Augmented uptake of neuraminidase-treated sheep red blood cells: participation of opsonic factors. Neuraminidase from Vibrio cholerae (VCN) was used to treat sheep red blood cells (SRBC) which were then incubated in vitro with murine peritoneal macrophages. The uptake of VCN-treated SRBC by macrophages was greater than the uptake of SRBC not treated with VCN. SRBC opsonized with normal mouse serum (NMS) were taken up to a greater extent than untreated SRBC. SRBC treated with VCN and opsonized with NMS were phagocytosed to a greater extent than untreated SRBC, VCN-treated SRBC, or opsonized SRBC. Evidence demonstrated that factors in serum from normal C3H/HeJ mice augmented the uptake of VCN-treated SRBC in greater amounts than of normal SRBC. These findings were discussed in relation to the increased immunogenicity of neuraminidase-treated cells.


Quantitation of avian RNA tumor virus reverse transcriptase by radioimmunoassay. A radioimmunoassay was developed that can detect and quantitate 3 ng or more of the avian RNA tumor virus reverse transcriptase. The assay detected no antigenic sites in Rous sarcoma virus alpha virions or in virions of a murine RNA tumor virus. About 70 molecules of reverse transcriptase were found per virion of avian myleloblastosis virus with this assay or with an assay based on antibody inhibition of enzymatic activity. The assay detected about 270 ng of enzyme per mg of cell protein in virus-producing cells; uninfected cells had much less antigenic material but contained some determinants able to displace radioactive antigen. No additional antigenic determinants on reverse transcriptase could be detected that were not found on the separated alpha subunit of the enzyme. Although sevenfold less sensitive than enzymatic activity as a measure of reverse transcriptase, the radioimmunoassay can detect antigen using small amounts of protein and in the presence of inhibtors.


Sindbis virus glycoproteins form a regular icosahedral surface lattice. Electron micrographs of negatively stained Sindbis virus particles show that the glycoproteins are organized with trimer clustering in a T = 4 icosahedral surface lattice.


Analysis of antigenic determinants of structural polypeptides of avian type C tumor viruses. Radioimmunoassays were developed for the 19,000, 15,000, and 12,000 molecular weight polypeptides of avian myeloblastosis virus and for the 19,000 and 12,000 polypeptides of RAV-0, a subgroup E avian tumor virus. Each polypeptide was shown to possess both group- and type-specific antigenic determinants, in contrast to the 27,000 mol wt polypeptide, which contained only group-specific determinants. The corresponding low-molecular-weight polypeptides of subgroup A, B, and E viruses were shown to be immunologically indistinguishable. The findings that low-molecular-weight polypeptides of subgroup C and D viruses reacted very differently in immunoassays for the respective polypeptides of avian myeloblastosis virus or RAV-0 suggest that subgroups C and D may have evolved differently form subgroups A, B, and E.


alpha-fetoprotein in noneoplastic hepatic disorders. Serum alpha-fetoprotein levels were measured by radioimmunoassay in 473 patients with biopsy-proved noneoplastic hepatic disorders; 22% had values greater than 40 ng/ml, whereas only 1 of 350 patients with nonhepatic benign diseases had a value greater than this. Levels exceeded 40 ng/ml in more than 30% of patients with various types of hepatitis, and in 0% to 15% with inactive postnecrotic cirrhosis, primary biliary cirrhosis, biliary tract obstruction, and alcoholic liver disease. Values greater than 500 mg/ml were observed solely in viral subacute hepatic necrois. Only one patient had a level exceeding 3,000 ng/ml, the concentration at which alpha-fetoprotein is detectable by agar-gel diffusion. Of 75 patients with hepatoma, serum alpha-fetoprotein levels exceeded 40 ng/ml in 69%, and exceeded 3,000 ng/ml in 48%. These studies indicate that serum alpha-fetoprotein levels are elevated in several nonneoplastic hepatic disorders when a sensitive assay is used; this phenomenon may reflect hepatic regeneration.


Scabies masquerading as dermatitis herpetiformis. Scabies can be easily mistaken for dermatitis herpetiformis because the two conditions have features in common, namely, pruritic papules, vesicles, and crusted erosions in the sacral and gluteal regions. In five patients with scabies who were initially judged clinically to have dermatitis herpetiformis, histological examination was decisive in the eventual correct diagnosis.


Ascending aorta-right pulmonary artery anastomosis in children with complex cardiac malformations. Long-term results in 30 cases. In this report, we shall analyze the results obtained with palliative treatment in 30 patients with congenital heart disease who were operated upon at the University Hospital of Caracas during the period 1968 to 1972. In all cases, an ascending aorta-right pulmonary artery anastomosis was performed. Although we believe that the Blalock-Taussig and Potts shunt are satisfactory operations in some cases, at the present time we prefer the aorta-right pulmonary branch anastomosis in Fallots tetralogy and other congenital heart diseases such as single ventricle. In Fallot's tetralogy, particularly, this procedure provides better results, because the anastomosis can be  closed through the aorta when these patients are later subjected to total correction with extracorporeal circulation.


Smoking and myocardial infarction.

Smoking and myocardial infarction. In a representative series of male patients with primary myocardial infarction the prevalence of smokers prior to infarction was higher than in representative population samples. The difference decreased with increasing age, Those patients generally had a somewhat more severe clinical course than those who continued to smoke. Nevertheless, those who stopped had only half the rate of non-fatal recurrences (P smaller than 0.01) and half the cardiovascular mortality-rate (P smaller than 0.05) of those who continued to smoke.


Clostridium defficiel in the urogenital tract of males and females. A study of the occurrence of Clostridium difficile in the urogenital tract of males and females revealed higher isolation-rates in patients attending the special (venereal-disease) clinic than in patients attending family-planning and urological clinics. The presence of Cl. difficile in patients with venereal diseases is being investigated to see if the organism is simply an opportunist infecting a urethra disturbed by some antecedent disease, or if it is perhaps a primary cuase of disease.


Tuberculin reaction in adult Nigerians with sputum-positive pulmonary tuberculosis. Forty-six of sixty-eight rural Nigerian adult patients with sputum-positive pulmonary tuberculosis (P.T.B.) had skin reactions of less than 10 mm. in response to 4 or 5 tuberculin units of purified protein derivative (P.P.D.). The size of the reaction correlated significantly with serum albumin and transferrin concentrations. The diminished reaction in these patients seems to be part of a generalized depression of cell-mediated immunity associated with undernutrition rather than a specific depression of P.P.D. reactivity associated with overwhelming antigen load. It is concluded that the tuberculin test is of no value in the diagnosis of P.T.B. in this community, either in individual cases or epidemiological surveys, unless combined with a biochemical assessment of the person's nutritional status.


Thymosin-induced reduction of "null cells" in peripheral-blood lymphocytes of patients with systemic lupus erythematosus. Although thymosin, a thymic hormone, has been shown to restore cellular immunity in NZB/NZW mice, its effect in human systemic lupus erythematosus (S.L.E.) and other auto-immune disorders has not been tested. The present study shows for the first time that the proportion of "null cells" in peripheral-blood lymphocytes of patients with active S.L.E. is significantly decreased after in-vitro thymosin treatment. Thymosin has no effect on the percentages of T cells, B cells, and "null" cells in peripheral-blood lymphocytes from normal controls and patients with inactive S.L.E. and active rheumatoid arthritis. These findings suggest that thymosin may play an important part in the pathogenesis and treatment of this condition.


Microplate enzyme-linked immunosorbent assay for chagas' disease. A microscale immunosorbent assay (E.L.I.S.A.) for the measurement of antibody in Chagas' disease (American trypanosomiasis) is described. The test was assessed on plasma samples from people living in Bahia, Brazil. 98% of the individuals with positive Trypanosoma cruzi immunofluorescent-antibody (I.F.A.) tests gave E.L.I.S.A. reading considered as positive. Less than 2% of those with negative I.F.A. tests had positive E.L.I.S.A. reactions. This simple test may be suitable for use in large seroepidemiological surveys.


A sebotrophic stimulus in benign and malignant breast disease. The sebum-excretion rate (S.E.R.) has been found to be increased in patients with benign as well as malignant breast disease. The S.E.R. was not increased in patients undergoing surgery for other diseases. It is considered that the sebotrophic hormone may also be mammotrophic. Drugs such as reserpine and the phenothiazines which increase sebum production may perhaps provoke benign as well as malignant breast disease.


Androgen-induced hepatoma.

Androgen-induced hepatoma. Three cases of hepatocellular carcinoma are reported in young men who had been taking androgenic-anabolic steroids. The tumours were histologically similar to those described in previous reports. The tumour progressed slowly in two patients during four and seven years of observation, but in the latter bony metastases occurred. In two patients the tumours regressed after administration of the drug was discontinued. These cases strengthen the evidence that exogenous androgenic-anabolic steroids may produce liver tumours. The use of these drugs should be confined to serious conditions in which they are known to be effective. Biochemical tests of liver function and serum alphs-fetoprotein estimation are not useful as screening-tests for hepatoma in patients taking androgens, and regular isotopic liver-scanning is recommended.


Alpha-fetoprotein in antenatal diagnosis of congenital nephrosis. Alpha-fetoprotein (A.F.P,) levels were found to ge significantly raised in maternal serum and amniotic-fluid samples form the 16th and 18th weeks of gestation in a woman with an apparently normal fetus but with histological evidence of congenital nephrosis of the Finnish type. Increased concentrations of A.F.P. in early pregnancy with a living fetus are therefore not specific for neural-tube defects; More likely they result from the fetal circulation. Extended investigations, including kidney morphology, should be done in cases of apparent false-positive A.F.P. tests.


The neonate's immunity gap, breast feeding and cot death. In many mammals infant behaviour imposes a period during which the young will only take the mother's milk. It is suggested that the immunological components of the milk serve in this period to augment the baby's immune system while he traverses from the antigenic isolation of a fetus to his independent defence. In humans almost all cot deaths occur during this phase. Diverse statistics relating to factors associated with greater risk of cot death are drawn on, suggesting that a number of seemingly unconnected factors can all (including lack of breast-feeding) be interpreted as potential immunity defaults. This interpretation lends support to the idea of an immune mechanism underlying cot death which in some way is an abnormal response resulting from the default and which, with at least one other precipitating mechanism, leads to death.


