotype this precursor substance is apparently converted to P1 and/or P antigens by the P1 or P2 genes.


Quantitation of ineffective erythropoiesis from the incorporation of [15N] delta-aminolaevulinic acid and [15N] glycine into early labelled bilirubin. I. Normal subjects. The incorporation of [15N] glycine into early labelled bilirubin and haemoglobin haem was measured in four haematologically normal subjects, using the clearance of [14C] bilirubin to measure total bilirubin production rate. Hepatic haem turnover was calculated from the incorporation of [15N]=sigma-aminolaevulinic acid into early labelled bilirubin. From the exprimental data previously published data in normal subjects a method is derived for the quantitation of ineffective erythropoiesis which can be applied to similar studies in patients with haematological disorders.


Quantitation of ineffective erythropoiesis from the incorporation of [15N] delta-aminolaevulinic acid and [15N] glycin into early labelled bilirubin. II. Anaemic patients. The incorporation of [15N]delta-aminolaevulinic acid and [15N glycine into haemoglobin haem and early labelled bilirubin was measured in subjects with various haematological disorders. The clearance of [14C bilirubin was used to measure bilirubin production rate, and the magnitude of the various sources of bilirubin production and the percentage ineffective erythropoiesis were calculated. Ineffective erythropoiesis was found to be a major factor in the production of the anaemia in patients with the following disorders: megaloblastic anaemia associated with the Lesch-Nyhan syndrome, thalassaemia intermedia, sideroblastic anaemia, and the anaemia of chronic disorders. In three patients with iron-deficiency anaemia ineffective erythropoiesis was increased, but was of minor importance in the production of the anaemia, while in two patients with aplastic anaemia and one with macrocytosis of alcoholism there was no increase in ineffective erythropoiesis.


Anti-Wrb, and other autoantibodies responsible for positive direct antiglobulin tests in 150 individuals. Eluates from the red blood cells (and sera whenever free autoantibody was present) of 150 individuals with positive direct antiglobulin tests, have been studied for antibody specificity. Of 87 patients with AIHA, 64 had autoantibodies reacting with all red cell samples including Rhnu11. Of these 64 anti-d1 autoantibodies, two were, and 32 contained, auto-anti-Wrb. Of 33 patients being treated with alphamethyldopa, who had developed positive direct antiglobulin tests, 23 had anti-d1 autoantibodies four of which contained auto-anti-Wrb. Of 30 haematologically normal donors with positive direct antiglobulin tests, 23 had anti-d1 autoantibodies, two of which were, and six of which contained, auto-anti-Wrb. The full specificities of autoantibodies, other than anti-Wrb and anti-d1, in the 150 patients are described, as are the natures of the protein red cell coatings that caused the positive direct antiglobulin tests. The presence of free serum autoantibody as a correlate of the three clinical conditions is reported. Several observations on auto-anti-Wrb are documented. The antibody can cause gross red cell destruction in vivo, but can be benign on other occasions; it occurs with approximately the same frequency in AIHA patients and "normal" donors with positive direct antiglobulin tests, but in fewer patients with alphamethydopa induced positive direct antiglobulin tests; it does not activate complement in vivo; and finally it may eventually provide a clue to the aetiology of AIHA.


Unbalanced globin chain synthesis in erythroid precursor cells of heterozygous alpha-thalassaemia. Globin biosynthesis was studied in both erythroid precursors and reticulocytes of three individuals with heterozygous alpha-thalassaemia. In contrast to the finding of equal or nearly equal alpha and beta chain synthesis in the marrow of patients with heterozygous beta-thalassaemia previously examined, our studies showed equal degrees of unbalanced globin synthesis in both reticulocytes and nucleated-erythroid cells of alpha-thalassaemia heterozygotes. Greater stability and less susceptibility to proteolysis of the excess beta-chain formed in alpha-thalassaemia may explain our findings.


Simultaneous inheritance of mutant isoenzymes of erythrocyte pyruvate kinase associated with chronic haemolytic anaemia. The heterogeneity of pyruvate kinase (PK) deficiency associated with hereditary haemolytic anaemia is emphasized by studies of a kindred harbouring two distinct mutant forms of this enzyme, both of which were kinetically defective with markedly decreased affinities for the substrate, phosphoenolypyruvate. The two isoenzymes, designated PK-Vancouver1 and PK-Vancouver2, were primarily distinguishable from one another by differences in maximum in vitro activities and by variations in response to fructose-I,6-diphosphate activation. When combined in proband erythrocytes to the exclusion of any normal PK, the isoenzymes were associated with a severe chronic haemolytic process with many of the features of PK deficiency of the more common quantitative type. Clinical laboratory screening tests for detecting PK deficiency may be falsely negative or equivocal in such cases.


A convenient and reproducible filtration technique for the determination of erythrocyte flexibility. A micro-cell filtration technique is described in which a silver membrane of 3 mum porosity is used. The apparatus consists of a membrane holder and disposable syringe only. A regeneration procedure which allows indefinite re-use of one membrane is described. Filtration proceeds under the hydrostatic pressure of the fluid column only. A locke-albumin solution has been developed as a suspension medium and adapted for cell washing by the addition of fibrinogen and cholesterol. A plot of the volumes of cells filtered against log time shows a linear relationship for normal erythrocytes. The filtered red cells are virtually undamaged. The overall precision of the method of the order of +/-2%.


Primary leucocyte alkaline phosphatase deficiency in an adult with repeated infections. An individual with repeated bacterial infections, eczema, hyperimmunoglobulin E, and a primary deficiency of leucocyte alkaline phosphatase is described. The Lap-deficient neutrophils from this patient had marginally deficient bactericidal activity particularly when challenged with high ratios of bacteria per neutrophil. Leucotactic, metabolic and morphologic features of the neutrophils from the patient were normal. Evidence is presented which contrasts this patient's condition with previously described primary or secondary deficiencies of LAP.


The 'inductograph'--a graph describing the limits of the latent phase of induced labour in low risk situations. The construction of an 'inductograph' is described which defines the rates of progress of the latent phase of labour in 80 per cent of a group of patients selected from a 'low risk' category. A standard induction regime was used, and changes in the uterine cervix were assessed quantitatively by a modified form of the Bishop scoring system.


Concentrations of free fatty acids in maternal and umbilical cord blood during elective Caesarean section. The concentration of free fatty acids was measured in blood taken from the umbilical artery and vein of 29 infants during elective Caesarean section and compared with levels in maternal venous blood. The mean venous-arterial (v-a) difference was 0.07 mEq/l. There was a direct and significant correlation between the umbilical v-a difference and maternal venous concentrations.


