Vaccination of leukemic mice with viable drug-altered leukemic cells. The treatment in vivo with anti-tumour drugs can induce an antigenic alteration of L1210 leukemia resulting in the rejection of an inoculum of 10 X 10(6) viable cells in syngeneic mice. As drug-induced antigens appeared in excess of any pre-existing tumour-associated transplantation antigens (TATA), viable altered cells have been used to sensitize syngeneic animals. Experiments showed that viable altered cells elicited stronger anti-TATA reaction than X-inactivated parental cells, as measured by host survival to a challenge of L1210 leukemia. TATA immunogenicity of parental cells has been preminent, in the strain of animals used, to determine the sensitizing effectiveness of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) cells. Host protection to an inoculum of parental tumours has been more proficient with the DTIC subline derived from highly immunogenic L1210Ha cells than from poorly immunogenic L1210Cr cells. Immunoprophylactic inocula, proper chemotherapeutic treatments and adoptive transfer of immune lymphocytes used in combination exerted a synergic host protection.


Platelet antibody determination by platelet factor 3 assay (comparison with radiolabelled serotonin release and platelet aggregometry). Platelet antibody determination by the PF3 test was carried out in 96 thrombocytopenic patients with various disorders, 31 repeatedly transfused patients with or without thrombocytopenia and 24 patients with autoimmune disease (SLE and myasthenia gravis) without thrombocytopenia. The frequency of a positive test was greatest in the patients with ITP (61%), SLE (50%) or a history of numerous blood transfusions (60%). The patients with myasthenia gravis also showed a considerable frequency (20%) of platelet antibodies detectable by the PF3 test. The PF3 test is less sensitive than the serotonin release test in detecting autoantibodies, but it is more sensitive than aggregometry in detecting isoantibodies and drug-related antibodies.


The mechanism of proteinuria in three different models of renovascular hypertension in the rat. The proteinuria was measured in two-kidney hypertensive rats, in rats made hypertensive by aortic stenosis, in one-kidney hypertensive rats and in a group of control sham-operated animals. It was significantly increased in those of the first and second groups in direct correlation with the PRA which was elevated, while it was only slightly raised in those of the third group with a normal PRA. Following removal of the clip the proteinuria decreased in the two-kidney hypertensive rats, whilst it increased in the other two groups. It is suggested that in the latter cases the increase in protein excretion after removal of the clip could be due to an increase in the blood flow and filtration rate of the revascularized kidneys, whilst in the former this effect could be masked by the constant decreases in proteinuria from the intact kidney due to the fall in the PRA.


Rapid clearance of HBe antigen and development of anti-HBe antibody in acute viral hepatitis. The behaviour of the HBe/anti-HBe system in AVH was evaluated, using Magnius technique, by testing serum samples from 47 patients; 29 of them were followed during the clinical evolution of the disease until complete remission was achieved. HBe was more frequent in samples taken from patients in the first 7 days after the onset of jaundice (18/33 = 54%) than in samples collected later (3/14 = 21%). During the clinical evolution of the disease we could always demonstrate the disappearance of HBe not later than 12 days after the onset of jaundice. In one patient studied from the incubation period HBe disappeared before any clinical or laboratory evidence of disease. In 8/29 cases (27%) anti-HBe developed starting from the 15th day of illness, but 4 of these had had no detectable HBe during the acute phase. No significant difference could be demonstrated between HBe +ve and -ve cases in the maximum values of SGPT and bilirubin and the duration of the disease. The changing pattern of the HBe/anti-HBe system could account for the different incidences of these markers reported by many authors in AVH. Our findings support the hypothesis that HBe develops in every HBsAg +ve AVH case. Therefore, it is not the presence of HBe in the early stage, but the persistence of this marker that might be important in predicting progression to chronicity.


Free urinary cortisol radioimmunoassay (application in the diagnosis of adrenal diseases). The availability of a specific antiserum has made it possible to develop in our laboratory a radioimmunoassay for free urinary cortisol which is quite simple and rapid to perform. No preliminary procedures of chromatographic purification are necessary, and no correction for losses is required. Precision and accuracy tests are satisfactory. Seventeen normal subjects, 10 obese subjects, 18 patients with Cushing's syndrome, 4 hypopituitaric patients and 4 with Addison's disease were studied. The values of free urinary cortisol were compared with those of urinary 17-OHCS, plasma cortisol and, in some cases, the cortisol secretion rate. In normal subjects, the mean free urinary cortisol was 77.22 +/- 7.74 microgram/24 h, in obese subjects it was 112.05 +/- 13.64 microgram/24 h, and in patients with Cushing's syndrome it was at significantly higher levels with a mean value of 488.06 +/- 64.39 microgram/24 h. There was no overlap between the values obtained in the first two groups and those of subjects with adrenal hyperfunction, and the results were similar to those shown by the cortisol secretion rate. The same was not true for urinary 17-OHCS and plasma cortisol. Thus, the assay of free urinary cortisol, that is the free biologically active circulating fraction, may provide a relatively simple alternative to measurement of the cortisol secretion rate, as a single differential test for the diagnosis of conditions with adrenal hyperfunction. Less satisfactory were the results obtained in patients with primary and secondary adrenal hypofunction. Another limitation of the method is its relative non-specificity, since the results of 16 urinary samples measured without preliminary chromatography were 29.6% higher than those after previous chromatographic purification. However, in our experience, this overestimation does not affect the value of the method as a screening test for the diagnosis of Cushing's syndrome.


Myocardial uptake of radiotechnetium in two cases of ventricular aneurysm after infarction. Two very similar cases of persistent positive myocardial scintigraphy with radiotechnetium are described and, in view of agreement of other medical, electrocardiographic, apexcardiographic and radiographic data, this can be ascribed to the presence of a parietal ventricular aneurysm after myocardial infarction.


Fasting serum cholecystokinin immunoreactivity in chronic relapsing pancreatitis. An increase in fasting cholecystokinin (CCK) levels has been reported in patients with pancreatic insufficiency, but the relationship of these findings to the clinical conditions has not been established. We, therefore, measured fasting serum CCK-like immunoreactivity in 70 patients with chronic relapsing pancreatitis (CRP) (38 non-surgically treated and 32 previously surgically treated) and in 44 healthy subjects. The radioimmunoassay detected three circulating forms of CCK. The mean value of the CCK levels in CRP (260.3 +/- 300.8 pg/ml) was significantly higher than that of the controls (56.6 +/- 61.7 pg/ml) (p less than 0.001), but in 39 (56.7%) of the 70 CRP cases the CCK was in the normal range. A smaller overlap with the controls was observed in the non-surgically than in the surgically treated patients (45 vs. 71.8%). In the 38 non-surgically treated CRP cases no relationship was observed between the CCK levels and each of the following parameters: age, length of history, presence or absence of pancreatic calcification, nutritional and alcoholic habits, and the results of exocrine function tests. The absence of the last-mentioned correlation is somewhat unexpected if the high CCK levels are due to the interruption of a feedback loop for CCK secretion. However, previous pancreatic surgical drainage and/or treatment with pancreatic enzymes, present in almost all these patients, could have an effect on CCK behaviour.


Gangliosides, sialoglycoproteins and glucocerebroside in the spleen and bone marrow of patients with beta-thalassemia major. Bone marrow and spleen samples were studied biochemically to elucidate the nature of the material stored in the large histiocytes present in beta-thalassemic patients. Only the protein-bound N-acetylneuraminic acid (NANA) content of the spleen of homozygous beta-thalassemic patients was significantly higher than that of controls. In the bone marrow, which contained a large number of thalassemic storage cells, the lipid-bound NANA and the glucocerebroside showed a moderate increase, while the amount of protein-bound NANA was much greater than that in controls. These results, in agreement with ultrastructural and histochemical observations, differentiate thalassemic storage cells from other storage cells found in diseases characterized by an increased destruction of blood cells and suggest that there may also be an impairment of the sialoglycoprotein metabolism of the red blood cells in homozygous beta-thalassemia.


[The provoked hypercalciuria test. Significance and limitations]. The calcium tolerance test is of diagnostic importance only in osteomalacia, which it helps to identify before bone biopsy when the static phosphocalcic parameters are not a deciding factor. However, the test does not make it possible to distinguish an osteoporosis from a cortisone osteopathy or an idiopathic hypercalciuria. In the first two diseases, the rates of urinary calcium elimination are comparable to that of normal individuals. It seems that the rate of urinary elimination of I.V. administered calcium is, approximately, all the more elevated as the level of iPTH is low; and, when the level of iPTH is low, the osteoid tissue seems less calcified than normally.


[[Calciuria and phosphaturia during fasting. Effect of calcitonin alone or with a thyroid hormonotherapy combination]. The author compares 4 groups of obese individuals subjected to fasting for 7 days: Some took no medication, the others received either triiodothyronine (100 to 150 microgram per day), or calcitonin (1 unit MRC per day) or both triiodothyronine and calcitonin. An increase in calciuria and phosphaturia was observed with either triiodothyronine or calcitonin. Triiodothyronine in association with calcitonin did not increase further the calciuria caused by calcitonin but increased phosphaturia. The author offers an explanation for these various observations.


[Coxarthroses due to ischemia. Ischemic coxarthropathy]. In the first part of their work, the authors present radiological, histopathological and experimental results showing that cartilage of the joint can be originally damaged by articular ischemia. In the second part, they analyze the clinical and radiological features of 40 cases of ischemic coxarthrosis, substantiated by histological examination: these are chronic coxarthropathies with changes in the cartilage without rupture of the femoral head but with medullary necrosis and often trabecular necrosis involving the head and the neck of the femur. These ischemic coxarthroses are most often well centered with a superior or supero-internal pinching and show few osteophytes. They constitute a group of coxarthrosis called "primitive", involving the structure because of a previous weakening of the cartilage.