Preoperative laparoscopy in diagnosis of acute abdominal pain. During 1973, 56 patients on one of three general surgical services at the Peter Bent Brigham Hospital, Boston, Massachusetts, who were judged to require hospital admission for acute abdominal pain were dividied into two groups. This division was determined by whether or not the physician responsible thought a definite diagnosis could be established on clinical grounds. 27 patients were thought to have a definite diagnosis and underwent laparotomy without preoperative laparoscopy; at laparotomy, 6 of these patients (22%) had no operable lesion. An additional 29 patients had severe abdominal pain and required observation in hospital. An exact diagnosis could not be clinically established in these patients, and many would in the past have required exploratory laparotomy. These 29 patients underwent laparoscopy resulting in all but 1 (4%) having the presence or absence of intra-abdominal disease requiring operative intervention definitely established. At laparoscopy, diagnosis was made in 18 patients who did not require laparotomy while 11 had disease requiring laparotomy after laparoscopy. No complications resulted from laparoscopy. The difference in the median length of stay and hospital charges resulted in a saving of one and a half days in hospital and $87 when laparoscopy rather than explatory laparotomy determined that acute  abdominal pain was caused by a condition not requiring surgical intervention.


Gastric-acid output, pepsin output, and lean body mass in normal and duodenal-ulcer subjects. Gastric-acid output bears a significant relationship to parietal cell mass and to lean body mass. The relationships of pepsin output to gastric-acid output and to lean body mass have been investigated in 13 normal subjects and 40 duodenal-ulcer patients. Peak pepsin output (P.P.O[I]) was stimulated by insulin-induced hypoglycaemia and the enzyme was assayed by Piper's method. Peak acid output to pentagastrin (P.A.O.[Pg] was obtained at a separate test. P.P.O.(I) correlated significantly with P.A.O.(Pg) in normal subjects (r equals 0-889, P less than 0-0001). P.P.O.(I) also showed good correlation with lean body mass (L.B.M.) (r equals 0-714, P less than 0-01), suggesting that P.P.O.(I) reflects peptic cell mass in normal subjects. In 40 duodenal-ulcer subjects there was no significant overall correlation of P.P.O.(I) with P.A.O(Pg) or with L.B.M. However, expressing the results as output of pepsin per milliequivalent of acid per kilogramme of lean body mass allowed separation of the ulcer patients into two groups whose ratios appeared to correlate with their symptomatic state at the time of testing: thus mean P.P.O(I) per meq. acid per kg. L.B.M. for duodenal-ulcer patients in relapse was significantly greater than the ratios for the patients in remission and for the normal group (P less than 0-001), suggesting either the presence of an increased sensitivity to insulin stimulation or a lack of pepsin inhibitor substance during a relapse of ulcer symptoms.


Abnormal leucocyte composition and sodium transport in essential hypertension. Cation transport and electrolyte composition were studied in leucocytes from 17 patients with uncomplicated essential hypertension. Significant increases in cell sodium and water contents, associated with a depression of the rate-constant for active sodium efflux, were found in the hypertensive patients. These abnormalities in cell sodium transport may possibly be related to mechanisms of hypertension.


Triglyceride-production rates in patients with type-4 hypertriglyceridaemia. A new method has been devised to study triglyceride-production rates in man. The clearance of plasma-triglyceride transported on very-low-density lipoproteins (V.L.D.I.) to peripheral tissues is inhibited by about 50 percent with protamine sulphate; and this results in a rise of blood-glycerides over 1 hour. In a group of nine patients with type-IV hypertriglyceridaemia (mean fasting glycerides 252 mg. per 100 ml.) the mean increment of plasma-triglycerides was 29.8 compared with 1.4 mg. per 100 ml. per hour for nine controls whose mean fasting glycerides had been only 105 mg. per 100 ml. Patients with fasting plasma-triglycerides greater than 400 mg. per 100 ml. showed a response to protamine more like controls. It is suggested that patients with type-IV hyperlipaemia and fasting levels of triglycerides less than 400 mg. per 100 ml. are secreting triglycerides into blood at greater rates than controls; whereas patients with sever hypertriglyceridaemia (levels greater than 400 mg. per 100 ml.) may have a defect of triglyceride clearance so that inhibition by protamine produces no further change in level of plasma glycerides.


Possible toxic water factor in coronary heart-disease. Many reports indicate a significant negative correlation between death-rates for coronary heart-disease (C.H.D.) and water hardness. A reverse situation exists in the twin Kansas cities, U.S.A. Kansas City, Kansas, has water which is more than twice as hard as the softened water of Kansas City, Missouri, from the same source. Serum cholesterol and triglyceride levels were similar, but blood-pressure was higher in Kansas City, Kansas, and this correlated with higher serum-sodium, lower serum-potassium, and a tenfold higher serum-cadmium. Serum calcium and magnesium levels were higher in Kansas, while copper, chromium, cobalt, and zinc were higher in Missouri. The serum studies were con ducted on two matched groups of 260 adults from each of the sample cities. Hypertension may account for the reverse C.H.D. rate noted and be cadmium related.


Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. A 5-year-old girl with a history of recurrent infection and anaemia has no measurable purine nucleoside phosphorylase (N.P.) activity in her red blood-cells. Her serum-immunoglobulin levels are normal, as are her antibody responses to thymus dependent and independent antigens. However, she has severe lymphopenia, pronounced depression of lymphocyte response to mitogenic and allogeneic cell stimuli, and greatly decreased T-cell rosette formation. Her parents are second cousins; their red cells contain less than half the normal level of N.P. activity. They also share an unusual N.P. isozyme pattern indicative of molecular hybridisation between catalytically active and inactive subunits, which strongly supports the assumption that they are heterozygous and their daughter is homozygous for a "silent" allele at the N.P. gene locus. Inherited deficiency of adenosine deaminase, an enzyme catalysing a reaction only one metabolic step away from that of N.P., is known to cause immunodeficiency. It is therefore very likely that this patient's lack of demonstrable N.P. activity is responsible for her syndrome.


Non-toxigenic Corynebacterium diphtheriae in a boarding school. A non-toxigenic strain of Corynebacterium diphtheriae var. gravis was isolated from 31 boys during an outbreak of sore throats at a boarding school of 15 staff and 134 pupils. Despite the non-toxigenicity of the strain involved, conventional isolation procedures were observed and all boys at the school were treated with antibiotics. Restrictions on the school were only relaxed when no further carriers were detected. The rationale of such management of an episode involving a non-toxigenic strain is discussed.


Phagocytosis in patients and carriers of chronic granulomatous disease. The phagocytic capacity of leucocytes from four patients and two carriers of chronic granulomatous disease (C.G.D.) was compared to that of normal leucocytes. Leucocytes from C.G.D. patients phagocytised more Staphylococcus aureus than did normal leucocytes after 5, 10, and 20 minutes of incubation. Phagocytosis by leucocytes from two carriers of C.G.D. was intermediate between that in the patients and in controls. In contrast, phagocytosis of Streptococcus faecalis, an organism readily killed by C.G.D. leucocytes, was similar for control and C.G.D. leucocytes. Enhanced phagocytosis may represent an attempt by leucocytes to compensate for a bactericidal abnormality. In addition, these observations may partly explain why carriers of C.G.D. are not more susceptible to infection despite abnormal leucocyte function. Detection of carriers using the described assay of phagocytosis appears relatively simple compared to previously described methods.


Lymph-node biopsy during simple mastectomy. The distribution of pectoral (external mammary) nodes identified during the operation and removed with the axillary tail of the breast was studied in 45 patients treated by simple (total) mastectomy. Up to 13 nodes may lie within the axillary tail, and these are continuous with the pectoral nodes. Lymph-nodes were identified in 90 percent of patients treated by simple (total) mastectomy without dissection of the axilla.


Antibody to cultured human insulinoma cells in insulin-dependent diabetes. Circulating antibodies to live tissue-cultured human-insulinoma cells were identified in 34 out of 39 insulin-dependent diabetic patients by an indirect immunofluorescent technique. The antibodies were unrelated to insulin therapy since 8 of 9 sera obtained before insulin-replacement treatment were antibody positive and the test results were not influenced by prior addition of porcine insulin to sera. The antibodies were of the IgM and IgG classes. The findings suggest that autoimmune mechanisms are important in the pathogenesis of most cases of insulin-requiring diabetes.


Is there an increase in monoamine-oxidase activity in depressive illness? In a group of depressed patients who had either been treated with or considered suitable for monoamine oxidase (M.A.O.) inhibitor therapy, a highly significant decrease in conjugated tyramine output was observed after an oral tyramine load compared with normal controls. However, there was no difference in conjugated isoprenaline output between the two groups after isoprenaline ingestion, even though this amine is almost solely metabolised by what is likely to be the same conjugation mechanism. Whilst some explanation in terms of altered gut motility is conceivable, it seems more likely that the apparent deficit in tyramine conjugation in depression represents an increase in functional M.A.O. activity. Consequently, this enzyme would metabolise a greater proportion of available amine, causing a proportionately large decrease in the smaller conjugate pool.


Controlled trial of glycerol versus dexamethasone in the treatment of cerebral oedema in acute cerebral infarction. 10 percent glycerol was given for 6 days to 30 patients who had had acute ischaemic cerebral infarction, and the results were compared with those obtained after treating 31 similar patients with dexamethasone (16 mg. per 24 hours for 6 days). 1 patient treated with glycerol died of haemoglobinuria and acute renal failure. 6 patients treated with dexamethasone died--3 from cerebral oedema and 3 from non-neurological complications (pulmonary embolism, myocardial infarction, and aspiration pneumonia). Improvement was significantly greater in the glycerol group after 8 and 15 days. No improvement was noted using either glycerol or dexamethasone in 7 patients with spontaneous intracerebral haemorrhage.


High blood-pressure: a risk factor for cancer mortality? Univariate and multivariate analyses have been made of the relationship of systolic and diastolic blood-pressure measured at study entry to subsequent 14-year mortality among 1233 White males originally age 40-59 in 1958 from the Chicago Peoples Gas Company prospective study. With age, serum-cholesterol, and cigarettes per day controlled, both elevated systolic and electaed diastolic blood-pressure in 1958 were found to be strongly related to subsequent mortality from cancer in the men of this study. The possibility that this finding was due either to an association between antihypertensive medication in general, and cancer, or to an association was found that could explain the excess cancer mortality among those with elevated blood-pressure in 1958, either with medication in general, or with reserpine and rauwolfia in particular. These findings thus pose the question, is high blood-pressure associated with an increased risk of death due to cancer?