Arterial pressures in non-pregnant women of child-bearing age in Ile-Ife, Nigeria. The range of arterial pressures in non-pregnant women between the ages of 15 and 44 years in Ile-Ife, Western Nigeria, has been determined from a randomly selected group of 626 women. The survey showed a low range of arterial pressures in the women. Blood pressures within the group showed a tendency to rise with age except in those who were aged 40 to 44 years, where the small numbers may have yielded the unexpected lower arterial pressure levels. Parity did not seem to have exerted any clear influence on the blood pressures of the subjects. The exception is in the age group 30 to 34 years where increasing parity was associated with a lower systolic blood pressure. The results of the survey suggested that essential hypertension and chronic renal disease were not likely to be significant factors in the high incidence of pre-eclampsia and eclampsia in the community.


Arterial pressures in Nigerian women up to mid-pregnancy. A group of 497 women whose pregnancies did not exceed 22 weeks and who were booked at the antenatal clinic between 1st August, 1971 and 31st January, 1972 have been included in a survey of arterial pressures in early pregnancy. The arterial pressures showed a low range and confirmed similar previous observations. The blood pressures among the primigravidae in the group were found to be lower than those of their Aberdeen counterparts. It was also found that the arterial pressures were lower than those of comparable non-pregnant women within the same community. The low arterial pressures in early pregnancy did not offer any special advantage in relation to the incidence of pre-eclampsia and eclampsia, diseases known to be prevalent within the community.


The management and natural history of severe dysplasia and carcinoma in situ of the uterine cervix. This report concerns 375 patients seen in Frederiksberg, Denmark, between 1951 and 1972: 103 of them had severe dysplasia and 272 of them carcinoma in situ of the uterine cervix. Thirty patients had no primary treatment: 9 of them developed invasive carcinoma, and 2 of these died; 12 patients had persistent intraepithelial abnormality of the cervix and the other 9 patients showed no abnormality after varying periods of observation. Recurrences after cone biopsy were noted in 9.5 and 10.1 per cent of patients with severe dysplasia and carcinoma in situ respectively, and in 2 per cent of patients who had an in situ carcinoma treated by hysterectomy. This made a total of 15 patients with recurrences. All were ultimately cured although two patients were found to have invasive carcinoma.


Treatment and survival in 631 patients with invasive carcinoma of the cervix. From 1951 to 1972, a total of 631 cases of invasive carcinoma of the cervix were diagnosed in Frederiksberg, Copenhagen, Denmark. Treatment was either by surgery or radiotherapy, a combination of both being rarely used. The crude five-year survival rates were 99 per cent in stage Ia, 79 per cent in stage Ib, 67 per cent in stage IIa, 45 per cent in stage IIb, 23 per cent in stage III, 5 per cent in stage IV and 63 per cent for all stages. The relative survival rates were respectively 100 per cent, 81 per cent, 73 per cent, 48 per cent, 26 per cent, 5 per cent and 66 per cent. Radical hysterectomy were found more effective than radiotherapy in stage Ib carcinoma of the cervix. This difference was not explained by age but other factors possibly playing a role are considered. The combination of surgery and radiotherapy is discussed and only seems indicated for patients with stage Ib carcinoma and lymph node metastases.


Effect of sterilization on menstrual blood loss. Menstrual blood loss was measured objectively in 25 women for up to three months before and for six to twelve months after tubal ligation. The operation made no significant difference to menstrual blood loss.


The distribution of neoplasm in patients dying after treatment of endometrial carcinoma. An analysis of 155 patients with endometrial carcinoma, first seen more than five years ago, shows that 31 per cent died with tumour. Trans-coelomic spread of tumour was the most frequent cause of death and occurred in 13.6 per cent of all patients and in 17.1 per cent of those who were operable. A second important cause of death was haematogenous spread of tumour (6.5 per cent). Local pelvic recurrence was the cause of death in 25 per cent of those who did not survive, and local spread was found in 2.2 per cent of operable patients. A rational approach to therapy for endometrial carcinoma is suggested.


A successful pregnancy following malignant phase hypertension. We describe a patient who had a successful pregnancy three years after starting treatment for malignant phase renal hypertension and two years after a nephrectomy for right renal artery thrombosis and an aorto-femoral graft for right common iliac artery thrombosis.


Problems in assessing effects of induction of labour on perinatal mortality. Data on births in the Oxford area for 1965 and 1972 are examined, and a model presented for analysing some effects of induction of labour during this period. It is suggested that this model is generally useful in understanding the various possible explanations for an apparent improvement in perinatal mortality figures.


The outcome of pregnancy in former oral contraceptive users. As part of a continuing major prospective survey, the outcome of 5530 pregnancies in former oral contraceptive (pill) users was compared with the outcome of 11 009 pregnancies in the control series of women who had never used the pill. In former pill users there was a significantly higher induced abortion rate. There was no increase in the reported spontaneous abortion rate, and there is evidence to suggest that the true spontaneous abortion rate may be materially lower in former pill users. The previous use of oral contraceptives appeared to have no adverse effect on subsequent births.


Maternal factors associated with fetal chromosomal anomalies in spontaneous abortions. The effect is described of maternal factors on the proportion of fetal chromosomal anomalies in a series of 2620 spontaneous abortions, of which 992 specimens were karyotyped. Maternal age was the most important factor associated with a rise in the proportion abnormal, followed by Social Class I or II and the use of oral contraception before conception. The problem of extrapolating from the proportion abnormal to absolute incidence of anomalies is discussed. In the case of increasing maternal age, the evidence suggests that the rise in incidence of spontaneous abortions with age is accounted for by an increased incidence of chromosomally abnormal fetuses. In the case of high social class and a history of oral contraception, the evidence on incidence is scanty and the rise in the proportion abnormal may either reflect a decrease in the abortion rate of chromosomally normal fetuses, or a small increase in the incidence of lethal chromosomal anomalies.


Changes in fetal and maternal heart rate during abdominal radiography in late pregnancy. Continuous recordings of maternal and fetal heart rate were made in 30 antenatal patients during simulated abdominal radiography in late pregnancy. Transient changes in fetal heart rate occurred in 43 per cent of patients in the supine position compared with 27 per cent in the prone position. Transient increase of maternal heart rate occurred in 37 per cent of patients. There was no evidence of revealed or concealed caval occlusion.