Aspects of the role of lecithin:cholesterol acyltransferase in metabolism of triglycerides. An increased TG secretion from the liver may lead to an increased secretion of LCAT. Studies on isolated rat hepatocytes have shown: 1. Oleic acid added to the medium stimulates TG and LCAT secretion in a similar way. 2. Cycloheximide, colchicine, 4-amino-pyrazolopyrimidine, and D-galactosamine depress the secretion of both TG and LCAT. 3. There is a positive linear correlation between TG and LCAT secretion in cell preparations from rats operated on with ventromedial hypothalamic lesions. Treatment of rats with orotic acid resulted in maintained plasma LCAT activity despite very low TG concentration. This indicates that LCAT secretion is not dependent upon an intact TG secretion.


A rapid method for lecithin:cholesterol acyltransferase estimation in human serum. All the described procedures for lecithin:cholesterol acyltransferase (LCAT) determination in the plasma have raised criticisms: Lack of sensitivity for methods using colorimetric determination of unesterified cholesterol or phosphatidyl-choline in plasma before and after incubation at 37 degrees C. Incomplete isotopic equilibrium of the free cholesterol substrate between the different lipoproteins in radioassay procedures. Gas-liquid chromatography methods cannot be used when LCAT activity is low. A new method, easier, more sensitive and accurate has been developed in our laboratory:plasma samples are delipoproteinized by coprecipitation with Intralipid, dextran sulphate, and calcium chloride. Cholesterol esterification is assayed by a short incubation (30 min) of 100 microliter delipoproteinized plasma and a 30 microliter of 3H-cholesterol-labelled substrate. About 15% of cholesterol is esterified in these conditions in 30 min (35 +/- 7 micromole/h/l). The LCAT reaction is linear for about one hour.


Investigation of relationship between lecithin:cholesterol acyltransferase activity and coronary atheroma, diagnosed by selective coronary angiography. 140 consecutive patients undergoing selective coronary angiography in the investigation of chest pain had fasting blood specimens collected. 24 specimens were unsuitable due to hemolysis or to incomplete coronary angiography studies. In the 116 remaining patients the serum was analyzed for total cholesterol, free cholesterol, and the initial rate of cholesterol esterification. LCAT activity was determined both as the percentage esterification per minute, and as nmols/ml/min. All the coronary angiograms were examined by a single cardiologist who was unaware of the results of the serum tests. Fixed predetermined criteria were used, resulting in all patients being classified as one of four groups. 36 patients had no detectable atheroma, 23 mild, 21 moderate, and 36 severe. Statistical analysis revealed a significant relationship between the presence and severity of coronary atheroma with the patient's age, and an equally strong relationship was found with the patient's total serum cholesterol. No statistically valid correlation could be found between LCAT activity (as determined by esterification in the patient's native serum) and atheroma. Free cholesterol levels also did not correlate with the presence of antheroma. An interesting finding was the presence of severe antheroma in a small number of patients with low normal level of serum cholesterol and high LCAT activity.


Lecithin:cholesterol acyltransferase as a possible diagnostic tool in ischemic heart disease. Basal values of lecithin:cholesterol acyltransferase (LCAT) were estimated in healthy subjects, in patients with the so-called risk ischemic heart diseases (IHD)--obesity, diabetes, hypertension, and hyperlipoproteinemia II--and in patients with a IHD-infarction of the myocardium. A precise method employing a 14C-4-cholesterol-labeled common normolipidemic substrate was used. A highly significant difference in the average values of LCAT activity between healthy men and women was found. LCAT in men with 'risk' diseases decreased, while in women it remained at the level of the reference group. To assess the dependence between LCAT-dependent indicators and IHD, criteria for evaluating the deviations from reference values were proposed. The number of deviations from the reference group increased in the sequence: obesity, hypertension, diabetes, hyperlipoproteinemia, and the infarction of the myocardium.


Gas chromatographic study of cholesterol esterification during postheparin lipolysis in vitro in hypertriglyceridemia. Direct gas chromatographic method for quantitative determination of plasma neutral lipids was used for the study of cholesterol esterification in vitro. Fully automated computerized method permits the determination of lipid classes (free cholesterol, cholesteryl esters, and triglycerides), as well as their fractions according to the molecular weight, without previous derivatization. All components are determined from one analysis. The method is highly precise and accurate. The coefficient of variation for free and esterified cholesterol is 1.21 and 1.11% in the concentration range 30--430 and 75--545 mg/dl, respectively. The LCAT activity was determined as a decrease in the free cholesterol concentration after one hour's incubation; from the same analysis, the recovery control as an increase in the esterified cholesterol concentration was calculated. The mean difference was 1.06%, maximum difference did not exceed 4%. The LCAT activity in the reference group was 97.2 +/- 28.2 mumol/l/h and was significantly lower than that in hyperlipdemic one. Intravenous administration of heparin had an inhibition effect in subjects with hyperlipidemia of type IV, while only slight changes in the reference group and an increase in hyperlipidemia of type III were observed.


Familial LCAT deficiency. Report of two patients from a Canadian family of Italian and Swedish descent. A 16-year-old male (S.F.) and his 21-year-old sister (D.H.) from a large family of Italian and Swedish descent had virtually identical lipoprotein pattern and complete absence of LCAT activity. Both had typical corneal opacities and mild anemia with target cells. S.F., but not D.H., presented with proteinuria, which has increased over three years of follow-up. His kidney biopsy revealed lipid deposits in the glomerular basement membrane. Ten relatives in 4 generations had normal LCAT activity and/or lipoprotein pattern. The patients and their relatives had haptoglobin type 2. Factors that might influence the different clinical presentation in our patients (previous renal disease, diet, abnormal lipoproteins), prognosis, and treatment (diet, enzyme replacement, cholestyramine) are discussed.


Phosphatidylcholine substrate specificity of lecithin:cholesterol acyltransferase. Lecithin:cholesterol acyltransferase (LCAT) has been partially purified by the combined method of ultracentrifugation and dextranblue-2000 4 B affinity chromatography. The enzyme was incubated with liposomes consisting of phosphatidylcholine-cholesterol in a molar ratio of 10/1. Chemically synthesized phosphatidylcholine substrates with labeled fatty acids in 1-and 2-position were chosen to evaluate the degree of transesterification. It was found that the fatty acid in the 1-position of phosphatidylcholine significantly influences cholesteryl ester formation, both by its direct involvement in the LCAT reaction and its contribution to the physico-chemical properties of phosphatidylcholine.


Lecithin:cholesterol acyltransferase deficiency associated with hepatic schistosomiasis mansoni. Plasma and erythrocyte lipid abnormalities occur in chronic human schistosomiasis mansoni and appear to be related to mild lecithin:cholesterol acyltransferase (LCAT) deficiency. Plasma LCAT activity is about 50% lower than normal in decompensated hepatosplenic schistosomiasis, whilst the plasma concentrations of cholesteryl ester and lysolecithin and decreased and that of lecithin increased in the earlier hepatointestinal and compensated hepatosplenic forms of the disease as well as in the later decompensated stage. Plasma lipoproteins are also altered in schistosomiasis. Agarose gel electrophoresis showed reduced alpha and pre-beta lipoproteins, whilst other studies consistently showed that lipoproteins from patient plasma are better substrates for LCAT than those of normal plasma. Erythrocyte cholesterol is increased in all forms of the disease, and the cells show increased resistance to lysis either in hypotonic media or in 0.3 M glycerol. The severity of these lipid changes clearly shows a gradation through the successive stages of the disease. In the experimentally infected mouse LCAT deficiency does not seem to be a feature of the disease, but several significant changes in plasma and erythrocyte lipids occur which contrast with those seen in human schistosomiasis.


Inhibition of lecithin:cholesterol acyltransferase in human plasma by dicarboxylic lecithins. The effect of dicarboxylic lecithins on the lecithin:cholesterol acyltransferase [LCAT] activity was studied with a partially purified preparation [approximately 24-fold]. The presence of dicarboxylic lecithins is followed by the inhibition of LCAT. The inhibition is proportional to the concentration of glutaryl-lecithin and is about 50% with 0.16 mM glutaryl-lecithin. For a higher concentration, the inhibition is total. The inhibition of LCAT activity was of a mixed type. It can be explained by a combination of competitive inhibition and interaction of glutaryl-lecithin with phospholipid, which changes the physical properties of lipid, making it less available for conversion into cholesteryl ester.


Studies on human hepatic cholesterol ester hydrolase in liver disease. Stokke has described a lysosomal cholesterol ester hydrolase (CEH) in human liver. To clarify the significance of this enzyme, we first modified Stokke's assay to enable CEH determination in hepatic needle biopsies. Studies established optimal pH of 4.6--5.2 and linearity of hydrolysis for at least 12 hours, using homogenates containing about 2 mg liver and radiolabeled cholesterol oleate as substrate. The assay was then applied to patients undergoing percutaneous needle biopsy. Hepatic CEH activity in alcoholic liver disease, obstructive jaundice and a variety of other hepatic disorders was not significantly different from that in histologically normal livers. In patients with acute hepatitis, however, mean CEH activity was more than 3-fold increased (P less than 0.01). Values paralleled SGOT levels, returned to normal as hepatitis resolved, and were unrelated to serum cholesterol levels or to lecithin:cholesterol acyltransferase activity. In contrast to CEH, activity of acid phosphatase, a standard lysosomal marker enzyme, was the same in hepatitic as in normal livers. We conclude that CEH can be assayed in needle biopsies of human liver, that its activity increases in acute hepatitis, and that this is probably not simply due to a nonspecific general increase in lysosmal enzymes.


Reversible inhibition of LCAT by penicillins. Kinetic and mechanistic investigations. A simple and rapid method is described for labelling serum lipoproteins with 3H cholesterol. According to the tracer data as well as cholesterol analyses, the velocity of ester formation in rat sera and beta-lipoprotein-depleted human sera decreased during incubations as a first order reaction. This suggests a level of chemical activity for cholesterol far below the Km of the enzyme. The reversible inhibition by three different penicillins showed a dependency of the inhibitor concentration which supports this notion. 50 per cent inhibition of the rat enzyme was obtained with 0.1 mM dicloxacillin, 0.3 mM benzylpenicillin, and 1.4 mM methicillin (water phase concentrations). The human enzyme was about 10-fold less sensitive. The mechanism of penicillin inhibition, investigated by stripping-recombination experiments with the 20-fold purified rat enzyme chromatographed on penicillin-loaded Sephadex G-25 columns, was found to be a dissociation of the enzyme into two components, an inactive apoenzyme and a coenzyme with a molecular weight below 1000.