New complement-fixation test for the human reovirus-like agent of infantile gastroenteritis. Nebraska calf diarrhea virus used as antigen. A complement-fixation (C.F.) test for the human reovirus-like agent of infantile gastroenteritis has been developed using the serologically related Nebraska calf diarrhoea virus (N.C.D.V.) as antigen. Most infants and children who shed the agent in stools and/or who demonstrated serological (C.F.) evidence of infection with a reovirus-like-particle-positive human stool-filtrate C.F. antigen also demonstrated serological evidence of infection when a concentrated N.C.D.V. preparation was employed AS C.F. antigen. The N.C.D.V., which was previously shown to be related to the human reovirus-like agent, was found to be related antigenically to the epizootic diarrhoea of infant mice (E.D.I.M.) virus also. Studies on the prevalence of C.F. antibody in sera from infants and young children revealed a pattern of rapid acquisition of antibody to both the human reovirus-like agent and the N.C.D.V. as over 80 percent of these individuals possessed antibody to each agent by 36 months of age. A strong positive association was found in the results obtained with the two antigens. The ready availability of cell-culture grown N.C.D.V., and its ability to serve as a "substitute" C.F. antigen for the human reovirus-like agent, should enable the serodiagnosis of many cases of disease due to the human agent and facilitate seroepidemiological studies of such infections. In addition, the observation that a large proportion of individuals infected with the human reovirus-like agent develop serological evidence of infection not only to the human agent but to the calf agent as well may have important implications in the immunoprophylaxis of disease caused by the human reovirus-like agent.


Hepatitis due to aflatoxicosis. An outbreak in Western India. Parts of Western India have experienced an outbreak of hepatitis affecting man and dogs and characterised by jaundice, rapidly developing ascites, portal hypertension, and a high mortality-rate. The disease was associated with the consumption of maize contaminated heavily with Aspergillus flavus. Analysis of contaminated samples showed that affected people could have consumed between 2 and 6 mg. of aflatoxin daily over a period of a month. A specimen of liver obtained at necropsy showed bileduct proliferation and giant cells. The disease appears to be a result of aflatoxicosis.


Sunlight and hypercalciuria.

Sunlight and hypercalciuria. Urinary calcium and magnesium excretion was measured in two groups of soldiers leaving the temperate climate of the united Kingdom for service in the Persian Gulf. In one group urinary calcium levels and magnesium/calcium ratios were similar, ten days after arrival in the Gulf during the "cold season", to those found in the U.K. The other group went to the Gulf in the "hot season", and calcium excretion rose immediately to levels comparable with those found in the first group after eight months. Mg/Ca ratios fell to levels seen in stonformers, and 2 of 91 soldiers followed up for three years have had urinary calculi. Increased exposure to sunlight seems to be the most likely cause of the hypercalciuria.


Ultrasound in the diagnosis of spina bifida. Three patients who were at risk of having a baby with a neural-tube defect were investigated by ultrasonic examination and alpha-fetoprotein (A;F.P.) estimation. In all three cases amniotic-fluid A.F.P. levels were significantly raised and pregnancy was terminated. In the first case ultrasound failed to detect a small lumbo-sacral meningocele; In the second case ultrasound successfully diagnosed a dorso-lumbar meningo-myelocele but did not recognise internal hydrocephalus. In the third case ultrasound did not define any lesion, and pathological examination of the fetus revealed no abnormality. It is concluded that ultrasonic examination is an important diagnostic technique in the antneatal investigation of spina bifida.


Pleomorphic virus-like particles in human faeces. Pleomorphic fringed particles bearing some resemblance to orthomyxoviruses and coronaviruses were seen in 90 percent of stools from south Indian children and adults but not in stools from neonates. This finding may be related to the abnormalities of intestinal structure and function common in this region of India.


Pathogenesis of nonketotic hyperosmolar diabetic coma. Two concepts are advanced to explain some fo the puzzling biochemical features found in nonketotic hyperosmolar diabetic coma. It is firstly suggested that an insulinised liver (reflecting residual beta-cell secretory activity) coexists with a diabetic periphery, thereby inactivating intrahepatic oxidation of incoming free fatty acids, which are directed largly along nonketogenic metabolic pathways such as triglyceride synthesis. This could account for the lack of hyperketonaemia. Secondly, it is hypothesised that within the liver enhanced neoglucogenesis occurs, due to the prevailing portal-vein into ratio of glucagon to insulin, and is mainly responsible for the development of massive hyperglycaemia.


Surgical treatment of typhoid perforation. The treatment of perforation of the ileum in 50 cases of typhoid fever is reviewed. Because of the risk of reperforation after surgical closure of a perforation, wedge excision of the ulcer if there is a single area of diseases bowel or segmental resection of the ileum if the ileum is more extensively affected are recommended.


Comparison of arrhythmia computer and conventional monitoring in coronary-care unit. Conventional methods of monitoring arrhythmias impose heavy demands on staff and are unreliable. On-line arrhythmia computers have been developed to overcome these problems, but there has been no critical evaluation of the functioning of such a system in a clinical setting. A comparison was made of the efficacy of two methods of monitoring in detecting arrhythmias in sixty-four patients in a coronary-care unit. Half the patients were monitored by a commercially available arrhythmia computer; the other half were monitored by conventional means with a rate-triggered alarm system. More than 99 percent of episodes of potentially serious ventricular arrhythmias were detected by the computer; 95 percent of patients with these arrhythmias were treated immediately. In those monitored by conventional means, a large proporation of such arrhythmias were unrecognised: only 17 percent of affected patients received immediate antiarrhythmic therapy. In 30 percent, treatment was delayed for several hours, and none was given in 52 percent. False alarms occurred with both systems but were more readily recognised as such in the computer-monitored patients. It is concluded that an arrhythmia computer improves the standards of arrhythmia detection, leads to quicker institution of treatment, and diminishes the demand on skilled staff.


Breath hydrogen as a diagnostic method for hypolactasia. Breath hydrogen (H2), collected by end-expiratory sampling, was measured in twenty-five patients with abdominal symptoms or diarrhoea after ingesting 50 g. of lactose. This was compared with established tests of hypolactasia. Fifteen patients with a blood-glucose rise of more than 20 mg. per 100 ml. had less than 4 parts per million (p.p.m.) rise in breath H2 at 2 hours. In contrast, ten patients with blood-glucose rises of less than 20 mg. per 100 ml. had more than a 20 p.p.m. H2 rise (mean 85.8 p.p.m. plus or minus s.d. 44.3) at 2 hours. Similarly, two patients with normal jejunal lactase activity had no significant H2 production, whereas six patients with hypolactasia had more than a 20 p.p.m. rise in H2. Symptoms related to milk or lactose ingestion were found to be unreliable. End-expiratory sampling of breath H2 would seem to be a simple, non-invasive, and accurate method of diagnosing hypolactasia, which is also very acceptable to patients. This should make it a valuable tool both in diagnostic gastroenterology and in epidemiological surveys.


Rubella-virus infection in juvenile rheumatoid arthritis. Antibody activity against mumps, measles, polio, and rubella viruses was determined in patients with juvenile rheumatoid arthritis (J.R.A.), rubella-vaccine associated arthritis, adult rheumatoid arthritis, other chronic systemic disorders (e.g., systemic lupus and dermatomyositis), and in a matched population of normal, non-rheumatoid (control) children. The antibody levels against mumps, measles, and poliovirus were similar in all patients. Rubella-antibody levels in rheumatoid arthritis and other systemic disorders were similar to those observed in controls. The mean rubella-antibody levels in rubella-vaccine arthritis were 4 times higher than in controls. The IgM and IgG rubella-antibody levels in J.R.A. were found to be 4-6 times higher when compared to titres observed in the controls. Highest antibody levels were seen in younger children with J.R.A. Detection of rubella-virus antigen was attempted by immunofluorescence in the sediment smears of synovial fluid of patients with J.R.A., adult rheumatoid arthritis, and other non-rheumatoid joint diseases. Specific staining for rubella virus antigen was observed in the synovial fluid of 33 percent of patients with J.R.A. No antigen was detected in the synovial fluid from other patients. These observations suggest a possible role of rubella-virus infection in J.R.A.


Masked primary (or tertiary) hyperparathyroidism. Two patients are described in whom the preliminary clinical and laboratory investigations suggested a diagnosis of osteomalacia, from gluten-sensitive enteropathy in one and from anticonvulsant therapy in the other. However, when the primary disease was corrected by diet and extra vitamin D, respectively, both patients developed hypercalcaemia. A standard hydrocortisone test in the second patient failed to reduce the hypercalcaemia. In both patients parathyroid tumours were found at operation. It is suggested that both patients had tertiary hyperparathyroidism in which the normally tell-tale hypercalcaemia was at first masked by the other abnormalities, and that this masking may account for some cases reported as having normocalcaemic primary (or tertiary) hyperpatathyroidism. Interpretation of total plasma-calcium is likely to be unreliable unless the 25-hydroxyvitamin-D levels can be shown or assumed to be normal.


Auditory evoked responses in multiple sclerosis. The early components of the auditory evoked responses (waves I-V) have been studied in 30 patients with multiple sclerosis. There were abnormalities in 22 patients. All patients with an internuclear ophthalmoplegia and half those with no detectable brainstem abnormality had abnormal responses, although none was clinically deaf.


Impairment of platelet function by growth-hormone release-inhibiting hormone. Synthetic cyclic growth-hormone release-inhibiting hormone (G.H.-R.I.H.) impaired platelet aggregation in each of four healthy men given 6-hour infusions. The effects lasted over 24 hours in three of them. There was no consistent change in platelet-counts during the infusions, but 18 hours after the end of the infusions there was a slight but significant increase in platelet-count. There was no change in prothrombin-time, partial thromboplastin-time, fibrinogen titres, and fibrinogen-degradation products. Incubation of G.H.-R.I.H. with blood in vitro did not affect platelet aggregation. Similar impairment of platelet function has been reported by others in baboons given linear G.H.-R.I.H. Infusions in the four healthy men studied also produced abdominal pain, dizziness, and diarrhoea in three, as have been reported in patients similarly infused. Although other side-effects or impairment of platelet-counts or bleeding-tendencies have not been reported in patients infused for up to 72 hours, caution should be exercised when using G.H.-R.I.H. over extended periods until further data on its toxicity are available.


Doxantrazole, an antiallergic agent orally effective in man. In-vivo studies have demonstrated antiallergic properties in doxantrazole when given orally to rats. These properties were confirmed in work with in-vitro preparations. No significant animal toxicity has been detected. 200 mg. given by mouth inhibited the immediate-type asthmatic response in volunteer patients challenged with specific antigen.