A comparison of the effect of extradural and parenteral analgesia on maternal plasma cortisol concentrations during labour and the puerperium. Maternal plasma levels of cortisol were measured serially by radioimmunoassay in two groups of 12 patients during induced labour and in the puerperium. One group was given continuous extradural analgesia throughout labour, the other group received pethidine and promazine in response to pain. Pre-induction cortisol levels were significantly higher in patients who were to have extradural analgesia but the percentage increase in plasma cortisol during labour was considerably less than in patients with parenteral analgesia; in second stage labour, mean cortisol levels were the same in the two groups. This study suggests that patients who had chosen to have extradural analgesia may have been more anxious before labour than the other patients but continuous, extradural analgesia suppressed to some extent the percentage increase in mean cortisol levels found during labour in patients given parenteral analgesia. In the puerperium, there was no difference in mean cortisol levels in the two groups.


A serial study of coagulation factors XII, XI and X in plasma in normal pregnancy and in pregnancy complicated by pre-eclampsia. A serial study of coagulation factors XII, XI and X in plasma has been carried out on 60 primigravidae, prospectively comparing those who remained normal with those who developed pre-eclampsia. In the normal group of 48 patients, the levels of all factors rose as pregnancy advanced, a secondary increase in factors XI and X occurring in the puerperium. Cord levels of all three factors were depressed. In the pre-eclampsia group of 12 patients, factor XII was significantly higher than in the normal group throughout the study, while factors XI and X were slightly lower. Observed changes failed to support the idea of a strong primary role for the coagulation mechanism in the pathogenesis of pre-eclampsia.


Induced abortion and secondary infertility. The role of induced (and spontaneous) abortions in the aetiology of secondary sterility was investigated. Obstetric and gynaecologic histories were obtained from 100 women with secondary infertility admitted to the First Department of Obstetrics and Gynaecology of the University of Athens Medical School and to the Division of Fertility and Sterility of that Department. For every patient, an attempt was made to find two healthy control subjects from the same hospital with matching for age, parity, and level of education. Two control subjects each were found for 83 of the index patinets. The relative risk of secondary infertility among women with at least one induced abortion and no spontaneous abortions was 3.4 times that among women without any induced or spontaneous abortions (95 per cent confidence interval 1.38-8.37). The relationship was statistically significant and indicated that in Greece, about 45 per cent of the cases of secondary infertility may be attributable to previous induced abortions.


Cervical mucus and identification of the fertile phase of the menstrual cycle. Nine healthy fertile women were studied during 29 menstrual cycles. A cervical mucus grading system, assessed by the patient and used in conjunction with basal body temperature, was correlated with plasma levels of luteinizing hormone (LH), oestradiol and plasma progesterone. The results show that a patient can be taught to predict the time of ovulation by observing the changes in the cervical mucus.


A study of the use of intermittent serum luteinizing hormone, progesterone and oestradiol measurements for the detection of ovulation. The value of luteinizing hormone (LH), progesterone (P) and oestradiol (E2) in serum as an index of ovulation and corpus luteum function was studied in blood samples collected at infrequent intervals during the menstrual cycle from 19 healthy Thai women. A serum P level of more than 3 ng/ml was detectable in 70 to 80 per cent samples obtained between days 20 and 25 and a P peak and/or E2 peak (greater than 150 pg/ml) were found at this time in 85 to 94 per cent of the cycles. In not more than 26 per cent of the cycles was an LH peak (greater than 150 ng/ml-LER-907) detected when all results were considered. A significant P and/or E2 peak on day 22 or 23 occurred in more than 78 per cent of 25 to 33 day cycles, whereas, the P and/or E2 peak was detectable in only 50 per cent of the cycles lasting less than 25 or more than 33 days. The postovulatory serum P levels were the ones most consistently raised in patients studied over several consecutive cycles.


Chorionic haemangiomata and abruptio placentae. Case report and review. A case of fetal death from abruptio placentae is reported in which the placenta was the seat of multiple chorangiomata. This association is believed not to have been fortuitous and a possible mechanism is suggested by which chorangioma may contribute to the pathogenesis of placental abruption. The incidence, morphological variation and clinical manifestations of placental chorangiomata are briefly discussed.


Pathology of practolol-induced ocular toxicity. The ocular side-effects of prolonged practolol administration concern the cornea and conjunctiva and are related to deficient tear secretion and the formation of an autoantibody which has an affinity for the intercellular zones of squanmous epithelium. Histopathological study of six cases, including a review of the necropsy findings in two, showed destruction of lacrimal gland tissue, epidermalization of the conjunctival epithelium, with epitheliolysis and stromal ulceration of the cornea leading to perforation in two patients. Immunoperoxidase studies showed fixation of specific antibody in the corneal and conjunctival epithelium but, in the one case in which the tissue could be adequately studied, complement fixation could not be demonstrated. Possibly, therefore, the immune response in patients with practolol-induced ocular damage is secondary to the epithelial disturbance rather than its cause.


Ageing and degeneration in the macular region: a clinico-pathological study. Clinical and pathological examination was performed on 378 eyes from 216 patients aged 43 to 97 years. This series represented eyes in which the fundi were normal or showed various manifestations of senile macular degeneration. The eyes were divided into six groups according to the histological appearance of a linear deposit at the base of the retinal pigment cells. Groups I and II were considered to represent normal ageing, Groups III and IV the progressive development of senile macular degeneration and Groups V and VI the end-results. Group I showed no basal linear deposit. Thickening and hyalinization of Bruch's membrane was noted as early as the fifth decade. Group II showed patchy development of the basal linear deposit in relation to thickened or basophilic segments of Bruch's membrane, or over intercapillary hyalinization extending to the level of the outer surface of the choriocapillaris. Almost all eyes in these two groups retained a normal fundus appearance but visual acuity declined with age even in the absence of other causes. In Group III the basal deposit formed a thin continuous layer associated with moderate degeneration of the retinal pigment epithelium. More than half the eyes had developed a clinical disturbance of pigmentation and in most vision was reduced. Group IV was characterized by thickening of the deposit and more pronounced disturbance of the pigment epithelium. Clinically most eyes showed coarse pigmentary changes and vision was in the order of 6/24. 14-3 per cent of eyes in this group showed early neovascularization from the choroid. In Group V the pigment epithelium disappeared to produce circumscribed areas of depigmentation. The basal linear deposit could be traced throughout the depigmented area in most eyes. Thin fibrovascular sheets were found beneath the pigment epithelium in 41-7 per cent of eyes. Group VI represented disciform degeneration. The basal linear deposit could often be demonstrated as a disrupted hyalinized layer incorporated into the scar. Disciform degeneration was an alternative end-result to geographical atrophy. In each group the clinical and histological findings may be modified by the presence of drusen or by atrophy of the choroid. The basal linear deposit consisted of banded fibres embedded in granular material lying between the plasma infoldings and the basement membrane of the retinal pigment epithelium. This deposit seems to be a manifestation of gradual failure of the pigment epithelium and proved to be the most suitable criterion by which to study the natural history of senile macular degeneration.