Lecithin:cholesterol acyltransferase activation and lipid binding by synthetic fragments of apolipoprotein C-I. Peptide fragments of apolipoprotein C-I (apoLP-C-I) have been synthesized by solid phase methodology. After  purification, each peptide showed the correct amino acid analysis and was a single band by polyacrylamide gel electrophoresis. In density gradient ultracentrifugation with vesicles of dimyristoyl phosphatidylcholine, peptide fragments 32-57, 24-57, and 17-57 formed stable complexes while 39-57 did not. With mixed vesicles of dimyristoyl phosphatidylcholine-cholesterol 20 micrometer of the fragments 32-57, 24-57 and 17-57 stimulated lecithin:cholesterol acyltransferase (LCAT) activity 50, 60, and 100%, respectively, of the value found for apolipoprotein C-I, while fragment 39-57 was inactive. The results indicate that residues 17-57 contain the structural requirements for LCAT activation by apoLP-C-I, and that residues 32-57 represent one of the major phospholipid-binding regions of apoLP-C-I.


Cross-cultural differences in the short-term prognosis of schizophrenic psychoses. Results of the 2-year followup of the patients included in the International Pilot Study of Schizophrenia (World Health Organization 1973) indicate that patients diagnosed schizophrenic on the basis of standardized assessments and clearly specified criteria demonstrated very marked variations of course and outcome over a 2-year period. Schizophrenic patients in the centers in developing countries had, on the average, considerably better course and outcome than schizophrenic patients in the centers in developed countries. Part of the variation of course and outcome was related to sociodemographic (e.g., social isolation and marital status) and clinical (e.g., type of onset and precipitating factors) predictors, but another larger part remained statistically unexplained. This suggests that variables usually used to describe psychopathology, the environment, and history of psychiatric patients in European and North American cultures may not account for cross-cultural differences. Clinical diagnosis on initial evaluation appeared to be a good predictor of subsequent symptomatology, but not of the length of the episodes, the total time during which the patient would be psychotic, pattern of course, or the degree of social impairment. A 5-year followup of the IPSS patients has also been completed, and the collected data are being analyzed.


Sex differences in concordance rates for schizophrenia: finding or artifact? The literature on schizophrenia has reported a trend toward higher concordance rates for females in both monozygotic and dizygotic same-sexed twins. The validity of this finding is open to question. Rosenthal (1961 and 1962) pointed out that females are more likely than males to become inhabitants of chronic wards. Most of the studies reporting a sex difference used resident hospital populations. Gottesman and Shields (1972) noted that the sex difference disappeared when samples were based upon consecutive admissions. Sex differences have vanished in recent studies both as a result of changing research methods and the changing role of women in society.


Remitting schizophrenia as a variant of affective disorder. Remitting schizophrenia is an important phenomenon in the United States largely because of the broad concept of schizophrenia used here. Clinical and family investigations of this condition suggest a close link between remitting schizophrenia and the affective disorders. However, the elevated morbidity risk of schizophrenia in first-degree relatives of remitting schizophrenics precludes the conclusion that remitting schizophrenia is simply a variant of affective disorders. The following testable hypothesis is consistent with the available data: remitting schizophrenia is a heterogeneous mixture of mania, unipolar depression, and typical schizophrenia. Mania and unipolar depression account for the majority of such disorders although schizophrenia may account for a sizable minority. Other disorders may be included in this mixture; but, their contribution to the remitting schizophrenias is probably small.


A 10-year followup of remitting schizophrenics. Fifty-one patients who on admission in 1959-62 were diagnosed schizophrenic and yet achieved full remission were followed for 4-16 years (average 10 years). Subsequently, 20 of the remitting schizophrenics relapsed, spent an average of 25% of the followup period hospitalized, and could unambiguously be relabeled chronic schizophrenia. Except for brief relapses in a few cases, 31 patients maintained full remission throughout the followup period. What was most significant was that on first admission the 20 remitting schizophrenics who became chronic were just as reactive (i.e., manifesting acute onset, precipitants, and good premorbid adjustment) and almost as "affective" (i.e., manifesting depression and heredity positive for affective psychosis) as the 31 patients whose remissions were sustained. These findings support the hypothesis that remitting schizophrenics are not necessarily a discrete type of schizophrenic requiring fresh labels. Rather, such patients may be more simply classified as schizophrenics who get predictably better after their first admission.


On the cogency of the ppi-pi effect.

On the cogency of the ppi-pi effect. The present paper discusses briefly the incompatibility between the propositions that (1) the preceding preparatory interval moderates the reaction time of the subsequent trial, and (2) and inability to maintain task-relevant vigilance is the cause of the schizophrenic's peculiar response patterns in reaction time experiments.


Cognitive and perceptual differences between schizophrenics and organics. Distinguishing between brain-damaged and schizophrenic patients remains a significant clinical problem. However, substantive and methodological difficulties have led to discouragement and consequent loss of interest in this area of differential diagnosis. Several models for making this distinction were proposed: cognitive, empirical-psychometric, attentional motivational, neuropsychological and information processing. In evaluating these models, three persistent methodological problems were identified: diagnostic inaccuracy, inadequate sampling, and difficulty in interpretation of the subject's performance. Various suggestions were made for resolving these difficulties through such means as equating samples for level of deterioration, utilizing modern, objective diagnostic techniques in the selection of samples, comparing subtypes of brain damage and schizophrenia, and using test procedures that have been shown to assess dispositional characteristics of the conditions under study, rather than their epiphenomena. It was suggested that recent substantive findings, mainly those involving neurological deficit in schizophrenia and detection of major behavioral differences among various subtypes of schizophrenia and brain damage, could be used in attempts to resolve the differential diagnostic problem under discussion. It was suggested that resolution of the methodological problems posed in combination with new substantive data concerning schizophrenic and brain-damaged patients may set the stage for a new start for investigating an old problem.


Animal models of schizophrenia: the case for LSD-25. Some of the difficulties of trying to establish an animal model of schizophrenia are first considered. Then, after a review of the evidence on the experimental psychopathology of schizophrenia, particularly that concerned with attention and arousal, it is concluded that the core feature which needs to be modeled in animals is some aspect of "input dysfunction." It is argued that, of the pharmacological strategies, LSD-25 comes nearest to meeting that requirement, for two reasons. First, the phenomenology of an LSD "model psychosis" closely parallels that of the natural disease. Secondly, the experimental effects of the drug, both in animals and man, are very similar to or can be closely aligned theoretically with those of schizophrenia. An example is quoted from work in the author's laboratory where LSD was found to produce psychophysiological effects virtually identical to those observed occurring naturally in acute psychotic patients and in normal subjects high in "psychotic" personality traits. It is suggested that the rejection of LSD as a drug model was premature, especially as the currently popular preference for amphetamine has not been vindicated, either by the latter's ability to mimic an important central feature of the psychotic state or by work on dopamine as a specific common mediator of amphetamine psychosis and of schizophrenia.


Habituation and conditioning of electrodermal responses in high risk children. Measures of skin conductance during rest and during experiments testing habituation and conditioning of the skin conductance response were obtained from 42 10-year-old male children, of whom 12 were at risk for schizophrenia and 30 constituted low risk controls. While typical habituation curves for skin conductance response were obtained from both sets of offspring, no differences were found between high and low risk subjects on trials to habituation, response magnitude, latency, or number of spontaneous responses. However, there was evidence suggestive of differential conditioning in the two groups of children as a function of risk status. High risk offspring produced significantly larger skin conductance responses to conditioning test trials than low risk offspring. High risk subjects were also significantly more responsive to the unconditioned stimulus (loud white noise) than low risk subjects, but half-amplitude recovery time did not differentiate between the two groups of children. Finally, high risk offspring manifested lower levels of tonic conductance during conditioning, but not during resting or habituation. These results lend support to two important recent findings by Mednick concerning autonomic differences between high and low risk children, but do not confirm his findings regarding generalization and half-amplitude recovery time.


Planning for the next generation of risk studies. Seventy longitudinal studies of social competence in children conducted over the past 3 decades are critically reviewed in an effort to pinpoint current and potential problems in conducting longitudinal research with samples of children at elevated risk for developing severe forms of psychopathology. The review outlines chronic problems in accurately specifying objectives, choosing adequate and appropriate samples, and selecting maximally useful predictor and outcome measures in this reseach area. A variety of institutional and organizational problems that make risk research difficult to undertake and to carry to completion are also described. A federation of risk projects, which could seek unified funding and coordinate institutional support, is suggested. In addition, new grant review procedures that embody coordination of management efforts between funding and research agencies are recommended as one possible alternative to present practices.


Further data concerning the relation between premorbid adjustment and paranoid symptomatology. This study examines the relationship between premorbid adjustment and paranoid status in acute schizophrenia. In order to avoid limitations of previous studies, premorbid adjustment (based on the UCLA Social Attainment Scale) was considered at five levels instead of the usual binary classification (good vs. poor) and paranoid symptomatology (using the Venables and O'Connor Scale) was considered rather  than paranoid diagnosis. In a sample of 112 first lifetime admission schizophrenics, a positive linear relationship was found between premorbid adjustment and paranoid symptoms. Definite paranoid symptomatology was largely absent at the lowest levels of premorbidity and increased progressively with more adequate  premorbid adjustment. The one exception to this linear trend was noted for the highest (most superior) level of premorbid adjustment where an increase of nonparanoid cases was observed.


Choosing control groups in the study of schizophrenic subtypes. The choice of comparison groups in the study of schizophrenic subtypes is discussed. Current research rests upon the comparison of schizophrenic subtypes and controls unselected for the subtype characteristics used to divide the schizophrenics. One cannot infer, on the basis of this type of group comparison, whether subtype differences are specific to schizophrenia or reflect general personality and behavioral characteristics. It is suggested, therefore, that control groups be selected for their comparability to the schizophrenics on subtype characteristics.