Management and advice at the grass roots. The new management structure of the National Health Service leaves a gap between multidisciplinary management at district level and the multiprofessional clinical teams caring for patients. This gap is not satisfactorily bridged by single-profession sector management or existing advisory machinery. This is most clearly seen for community services, and experience of a possible solution in an experimental community hospital setting is described.


Randomised clinical trial of strategies for improving medication compliance in primary hypertension. 230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these men's compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.


Plasma exchange in the management of homozygous familial hypercholesterolaemia. Two young women with homozygous familial hypercholesterolaemia and coronary and aortic atheroma were treated by repeated plasma exchange, using a continuous-flow blood-cell separator, for 4 and 8 months. A pronounced reduction in plasma cholesterol and low-density lipoprotein (L.D.L.) concentrations was achieved by exchanging each patient's plasma with cholesterol-free plasma protein fraction (B.P.), at 3-weekly intervals on an outpatient basis. By pre-labelling the patients' cholesterol with 14-C and comparing the specific activity of the cholesterol in adipose tissue with that in plasma, evidence was obtained of an influx of tissue cholesterol into plasma after each exchange. There was no side-effects and both patients lost their angina. Plasma exchange offers a new and practical approach to the long-term management of this lethal disorder and may also provide information about the possible reversibility of human atheroma.


Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. The recovery of Salmonella typhi from blood, rectal swab, urine, bone-marrow, and rose spots was compared in 62 patients with typhoid fever, most of whom had received some antibiotic therapy before presentation. S. typhi was isolated from culture of bone-marrow in 56 patients (90%); in contrast, S. typhi was recovered from blood in only 25 (40%), from stool in 23 (37%), and urine in 4 (7%). S. typhi was isolated from 24 (63%) of 38 patients who had rose-spot cultures. If culture sites had been limited to blood, stool, and urine, the bacteriological diagnosis would have been missed in 24 patients.


Modification by propranolol of cardiovascular effects of induced hypoglycaemia. The cardiovascular effects of hypoglycaemia, with and without beta-blockade, were compared in fourteen healthy men. Eight received insulin alone, and eight, including two of the original insulin-only group, were given propranolol and insulin. In the insulin-group the period of hypoglycaemia was associated with an increase in heart-rate and a fall in diastolic blood-pressure. In the propranolol-insulin group there was a significant fall in heart-rate in most subjects and an increase in diastolic pressure. Typical S-T/T changes occurred in the insulin-group but in none of the propranolol-insulin group. Hypertension in diabetics prone to hypoglycaemia attacks should not be treated with beta-blockers because these drugs may cause a sharp rise in blood-pressure in such patients.


Use of co-trimoxazole in chronic renal failure. Twenty patients with chronic renal failure and either urinary or respiratory tract infection were treated with co-trimoxazole. Seventeen patients showed no deterioration in renal function while receiving co-trimoxazole. Deterioration in renal function during treatment in the other three patients was due to factors other than administration of the drug. It is concluded that co-trimoxazole can be used in patients with chronic renal failure provided the dose is adjusted according to the degree of renal failure.


Breast cancer, prostaglandins, and bone metastases. Human malignant breast tumours from 23 patients contained and synthesised more prostaglandin-like material than normal breast tissue from the same patients or benign neoplasms (5 patients). Bone metastases were associated with tumours having high levels of P.G.-like material, which usually resembled P.G.F compounds, and this may be important since some P.G.S are potent bone-resorbing substances.


Growth-hormone release-inhibiting hormone in gastrointestinal and pancreatic D cells. The normal pancreatic D cell has been well recognised since 1931, but its secretory product has not been identified with certainty. Combined immunocytochemical methods, and histological methods for endocrine granules, have demonstrated that it contains a product with G.H.-R.I.H.-like immunoreactivity. G.H.-R.I.H. has also been localised in the upper gastrointestinal tract, tentatively in the morphologically similar D cell of the Wiesbaden classification. The potent actions of this peptide on pancreatic and gastrointestinal function suggest that it may play an important role in digestive physiology.


Grey-scale ultrasonography for monitoring industrial exposure to hepatotoxic agents. Industrial exposure to several potentially hepatotoxic agents, such as vinyl-chloride monomer may occur, and there is a need for non-vasive, diagnostic techniques to detect and monitor progressive pathological processes in liver or spleen. Grey-scale ultrasonography permits display of detailed anatomy and pathology in the liver, portal veins, and spleen. The combination of fine resolution, non-invasiveness, absence of ionising radiation hazard, and portable equipment makes the technique ideal for screening populations at risk.


Errors in metabolic regulation. A common group of metabolic disorders. It is postulated that errors in metabolic regulation occur when aminoacid subsitutions or conformational changes occur at allosteric sites on proteins. The cell thus contains its full complement of enzymes, carrier proteins, and receptors, but these proteins do not respond normally to microenvironmental agents such as hormones or activator or inhibitor metabolites. Regulatory errors differ from the classical inborn errors in a number of respects: they can  be acquired as well as inherited, when due to defects at allosteric inhibitory sites they lead to loss of regulation of metabolic pathways with oversynthesis of metabolic products without gross accumulation of abnormal intermediates, and they can be treated, in principle, by enzyme inhibitors rather than by enzyme replacement, as for inborn errors.


Cigarette smoking and respiratory ill-health in the British army. The smoking habits and morbidity experiences of a cohort of soldiers have been studied from 1959 to 1969. In 1959 the cohort contained 4052 junior entrants to the Army, aged 15-18; in 1969 there remained 1412 men, by then aged 25-28. Between 1964 and 1969 there has been a slight but significant decrease in the prevalence of smoking, but amongst the smokers there has been little change in the number of cigarettes smoked. The cohort's 1969 prevalence of smoking was slightly above the national average of 70% for males of the same age, but the servicemen are heavier smokers than their civilian counterparts. Comparison of the morbidity experience for respiratory conditions in terms of inpatient admissions over 10 years reveals a significant excess for smokers of twenty or more cigarettes a day when compared with non-smokers. The difference between the two categories represents an estimated 130 days of inpatient care per 1000 men per year.


Comparison of procainamide and mexiletine in prevention of ventricular arrhythmias after acute myocardial infarction. The incidence of ventricular arrhythmias after myocardial infarction has been compared in a controlled study of procainamide, mexiletine, and placebo. Sixty male patients who has sustained a myocardial infarction and had received lignocaine for ventricular tachycardia or ventricular ectopic beats which were R-on-T, multiform, or close-coupled took part. The efficacy of the drugs was evaluated by continuous 24-hour recordings of the electrocardiogram on the 4th and 10th days after admission to the study. Procainamide was given as 500 mg. 4-hourly and mexiletine as 250 mg. 8-hourly with corresponding placebo regimens for 12 days. 77% of patients receiving placebo showed serious ventricular rhythm disorders compared with 33% receiving antiarrhythmic therapy (p smaller than 0.05). Although only 35% of patients receiving procainamide achieved accepted therapeutic plasma concentrations compared with 95% of those receiving mexiletine, both drugs were equally effective antiarrhythmically. The only major adverse effect of therapy noted was development of a positive antinuclear factor in a procainamide-treated patient. These results demonstrate the efficacy of oral antiarrhythmic agents in the management of ventricular arrhythmias after acute myocardial infarction. Mexiletine has the advantage of less frequent administration and lower toxicity.


Outcome of surgery in 40 children with temporal-lobe epilepsy. Temporal-lobe epilepsy commonly has its origins in childhood, particularly when the lesion involved is mesial temporal (Ammon's horn) Sclerosis. Evidence suggests that this lesion is probably a common cause of chronic epilepsy in adults and that often it is probably the result of a severe febrile convulsion in infancy. 40 children, fifteen years of age and younger, who had an anterior temporal lobectomy were followed up for one to twenty-four years. The findings confirm those already established in adults, that the best results of surgery, not only in seizure relief but also in behaviour, are obtained when mesial temporal sclerosis is the lesion found at operation, and also indicate that a severe febrile convulsion in infancy is often the chief provocative factor in the development of epilepsy.


Influence of treatment with diet alone on oral glucose-tolerance test and plasma sugar and insulin levels in patients with maturity-onset diabetes mellitus. Oral glucose-tolerance test (O.G.T.T.) plasma sugar and insulin levels were measured in 118 newly diagnosed maturity-onset diabetic patients before and after treatment with diet alone for periods of 2 and 6 months. The results of glucose-tolerance tests carried out during treatment could be predicted from the initial test and the weight reduction between the tests. This prediction was not improved by the addition of further variables, including age, obesity, and plasma-insulin levels during the first test. The change in O.C.T.T. plasma-insulin between the first and second tests was predicted by the result of the initial tests, the improvement of glucose tolerance between the two tests, and the degree of weight reduction. 95% of the group achieved some improvement of glucose tolerance after 2 months of dietary treatment, and 59% of the group achieved adequate diabetic control by this time. It is concluded that treatment with diet alone should be the first-line management for patients with newly diagnosed maturity-onset diabetes mellitus.


Morbidity and mortality in pseudopolycythaemia. A follow-up of 35 patients with pseudopolycythaemia showed that symptoms, high packed-cell volumes, and low plasma volumes persisted in most patients. The death-rate in these patients was six times greater than expected. Patients with pseudopolycythaemia are often regarded as having a good prognosis; however, this view should be revised in the light of these findings.


Measurement of liver-cadmium concentrations in patients and industrial workers by neutron-activation analysis. A new, rapid, non-invasive technique for measuring tissue-cadmium concentrations in patients and industrial workers has been designed and developed with a view to studying the cadmium content of the liver. The method utilises the principle of neutron-activation analysis whereby the specific changes produced by the inter action of nuclei and neutrons are analysed. Liver-cadmium content has been studied in cadavers and in four men with known of suspected cadmium poisoning. The patients all showed very high liver-cadmium levels of between 35 and 200 p.p.m. compared with under 1.0 p.p.m. in non-exposed subjects. The dose of radiation used in clinical studies was 0.4-1.0 rem and the detection limit of cadmium was 1.0 p.p.m.