Unilateral retinitis pigmentosa sine pigmento. A patient presented with unilateral findings of night blindness shown by impaired rod function and dark adaptation, constricted visual fields with good central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impaired electro-oculogram. There were none of the pigmentary changes usually associated with retinitis pigmentosa. The unaffected right eye was normal in all respects. Therefore the case is most probably one of unilateral retinitis pigmentosa sine pigmento.


Ocular findings of elderly cases of homozygous sickle-cell disease in Jamaica. The ocular fingings in 60 patients with homozygous sickle-cell disease over the age of 40 years have been described. Peripheral retinal vessel disease was common and appeared to increase with age. Retinitis proliferans was common among older patients in the group. Angioid streaks occurred in 13 (22 per cent) patients.


Ocular toxocariasis in adults.

Ocular toxocariasis in adults. Human infection by toxocara larvae has been thought to be predominantly a disease of young children, but the percentage of the population with antibodies to this nematode worm has recently been shown to increase with age. Although a definite diagnosis of ocular toxocariasis can be made only by identifying the larva histologically, the evidence in three cases presenting with recent uniocular loss of vision strongly suggests that adults may also be affected. The lesions noted on ophthalmoscopy closely resembled toxocaral granulomata in children. Toxocaral fluorescent antibody tests were positive in each case.


Synapse formation in retinoblastoma tumours. Developing photoreceptor-like cells in retinoblastoma tumour fleurettes were found to contain apical tight junctions, mitochondrial-filled inner segment regions with cilia, and basally located synaptic ribbons and vesicles. Synaptic contract appeared to be established with adjacent neuronal-like elements. We suggest that photoreceptor differentiation in retinoblastoma tumours follows a sequence similar to normal human photoreceptor embryogenesis.


Indocyanine green fluorescence angiography of the choroid. Indocyanine green fluorescence (ICG) angiography of the choroid gives better visualization of the choroidal vessels than does fluorescein angiography. We found that the detachment of the pigment epithelium seems bigger on ICG than on fluorescein angiograms, and pigmented lesions are more clearly delineated.


Multilobed uveal melanoma masquerading as postoperative choroidal detachment. A case of multilobed malignant melanoma with a haemorrhagic retinal detachment which mimicked a postoperative choroidal detachment is described. Because the lesion showed no resolution six weeks after cataract surgery a tumour evaluation was undertaken. The diagnosis was established with a positive radioactive phosphorus uptake (32P) test and biopsy of the intraocular mass. A suggested approach to the diagnosis in such difficult cases is proposed.


Retinal microscope.

Retinal microscope. An instrument is described that provides a stable magnified image for ophthalmoscopy and a low power operating microscope combined to allow greatly improved fundal inspection and to eliminate the need to change instruments during detachment surgery.


Viscosity and retinal vein thrombosis.

Viscosity and retinal vein thrombosis. Whole-blood and plasma viscosity with haematological and biochemical investigations were measured in 44 patients with retinal vein occlusion. The patients were subdivided on the basis of fluorescein angiographic findings into: 1. Those with large areas of capillary non-perfusion. 2. Those with small areas of capillary non-perfusion. 3. Those with an intact capillary pattern. Capillary non-perfusion in retinal vein occlusion is associated with a higher morbidity owing to the complications of retinal neovascularization. Significantly higher values of whole-blood viscosity, packed cell volume, and yield stress have been found in patients with capillary non-perfusion than in those without. These differences may be of critical importance during the episode of retinal vein occlusion and suggest an aetiological factor in the development of capillary non-perfusion. Higher whole-blood and plasma viscosity values and plasma fibrinogen levels have also been shown in the whole retinal vein occlusion group compared with a control group of 30 individuals. These differences may be a factor in the development of retinal vein occlusion but their precise role is difficult to evaluate. Further biochemical investigations in the vein occlusion group supported the strong association with arterial disease and suggested a higher incidence of biochemical abnormalities in those patients with capillary non-perfusion.


Fluorescein angiography and its prognostic significance in central retinal vein occlusion. To determine the prognostic value of fluorescein angiograms in central retinal occlusion 75 patients presenting within the first three months of their initial visual symptoms were studied prospectively. The prognosis was found to be best (complete or partial resolution) in eyes with good capillary perfusion, an intact perifoveal capillary arcade, and leakage only from terminal venules and veins. A broken perifoveal capillary arcade and much capillary leakage, even in the absence of obvious capillary closure, were precursors of permanent macular oedema. All eyes with extensive capillary closure developed severe complications such as thrombotic glaucoma and neovascularization (pre-retinal fibrosis), and all became blind. Macular transit time and leakage from arteries and veins were not used as prognostic features. Fluorescein angiography during the first month of the initial visual symptoms was of prognostic value only in those cases with poor prognosis. The three-month angiogram was an accurate indicator of the visual outcome in all cases.


Central retinal artery occlusion (reversible in sickle trait with glaucoma. We report a case of central retinal artery occlusion in an 18-year-old black woman with sickle-trait haemoglobinopathy and acute glaucoma after hyphaema. The central retinal artery occlusion occurred immediately after treatment of the glaucoma with osmotic agents, raising the possibility that they played a precipitating role. We suggest that osmotic agents be used with extreme caution in sickle patients with glaucoma. The occlusion was treated by anterior chamber paracentesis with eventual return of good vision. The reversibility of retinal and optic nerve function after total ischaemia is discussed.


Macular and perimacular vascular remodelling sickling haemoglobinopathies. The posterior pole vasculature of 100 patients with different sickling haemoglobinopathies was studied prospectively over a period of three years. Various abnormalities of the posterior pole vasculature were seen in 29 per cent of the patients. Continuous remodelling of the macular and perimacular vasculature occurred. Visual acuity was variably affected and sometimes remained intact.


Acute vitreous haemorrhage: a clinical report. In the first hours after a vitreous haemorrhage dense enough to obscure the reina, the blood is usually confined to the posthyaloid space in an aqueous phase. Binocular occlusion and elevation provides sufficient immobilization of the eyes in nine out of 10 patients for the blood cells to settle to the bottom of the space and make the retina available for examination and repair. Blood enters the vitreous gel through holes that develop in the posterior hyaloid membrane. Blood in the gel does not settle and requires months to clear.


Diabetic retinopathy with normal glucose tolerance. A case is reported of a patient with typical diabetic retinopathy, but with normal glucose tolerance. Previously reported cases are reviewed and it is concluded that in such patients the diabetes is probably latent, the retinopathy being discovered during a period of natural or induced remission.