Do schizophrenics give rare word associations? For the past 50 years, researchers have been trying to demonstrate that schizophrenics give uncommon word associations. Although secondary sources largely agree that these demonstrations have been successful a review of the most frequently cited studies reveals that there has been an uncritical acceptance of inadequately documented data. Errors in experimental design, methodology, and even data analysis are described. The support that these data provide for the hypothesis that schizophrenics give rare word associations is illusory. Theories based on the relationship between schizophrenia and rare word associations should either be revised or supported by empirical evidence that such a relationship exists.


Xerographic parenchymal patterns and breast cancer. The xerographic mammography records of 3,002 patients with breast disease were reviewed and classified according to the criteria of Wolfe. The parenchymal P2 pattern occurred in 59% of patients with cancer and in only 16,9% patients under the age of 40 without cancer, but the incidence of the DY pattern was much the same in patients with cancer and in those without cancer in almost all the age groups studied. The incidence of the P2 pattern tended to rise slightly in patients without cancer, whereas the incidence of the DY pattern tended to remain the same in all groups. The findings of Wolfe and others have been confirmed by this study, which also supports the suggestion that women under the age of 40 undergo a baseline xerographic examination of the breasts for cancer and that subsequent screening be based on the presence of a P2 pattern. This will involve a selection of 16,9% of the under 40-year-old subjects without cancer who might, on screening be expected to show 60% of the cancers in each decade after the age of 40. This information coupled with other factors indicating a high risk for the development of breast cancer, such as florid epithelial dysplasia, a previous history of breast cancer or a family history of breast cancer, should increase the yield of early carcinomas at a preclinical stage and reduce costs of a screening programme.


The visual evoked potential in children after kwashiorkor. An index of the long-term effects of kwashiorkor on the electrocortical development of the child was obtained by recording the visual evoked potential (VEP) of 4 groups of children aged 6--12 years. The malnourished group, consisting of 30 Black children hospitalized for treatment of kwashiorkor during the first 27 months of life, was age-matched with 3 control groups. Some evidence of right hemisphere VEP deficit was found in the kwashiorkor group.


[The painful foot].

[The painful foot]. The different causes of painful feet, most of which are obvious, but neglected, are discussed. With a good history and examination, almost all the causes can be detected and treated in a simple manner.


Trichomoniasis treated with a single dose of benzoylmetronidazole. A single 2-g dose of benzoylmetronidazole (Flagyl suspension) was given to patients with vaginal trichomoniasis in the second and third trimesters of pregnancy. The preparation was well tolerated, there were very few side-effects and the overall cure rate after 7 days was 97,6%.


Successful drug treatment of schistosomal myelopathy. A case report. In a patient who presented with quadriplegia a large mass was demonstrated radiologically in the cervical part of the spinal canal. The patient came from an area where there is a high prevalence of schistosomiasis, and antischistosomal antibodies were present in the serum. Treatment with the antischistosomal drug niridazole led to a total clinical recovery and almost complete disappearance of the myelographic filling defect.


The effect of thyrocalcitonin therapy and phosphate deprivation on tumoral calcinosis. Six siblings were screened for clinical and biochemical evidence of tumoral calcinosis. The 3 brothers showed all the characteristic manifestations of this entity. Two of them were treated for an initial period of 6 months with large doses of thyrocalcitonin, with virtually no response. After a 9-month equilibration period they were treated by phosphate depletion, and at the end of 6 months they were re-investigated. There was no appreciable objective or radiological difference in the extent of the masses. It was concluded that, in these 2 patients, surgical excision of the tumours was the only feasible form of therapy.


Computed axial tomography of the body with the EMI general purpose scanner. A preliminary assessment. Computed axial tomography (CAT) of the brain has already proved itself to be the first line in the diagnosis of intracranial lesions. With the installation of the EMI (CT 5005) general purpose scanner at Garden City Clinic in mid-October 1977, we have been utilizing this technique not only on the cranium but on the rest of the body as well. It has proved an invaluable diagnostic tool, in that the diagnosis can often be made with this technique alone. It short-circuits many of the sophisticated routine X-ray studies which require hospitalization, an anaesthetic, and time lost to the patient and doctor. In many cases it has obviated the need for an exploratory laparotomy. In most cases the technique can be performed on outpatients; the patient is perfectly relaxed during the scan, and may be saved days in hospital. There are limitations, however, and patients should be carefully selected. A discussion of the indications for body scanning in both our own and overseas experience therefore seems in order.


Spontaneous labyrinthine window rupture. Spontaneous labyrinthine window rupture has been increasingly recognized in recent years. Seven such case histories and details of subsequent management by tympanotomy and fat graft plugging of the fistulae are reported. The importance of a history of physical stress preceding onset of symptoms is emphasized in the case of certain patients who presented with sudden hearing loss accompanied, in some cases, by tinnitus or vertigo. The first 5 patients were reported in a paper presented in October 1977 at the First South African National Otorhinological Congress in Cape Town.


Incidence of hyaline membrane disease in the Cape Coloured. Hyaline membrane disease (HMD), which carries a significant mortality and morbidity, is usually a disorder of the preterm infant. Several workers have shown that there is a lower incidence in the Black and Coloured neonate than in the White neonate. These studies have not excluded the growth-retarded baby, in whom the functional maturation of vital organs may be accelerated. This article examines the incidence of HMD among appropriately grown Cape Coloured infants and compares this with the incidence in White infants.


Renal echinococcosis in children. A report of 2 cases. Two cases of renal echinococcosis in children are described. In one of the children the lungs and liver were involved as well. The pathology, diagnosis and treatment, as well as the usefulness and limitations of the Casoni skin test and serological tests, are discussed.


An approach to the management of children with cleft lip or palate. A number of the more common problems which may be encountered in the management of children born with cleft lip and/or cleft palate is discussed. Present-day concepts of aetiology, parental counselling and timing of surgery are referred to and contentious aspects of management are mentioned.


Further local experience in the treatment of acute non-lymphoblastic leukaemia. Ninety-two patients suffering from various forms of acute non-lymphoblastic leukaemia were seen at the Johannesburg General Hospital between January 1972 and December 1977. Seventy-four completed at least one course of therapy, and were therefore available for evaluation. Three basic regimens were used for inducing remissions. These included daunorubicin and cytosine arabinoside (regimen 1-19 patients); larger doses of daunorubicin together with cytosine arabinoside (regimen 2-29 patients); and a combination of cyclophosphamide, vincristine, cytosine arabinoside and prednisone (regimen 3-22 patients). Regimen 3 was normally used only in older patients. Supportive measures included the use of red cell, granulocyte and platelet transfusions. Complete remission rates with the 3 regimens were 36,8%, 55,1% and 40,9% respectively, with corresponding partial remission rates of 5,2%, 0% and 18,1% respectively. The mean duration of survival in those patients who achieved remission was 10 months, 18 months and 8 months respectively. In addition, a complete remission rate of 28,6% was obtained in 14 patients, 10 of whom had relapsed while being treated with other regimens and who were later treated with an 8-drug combination (TRAMPCOL).


Psychosomatic gastro-intestinal disease. Psychosomatic disease is the commonest disorder in clinical gastro-enterology. It may be of primary importance in the patient's presentation, or act in a secondary role to modify organic disease and its management. Careful history-taking is essential in differentiating whether symptoms arise as a result of psychological stimuli or organic disease, as the effects may be indistinguishable to the patient. Organic disease should always be excluded by appropriate screening investigations.


The effect of gastrin on gastric ulceration in pigs after bile duct ligation. Pigs develop gastric ulceration spontaneously and after bile duct ligation. Despite increased basal acid secretion, serum gastrin levels are not elevated, and a possible 'protective' role of gastrin was proposed. Continuous intravenous infusion of synthetic human gastrin did not protect from gastric ulceration, but was associated with simultaneous duodenal ulceration. Another ulcerogenic mechanism must be invoked.


Fractures of the tibial shaft.

Fractures of the tibial shaft. The closed treatment of fractures of the tibial shaft will usually result in bony union within a period of 4 months. Early weight-bearing in a suitable cast or cast brace is advised. Infection following open reduction is often undetected until months or even years have elapsed. When infection occurs, union is delayed on average for 4 years, and amputation is not infrequently the end-result.


Prescribing exercise--walking and jogging. The family doctor is the ideal person to lead his patients back to a form of existence which is more dynamic and health-promoting than their customary way of life. Many basic fears of doctors are unfounded, for it is not difficult to acquire a knowledge of the ergological principles involved in natural movement and sport. Patients should be guided into 'forgetting' about their ailments, but at the same time remembering their limitations. The prescription of sensible forms of exercise, e.g. walking and jogging, is advocated. Some tried and sensible programmes are given.


'Men must work and...'.

'Men must work and...'. Women have been deeply involved in the social changes that have taken place in Western society during the last 30 years; the most significant transformers have been 'the pill' and television. As a result of an accelerated emancipation, women have become more assertive; pari passu men have become less dominant, more children have been deprived and the elderly have been increasingly extruded. Mature women have been adversely affected by the loss of charisma of fertility and motherhood, by changes in female reproductive physiology, by the uncertainty of marriage and its alternatives, by increased work and by the emphasis now placed on youth and sexuality. These stresses have been accompanied by a rise among women of 'male' behavior and 'male' diseases, as well as by an increase in self-poisoning, completed suicide and the 'female' disease of depression.


Observations on some locally available products. A physical grading of some well-known sunburn protectors is described as a guide to the choice of preparation.


Systemic lupus erythematosus associated with mixed cryoglobulinaemia and circulating anticoagulant. We describe a 30-year-old woman with systemic lupus erythematosus (SLE), in whom the only evidence of the disease, during the 10 years before diagnosis was established, was an accelerated erythrocyte sedimentation rate and a positive Wassermann test. Her disease was characterized by the presence of an anticoagulant without indication of bleeding, mixed cryoglobulinaemia, steroid-resistant renal damage, and persistent false-positive tests for syphilis. The relationship between these results and the presence of anticoagulant, mixed cryoglobulinaemia and renal damage in patients with SLE are discussed.


Breast reduction.