Possible pathogenic role of endotoxin in Reye's syndrome. Evidence of circulating endotoxin was sought in children with Reye's syndrome, on the thesis that severe hepatic failure is likely to result in loss of capacity to detoxify intestinal endotoxins entering the circulation. A modification of the Limulus assay was used to demonstrate high levels of endotoxin-like activity (E.L.A.) in nine comatose patients with Reye's syndrome and in one of the two non-comatose patients. The symptom-free sibling of one patient had raised liver enzymes and a negative Limulus test. Plasma E.L.A. correlated significantly with degree of electroencephalographic disturbance early in the course of the illness. E.L.A. was also found in both of two cerebrospinal fluids evaluated. Preliminary in-vitro characterisation of this substance indicated that it resembled endotoxin derived from anaerobic intestinal bacteria. Intestinally derived endotoxin could be one factor in the pathogenesis of encephalopathy and other features of Reye's syndrome.


Survival after 40 minutes; submersion without cerebral sequeae. Cardiopulmonary resuscitation and rewarming were successful in a 5-year-old boy who had been submerged for 40 minutes in ice-cold fresh water. Severe metabolic acidosis  was corrected by intravenous infusion of sodium bicarbonate solution before spontaneous circulation could be re-established. Fulminant pulmonary oedema developed after re-establishment of spontaneous circulation. This was efficiently reversed by positive-end-expiratory-pressure ventilation. During 2 days of treatment of a respiratory the patient gradually regained consciousness; the endotracheal tube was then removed and the patient immediately started talking intelligently. The patient went through a period of slow cerebration and motor dysfunction but recovered rapidly, and on examination 13 months after the accident all findings were normal.


Chronic antigenic stimulation, herpesvirus infection, and cancer in transplant recipients. An increased incidence of malignancy has been reported in transplant recipients. The pathogenesis of this increase was originally attributed to immunosuppressive therapy. However, not all tumours are increased in proportion to their occurrence in the general population-75% of reported tumours are lymphorproliferative or carcinoma of the skin, lip, or cervix. This cannot be explained by impaired immunosurveillance, and alternative hypotheses must be considered. 90% of transplant recipients develop clinical or serological evidence of herpesvirus infection. Herpesviruses have been implicated in the pathogenesis of lymphorproliferative tumours and carcinoma of the skin and cervix. They can remain in latent form and be reactivated by allogeneic stimulation and/or immunosuppression. These viruses localise to skin, cervix, and neural tissue-i.e., exactly those sites where cancer develops in transplant patients. Herpesvirus infections in association with the presence of an allogeneic graft in an immunosuppressed patient may be responsible for the increased incidence of both lymphoproliferative tumours and carcinoma of the skin, lip, and cervix in the transplant recipient.


Porcine streptococci causing meningitis and septicaemia in man. From 1968 to 1974 seven cases of septicaemia and purulent meningitis caused by porcine streptococci of the Lancefield group R and three cases caused by similar streptococci lacking R antigen occurred in the Netherlands. Bacteria isolated from all ten patients shared the characteristics of a biochemically well defined bacterial species (provisionally called Streptococcus subacidus) which until 1968 was only found in pigs. Nine of the ten patients had had intensive contact with live or slaughtered pigs.


Effect of intravenous B.C.G. in guineapigs and pertinence to cancer immunotherapy in man. Intravenous injection of heat-killed or irradiated B.C.G into tuberculin-positive guineapigs produced macroscopic lesions in the lung when examined 10 days or 4 or 6 weeks later. Microscopically, granulomas typical of a delayed hypersensitivity reaction were seen. Intravenous B.C.G. in normal guineapigs did not produce lesions. At equivalent doses to the killed vaccine, viable vaccine caused only mild lesions. Liver lesions were also found on early examination but by 4 weeks had almost resolved. Acid/alcohol-fast bacteria were only rarely detected. Purified portein derivative did not produce lesions, and antihistamine treatment did not modify the results. These results suggest that B.C.G. should be given by the intravenous route for cancer immunotherapy in man with great caution, especially in tuberculin-sensitive persons. The guineapig observations stress that hypersensitisation is a potential complicating feature of cancer immunotherapy, and this is discussed in the light of published clinical experience of B.C.G. by various routes. It is concluded that B.C.G. vaccines with a high proportion of viable organisms are to be preferred.


Infection caused by Proteus mirabilis strains with transferrable gentamicin-resistance factors. During a period of 10 weeks, four patients in one hospital became infected with gentamicin-resistant Proteus mirabilis. In two of them septicaemia associated with indwelling catheters developed, one had urinary tract and wound infections, and in the fourth patient the organism was isolated from a superficial wound. The P. mirabilis strains showed multiple drug resistance. Strains form the first three patients were apparently identical and were sensitive to tobramycin. Their gentamicin resistance was not transferable to Escherichia coli K12, but could be transferred to another strain of P. mirablilis (PM13-3). The fourth strain was resistant to tobramycin; its gentamicin/tobramycin resistance was transferable to E. coli K12.


Postoperative thrombosis in Thai women.

Postoperative thrombosis in Thai women. The 125-I-labelled fibrinogen infusion test and phlebography were used to detect evidence of the postoperative development of deep-vein thrombosis (D.V.T) in the legs of 117 Thai women who had abdominal hysterectomy for benign conditions and of 52 who had major pelvic surgery for malignant disease of the ovary, uterus, and cervix. D.V.T. was demonstrated in 1.7% and 3.8%, respectively. Comparison of these results with an almost identical study in Oxford showed that D.V.T. was significantly more common in women in England - i.e., 12% and 35% in those with benign or malignant diseases, respectively.


Congenital cytomegalovirus infection  after maternal renal transplantation. Congenital cytomegalovirus infection was found in an infant  whose mother had a successful renal transplant and was treated with immunosuppressant therapy before and during pregnancy. Although so far not experiencing any untoward infections, the child had impaired T-lymphocyte function and subnormal serum-IgA.


Why are ovarian teratomas benign whilst teratomas of the testis are malignant? A mechanism is suggested to account for the fact that most ovarian teratomas are benign (dermoid cysts) whereas testicular teratomas are almost always malignant. The mechanism advanced assumes that malignancy is cause by a recessive mutation, and then shows that the known facts of germ-cell development will produce the homozygous (malignant) state in the male but the heterozygous counterpart in the female. It is proposed that the benign nature of ovarian teratomas is a reflection of this heterozygous genotype.


Sheltered groups in open industry. A new approach to training and to employment. The Department of Employment has now accepted that groups working under supervision in open industry are superior to sheltered workshops in the management and retraining of the disabled. A scheme  along these lines has been organised in Bristol for twelve years, and experience with the scheme suggests that, for former patients of mental hospitals, the approach is the right one. It is most acceptable to the patient and has the advantage of giving the patient the best chance of becoming self-sufficient.


[The effectiveness ot thyroid-hormone therapy following goiter-resection]. The effectiveness of a postoperative thyroid-hormone therapy in preventing a goiter-recidiv was investigated two years after goiter-resection.  Of 3381 patients with goiter, who were operated on in the years 1964 to 1973 in the Surgical Department of the Krankenhaus Nordwest in Frankfurt/Main, Germany, 129 patients who were operated on in the first six months of 1969, were questioned and examined in a follow-up study.  A rezidiv-goiter was found in 4, 6 p.c. of patients.  If only palpable recidiv-goiters are taken into consideration 2, 3 p.c.), patients without postoperative thyroid-hormone therapy developed a recidiv goiter twice as often as patients with thyroid-hormone therapy.


[Results of palliative operations concerning the gastrointestinal tract]. At the Surgical Clinic of the University Erlanten-Nürnber 61 per cent of the carcinoma of the oesophagus, 57 per cent of malignant tumors of the stomach and 28 per cent of all tumors of the large bowel and the rectum could not be operated radically.  If there are no metastases in other organs or a wide-spread peritoneal dissemination a palliative procedure is advisable.  Resection of the tumor itself has been the most effectful prodedure in cases of palliative treatment.  Gastrostomies, bypass-anastomoses and protheses have been comparatively less successful.  Radiation is indicated only in cases of squamoun cell-carcinoma of the oesophagus.  In cases of the carcinoma of the rectum located in the middle and lower part causing a severe stenosis coagulation is an effective treatment.


[The problems and clinical aspects of primary malignancies of the small intestine (author's transl)]. From 1954 to the end of 1973, 6432 patients were admitted to the Munich University Surgical Hospital for the treatment of malignant tumors of the digestive tract. 42 cases (0.66 percent) affected the small intestine, including the duodenum, but excepting tumors of the ileocecal region, peripapillar duodenal carcinoma, metastatic tumors of the small intestine and mesenteric tumors. The fate of all 42 patients with malignant tumors of the small intestine (6 carcinoids, 15 sarcomas and 21 carcinomas) was elucidated. 14 per cent of the malignant tumors were found in the duodenum, 27 percent in the jejunum and 59 per cent in the ileum.


[Transurethral electroresection of prostatic adenoma (author's transl)]. The affliction of disturbances of the voidance of urine in aging men is becoming an ever more frequent medical problem because of the rising life expectancy of our population. The cause of the urinary obstruction is fibromyoadenomatosis of the paraurethral glands which may develop at any time after the age of 40. Transurethral electroresection ist the ideal method for the complete removal of a small to medium sized prostatic adenoma. Once the technique of resection has been mastered, complications are always absolutely avoidable and rare.


Influence of N2 or O2 on two alkylating agents in Neurospora crassa. Previous studies have indicated that the alkylating agent, 2-methoxy-6-chloro-9-(3-[ethyl-2-chloroethyl]aminopropylamino)acridine dihydrochloride (ICR-170), induces much more killing and mutation in conidia of Neurospora crassa treated in an atmosphere of N2 than in an atmosphere of O2. It was desirable to determine if a similar effect--more killing and mutation in N2 than in O2--could be observed with two other known alkylating agents, beta-propiolactone (BPL) and ethyl methanesulfonate (EMS), in the same test system. Conidia of a heterokaryotic strain of N. crassa were bubbled with N2 or O2 during treatment with BPL or EMS. Forward-mutation was measured in the ad-3 region by a direct method. The results indicate that N2 or O2 do not influence the lethal and mutagenic activities of BPL or EMS during treatment of conidia. Hence the influence of N2 or O2 on the lethal and mutagenic activites of ICR-170 is different from the influence of these gases on BPL or EMS using the ad-3 test system in N. crassa.