Spheroidal degeneration of cornea and conjunctiva. A study of almost 1000 outpatients at a London eye hospital showed the presence of asymptomatic yellowish, spheroidal deposits in the peripheral cornea or conjunctiva, or both, in about 6 per cent, with a preponderance of males and older subjects among those affected. This prevalence is less than is observed in people in countries exposed to higher levels of sunlight. Histological study of the deposits showed some tinctorial similarities with pseudoelastic fibres of pingueculae, with which they were sometimes associated, but also significant differences suggesting that the spheroidal deposits might be a composite of degenerate collagen and a second non-collagenous protein. Until a more precise terminology is feasible we suggest that a purely descriptive name such as spheroidal degeneration or droplet keratopathy should be used to describe this entity.


Contact lenses at high altitude: experience on Everest south-west face 1975. Five members of the British Everest Expedition 1975 were equipped with hydrogel contact lenses. Some clinical observations are made about the performance of these lenses. Two men were able to use them up to an altitude of 24,000 ft, where the ambient oxygen tension is of the order of 55 mmHg.


Acute endocrine exophthalmos.

Acute endocrine exophthalmos. A case is reported of acute endocrine exophthalmos in a 60-year-old clinically euthyroid male diabetic and the rapid response to steroid therapy is described. The exophthalmometer was used to assess objectively the variations of the exophthalmos.


Retinal vascular changes in congenital hypertrophy of the retinal pigment epithelium. The overlying retinal blood vessels were abnormal in five cases of congenital hypertrophy of the retinal pigment epithelium. This illustrated the well-recognized association between outer retinal degeneration and obliteration of the overlying retinal vasculature. The proposed pathophysiological mechanisms, however, seem inadequate to explain completely the morphological changes of the retinal blood vessels in the presence of atrophy of the outer retina.


Retinal vascular changes in bull's eye maculopathy. A case of maculopathy mimicking chloroquine toxicity without exposure to the drug is described. The peripheral retina showed sheathing and arterio-venous anastomosis with poor perfusion of the retinal circulation.


Ocular findings in a case of fucosidosis. The ocular findings in a case of fucosidosis are described and the differential diagnosis is discussed. It is suggested that the level of alpha-L-fucosidase should be estimated in cases of bull's eye retinopathy.


Annular choroidal sclerosis.

Annular choroidal sclerosis. This is a case description of a rare fundus condition known as annular choriodal sclerosis. No more than four previous cases have so far been reported. In this article consideration is given to the pathogenesis of the disease and a possible familial link.


Aetiology of keratoconus.

Aetiology of keratoconus. Keratoconus has a common association with atopic conditions. Most keratoconus patients rub their eyes excessively. Eye-rubbing is considered the dominant aetiological factor in two-thirds of patients with keratoconus who progress to contact lens wear. A classification of keratoconus based on the dominant aetiological factors is proposed. No significant psychoneurotic factor was found in the keratoconus patients compared with patients in the control group.


Corneal changes in patients treated with clofazimine. Fine, brownish lines, similar to chloroquine keratopathy, were observed in two of 19 psoriatic patients given clofazimine. There was no functional disturbance and the changes were reversible.


Clinical manifestations secondary to soft contact lens wear. The study of 151 patients wearing soft hydrophilic lenses for one year revealed no gross irreversible lesions with loss of vision. But of significance was the presence of superficial lesions of the corneal epithelium, and chronic stromal oedema. While no significant loss of wearing time was noted for women taking the pill, the decrease in tear secretion in those patients with a latent dry eye problem could just alter the balance to produce intolerance. From this report it is the long-term changes to the tissues that remain to be fully investigated for soft hydrophilic lenses.


Subconjunctival and episcleral lipid deposits. Biomicroscopical examination of the bulbar conjunctiva and anterior episclera of 1000 randomly selected outpatients showed the presence of multiple discrete lipid globules in 30 per cent. The lipid deposits were asymptomatic. Their prevalence was age-related, while their distribution and composition were consistent with origin from the conjunctival blood vessels.


Recurrence of astrocytoma of optic nerve after 48 years. A tumour presumed to be a juvenile glioma of the optic nerve was removed by a Kronlein procedure from a 4-year old boy in 1925. In 1973 a severe proptosis made it necessary to remove the atrophic eye and a large retro-ocular tumour. Histological examination, supported by electron microscopy, showed the second tumour to be an anaplastic pilocytic astrocytoma. The possible histogenesis and this unusual behaviour pattern are discussed.


Fertilizer calcium as a factor affecting the voluntary intake, digestibility and retention time of pangola grass (Digitaria decumbens) by sheep. 1. Pangola grass (Digitaria decumbens) grown with and without calcium fertilizer was cut at three stages of regrowth to measure voluntary intake of dry matter (DM) and digestibility of various components of the dried-grass diet by sheep kept in metabolism crates. To determine the extent of a simple Ca deficiency half the sheep on each diet was supplemented with 1-4 g Ca/d. Retention times of the various dietary components in the reticulo-rumen were also determined. 2. Feeding a Ca supplement had no effect on voluntary intake or digestibility. 3. Ca fertilizer increased the Ca content of the grass from 2-2 to 3-8 g/kg DM and DM digestibility from 0-455 to 0-476 (P less than 0-01) due to an increase in the digestibility of the hemicellulose. 4. Voluntary intake was increased from 38-8 to 43-2 g/kg body-weight0.75 per d by Ca fertilizer due to an 18% reduction in the period of time the DM was retained in the reticulorumen. 5. Regressions relating voluntary intake to DM digestibility for the Ca-fertilized and control grass were significantly different (P less than 0-01). When compared at the same DM digestibility the voluntary intake of the Ca-fertilized grass was 2-6 g/kg body-weight0.75 per d higher than that of the control. 6. It was concluded that Ca fertilizer increased both DM digestibility and voluntary intake as a result of changes in the structural composition of the grass and not by a simple increase in the Ca content of the diet.


Amino acid metabolism in the piglet. 2. Influence of fasting on plasma free amino acid concentration and in vivo oxidation of methionine, isoleucine and threonine. 1. The influence of a 24 h fast on the concentrations of free amino acids in the plasma, and upon the oxidation rates of methionine, isoleucine and threonine was studied (using early weaned, 4-week-old piglets which were receiving a semi-purified diet. 2. There was no change in the total concentration of the essential amino acids as a result of the 24 h fast: the concentration of the branched-chain amino acids increased, but the effect of this was offset by decreases in the concentrations of arginine, histidine, lysine, methionine and phenylalanine. There was a reduction in the concentration of the non-essential amino acids. 3. The piglets received infusions of L-[I-14C]methionine, L-[U-14C]isoleucine and L-[U-14C]-threonine, and the recovery of the label in carbon dioxide was determined. Less than 5% of the activity from methionine was recovered in the CO2 from the fed piglets, whereas 12% was recovered from the fasted piglets. The corresponding values with threonine were 11 and 19% but there was no effect of fasting on the recovery of the label from isoleucine in CO2. 4. The initial dilution of a single dose of a labelled amino acid infused into the bloodstream depends on the plasma concentration of the amino acid. Nutritional regimens may effect the free amino acid concentration in the plasma. Thus comparisons based upon direct determination of activity recovered in CO2 from the labelled dose of an amino acid with animals on different nutritional regimens could not misleading, unless the differences in the concentrations of the amino acid in the plasma are considered.