Breast reduction. Large breasts cause problems mainly because of physical discomfort and/or associated emotional problems, and surgery is sought primarily for these rather than for purely cosmetic reasons. Indications for carrying out a breast reduction are given, and important questions are posed and answered to help elucidate many of the factors pertaining to the operation. The overall results that can be expected as well as the possible complications are discussed. A table listing complications in a series of 50 patients is shown. In conclusion, the degree of patient satisfaction that can be expected is briefly discussed.


Minor psychological problems in a multiracial student population in Rhodesia. Experience in the student health service at the multiracial University of Rhodesia suggests that, although the aetiology and manifestations of minor psychological problems are affected by cultural factors, similarities between students of different races are more marked than are divergencies. The students' problems are similar to those reported from universities in other countries.


Community paediatrics in Cap Bon, Tunisia. The author spent an undergraduate elective period in Tunisia, and some of the features of a community health scheme in rural Cap Bon are described, such as the use of auxiliaries and standardized techniques.


Drug research, development and expenditure - what about the future? Drug research and development today is an undertaking requiring special skills and understanding, formidable financial resources and the closely co-ordinated co-operation of everyone concerned with the drug programme in all its aspects. Incorrect results, wrong deductions or decisions and unrealistic delays due to bureaucratic obstructions, all have an adverse effect in the final analysis. The price (financially and otherwise) we have to pay for the end-product is invariably intimately related to what happened during the entire development process. Everyone connected with drug development, in whatever capacity, has a moral obligation to ensure that the development programme follows a path which is as smooth as possible.


Repair of a urethral stricture with omentum. A case report. The surgical management of a case of urethral stricture with a pedicle graft of omentum is reported. The reasons for using this method are discussed and it is reported since the method has not previously been described.


Touraine-Solenti-Golé syndrome. A case report. Touraine-Solenti-Golé syndrome, characterized by familial acromegaly without the implication of growth hormone in the genesis, and by pachydermia, is reported in a woman aged 62 years with the classic manifestations of acromegalic diabetes, but with no thyroid or lung diseases. The syndrome is discussed, and is followed by a clinical description of our patient.


Clinical and electrophysiological observations with disopyramide in drug-resistant and recurrent symptomatic arrhythmias. Seventeen patients with recurrent symptomatic arrhythmias were treated with oral disopyramide (DP). Fifteen of the 17 patients had received other currently conventional anti-arrhythmic therapy, to which only 1 patient responded, yet 13 of these 15 patients with resistant arrhythmias responded to DP. Electrophysiological studies were performed on 9 patients. The most impressive electrophysiological findings were the depressant effect of DP on ventricular automaticity and its action in slowing conduction through the His-Purkinje system (including the bundle branches) without depressing sino-atrial rate and atrioventricular (AV) nodal conduction time. Retrograde ventriculo-atrial (VA) conduction was markedly prolonged in 4 patients with reciprocating supraventricular tachycardia (SVT), including 2 patients with Wolff-Parkinson-White syndrome. All 4 patients with reciprocating SVT appear to be cured of their arrhythmia, probably by this mechanism.


Fractures and dislocations of the ankle joint. The classification of fractures of the ankle joint is based on the mechanism of injury, which provides the clue to successful reduction. The physiological movements of the ankle and foot are defined, and the pathological movements associated with injury are described.


The effect of paraquat on the respiration of lung cell fractions. The in vitro effects of paraquat on the aerobic metabolism of lung and liver homogenates, as well as on the oxygen consumption of isolated rat and rabbit lung mitochondria, were investigated. It was found that the endogenous oxygen uptake of a 40% lung homogenate was similar to that of a 10% liver homogenate, and that succinate (20 mM) was well oxidized by both homogenates. About 14% of the basal respiration rate was due to cyanide-insensitive oxidative systems in lung and liver homogenates. Paraquat (1 mM and higher concentrations) induced an acute and highly significant increase in the cyanide-insensitive oxygen utilization. We were able to recover about 5% of the protein in the supernatant (1,000 g) of the original homogenate as mitochondrial protein. Only results obtained from mitochondrial preparations with a respiratory control ratio between 2,7 and 3,3 were used in the final analyses, and the normal state 3 respiration values of rabbit and rat lung mitochondria were 45,2 +/- 5,3 and 38,7 +/- 2,9 nmol oxygen per mg protein per minute respectively. Paraquat in concentrations up to 0.5 mM had no significant effect, but higher concentrations up to 1 mM induced a highly significant inhibition of mitochondrial oxygen consumption. When slices were pre-incubated with 1 mM and with 0,01 mM paraquat in the incubation medium, the oxygen consumption of the mitochondria isolated after 2 hours and 4 hours respectively, was significantly reduced.


Six years' experience of symphysiotomy in a teaching hospital. One hundred and sixty-one symphysiotomies were performed at Harari Maternity Hospital, Rhodesia, over a 6-year period. Indications for the operation are discussed and fetal and maternal results reviewed. Seventy-two patients suffered from postoperative complications but the majority of these were minor and of short duration. Multiparous patients did not have a higher morbidity than did primiparous ones. It is concluded that symphysiotomy has a useful role to play in a teaching hospital, provided it is performed by an experienced surgeon on carefully selected patients.


The duration of normal labour in Cape Town whites. The durations of the various stages of normal labour in White patients delivered at Mowbray Maternity Hospital, Cape Town, have been estimated for parity groups 1, 2, 3 and 4 and over. A significant correlation between age and the duration of the second stage was found in the para 2 group (r = 0,23, P less than 0,05). Previous abortions, marital status and oxytocic augmentation had no significant effect. The mean durations of the 1st and 2nd stages in primigravidas were significantly longer than in multigravidas. The upper limits of normal for the durations of the 1st and 2nd stages and the duration of the active phase were calculated. The mean duration of the 3rd stage was approximately 5 minutes.


Technical problems and early complications of laparoscopic sterilization done on a day-case basis. Two hundred and sixteen patients were selected for laparoscopic sterilization on a day-case basis. Patients were sterilized by electrocautery, by applying Silastic bands (Falope rings), and by means of Hulka-Clemens clips. Three patients required laparotomy and 35 patients were discharged the day after the operation. By the 3rd day 146 (69%) and by the 5th day 184 (86%) patients had returned to their routine work. From the technical and immediate postoperative point of view, there appears to be relatively little difference  between the three techniques. There may be slightly more risk of thermal complications with bipolar cauterization, a slightly highly incidence of postoperative abdominal pain with the Silastic band applicator, and slightly more difficulty in applying the Hulka-Clemens clip. These problems are all reduced by experience and proper training of the operator, which is essential. Our experience confirms that laparoscopic sterilization is safe, efficient, and feasible as a day-case procedure, and that it has major advantages in terms of patient convenience and acceptability as well as reduction in hospitalization costs.


Amniocentesis in high-risk pregnancies in a rural hospital. A series of 100 successive amniocenteses performed on rural patients with high-risk pregnancies is described. The shake test was found to correlate well with gestational age as well as with fetal lung maturity, a practical point of importance in areas without facilities for estimating the lecithin/sphingomyelin (L/S) ratio. While the procedure is not without risk, and the shake test should not be used as the sole criterion in management, amniocentesis is useful to those working with minimal facilities among a poorly educated community who have a high rate of obstetric complications.


Obstetric care in a rural population.

Obstetric care in a rural population. The results of a survey of a rural population requiring obstetric care are presented. It was found that 56,6% of this population had significant risk factors which warranted hospital delivery. A plea is made for the provision of more 'waiting mothers' areas', especially by provincial hospital authorities, to overcome the problems of communication experienced in rural areas. It is concluded that 85% of patients at risk can be detected by meticulous antenatal screening and be admitted to such waiting areas before the onset of labour, with a consequent improvement in perinatal and maternal mortality rates. The need for the provision of adequate postnatal facilities is discussed, and comments are made regarding the implications of the survey with regard to staff utilization.


Effect of the duration of dexamethasone treatment on the total phospholipid content of amniotic fluid. Obstetric patients requiring premature termination of pregnancy with low levels of surfactant in the amniotic fluid were given dexamethasone for 2 or 7 days to assess the effect of the duration of treatment on the total phospholipid content of the amniotic fluid. A significant  rise in lung surfactant occurred in both groups, but dexamethasone administered for 7 days was not more effective than 2 days' administration. It is suggested that it is not the duration of treatment, but the stage of pregnancy or the functional maturity of the fetus at the time of administration of dexamethasone that affects the outcome.


The prediction of fetal pulmonary maturity from amniotic fluid contaminated by vaginal secretion. Many patients are admitted with premature rupture of the membranes draining amniotic fluid contaminated with vaginal secretions, and the fluid is used for tests of fetal pulmonary maturity. Among 15 patients contamination of amniotic fluid by vaginal and cervical secretions was found to result in a rise in the bubble score in 6 and a rise in total phospholipids (TPL) in 12.


Ovarian abscess. A case report and review of the literature. An isolated ovarian abscess, unassociated with tubal lesions, is a rare occurrence. A case is described and the literature reviewed, with special consideration of the associated aetiological factors.


Chronic hypercapnia and radiological changes in the pituitary fossa. A consecutive series of ten patients with chronic bronchitis and hypercapnia were studied. All seven patients with chronic hypercapnia and one patient with intermittent hypercapnia showed evidence on skull radiographs of raised intracranial pressure. In five male and three female chronic bronchitics matched for age and ventilatory impairment, but without hypercapnia, no such radiological abnormalities were shown. The clinical significance and pathophysiology of this hitherto unreported finding is discussed. It would appear that in some cases the chronicity of hypercapnia may be diagnosed from a radiograph of the pituitary fossa.


Reproducibility and comparison of responses to inhaled histamine and methacholine. The efficiency of a standardised inhalation test procedure was studied by examining the reproducibility of responses to histamine and methacholine. In addition, the responses to the two agents were compared. Each set of duplicate tests was carried out on a separate day within one week, and all factors known or presumed to influence responses were carefully controlled. The results were expressed as the provocative concentration of the agent causing a 20% fall in forced expired volume in one second (PC20). Responses to histamine and methacholine were highly reproducible (coefficients of determination [r2] = 0.994 and 0.990 respectively). Responsiveness to histamine correlated closely with responsiveness to methacholine (r2 = 0.85). There was a small but significant cumulative dose effect with methacholine (P less than 0.01) but not with histamine. Side effects of throat irritation, flushing, and headache were more frequent with histamine than methacholine, and were dose-related. The high level of reproducibility indicates the efficiency of the test procedure. The similar severity of effects by agents with different mechanisms of action suggests that the primary cause of non-specific bronchial hyperreactivity lies at the level of bronchial smooth muscle.