ADH release from cut pituitary stalk and intact pituitary gland during amygdala stimulation at various frequencies in rats. Changes in antidiuretic substance (i.e., vasopressin) release from the cut pituitary stalk and the intact pituitary gland were observed during electrical stimulation of amygdala medial nucleus. Electrical pulses of 4 or 36 cycles per second (cps) were used and in both cases the same energy (about 2.160 nanowatt seconds) per 1.5 sec-train of electrical pulses remained constant. Antidiuretic substance release from the hypothalamic end of the cut pituitary stalk and from the intact pituitary gland increased during the 36-cps electrical stimulation of amygdala medial nucleus, however the 4-cps electrical stimulation of this structure did not produce any changes in these processes. The results obtained indicate that the medial nucleus of amygdala is able to change the function of the hypothalamo-hypophysial system and can be motivated with high frequency stimulating pulses.


Amyloidosis: a rational approach to diagnosis by intraoral biopsy. Amyloidosis and its oral manifestations are briefly described. The techniques for antemortem tissue diagnosis of amyloidosis are reviewed and evaluated. In screening for amyloidosis, biopsy of specific oral lesions (when present) is recommended instead of the traditional biopsy of normal-appearing gingiva. This approach is illustrated with four cases. Although rectal biopsy is generally accepted as the screening technique of choice, it is suggested that intraoral biopsy be considered as an easier, safer, more comfortable, and possibly more fruitful technique. It is advocated that in cases of both documented and suspected amyloidosis both intraoral and rectal biopsies should be performed in order to help provide documentation of the most useful technique for routine screening.


Congenital analgesia. Report of a case.

Congenital analgesia. Report of a case. A case of an injured, necrotic tongue in a child of 12 months was investigated. It was found that the patient was suffering from congenital analgesia. The injury was due to errupted lower incisor teeth, and the injury healed following their extraction. We believe that in cases of repeated self-injury of the tongue some form of sensory disturbance should be considered.


Histocompatibility and tooth transplantation in the rabbit. Allogeneic orthotopic tooth transplants in the rabbit appear to stimulate transplantation immunity reactions comparable to those encountered with the transplantation of other organs. Intact untreated teeth were shown to be as quantitatively immunogenic as skin grafts between unrelated animals. Histocompatibility matching of donor and recipient and removal of pulpal tissues were demonstrated to be effective means of ameliorating the immune response to allogeneic orthotopic tooth transplants in the rabbit.


[Value of the test using TRH in the exploration of thyroid diseases]. The discovery and the synthesis of the thyrotropin-releasing hormone (T.R.H.) has given rise to a new test able to explore the function of the thyroid and the pituitary. Intravenous injection of T.R.H. determines a short elevation of T.S.H. in the plasma. In hyperthyroidism and in hot nodules the response is abolished. In hypothyroidism, the response depends on the localization of the lesion: exaggerated response in thyroid lesions, diminished or abolished response in pituitary problems, delayed response in hypothalamic lesions. This new test will definitely have an important diagnostic role in difficult clinical problems.


Diabetes mellitus: changes in the transport properties of isolated intestinal microvillous membranes. Isolated, small intestinal microvillous membranes from normal and acutely diabetic rats were compared with respect to D-glucose transport. D-Glucose was accumulated to a greater extent by diabetic membrane vesicles when supplied with energy in the form of a NaC1 or a NaSCN gradient across the vesicle membrane. The difference appeared to be caused by an ability of the diabetic membranes to maintain a higher driving force for active D-glucose transport and not by changes in the glucose "carrier." Increasing the glucose-independent Na-+-conductance of the membrane with monactin or gramicidin D reduced the active accumulation of D-glucose by membrane preparations from both control and diabetic groups. Concentrations of monactin and gramicidin D in the incubation medium of membrane vesicles from diabetic animals could be adjusted so that their D-glucose transport became indistinguishable from that of membranes from normal animals not treated with ionophores. These observatins suggest the microvillous membranes as one site where changes occur in acute diabetes. In addition, the change in the transport properties of the isolated membranes offer a rational explanation for the simultaneous elevation of active intestinal sugar, amino acid, and bile salt transport observed for intact intestinal tissue.


Group-specific component (Gc) proteins bind vitamin D and 25-hydroxyvitamin D. Group-specific component (Gc) proteins are human plasma proteins for which a worldwide polymorphism exists. As yet no functional role has been assigned this protein. We show that the products of both Gc alleles, proteins Gc 1 and Gc 2 (distinguished electrophoretically), bind substantial quantities of vitamin D and 25-hydroxyvitamin D. Three lines of evidence are reported: (1) Polyacrylamide gel electrophoresis and autoradiography of serum labeled with (14-C)vitamin D3 revealed patterns of radioactive bands identical to those expected of the two Gc alleles. Population gene frequencies for these proteins binding vitamin D were in the range of those reported for Gc, and individuals of known Gc phenotype were found to have the corresponding vitamin-D-binding phenotype. (2) Immunoelectrophoresis and autoradiography of labeled serum reacted against antiserum to human Gc revealed labeling by (14-C)vitamin D3 of Gc-antibody precipitation ares. (3) (14-C)vitamin D3 or 25-hydroxy(3-H)vitamin D3 was found to coprecipitate specifically with Gc in serum incubated with Gc antiserum. Use of these techniques demonstrated further that plasma proteins that bind vitamin D and that are immunologically similar to human Gc are found in mouse, rat, cow, horse, dog, rhesus monkey, and chimpanzee. We propose that Gc and "vitamin-D-binding alpha-globulin" are in fact the same portein, and that the ability of Gc to bind vitamin D may be directly related to the action of selection on this locus. These techniques may also find application in the study of other plasms transport proteins.


Tumor-associated transplantation antigens in immune rejection of mouse malignant cell hybrids. The inability of mouse cell hybrids derived from two malignant parental cells to produce tumors in syngeneic F1 hosts was analyzed. YC hybrids, derived from the fusion of C1.1D and L1210 clls, failed to induce any tumor in adult mice, while 91% of x-irradiated newborn mice developed tumors and died. Some telocentric chromosomes were lacking in hybrid tumors; however, none of the immunologically intact adult mice developed tumors when grafted with tumors grown in x-irradiated newborn mice. This indicates that histocompatibility factors interfered in the failure of YC tumors to grow to adult hosts. Syngeneic F1 mice immunized with Y2C hybrid cells had cytotoxic antibodies against Y2C hybrids and C1.1D and L1210 parental cells. Complete absorption of cytotoxic antibodies directed against hybrid cells by mixtures of both parental cell lines demonstrates the absence of any new antigen on hybrid cells.Hyb rid cells had a higher density of C1.1D-tumor antigenic sites, as compared to C1.1D parental cells. This possibly explains the higher antigenicity and/or the higher sensitivity to immune lysis of hybrid cells.


Ability of tryptophan tRNA to hybridize with 35S RNA of avian myeloblastosis virus and to prime reverse transcription in vitro. Selected species of 4S RNA of chick embryo cells will hybridize in vitro with 35S RNA of avian myeloblastosis virus. A major tRNA component of the hybridizable 4S RNA is tryptophan tRNA. A hybrid prepared from purified tryptophan tRAN and 35S RNA of avian myeloblastosis virus in vitro is an efficient templateprimer for DNA synthesis catalyzed by reverse transcriptase (RNA-dependent DNA polymerase).


Two antigenically distinct species of human interferon. Rabbit antisera prepared against interferon produced in human fibroblast cell cultures stimulated with poly(1).poly(C) neutralized the activity of interferon preparations produced in various human fibroblast cultures timulated either with poly(1)poly)C) or with viruses. However, these antisera showed no detectable neutralizing activity against interferon produced in cultures of human leukocytes. On the other hand, most rabbit antisera against the human leukocyte interferon were active in neutralizing both homologous interferon and fibroblast interferons. A preparation of antiserum against leukocyte interferon, active against both leukocyte and fibroblast interferons, was shown by affinity chromatography to have two distinct antibody populations, one of which was specific for the fibroblast interferon. We conclude that the heterologous neutralizing activity of sera from rabbits immunized with leukocyte interferon is liekly to be due to the presence of two antigenic species of interferon. The major antigenic species of leukocyte interferon preparations (designated "Le") is distinct from huamn fibroblast interferon. The minor species of leukocyte interferon ("F") is either identical with, or closely related to, interferon produced in human fibroblast cultures.


Isolation of Escherichia coli mutants defective in enzymes of membrane lipid synthesis. A new method has been developed which permits the rapid screening of E. coli colonies for mutants with defective enzymes of phospholipid metabolism. In this procedure, a disc of filter paper is pressed down on an agar plate containing several hundred colonies of mutagen-treated cells, after which the paper is lifted off. In the process the colonies are transferred to the paper, giving rise to a replica print of the master plate. The few cells from each colony left on the master keep growing in the original pattern. The pattern of colonies is also retained on the filter paper, even after the cells are rendered permeable with lysozyme and EDTA. Colonies treated in this manner remain absorbed to the paper, where they can convert sn-(U-14-C)glycero-3-P to phosphatidyl(U-14-C)glycerophosphate, dependent on added CDP-diglyceride. Unrelated reactions of sn-(U-14-C)glycero-3-P that may obscure the synthesis of phosphatidyl-glycerophosphate are inhibited by the addition of reagents poisoning energy generation. The radioactive phospholipid that forms around each colony on the paper is precipitated in situ with trichloroacetic acid, and unreacted sn-(U-14-C)glycero-3-P is washed away. After autoradiography, the colonies on the filter paper are stained with Coomassie blue. When the autoradiogram is superimposed on the strained paper, mutants are identified as blue colonies lacking a black halo. With this method, 20,000 colonies were screened in several days. Four mutants were identified with low levels of CDP-diglyceride:snglycero-3-P phosphatidyl transferase (EC 2.7.8.5, GLYCEROL-PHOSPHATE PHOSPHATIDYLTRANSFERASE, PHOSPHATIDYLGLYCEROPHOSPHATE SYNTHETASE) IN EXTRACTS. With a similar assay, 10,000 additional colonies were screened for mutants with altered CDP-diglyceride:L-serine O-phosphatidyltransferase (EC 2.7.8.8, phosphatidylserine synthetase), and four strains were found in which the enzyme is thermolabile. The screening technique described here is termed replica printing and should be applicable not only to studies of phospholipid metabolism but also to nucleic acid and protein synthesis.