Nitrogen metabolism in calves. Effect of giving different amounts of dietary casein with and without formaldehyde treatment. I. Calves were given a basal diet of straw and flaked maize (12 g nitrogen/kg dry matter (DM)) or diets with some flaked maize replaced by untreated (UT) casein or formaldehyde-treated (FT) casein to give 19, 29 or 34 g N/kg DM. 2. At all intakes rumen ammonia concentrations were lower and amounts of total-N, non-ammonia-N and amino acid-N entering the duodenum were high when FT-rather the UT-casein supplements were given. 3. Direct measurement of casein entering the duodenum indicated that giving FT rather than UT casein led to much greater amounts of dietary casein escaping degradation in the rumen (70--90% compared to 10--20%). Calculated values for fermentable N indicated that with this low degradability diets containing FT-casein would have provided inadequate N for maximum microbial synthesis in the rumen, and this probably accounted for the marked reduction in amounts of non-casein-N entering the duodenum when FT rather than UT casein was given. 4. Amino acid patterns in duodenal digesta samples after giving the basal diet or diets containing UT-casein were similar. Giving diets containing FT-casein led to changes in this pattern which could sometimes, although not always, be accounted for by estimated differences in proportions of dietary and microbial proteins. 5. At the highest level of N intake FT-casein-supplemented diets led to significantly higher concentrations of most essential amino acids and lower concentrations of most non-essential amino acids in plasma than did UT-casein-supplemented diets. Plasma urea concentrations increased with increasing N intake but were not significantly different for UT- and FT-casein-supplemented diets.


The ileum of the sheep as a site of protein digestion. 1. In order to study the ability of the ileum of the sheep to digest and absorb protein, casein or gluten were infused into the intestine of rams through cannulas inserted at distances of 0-05, 7, 9 and 15 m from the pylorus. Amounts of casein or gluten containing 10-20 g nitrogen were infused during 24 h, in animals given a low-N diet. 2. N balance was negative during the preliminary period when no infusion was given; infusion of casein or gluten increased the daily N retention to 5-15 g. 3. Infusion of proteins into the intestine did not induce an increased activity of pancreatic proteases in digesta withdrawn from the lower part of the intestine. 4. The increased N retention after the infusion of proteins into the lower part of the intestine indicates a considerable capacity of this section of the intestine to digest and absorb proteins.


The effect of cold exposure of sheep on digestion, rumen turnover time and efficiency of microbial synthesis. 1. Six closely shorn sheep were given brome grass (Bromus inermis) pellets at 1 h intervals and maintained at ambient temperatures of --I to Idegree and 18--21degrees for 28 d. Measurements of digestion were made during the last 10 d of temperature exposure. 2. Cold exposure resulted in a reduction in apparent dry matter (DM) digestibility from 0-482 to 0-450, and of apparent digestibility of organic matter (OM) from 0-511 to 0-477. Neither apparent digestibility nor retention of nitrogen was affected. 3. Apparent digestibility of OM in the rumen decreased from 0-300 to 0-242 with cold exposure, and was highly correlated with turnover time in the rumen of 103Ru, which was used as a particulate marker. 4. The efficiency of microbial synthesis (g N incorporated into microbial cells/kg OM apparently digested) was correlated with the dilution rate of the solute marker (51Cr) and with the turnover time of the particulate marker (103Ru) in the rumen. 5. Digestion in the intestine of DM and OM accounted for significantly more of apparent digestion in the whole gastrointestinal tract for sheep kept in the cold than for sheep kept in the warm. The apparent digestibilities of DM and OM entering the intestine were similar in sheep on both treatments, but significantly more non-ammonia-N was digested in the intestines of cold-exposed sheep. 6. The influence of dilution rate of rumen fluid on the efficiency of synthesis of microbial cells in the rumen is discussed.


The histological effects of copper and zinc on chick embryo skeletal tissues in organ culture. 1. The effects of copper and zinc on organ cultures of chick embryo cartilage and bone maintained in low-trace-metal, chemically defined media for up to 8 d were studied macroscopically, histologically and histochemically. Length and wet-weight measurement of explants were assessed statistically. 2. No effects were found with Cu concentrations of 0-5-1-5 mug/ml medium. Between concentrations of 5 and 40 mug Cu/ml medium, lengths and wet-weights of cartilage cultures decreased significantly (P less than 0-001) compared with controls. The decrease was directly proportional to increasing Cu concentration, and that of the length was greater with increasing period of culture (P less than 0-001). 3. With 5--20 mug Cu/ml medium cartilage and bone became yellow in colour, and chondrocytes were swollen, rounded and basophilic. They were detached from their lacunae and the quantity of matrix was reduced. Loss of alkaline phosphatase (EC 3.1.3.1) activity and disappearance of glycogen accompanied the degeneration. Osteogenesis ceased, cells failed to divide and mature, lost their enzymes and died. Cu did not accumulate in the bone matrix. 4. The direct toxic effects of Cu for cartilage and bone may underlie some of the skeletal changes in hepatolenticular degeneration (Wilson's disease). 5. As Zn concentrations were increased from 2-5 to 7-5 mug/ml medium, lengths and wet-weights of cartilaginous cultures were significantly increased (P less than 0-001). As Zn concentrations were further increased (from 10 to 40 mug/ml medium), lengths and wet-weights were significantly decreased (P less than 0-001). 6. Zn stimulated chondrocyte division and vacuolation of cytoplasm. With higher Zn concentrations toxic changes of granular basophilia, lacunar detachment and necrosis were seen. Differentiation and functioning of osteoblasts, osteoclasts and chondroclasts were stimulated by Zn. 7. Zn was found in bone matrix, osteoblasts, osteocytes and hypertrophied chondrocytes.