Interpretation of increases in the transfer coefficient for carbon monoxide (TLCO/VA or KCO). During a 15-month period, 27 patients were seen in a routine clinical pulmonary function laboratory in whom the transfer coefficient (TLCO/VA or KCO), measured by the single breath technique, was increased. Pulmonary haemorrhage accounted for two-thirds of the cases; in them sequential measurements of KCO were able to monitor the onset and cessation of bleeding. In the remaining cases the cause of the increase in KCO remains uncertain. All patients had a reduction in vital capacity. Experiments in six normal subjects showed that KCO rose as the breath-holding lung volume was reduced, but that this was insufficient to account for the raised KCO in patients with reduced volumes. Partitioning of the two components of TLCO at different lung volumes in three normal subjects showed that an increase in pulmonary capillary blood volume per unit alveolar volume was chiefly responsible for the increase of KCO in normal subjects at lower lung volumes. The membrane diffusing capacity changed less than predicted per unit volume, suggesting that the thickness of the air-blood barrier remains fairly constant as the lung expands or contracts.


Potassium studies in chronic obstructive airways disease. Seventeen male patients with chronic obstructive airways disease in remission were separated into two groups according to arterial carbon dioxide tensions. Hypercapnia was associated significantly with hypoxia and increased red cell volume whereas normocapnia was not. Normocapnic patients were significantly lighter than those with hypercapnia. Total body potassium (TBK) measured by the whole body monitor was significantly low in two of the patients studied (P less than 0.005). The mean value for TBK for the normocapnic group as a whole was significantly low (P less than 0.005), but the mean value for the hypercapnic group was not. Serum potassium and erythrocyte potassium concentrations were normal even when TBK was low, and diuretics had no apparent influence on these potassium values. Of four patients (two in the series and two others) who had TBK measured after a recent episode of cor pulmonale, three had significantly low values. The only previous studies using a whole body monitor to measure TBK in chronic obstructive airways disease found no such low values, though other workers estimating exchangeable potassium by isotope dilution techniques had found evidence of gross potassium depletion. It is concluded that low TBK does indeed occur in patients with chronic obstructive airways disease and that gross depletion is more likely to follow an episode of cor pulmonale.


Pulmonary artery pressure in thoracic scoliosis during and after exercise while breathing air and pure oxygen. Pulmonary artery catheterisation was carried out in 25 scoliotics aged 13 to 67 years (mean 30.7). Each then performed a progressive exercise test breathing air, and 11 performed a similar test breathing pure oxygen. The mean pulmonary artery pressure (PAP) increased linearly with oxygen uptake (VO2) and with the work rate. The pressure responses have been described in terms of ther intercept and rate of rise of pressure (sPAP/VO2 and sPAP/work rate). sPAP/VO2 was unrelated to the anatomical features of the scoliosis, or to PaO2. It was inversely related to vital capacity, functional residual capacity, and total lung capacity. Inspiration of pure oxygen lowered the resting pressure by a mean of 3.2 mmHg but only decreased sPAP/work rate by 9%. The maximum pressure reached during exercise was diminished by a mean of 5.2 mmHg when pure oxygen was breathed. The mean pressures were shown to fall exponentially after exercise. The time constants were proportional to sPAP/VO2 and to the final pressure reached during exercise. Inspiration of pure oxygen did not effect the time constants but decreased the post-exercise pressure load by lowering the final pressure during exercise.


The primary immune response of patients with different stages of squamous-cell bronchial carcinoma. Using the indirect ELISA technique, the IgM, IgG, and IgA antibody response to the primary test immunogen Helix pomatia haemocyanin (HPH) was studied in 30 patients with various clinical stages of primary squamous-cell bronchial carcinoma and compared with values obtained in 15 controls matched for sex, age, smoking habit, and presence of chronic bronchitis. Patients with disseminated disease (stage III) showed a significant decrease in IgG and IgA antibody response (P less than 0.001), but IgM antibodies were relatively high and not different from the controls. Although normal IgG and IgA antibody titres were found at the peak response two weeks after immunisation in patients with localised disease (stage I), these antibody titres showed a significantly more rapid decline after serial investigations at eight and 14 weeks after immunisation compared with the controls (P less than 0.001) despite total removal of the tumour burden at c four weeks after immunisation. In-vitro HPH-induced lymphocyte transformation was considerably decreased in state I patients (P less than 0.01) as well as in stage III patients (P less than 0.001). The results suggest that patients with squamous-cell bronchial carcinoma develop impaired T-cell function, which gives rise to a defective antibody response and in-vitro lymphocyte reactivity to the T-cell dependent primary immunogen HPH.


Deep vein thrombosis after thoracotomy.

Deep vein thrombosis after thoracotomy. In a prospective study of 183 patients undergoing lateral thoracotomy the 125 I fibrinogen uptake test and perioperative heparin prophylaxis for deep-vein thrombosis were investigated. There was an incidence of deep vein thrombosis in 51% in untreated control patients. The heparin prophylaxis effectively reduced the incidence of deep venous thrombosis to 28% (P less than 0.005) without increasing postoperative blood loss. Unilateral thrombosis was found to be significantly more frequent in the leg opposite the side of the thoracotomy (P less than 0.005). The 125I fibrinogen test is essential in assessing methods of prophylaxis but is not recommended as a routine.


Pulmonary function in coal workers with Caplan's syndrome and non-rheumatoid complicated pneumosoniosis. This retrospective study compares the pulmonary function of 24 coal workers with Caplan's syndrome with that of 36 subjects with non-rheumatoid progressive massive fibrosis (PMF). Allowing for differences in radiographical category, age, years worked underground, and smoking, obstruction to air flow as reflected in the one-second forced expiratory volume, the vital capacity, and the ratio of residual volume to total lung capacity, was significantly less in subjects with Caplan's syndrome. No significant differences in transfer factor were found. These findings may be explained by the different pathological features of the two entities. Selection bias does not appear to be responsible for the differences observed between the groups, but studies designed to eliminate this would be desirable.


Respiratory function measurements in a cohort of medical students: a ten-year follow-up. A cohort of medical students first seen in 1962 has now been examined for a third time. The prevalence of symptoms of cough, phlegm, and breathlessness among them has remained low, and smoking habits have been light in comparison with those of the general population. Results of the three successive sets of measurements of lung function indicate that, in general, optimum values were reached in the early 20s, with little further change up to age 29. There was some evidence of reduced ventilatory capacity in subjects with histories of acute chest illnesses.


The applicability of the gland/wall ratio (Reid-Index) to clinicopathological correlation studies. We studied at necropsy the bronchi of 49 subjects whose lung function has been measured during life. In each case the glands were examined in three bronchi by measuring the gland/wall ratio (Reid-Index) and by point-counting. The results of the two methods were compared: the data of the gland/wall ratio were normally distributed while those of the volume density established by point-counting were not. Gland/wall ratio and volume density of glands correlated moderately (RSp = 0.524). The function between them was not linear, in contrast with that between gland/wall ratio and gland thickness. The stereological background of these functions is discussed. In 34 subjects without restrictive lung disease FEV1 correlated inversely with the volume density of glands (RSp = -0.396), but not with the gland/wall ratio (Reid-Index)(RSp = -0.243). This discrepancy probably results from the different distribution of the data obtained by the two methods and from the non-linear function between them. These findings indicate that the gland/wall ratio (Reid-Index) is less applicable to clinicopathological correlations than the volume density of glands established by point-counting.


Lung volumes and distensibility, and maximum respiratory pressures in thyroid disease before and after treatment. Lung volumes, static pressure volume curves of the lung, and maximum respiratory pressures were measured in six patients with thyrotoxicosis and three with myxoedema before and after treatment. After treatment three of the thyrotoxic patients had increases in vital capacity of the same order as previously reported, but in contrast to previous reports, the lung volume changes were not associated with, nor due to, concomitant changes in respiratory muscle performance. Static pulmonary compliance increased in four of the six patients. The initial findings were more in keeping with the presence of pulmonary congestion. Only one of the myxoedematous patients had any significant increase in vital capacity after treatment, and in her case this was clearly attributable to increased inspiratory muscle force.


Late presentation of primary pulmonary lymphangiectasis. Pulmonary lymphangiectasis can occur either as a primary change or secondary to chronic congestion. Primary lymphangiectasis is generally considered to occur exclusively in young children. This report describes three male patients, aged 13, 16, and 19 years, in whom the changes are limited to one lobe or to two lobes and the mediastinum. So far as could be ascertained these patients are the oldest reported. Lymphangiectasis should be considered in the clinical differential diagnosis of "pulmonary cysts" in children and young adults.


An unusual mucous cyst of the lung.

An unusual mucous cyst of the lung. A 68-year-old woman presented with a multilocular mucous cyst of the lung. At operation numerous seedling cysts were present on the parietal pleura, and the appearances strongly resembled those found in pseudomucinous cystadenoma of the ovary. The histological features suggested that the lesion was an unusual benign mucous cyst of the bronchus. After lobectomy and removal of pleural masses the patient has remained free from recurrence for five years.


Mediastinal thoracic duct cyst.

Mediastinal thoracic duct cyst. A case of mediastinal thoracic duct cyst is described; it is believed to be the first to be reported in Britain. Five surgically treated cases have been reported but in none was the diagnosis made before operation. Symptoms are caused by pressure of the cyst on the trachea and oesophagus and my be aggravted by eating a fatty meal. Differential diagnosis from other mediastinal tumours, especially bronchogenic cyst and neurofibroma, could perhaps be established before operation by lymphangiography.