Human globin gene analysis for a patient with beta-o/delta beta-thalassemia. Complementary DNA (cDNA) was prepared with RNA-dependent DNA polymerase from human globin messenger RNA (mRNA). Annealing and translation experimenta with total mRNA from circulating cells from a patient with heterozygous beta/heterozygous beta-delta-o thalassemia (beta-o/delta beta-o-thalassemia) demonstrated no detectable mRNA for beta-globin. cDNA enriched in sequences homologous to beta-globin mRNA was prepared by hydroxylapatite fractionation of hybrids formed between beta-o/delta beta-o-thalassemic mRNA and cDNA made from mRNA from a patient with alpha-thalassemia (hemoglobin H disease). The rate of annealing of this beta-enriched cDNA to normal human nuclear DNA was that of a sequence present as only a single copy per haploid genome. The beta-enriched cDNA annealed to the beta-o-delta beta-o-thalassemia total DNA with approximately the same kinetics as to normal DNA, indicating that no total gene deletion of beta-globin genes from the diploid genome has occurred, although the accuracy of the technique could not exclude with certainty a partial deletion or a deletion of a beta-globin gene from only one of the haploid genomes. This demonstrates that at least one of the beta-o- or the delta beta-o-thalassemia haploid genomes in this case contains a substantially intact beta-globin gene.


Isolation from the asian mouse Mus caroli of an endogenous type C virus related to infectious primate type C viruses. Treatment of a cell line derived from the Asian feral mouse Mus caroli with 5-bromodeoxyuridine induces an infectious, xentropic type C virus. This virus shares strongly cross-reactive reverse transcriptase (RNA-dependent DNA polymerase) and p30 antigens and crossinterferes with type C viruses isolated from a woolly monkey (SSAV) and gibbon apes (GALV). By similar criteria, the caroli virus is much less related to previously described type C viruses of the laboratory mouse, Mus musculus. Induction of virus from 10 of 13 single cell clones indicates that the virus is endogenous in Mus caroli cells. Thre results suggest that infectious primate type C viruses arose by trans-species infection(s) of certain primates with endogenous type C viruses from MUs caroli or a closely related Mus species.


Recognition of immunoglobulin idiotypes by thymus-derived lymphocytes. The ability of thymus-derived lymphocytes (T cells) from BALB/c mice to recognize the individually specific antigenic determinants (idiotypes) of BALB/c myeloma proteins was tested. Spleen cells from donor mice immunized with a given myeloma protein greatly augmented the response of hapten-specific bone marrow-derived, thymus-independent lymphocytes (cells) to a hapten conjugate of the immunizing myeloma protein. This helper effect was specific for the myeloma protein idiotype; responses to hapten conjugates of similar myeloma proteins, bearing different idiotypic determinants, were not augmented by these spleen cells. That the helper cell is a T cell was shown by its marked sensitivity to cytolysis with an isoantiserum specific for T cells (anti-Thy-1-2) and complement. The discrimination between idiotypes by such T cells is roughly comparable to that of the antibody produced by the donors of the helper cells.


A p60 polypeptide in the feline leukemia virus pseudotype of Moloney sarcoma virus with murine leukemia virus p30 antigenic determinants. A 60,000-dalton polypeptide (p60) has been identified in the feline leukemia virus (FeLV) pseudotype of Moloney sarcoma virus [MSV(FeLV)]. This polypeptide is present in the purified virus complex in concentrations greater than either the murine p30 or the feline p27. Purified p60 crossreacts immunologically with murine p30 group antiserum and contains several interspecies determinants, whereas the group specific determinant of FeLV p27 is not detected. Comparison of peptide fingerprints of p60 and murine p30 show many peptides in common. Limited digestion of p60 with either trypsin or chymotrypsin produced p30-35 and p20 peptides which retain the MuLV p30 group and interspecies antigenic activities. The p30 produced by both enzymes comigrates in polyacrylamide gels with the murine p30 of MSV(FeLV), thus suggesting that p60 may be an uncleaved precursor to p30.


Establishing standing and walking behavior in a physically handicapped, retarded child. A physical therapist using reinforcement procedures worked for three months with minimal success on pulling to standing and pushing off to walk as target behaviors for a physically handicapped retarded child. The physical therapist then changed his role and used an attendant staff to work on the target behaviors in a two-and-one-half month treatment program. Pretreatment and posttreatment time sampling of the child's on-feet behaviors following the treatment program. The results of this one case suggest that the consultation role of the physical therapist might provide a more efficient treatment than a direct treatment role in an institutional setting.


Radiation therapy of the liver metastatic disease. Eight patients with symptomatic liver metastasis from different primary tumours received palliative radiation therapy. Daily doses of 150-200 r calculated in the mid-liver plane were delivered. The total dose employed was 2,500 r given in 3 weeks. Six patients responded good, one reasonable and one patient failed to respond to radiation. Liver function tests and liver scans also reflected the treatment response. All eight patients tolerated the treatment and no mortality due to treatment was recorded.


Viewbox seminar: a new method for teaching roentgenology. The American College of Radiology designed a "crash" program to train radiologists to interpret and classify the radiological manifestations of coal workers' pneumoconiosis. This Viewbox Seminar combines two pedagogic techniques, group viewbox study, and a test-teach-test sequence of instruction that compels active participation in the learning process. Weekend scheduling and good location and transportation connections facilitate attendance, making this an excellent way to teach large groups of radiologists certain subtleties of radiology in a short time.


Observations of mechanisms of attachment in the green alga Ulva mutabilis Føyn. An ultrastructural and light microscopical study of zygotes and rhizoids. The development of the rhizoid cells of the green alga Ulva mutabilis was investigated at the ultrastructural level paying special attention to the mechanism of attachment of the plant. Cytochemical data concerning the initial settling of the early zygote are also given. On the basis of histochemical staining and enzyme treatment it is concluded that the adhesive material secreted by the rhizoid cells is chemically different from that secreted by the zygote during the initial settling of the alga.


Prostaglandin F2alpha and human prostatic affinity for testosterone. Earlier work had shown that the lactogen, LTH and HPL, foster testosterone binding by the prostate. This study was undertaken to see if prostaglandin F2alpha would oppose the effect of the lactogen on the prostate as it does the luteotrophic action of the hormone on the corpus luteum. When it was found instead that the PGF increases steroid binding and that its interaction with lactogen was neither antagonistic nor additive, attention was directed to further characterization of prostaglandin's effect. A dosage/response study of F2alpha alone showed that concentrations of 4 ng/ml and 40 ng/ml increased binding but that 400 ng/ml did not. Glands with stromal hyperplasia and/or inflammation were not responsive than those with epithelial hyperplasia. Assays of water extracts of the tissue revealed concentrations of about 340 ng of F2alpha per gram fresh weight and that the concentration varied inversely as the beta-glucuronidase activity. If the enzyme level is considered an index of the epithelial cell density within the specimen, the inverse relationship suggest a non-epithelial (stromal) site of prostaglandin concentration.


Complement components in normal serum and plasma quantitated by electroimmunoassay. Sjöholm, A. G. Complement Components in Normal Serum and Plasma Quantitated by Electroimmunoassay. Scand. J. Immunol. 4, 25-30, 1975. The concentrations of C1q, C1s, C3, C4, C5, C3 proactivator, and C1 inactivator in serum and EDTA plasma from 100 normal adults were determined by electroimmunoassay. The normal range of each of the proteins is given. The C1q values varied more closely with the C1s values than with the levels of the other complement components. C3, C5, and C3 proactivator seemed to form a fairly interdependent group. The reproducibility of double determinations (interplate variation) was 4.9% to 7.9%. The variation of the complement component levels on repeated sampling from normal individuals was investigated. Also, repeated freezeing and thawing and storage at room temperature of serum and plasma were studied for their effect on the quantitation of the complement components. C3 and C4 values obtained by electroimmunoassay were in agreement with the values obtained by single radial immunodiffusion.


Mechanism of b-lymphocyte activation: failure to obtain evidence of a direct role of the Ig receptors in the triggering process. Experiments were designed to test two hypotheses of B-cell activation by antigen: the cross-linking concept, postulating that a suitable degree of antigen-induced cross-linking of the Ig receptors is sufficient for immunocyte triggering, and the two-signal hypothesis, suggesting that a first signal delivered by antigen interacting with the Ig receptors followed by a second signal given by, for example, a polyclonal B-cell activator is necessary for activation. The results did not support either of these hypotheses. Thus, the hapten FITC coupled to human serum albumin and human gammaglobulin in different conjugation ratios failed to activate B cells, whether the hapten-protein conjugates were soluble or precipitated, whether the experiments were carried out in the presence or absence of different concentrations of sera from different species, and irrespective of the day of assay. Furthermore, the same FITC-protein conjugates or FITC itself coupled to Sepharose particles failed to induce a specific anti-FITC response, even though a range of 10-9-fold concentrations of FITC were used. In contrast, FITC coupled to lipopolysaccharide (LPS) regularly induced a primary anti-FITC response in all the above systems, whether FITC-LPS was soluble or coupled to Sepharose particles. The conjugation ratio of FITC to LPS was within the range of epitope densities used with FITC-protein conjugates. Analogous studies were performed with the above compounds and, in addition, NNP-cap and fowl gammaglobulin, added alone or together with LPS to lymphocyte cultures. In no case did the antigen plus LPS give a better specific anti-FITC response than LPS alone, irrespective of the culture conditions, the epitope densities, the physical form of the conjugates, and whether they were bound to Sepharose particles or not, although this would be expected in terms of the two-signal concept. The results are compatible with the one nonspecific signal hypothesis, ascribing a passive role to the Ig receptors and an active triggering function to thymus-independent antigens. Therefore, the ability to trigger B cells directly will depend on the nature of the carrier, triggering being achieved if the carrier is a polyclonal B-cell activator; the epitope density and the degree of cross-linking of Ig receptors are unimportant for delivering the triggering signal, although they can facilitate the binding of the conjugate to the specific B cells.


Mouse cell-mediated lympholysis assay in serum-free and mouse serum-supplemented media: culture conditions and genetic factors. We describe a miniaturized cell-mediated lympholysis assay for measuring the activity of cytotoxic lymphocytes generated in mouse mixed leukocyte cultures (MLC), using either serum-free or mouse serum-supplemented media. Mixed reactions of strain combinations possessing various genetic differences at H-2 produced cytotoxic lymphocytes with cytolytic activity against cells of the donor used in the sensitization phase. Results suggest that both serologically defined and lymphocyte-defined determinants can act as effective target antigens on target cells. In contrast, no cytotoxic lymphocytes were generated against products of non-H-2 loci--M-locus, theta, or other non-H-2 antigens--that induce MLC activation.