The role of the gut microflora in the utilization of dietary urea by the chick. 1. In a preliminary experiment, growth of conventional chicks given a basal diet containing adequate amounts of all the essential but none of the non-essential amino acids was improved by supplements of 10-3 g urea or 50-4 g glutamic acid/kg diet or both. 2. In the main study the effects of supplementing the basal diet with 20-6 g urea/kg were compared in groups of sixteen germ-free and conventional chicks. 3. The germ-free chicks did not benefit from the urea supplement whereas the conventional birds showed improved food conversion efficiency and significantly better growth. 4. In both environments nitrogen retention ((mg N intake-mg N excreted)divideg food intake) was higher in the birds given urea, but N utilization ((mg N intake-mg N excreted)dividemg N intake) was reduced. This reduction was greater in the germ-free birds. 5. There was a small increase in plasma ammonia concentration in the germ-free birds given urea but a significantly greater increase in the corresponding conventional group. 6. Plasma uric acid concentrations were variable in both groups, and much lower than the normal range. They followed a similar pattern to the plasma ammonia values. 7. More insoluble N was excreted by the conventional chicks given urea than by the corresponding germ-free group, or by either group given the basal diet. 8. It was concluded that the gut micro-organisms are responsible for the growth-promoting effect of urea, presumably through release of ammonia by bacterial ureas (EC 3.5.1.5) and its consequent incorporation into amino acids.


Influence of fructose feeding on individual enzymic reactions in the formation and metabolism of bile acids in rat liver homogenates. 1. Rats were maintained for 10 d on a semi-synthetic diet containing 700 g glucose or 700 g fructose/kg. Individual enzymic reactions in bile acid synthesis and metabolism were studied by measuring the 7alpha-hydroxylation of [4-14C]cholesterol, and 12alpha-hydroxylation of 7alpha-[6beta-3H]hydroxy-4-cholesten-3-one, the 26-hydroxylation of 5beta-[7beta-3H]cholestane-3alpha,7alpha-diol and the 6beta-hydroxylation of [3H]lithocholic acid in liver homogenates. 2. The serum cholesterol level was approximately the same in both groups of animals, but the serum triglyceride level was almost twice as high in the fructose-fed rats compared to the glucose-fed rats. 3. The 6beta-hydroxylation of [3H]ithocholic acid was increased by about 20% in the fructose-fed rats compared to the glucose-fed animals. The activities of the other enzymic reactions studied did not differ significantly between the two groups of animals. The findings are discussed in relation to previous knowledge concerning mechanisms regulating triglyceride, pre-beta-lipoprotein and bile acid synthesis.


A system for automatic collection and removal of urine from male farm animals. A system for collection and removal of urine has been developed, consisting of a peristaltic pump controlled by an electronic switch activated by the presence of urine in a funnel and in tubing. For optimum performance, it is necessary to clean parts at regular intervals.


The copper status of beef cattle in Northern Ireland. 1. Serum caeruloplasmin (ferroxidase I;EC 1.16.3.1) activity has been used as an indicator of copper status of cattle to survey beef herds in Northern Ireland. 2. The main survey covered some 20 000 cows on 1200 farms. 3. The results are reported in the form of a map showing area where herds of low and very-low Cu status predominate. Clinical signs of Cu deficiency in calves were encountered in only two areas.


Energy losses associated with oven-drying and the preparation of rat carcasses for analysis. 1. The effect of oven-drying on the heat of combustion of rat carcasses was studied and found to produce losses of 10% of the original energy content. Oven-drying also produced a small loss of nitrogen. 2. A method of carcass preparation not involving oven-drying was tested and found to produce suitably homogeneous samples for analysis without any loss of energy.


The use of pivalic acid as a reference substance in measurements of production of volatile fatty acids by rumen micro-organisms in vitro. 1. A procedure is described for using pivalic acid as an inert reference substance in determination of changes in concentrations of volatile fatty acids (VFA). 2. Pivalic acid in concentrations of up to 80 mmol/1 had no effect on production of methane or VFA by rumen contents. 3. Pivalic acid was inert during incubation with rumen contents from sheep given different diets and with samples taken at different times with respect to feeding.


Solution conformation of a retro-D analogue of tocinamide. The solution conformation of a retro-D analogue of tocinamide H-D-Cys-D-Asn-D-Gln-D-aIle-D-Tyr-NHCH2CH2S was examined using proton magnetic resonance and circular dichroism spectroscopy. The observations support major contributions to the conformational distribution from structures with a type I beta turn in the sequence D-Asp-D-Gln-D-aIle-D-Tyr. This is topologically similar to the beta turn proposed for oxytocin, L-Tyr-L-Ile-L-Gln-L-Asn, but with the polarity of the CONH groups reversed along the chain; the peptide is, however, hormonally inert. In conjuction with nuclear magnetic resonance data, the circular dichroism spectra are interpreted to indicate that the region of the peptide ring near the disulfide occurs in at least two different conformations. One of the side-chain carboxamides, probably that of asparagine, appears to be intramolecularly associated rather than freely exposed to solvent.


Membrane surface properties other than charge involved in cell separation by partition in polymer, aqueous two-phase systems. When aqueous solutions of dextran and of poly-(ethylene glycol) are mixed above certain concentrations, immiscible, liquid two-phase systems are obtained which are useful for separating cells by partition. Some salts partition unequally between the phases, giving rise to an electrostatic potential difference between them. Partition of cells has therefore been thought to depend predominantly on membrane charge. We now report two instances in which membrane charge either does not determine or is not the main determinant of cell partition. (A) Cell partition coefficients in phase systems approaching the critical point (the component concentrations below which a homogeneous solution occurs) increase, even in phase systems in which the phase potential difference is practically zero. Furthermore, in such systems, the partition coefficient of (human) erythrocytes is not reduced by complete removal of sialic acid. (B) Rat and mouse erythrocytes have sizable partition coefficients in a phase system away from the critical point with no potential difference between the phases. Cell surface interaction with the polymers is probably responsible for cell partition in these cases. Partition studies on erythrocytes from nine mammalian species in phases near the critical point with and without electrostatic potential differences reveal major species-specific differences in the membrane charge/noncharge components. A correlation has been found, in phases near the critical point that have essentially no electrostatic potential difference, between partition coefficient and the ratio of poly/monounsaturated fatty acids in the membranes of red cells from different species. Our present results thus provide parameters for the separation of cells by partition in addition to or instead of membrane charge depending on the polymer and salt composition and concentration selected.


Ligand-induced polymerization.

Ligand-induced polymerization. Three models of ligand-induced polymerization are considered, encompassing dimerization of acceptor-ligand complex and cross-linking of monomer units via a ligand bridge to form either dimer or linear chains. For each model a binding equation is developed and examined in terms of limits, form, and intersection within a family of curves, each member constructed with fixed but different total acceptor concentration. The characteristics of the binding curves that emerge are correlated with those found by examining the dependence on ligand concentration of either the weight-average molecular weight of the acceptor constituent or a function of it. In the latter plots, a maximum exists for the cross-linking models at the same ligand concentration that the corresponding binding curves intersect: the existence of the maximum implies that at saturating concentrations of ligand only monomeric acceptor constituent remains. The practical implication of these findings is discussed in terms of experimental systems reported previously in the literature. In addition, particular comment is made on the forms of binding curves for the three models, which assume shapes generally associated with positive and negative cooperativity. Finally, comparison is made with those systems in which a shift toward polymeric constituent is effected by ligand perturbation of a preexisting association equilibrium.