Diagnosis of a thoracic inlet tumour by transbronchial biopsy. A 67-year-old man presented to the pulmonary service with left shoulder and arm pain. Examination disclosed a left Horner's syndrome. Supraclavicular exploration at another hospital was not helpful. Transbronchial biopsy through a flexible fibreoptic bronchoscope retrieved tissues showing poorly differentiated carcinoma. There are no previous reports of the use of the technique in the diagnosis of a Pancoast tumour with a normal standard chest radiograph.


HLA antigens in two Iranian populations: the Armenians and the Jews. The distribution of HLA phenotype, genotype and haplotype frequencies was studied in two Iranian populations, the Armenians and the Jews. Although the frequencies of most antigens in the Armenians have approximately the average Jewish values, haplotype frequencies are quite different between the two populations. The frequencies of antigens in Iranian Jews are more similar to those in the Mazandaranies, a group of non-Jewish Iranians, than to the Jewish populations from Yemen and Cochin, India.


Application of a computer program for the mapping of a gene locus to the disputed PGM3 localization on human chromosome 6. The program GENEMAP, which performs the computations of a model for the mapping of a gene locus (Baur & Spitzer 1978), is applied to the localization of the phosphoglucomutase 3 with family data as published by Lamm et al. (1972), Rittner & Kalbheim (1975), Albert et al. (1977) and Kömpf et al. (1977). On the basis of Lamm's recombination fractions the combined odds were 13 : 1 in favor of an orientation of PGM3 to the HLA--B-side.


Morphological studies on the mantle of the fresh-water mussel Amblema (Unionidae): scanning electron microscopy. The scanning electron microscope has been used to describe the surface morphology of the mantle in mantle-shell preparations from the fresh-water mussel Amblema. In some regions (adductor muscle insertions), the mantle is firmly attached to the shell. In other areas (along the main course of the mantle), transient adhesions between the outer mantle epithelial cells and the nacre appear to temporally further compartmentalize the extrapallial fluid possibly as a prerequisite for the initial crystallization phenomenon. At the mantle edge, as well as at the isthmus, the periostracum was seen to extrude from the periostracal groove. At the siphonal edge, peculiar finger-like processes were identified; these may represent primitive photoreceptors. The epithelial cells of the outer mantle epithelium are all microvillated whereas those of the inner mantle epithelium are both microvillated and ciliated. Specific differences in surface morphology are described for various regions of the outer mantle epithelium. These may be related to precise regionalized functional differences of this tissue. Several functions of the mantle, in addition to shell formation, and based on its various morphologies, are also discussed.


The epitheliomuscular cell of hydra: its fine structure, three-dimensional architecture and relation to morphogenesis. Ectodermal epitheliomuscular cells of Hydra attenuata were studied by transmission and scanning electron microscopy, and a three-dimensional model was constructed. These cells are cuboidal to columnar, and each cell has one muscle process arising from the basal portion of the oral-facing surface and one from the aboralsurface. Adjacent epitheliomuscular cells are joined apicolaterally by septate junctions. Numerous gap junctions occur between adjacent epitheliomuscular cells and are irregularly distributed along the lateral and basal aspects. Finger-like interdigitations and specialized folds (couplers) also occur along the basal and lateral aspects and interlock adjacent epitheliomuscular cells. In the basal portion of these cells, myofilaments are aggregated into myonemes which are oriented in the oral-aboral axis of the polyp. Myonemes dominate the cytoplasm of muscle processes. Myofilaments are also aggregated in the basal cytoplasm of the cell body when the cell body is in contact with the mesoglea but are sparse or absent when the cell body rests upon other muscle processes. Epitheliomuscular cells and associated muscle processes rest upon other processes and the mesoglea and show variations in these relations. A muscle process and associated cell may rest upon another process; the process may then extend under the preceding process and cell body. This configuration, and variations, present a woven or braided network of muscle processes which collectively form a sheet of muscle on the mesoglea. The interdigitations, couplers and gap junctions between epitheliomuscular cells and the woven network of muscle processes present a cytological basis for the observations that the ectoderm in hydra behaves as a coherent sheet along the body column.


The trichurid egg-shell: evidence in support of the Bouligand hypothesis of helicoidal architecture. Electron microscopy of thin sections and freeze etch replicas of the eggs of the nematodes Trichuris suis and T. muris is used to provide evidence in support of the Bouligand hypothesis of helicoidal architecture. The evidence presented is as follows: 1. The specific objections to the Bouligand model raised by Dennell (1974) and Dalingwater (1975b) are answered by reference to a pyramid of helicoidal tissue in which the corners are blunt. 2. Sections cut normal to the plane of the laminae do not show parabolic patterning. Parabolae appear if the section is tilted--their direction depending upon the direction of tilting. 3. Freeze etching allows the direct visualization of helicoidal architecture. Fibres are parallel within any one lamina but the fibre direction rotates by an angle of 9 degrees in successive laminae. Parabolic arcs are made up of short lengths of straight fibres--curved fibres were not observed. Planes of sectioning producing single and double spiral artifacts are described and the formation of these artifacts discussed. The sense of rotation of the helicoid is shown to be asymmetrical about any mid-plane through the egg.


Modified pore canals in the cuticle of Gammarus (Crustacea : Amphipoda); a study by scanning and transmission electron microscopy. A novel type of pore canal is described from the cuticle of three species of Gammarus. Each canal passes from the epidermis vertically through the endocuticle and exocuticle, and in the most distal layers of the latter is slightly expanded. Before entering the epicuticle the canal narrows, forming a neck the base of which is encircled by an electron-dense collar. Several tubular structures arise from the collar and pass distally into the reticular innermost regions of the epicuticle. Within the neck and just below its opening at the cuticle surface, a rod-like structure is inserted; this protrudes a short distance from the pore. Each pore canal is connected to many necks; the openings of the latter are aligned in rows over the surface, the openings and rows being about 0.15 and 1.0 micron apart, respectively. Changes in the pore and canal contents are visible and their significance is discussed.


The fibrous structure of coelacanth scales: a twisted 'plywood'. Isopedin is a network of collagen bundles present in the scales of most fishes. The scales of coelacanths show a remarkable three-dimensional arrangement of this network which is similar to a regularly twisted plywood. The successive fibrous layers cross at an angle which differs slightly from a right angle. It results that the whole system is twisted. The progressive rotation of the fibril direction is right-handed. Certain preferential orientations of fibrils have been observed, namely parallel to the growth rings. Such arrangments also exist in the embryonic cornea of birds and in the cuticle of certain insects, but do not present such an extensive and regular development.


Fine structure of axons associated with the salivary apparatus of the cockroach, Nauphoeta cinerea. Previous studies have shown that the neurotransmitter at the salivary gland of the cockroach is probably dopamine. An ultrastructural study of the innervation of these glands was made. It was concluded that there are two types of axon present designated type A and type B. Type A axons possess small agranular eliptical vesicles and large granular vesicles, whereas type B possess only large granular vesicles of larger diameter than those found in type A. The relationship of these types of axon to the cells of the acini is discussed. It is concluded that type A axons are catecholaminergic.


The pituitary cleft of the rat: an electron microscopic study. The epithelium of the pituitary cleft and its colloid have been studied at the ultrastructural level in normal, adrenalectomized, castrated, dehydrated and lactating adult rats. Both control and experimental animals showed cells in different stages of degradation inside the cleft and mixed with the colloid. These exfoliated cells seems to have originated from the cleft's epithelium of the adjacent granular cells. In adrenalectomized and castrated rats the rostral epithelium of the cleft had large intercellular spaces that in some instances appeared to open directly into the cleft. Occasionally, the adenohypophysial canaliculi of the adrenalectomized rats were also seen connecting with the cleft. In lactating and castrated animals dark cells appeared more frequently in the rostral and caudal epithelium of the cleft. The results obtained suggest that the colloids is originated at least in part by involuted pituitary cells. There is also evidence that the follicular cavities of the Pars distalis and the cleft are continuous structures.


Fine structure of the myotendinous junction of lathyritic rat muscle with special reference to connectin, a muscle elastic protein. The fine structure of the myotendinous junction of the skeletal muscle of lathyritic rats caused by beta-aminopropionitrile was investigated. In the junction there are finger-like processes of muscle fibers, in which thin filaments were extended from the last Z lines of myofibrils and attached to the sarcolemma of the processes. By the heavy meromyosin decoration technique, these thin filaments were identified as actin filaments. In the lathyritic muscle, the thin filaments were markedly fewer in number and distributed sparsely in the sarcoplasm. The content of connectin, an elastic protein, which is localized in myofibrils and also in sarcolemma was significantly decreased in the lathyritic muscle. A possible relationship between the changes in the fine structure of the myotendinous junction and in the connectin contents is discussed.


Comparative stereology of the mouse and finch left ventricle. The volume fractions and surface per unit cell volume of some subcellular components of the left ventricles of the finch and mouse were quantitated by stereologic techniques. These species were chosen for study because they have similar heart rates but differ morphologically in some respects: fiber diameter is larger in the mouse; the mouse has transverse tubules while the finch does not; and the finch has a form of junctional sarcoplasmic reticulum (JSR), extended JSR (EJSR), located in the cell interior with no direct plasmalemmal contact, while the mouse interior JSR (IJSR) abuts on transverse tubules. Our data show that the volume fraction (Vv) and surface area per unit cell volume (Sv) of total SR, and free SR (FSR) are similar. The volume fractions of mitochondria, myofibrils, and total junctional SR were also similar. The Sv of the cell surface of the finch was similar to the Sv of the cell surface of the mouse (Sv-plasmalemma plus Sv of the transverse tubules). The principal difference was in the distribution of JSR; the mouse peripheral JSR (PJSR) represents only 9% of the total JSR, while the finch PJSR accounts for 24% of the bird's JSR. The similar volume fractions of total junctional SR (PJSR + EJSR in the finch; PJSR + IJSR in the mouse) suggest that the EJSR is not an embryologic remnant, and raises the possibility that some function of JSR is independent of plasmalemmal contact.