The P-component of amyloid of human islets of langerhans. The P-component of amyloid was found in extracts of pancreases with islet amyloidosis. In double immunodiffusion this P-component showed lines of identity with isolated purified human P-component, normal human serum, and an extract of amyloid-rich liver tissue from a patient with primary systemic amyloidosis. The finding supports the theory that the P-component is present in all native human amyloid irrespective of type.


Tetanus toxin: direct evidence for retrograde intraaxonal transport. The neurotoxin tetanospasmin causes tetanus when it reaches the central nervous system. In this autoradiographic study, 125-I-labeled tetanospasmin was injected into the leg muscles of rodents, and the nerves supplying these muscles were crushed. The labeled toxin accumulated within axons on the distal side of the crush. This study provides direct evidence for retrograde axonal transport of a macromolecular toxin that acts at synapses in the central nervous system.


Bradycardia during human diving.

Bradycardia during human diving. The bradycardial response to the diving reflex, which occurs in man and in diving animals, is thought to be a physiologically protective oxygen-conserving mechanism whereby the animal is kept alive during submergence. The physiology and nervous pathways are not yet fully understood, but several investigators have pointed out the potentially fatal outcome of an accentuated diving reflex. the CO2 content of the peripheral venous blood has been proved variable and unpredictable during the hyperventilation-breath-hold dive cycle in man. A group of 8 male divers (average age 34 years) was investigated during breathhold dives to 3,3 m in a swimming pool. Heart rates were recorded and compared at various stages during breath-hold and SCUBA (self-contained underwater breathing apparatus) dives, viz. when resting on the surface, breath-holding, hyperventilating and swimming underwater. Two divers performed extreme breathhold endurance tests lasting 135 seconds underwater. All divers had a tachycardia after hyperventilation and a bradycardia after breathhold diving, lasting 80-100 seconds. Extrasystoles were recorded during some of the breathhold dives. Prolonged submergence caused extreme bradycardia (24/min) with central cyanosis. Bradycardia during diving may be a physiological )2-conserving reflex or the start of a pathophysiological asphyxial response.


Carcinoma of the thoraco-abdominal oesophagus. A new approach in the management of carcinoma of the thoraco-abdominal oesophagus, by means of pre-operative chemotherapy, in the form of Methotrexate and irradiation, followed by a one-stage resection, using a thoracic/abdominal approach, is described. This resulted in a marked tumour regression without leading to difficulty with operative management.


[First clinical results of radiotherapy following partial synchronization by bleomycin]. On the Ehrlich-ascites tumor and on the solide Ehrlich carcinoma of the mouse, bleomycin causes a large fixation in the (G2+M)-phase of the cell cycle of the tumor cells.  Even in certain human solide tumors, after the application of bleomycin in a predetermined period an increase of the G2 portion of the proliferating cells can be observed.  By individual control which can be peraformed rapidly and with high accuracy by impulse cytophotometry, this partial synchronisation effect can be used for radiotherapy.


[Semi-deep radiotherapy under high-kilovoltage conditions]. The semi-deep radiotherapy, performed by high-kilovoltage technique, fills a gap between superficial and megavolttherapy, as it renders possible an irradiation in focal depth of 2--4 cm, while largely preserving the deep underlying tissue.  Besides which, every form of radiotherapy can be used, as under conventinal conditions.  A further advantage exists in the markedly greater skin tolerance and in the low bone absorption of high-kilovoltage radiation, so that much higher focal doses can be achieved.  This means that--in superficial processes--the high-voltage technique can replace the much more expensive therapy with accelerated electrons.  The RT 305 equipment for high-voltage technique can be especially recommended for the following indications: 1. Skin and limph node metastases as well as tumors and metastases which are not situated deeper than 5 cm below the skin surface.  Hereby, thean be exposed up to 8000 R, by small or medium cone.  At the same time, in comparison to conventional X-ray therapy, the deep tissue is largely preserved.  2. Postoperative radiotherapy of tumors situated right under the skin.  3. Radiotherapy of inoperable breast cancer.  4. Irradiation of relapses on pre-exposed skin.  5. We assume that the high-voltage technique is also suitable for primary radiotherapy of larynx carcinomas, although we have no personal experience of this.  6. The palliative irradiation of deep tumors with the RT 305, due to its preservation of the skin and the relatively low bone absorption, can be performed more easily than with conventional X-ray therapy.  The method of choice, however, is the megavolt-therapy.  7. Degenerative diseases and arthroses.


[Primary radiotherapeutic eutic results of uterine carcinoma in the years 1960 to 1968]. A report is given of 448 cases of corpus carcinoma, treated by primary radiotherapy in the I-st Gynecological University Hospital in the years 1960 to 1968.  The 5-years-healing rate in this period was 50.4 percent.  It is emphasized that the cases represent a negative selection, as only inbetween the ages of 61 and 90 years.  Two women died primarily from pulmonary embolism (0.4 percent).  In  two patients a rectovaginal fistula developed.  The increasing number of patients with diabetes mellitus (23.2 percent) is striking.


[Treatment of advanced neoplasms in the jaw]. Report is made about the combined therapy with cytostatics (methotrexate - bleomycin) and irradiation in patients with extended tumors in the gnathic region. Ten patients in whom a radical therapy with conventional methods did not promise any success, were treated with intra-arterial infusions of methotrexate and bleomycin and simultaneous irradiation. At present, eight patients are tumor free (observation time 4-14 months after termination of therapy). Although radiation doses and doses of cytostatics were high, only insignificant side effects were stated; consequently, the treatment had to be terminated in none of the patients.


The possible role of i region determined cell surface molecules in the regulation of immune responses. An hypothetical model has been presented by which I region determined cell surface molecules (Ia antigens) mediate the collaboration between T cells and B cells leading to control of the humoral immune response. The model proposes an analogy between Ia antigens and the constant regions of Ig chains. The absolute requirements of this model are: a) On the B cell the Ia antigen is closely associated with the Fc receptor; b) On the T cell the Ia antigen is closely associated with the product of a linked variable region gene which functions as a specific T cell binding site; and c) The interaction between the T cell Ia molecule and its B cell counterpart leads to B cell activation. By the proposed interactive model no additional Ir gene products are required to explain current concepts of Ir gene function. The experimental evidence from our own laboratory and elsewhere upon which this model is based has been reviewed and a variety of consequences and predictions of the model have been examined. There are numerous aspects of the model which, because of a lack of hard data, are open to alternative explanations. The possible usefulness of this model should lie in its ability to suggest further experiments to elucidate the mechanism of B cell activation and control of the immune response.


B lymphocyte activation and lattice formation. When B lymphocyte activation is viewed within the general context of the clonal selection theory it is seen that this complex process must, under normal physiological conditions, be initiated only after antigen recognition by the B cell, that is, after antigen binding to the cells immunoglobulin receptors. The cross linking of receptors by effectively multivalent antigens, so as to form a receptor-antigen lattice may be generally required for activation. A theory is developed for the rate of lattice formation in the presence of inhibition by free hapten. It is shown that free hapten can very effectively inhibit the rate of lattice formation, particularly on high affinity cells, even though it cannot compete with multivalent binding at equilibrium.


Decreased antigenicity of mouse blastocysts after activation for implantation from experimental delay. The antigenicity of mouse blastocysts in experimentally delayed implantation and after activation from delay by estradiol administration were determined by two different methods. CBA blastocysts were incubated in C57BL/6J anti-CBA serum, and the amount of antibodies bound to the blastocysts was traced by -125-I-conjugated sheep antimouse gamma-globulin (isotope antiglobulin technique) and sensitized sheep red cells (mixed haemadsorption technique). With both techniques it was possible to demonstrate that mouse blastocysts in experimental delay of implantation possess alloantigens, and that this antigen expression has decreased markedly 14 hr after activation for implantation. It is suggested that this phenomenon may be of significance for noncognition of the allogeneic conceptus during pregnancy.


The incidence of hepatitis-B-antigen and anti-hepatitis-B among blood donors in Ndola, Zambia. Hepatitis-B antigen (HBsAG) was detected in the sera of 29 or 250 (11.6%) blood donors in Ndola, Zambia, most of whom were prisoners or students. The incidence among prisoners was 15.1%, among students only 1.6%. Thirteen sera were subtyped, nine carried the y and four the d antigenic determinant. Although there was a marked difference in the incidence of HBs antigen between prisoners and students, when donors were tested for antibody to HBsAg (anti-HBs) this positive. Overall, anti-HBs was detected in 132 of 250 blood donors (52.8%). The sensitivity of radioimmunoassay, counter-immunoelectrophoresis and a newly developed passive haemagglutination (PHA) test, employing tanned formalinised antibody coated turkey erythrocytes, was compared. Although radioimmunoassay provided the most sensitive method, the PHA test compared extremely favourably and was considered to be particularly suitable for use in the tropics.


Hepatitis B antigen, alpha1 fetoprotein and liver disease in the eastern highlands of Papua New Guinea. The sera from 89 patients from the Eastern Higlands of Papua New Guinea, all with histologically diagnosed liver disease, were tested for Hepatitis B Antigen (HB Ag) and Hepatitis B antibody (HB Ab) and alpha1 fetoprotein (AFP) by a variety of techniques which included radioimmunoassay. In the three main forms of liver disease, viral hepatitis, cirrhosis and hepatoma, HB Ag was found with a higher frequency than in patients with non specific liver disease. The frequency of HB Ab was decreased in cirrhosis and hepatoma. AFP was detected in all hepatoma patients by radioimmunoassay, levels being very high in most subjects. In hepatitis, cirrhosis and non specific liver disease, elevated levels of AFP were again frequently present, but at generally lower levels. It is conlcuded that HB Ag and AFP frequency and levels in liver disease are similar to those reported from other tropical countries. Further study is required to elicit the cellular immunological changes in liver disease.


Isolation and identification of leptospira hardjo from cattle in Argentina. A serological evaluation was done on the prevalence of bovine leptospirosis in Argentina. In 1,857 serum samples obtained from the major cattle raising areas of the country, 59.1 percent showed leptospiral agglutinins in the microscopic-agglutination test. The most frequent leptospiral antigens showing antibody reactions were the hebdomadis group serotypes, of which 45.8 per cent of the sera reacted to Leptospira hardjo with titres ranging from 1:100 to 1:25,600. Six Leptospira isolations were made from 161 bovine kidneys collected at local abattoirs. Their isolation and subsequent identification as serotype L. hardjo is described. This study reports on L. hardjo in cattle of Argentina for the first time and confirms the need for improved cultural methodology for its isolation.