Chromatic models. Interactions between DNA and polypeptides containing L-lysine L-valine: circular dichroism and thermal denaturation studies. The interaction of calf thymus DNA with statistical copolymers of L-lysine and L-valine [poly(L-Lys100f-Lvalf)] and block copolymers [poly(L-Lys)100f-poly(L-Val)f] were investigated as a function of ionic strength using circular dichroism (CD) spectroscopy. It was found that valine suppresses the ability of the copolymer-DNA complexes to yield a psi-type CD spectra as found for poly(L-Lys)-DNA [Jordan, C.F., Lerman, L.S., and Venable, J.N. (1972), Nature (london), New Biol. 236, 67] and lowers the ionic strength at which CD distortion occurs. Thermal denaturation, simultaneously monitoring 280-nm ellipticity, [theta]280, and hyperchromicity, h280, was carried out on annealed complexes of poly(L-Lys)-DNA, poly(L-Lys84.5-L-Val15.5)-DNA, poly(L-Lys)87.2-poly(L-Val)12.8-DNA,  and directly mixed complexes of poly(L-Lys)-DNA, IN 2.5 X 10(-4) MEDTA, pH 7.0 solution. The CD denaturation of uncomplexed DNA at several ionic strengths was also determined to examine pre-melting. Despite the inability of both statistical and block copolymers of L-Lys and L-Val to form psi-type complexes with DNA, they bind as well to DNA as does poly(L-Lys) and give rise to a thermal denaturation pattern showing bound peaks between 90 and 100 degrees C, seen clearly with CD denaturation. The thermal denaturation of mixed and annealed complexes of poly(L-Lys)-DNA shows similar patterns in hyperchromicity changes as a function of temperature but very different CD melts. From the CD melt of annealed poly(L-Lys)-DNA, it appears that aggregation and long-range order of the complex are significant in low salt (2.5 X 10(-4) MEDTA) as well as in 1.0 M NaCl. These studies further illustrate the importance of the nature of nonionic interactions (hydrophobic) between polypeptides and DNA in determining the behavior of their complexes, such as causing condensation into higher order asymmetric structures. In light of these observations, the possible significance to the CD melting of chromatin and the validity of identification of C-form DNA by CD spectroscopy are discussed.


Angular scattering analysis of the circular dichroism of biological cells. 1. The red blood cell membrane. A quantitative interpretation of the distorted circular dichroism spectrum of red blood cell membranes is presented including the effects of the intense small angle scattering and light detection geometry of our spectrophotometers. Corrected spectra have been obtained by nondestructive methods which correspond to an in situ membrane protein conformation of 45% alpha helix, 10% beta sheet, and a conformational precision of better than +/- 10%. Forward scattering calculations which neglect the small angle scattering collected by conventional phototube acceptance angles are shown to be unsuitable for red cell membranes. Ultraviolet refractive index dispersion has been estimated for the membranes together with an evaluation of the sensitivity of the calculated spectrum to this variable. Angular scattering and circular dichroism calculations are extended to two alternative models for the location of hemoglobin in "pink ghosts", and it is indicated that this approach might help in resolving the question whether residual hemoglobin is in solution inside the ghost, or is part of its membrane.


Calculation of absolute rates of RNA synthesis, accumulation, and degradation in tobacco callus in vivo. Uptake and incorporation data were used to calculate an absolute rate of ribonucleic acid (RNA) synthesis by assuming that incorporation of radioactive nucleosides into RNA was a first-order function of the nucleoside triphosphate cellular pool. Homogenized tissue was separated into an RNA and cellular pool fraction. Methods were developed to directly measure the specific radioactivity of specific nucleosides in each fraction. Exogenous [3H]uridine was taken up by the cells, converted to I[3H]uridine triphosphate ([3H]UTP) and [3H]cytidine triphosphate ([3H]CTP), and incorporated into RNA. All of the radioactivity in RNA was contained in either uridine or cytidine. The average rate of RNA synthesis (20 mg of RNA (g of RNA)-1h-1) was calculated from changes in the specific radioactivity of uridine or cytidine in RNA and UTP or CTP in the pool. Since ribosomal RNA does not turn over in exponentially growing tissue, its rate of synthesis was measured (14 mg g-1h-1) and compared with the rate of accumulation of RNA (12 mg g-1h-1). The similarity between ribosomal RNA synthesis and total RNA accumulation confirmed the assumption that these methods measured an absolute rate of RNA synthesis.


Angular scattering analysis of the circular dichroism of biological cells. 2. The red blood cell. A detailed interpretation of the grossly distorted ultraviolet absorption and circular dichroism spectra of the intact red blood cell is given, including an evaluation of the effects of protein conformation, detector geometry, cell hemoglobin content, and refractive index on the calculated cell spectra. The origins of the major differences between cell and hemoglobin solution spectra were quantitatively accounted for in terms of differential scatter and absorption flattening, with the latter effect dominating the picture. The relatively low sensitivity of the red blood cell suspension circular dichroism spectrum to hemoglobin conformation is due to the order of magnitude flattening of circular dichroism intensity. The importance of accounting for instrumental light detection geometry and the intense small angle scattering (less than 8 degrees) for a range of particle sizes (0.1-5 mum) is made clear.


Intramitochondrial localization and proposed metabolic significance of serine transhydroxymethylase. Serine transhydroxymethylase is a latent enzyme of intact rat liver mitochondria. The enzyme is neither solubilized by the selective removal of the outer membrane with digitonin, nor inactivated by concentrations of diazobenzenesulfonate that do not penetrate the inner membrane, but that do inhibit solubilized serine transhydroxymethylase. Swelling of mitochondria was studied in isoosmotic solutions of substrates under conditions that would define transport as neutral uniport, anion-hydroxyl exchange, anion-anion exchange, or electrophoretic. L-Serine and glycine appear to be rapidly taken up by a nonelectrophoretic uniport mechanism, while folate and tetrahydrofolate are not tranported. The results localize the enzyme in the matrix and indicate that the latent activity results from a lack of tetrahydrofolate transport across the inner membrane. Based on these results, the dual localization of serine transhydroxymethylase in the mitochondria and the cytosol is proposed to provide a one-carbon shuttle system to link one-carbon metabolism in the two-cellular compartments.