Layered membranes: a diffusion barrier to gases in teleostean swimbladders. Flattened cells are dispersed in an overlapping fashion within the submucosa of closed (physoclistous) swimbladders. Within the cells are located round platelets best seen by phase or interference type microscopy. At the electron microscope level the platelets are revealed as repeated, numerous layers of membranous discs. Each disc is a bilayer with an enlarged rim. The bilayer is strongly and preferentially reactive to osmium tetroxide. Swimbladder walls are known to be highly resistant to passage of gases. The randomly disposed platelets with the highly ordered layering of membranes may provide that physical resistance to gas movement.


The successful use of work oxen in agricultural development of tsetse infested land in Ethiopia. For the past five years a herd of work oxen, now numbering some 450 individuals, has been maintained under the protection of trypanocidal drugs on a settlement scheme in an area of western Ethiopia infested with tsetse. This paper describes the environmental conditions and the epizootiology of trypanosomiasis in the oxen and in the vector, Glossina morsitans. It is concluded that with the strategic use of drugs, oxen can be kept alive and perform useful agricultural work, in areas of high tsetse challenge, provided reasonable standards of veterinary supervision and management are maintained.


A new outbreak of sheep scab (Psoroptes ovis) in Lesotho and the measures taken to control it. Psoroptic mange in sheep was reintroduced to Lesotho in 1975. The course of the disease outbreak, the problems encountered in attempting to limit its spread and the eventual introduction of a simultaneous dipping policy backed by legislation are described.


Salmonellae from dogs in Vom, Northern Nigeria. Examination by culture of single faecal samples from 120 domestic dogs in the Vom area of Nigeria showed 22 (18 per cent) of the animals to be excreting Salmonella organisms. One of the dogs yielded two and another three different serotypes. The total number of Salmonella serotypes isolated in the survey was 21. Dogs may be important in Nigeria as agents for the transmission of salmonellosis to man and domestic livestock.


Treatment of the repeat breeder cow syndrome in Kenya. One hundred repeat breeder dairy cows have been studied in detail. Although clinically 60 per cent of them were normal bacteria were isolated from the uteri of the majority (90 per cent). Thirty per cent of these isolates were mixed. Intra-uterine infusion of the uteri with diluted Lugol's Iodine solution, supplemented in a few cases by antibiotic therapy, resulted in a 62 per cent conception rate compared with 26 per cent in the control group. It is concluded that dilute Lugol's Iodine is a useful treatment for repeat breeder cows under conditions similar to those described.


ORF in sheep and goats in Nigeria.

ORF in sheep and goats in Nigeria. Orf virus was demonstrated in biopsy material taken from lambs during an outbreak of the disease on the University of Ibadan Teaching and Research Farm. Clinical cases were also seen in goats. The confirmation of orf in Nigeria is discussed in relation to peste des petits ruminants, an important virus disease of small ruminants in West African countries.


Nutritive value of Leucaena leucocephala for growing bull calves. Twelve cross-bred (Holstein X Gir) bull calves (11-12 months of age) were divided into two groups and fed over a 90 day period on two levels of leucaena. Animals in Group I were offered leucaena ad lib. whilst those in Group 2 received a restricted amount of leucaena plus a mixture of sorghum straw and molasses (75:25) fed ad lib. Digestibilities of dry matter, crude protein, acid detergent fibre and neutral detergent fibre for leucaena are presented. The live weight gain was significantly (P less than 0.05) higher in animals fed leucaena ad lib. than in those fed a restricted amount of the forage. The animals did not show any symptoms of toxicity during the experimental period.


Liveweight performance of crossbred and Zebu cattle grazing on native or Rhodes grass pastures. Two experiments are described involving 33 crossbred (mainly Simmental and Jersey X Zebu) and 33 Zebu (Horro and Boran) bulls and steers. In experiment I, growth rates of crossbred and Zebu cattle rotationally grazed on either native pasture or Rhodes grass (Chloris gayana) were compared during a 140 day grazing period at a stocking rate of 2.4 animals/ha. In experiment II, growth rate of cattle rotationally grazed for 140 days on native pasture was compared with that of a similar group grazed on Rhodes grass either rotationally or continuously at a stocking rate of seven animals/ha. On native pasture the average daily gain by Zebu animals was similar to that of the crossbreds whilst on Rhodes grass liveweight gain of Zebu animals was lower than that of the crossbreds. Daily gains of cattle were significantly (P less than 0.01) greater on continuous compared with rotationally grazed Rhodes grass.


Descriptive epidemiology of cancer of the larynx in the province of Torino, Italy. Age-standardized incidence rates of cancer of the larynx in men from 1965-1969 were 14.7/100,000/year in the city of Torino and 8.4 in the non-metropolitan area of the province. These rates are among the highest in Europe. The geographical distribution of cancer of the larynx has been investigated in the non-metropolitan area considering two geographical entities, i.e., the 291 towns and the 12 ecological zones/subzones of the area. The incidence of cancer of the larynx in men was unrelated to the population of towns in 1961, whereas it was positively correlated to indexes of general industrialization as well as to those related to industrialization in the mechanical processes. Tobacco and alcohol consumption have not been taken into account. In order to validate the methodology, the investigation was extended to bladder cancer and to cancer in the children. The former was correlated with general and chemical + rubber industrialization, whereas the latter was not correlated with any industrial process.


Mass screening for early breast cancer detection. In 1969 the Center for Social Diseases of Florence started a screening program for early breast cancer detection. The female population over 40 years of age of a group of outlying towns of the District was invited. From January 1969 till March 1977, 21,725 women have been examined in the program. Mammography was the diagnostic procedure of choice, followed by physical examination if necessary. Negative cases were controlled with biennial mammography. This paper summarizes and evaluates the results of this screening program. At first mammography, 67 cancers were detected, 37% of which were clinically unapparent, 62.3% staged T1A, and 52% N--. The average stage at diagnosis is certainly better than the average stage of cancers diagnosed in unscreened women, thus a better prognosis is expected. Actuarial survival rate of detected cancers was 94 +/- 3.7% at 5 years. False negative and false positive cases are reported. The possibility of hazards in the use of repeated mammography in mass screening is discussed. According to reported data the value of this screening program in terms of secondary prevention (early diagnosis) is confirmed.


Response to neoplastic antigens in human oncology: assessment and results of LIF (leucocyte inhibitory factor) test in breast cancer patients. The leucocyte inhibition factor (LIF) test, revealing the inhibition of leucocyte migration from capillary tubes, was studied with leucocytes from 47 patients with breast cancer, from 14 patients with benign breast tumors, and from 56 normal subjects. As antigens we used formalin-fixed tumor cells. The LIF assay was positive in 38/47 (80.8%) breast cancer patients, in 10/14 (71.4%) benign breast tumor patients, and in 13/56 (23.2%) normal subjects. The negative LIF assays were higher with leucocytes from patients with metastases than with those from patients with no metastases. We found no correlation between the LIF-test response and the histopathologic pattern of the tumors, type of treatment (almost always surgical), and remission or relapse state of our patients at the time of testing.


Estrogen receptor in human breast cancer in relation to tumor morphology and endocrine therapy. The presence of estrogen receptors (ER) was determined in 111 human breast cancer specimens. In 61% of the tumors, specific estrogen binding was found and in 39% of the tumors ER was absent. In 69 tumors no correlation was found between the histological grading of the tumor and the level of ER. The values of ER in tumors from patients over 50 years of age were usually much higher than those for patients under 50 years of age. Different methods of endocrine therapy were applied in 20 patients. In 10 of 15 patients with ER positive tumors, endocrine therapy resulted in remission. Only 1 of 5 patients with ER negative tumors responded with remission. It is concluded that estimation of ER in tumor tissue is helpful in the selection of patients for endocrine therapy.


Protein loss after radical mastectomy as a cause of postoperative hypoalbuminemia. The concentrations of serum albumin and the cumulative loss of albumin through the drainage tubes were followed in 14 patients who underwent radical mastectomy for cancer. The concentration of serum albumin declined during the postoperative period, and the nadir was on the 5th day. On the first 5 days a good correlation was observed between hypoalbuminemia and loss of albumin from the wound. After this period, hypoalbuminemia persisted unchanged although small quantities of albumin continued to be lost through the drains. It is concluded that in surgery complicated by abundant serum discharge, the albumin loss may be the main cause of postoperative hypoalbuminemia.


Proposal for a new histopathological classification of the carcinomas of the nasopharynx. A new classification scheme for malignant tumors of the nasopharynx is proposed in which the undifferentiated carcinoma of nasopharyngeal types as a prominent position. This term replaces the previous obsolete term lymphoepithelioma on the basis of its clinicopathologic identity, its separation from squamous cell carcinoma, and its potential origin from anatomical areas other than the nasopharynx.


Bronchial involvement by Hodgkin disease. Two cases of Hodgkin disease, lymphocyte depletion type, with bronchial involvement are described. One patient revealed involvement of the right upper lobar bronchus, the other patient of the left main bronchus. The correct diagnosis was made by fiberbronchoscope examination with cytologic brushing and biopsy. That bronchial involvement by Hodgkin disease is very rare is confirmed by the literature, where only 20 cases have been so far reported.


Malignant pleural mesothelioma.

Malignant pleural mesothelioma. A series of 12 cases of mesothelioma is presented, and the data in the literature is reviewed in an attempt to formulate a program of treatment for this malignant, fast-growing and rapidly fatal tumor.


Hairy cell leukemia: enzyme-histochemical and ultrastructural investigation of one case. The investigation was carried out on blood smears, bone marrow aspirates, one lymph node biopsy, and the surgically removed spleen of a 53-year-old man with hairy cell leukemia. In the blood smears stained with May-Grünwald-Giemsa, 60 to 70% of the hairy cells contained tubular inclusions that corresponded to the ribosome-lamella complexes demonstrated at electron microscopy. In blood smears, imprints and cryostatic sections of the lymph node and of the spleen, hairy cells revealed tartrate-resistant acid phosphatase, beta-glucuronidase and adenosine-triphosphatase activity. In the spleen neutral esterase and alkaline phosphatase demonstrated the numerical increase of the histiocytes, which ultrastructurally displayed phagocytic activity. The presence in the spleen of pseudosinuses lined by hairy cells was confirmed by electron microscopy as well as by cytoenzymology.