Genetic control of the antibody response to sperm whale myoglobin in mice. The antibody response to the main chromatographic component IV of sperm whale myoglobin in mice has been shown to be under the control of both H-2-linked and non-H-2-linked genes, using an assay which measures antibody concentration independent of affinity. The effect of non-H-2 background genes was such that for a given H-2 haplotype, mice of the A background were higher responders than those of the B10 background. Among congenic mice of all the same background, mice of haplotypes H-2d,s were high responders, while those of haplotypes H-2k,b,q were low responders. Use of intra-H-2 recombinant strains B10.A, B10.A(5R), A.TL, and D2.GD allowed mapping of at least two H-2-linked Ir genes, both within the I region, one tentatively mapping in I-A, designated Ir-Mb-1, and one mapping to the right of I-E and left of H-2D, designated Ir-Mb-2. Strains bearing both genes or only Ir-Mb-1 were high responders, while those bearing Ir-Mb-2 were intermediate responders. When the concentration of antimyoglobin antibodies which bound to [14C]-fragment (132-153) of myoglobin was measured in the same sera described above, levels in the B10.A sera were low like those of the B10.BR rather than intermediate between the levels of the B10.BR and the high responding B10.D2, as for myoglobin, whereas levels in the D2.GD sera were still high. It is therefore suggested that the 2 or more genetically defined H-2-linked Ir genes each control the response to a different chemically defined determinant or group of determinants on myoglobin. Further studies with other fragments are in progress to test this hypothesis.


Genetic control of the immune response to staphylococcal nuclease in mice. Genetic control of the immune response to staphylococcal nuclease in mice is detectable at several levels. At least one H-2-linked Ir gene controls 1) the relative proportions of antibodies to different determinants on nuclease when whole nuclease is the immunogen; 2) the immunogenicity of isolated fragments of nuclease, corresponding to the same regions or determinants; and 3) the T-lymphocyte proliferative response to nuclease and to its fragments. It is concluded that a model in which Ir-gene control is determined by the recognition by T lymphocytes of a single "carrier" determinant for the whole molecule does not adequately explain this system. Evidence is presented for the existence of more than one such H-2-linked Ir gene in the T-cell proliferative response. In addition, a non-H-2-linked gene(s) is described which controls the overall level of antibodies to nuclease, i.e., the aggregate of all the antibodies of different subspecificities which have in common that they bind to some part of the nuclease molecule. Evidence is also presented that T lymphocytes, as well as the receptors involved in Ir-gene function (whether or not these are T-lymphocyte receptors), are less sensitive to conformational differences between native nuclease and its isolated fragments than are the antibodies ultimately made. This insensitivity to conformation may reflect the recognition of determinants which are shorter or more flexible in the native state than those recognized by antibodies.


Complexity of cell interactions: analysis using antigens under Ir gene control. The properties of three I region associated immunoregulatory factors involved in cell interactions are described. These are antigen specific T helper factor, suppressor factor produced by metabolically active T cells and genetically restricted factor, which is produced by macrophages and is involved in T helper cell induction. The use of these factors to analyse cell interactions is discussed.


L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT): A probe for regulatory mechanisms in antibody responses. The synthetic random terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) has been used as a probe to investigate regulatory mechanisms in antibody responses in tissue culture systems. In this brief review, the mechanisms of H-2 linked Ir gene control of antibody responses to GAT and genetic restrictions governing Mphi-immune T cell interactions in antibody responses to GAT are summarized.


The nature and functions of specific immune response genes and their products. Antibodies produced by inbred mouse strains immunized with the random synthetic polypeptide poly (Tyr,Glu)-poly(DLAla)--polyLys denoted (T,G)-A--L were found to be specific mainly to the ordered peptide Tyr-Tyr-Glu-Glu. Low responder H-2k mice, upon immunization with either the random (T,G)-A--L or the ordered (T-T-G-G)-A--L coupled to methylated bovine serum albumin (MBSA), produce antibodies with comparable titers to those observed in high responder H-2b mice following immunization with the antigens alone or with their complexes with MBSA. A comparison of the above antibodies have led to the conclusion that low responder mice, upon immunization with the synthetic antigens complexed with MBSA, produce antibodies of the same specificity and quality as those of high responders (as shown by the isoelectric focusing technique) and they also have the same affinity and heterogeneity as antibodies of H-2b mice (measured by equilibrium dialysis and antigen binding capacity assay). Anti-idiotypic sera to anti-T,G)-A--L antibodies of C3H.SW (H-2b,Ig-1a) mice were raised in guinea pigs. C3H.SW anti-(T,G)-A--L antibodies from different pools cross reacted idiotypically. Anti-(T,G)-A--L antibodies of CWB (H-2b, Ig-1b) mice did not react with the anti-idiotypic serum suggesting linkage between the genes coding for idiotypes and allotypes. C3H/DiSn (H-2k, Ig-1a) anti-(T,G)-A--L antibodies elicited by immunization with (T,G)-A--L complexed to MBSA reacted with the anti-idiotypic serum to the same degree as C3H.SW anti-(T,G)-A--L antibodies, confirming the similarity between the high and low responder anti-(T,G)-A--L antibodies. C3H.SW (H-2b) mice as well as C3H/DiSn (H-2k) mice were found to be capable of producing an antigen specific factor from "educated" T cells which replaces the helper effect of T cells in the process of antibody production. On the other hand B cells of H-2k mice were not triggered by a factor of either high or low responder specific T cells. The activity of a C3H.SW (T,G)-A--L specific T cell factor was removed after passage on a Sepharose column coupled to the anti-idiotypic serum prepared against C3H.SW anti-(T,G)-A--L antibodies, suggesting similarity between the antigen specific T cell factor and the B cell recognition system. A (T,G)-A--L specific factor produced by C3H/DiSn (H-2k, Ig-1a) "educated" T cells reacted with the anti-idiotypic serum as well. Thus, C3H.SW high and C3H/DiSn low responder (T,G)-A--L specific T cell factors cross react at the level of their binding site for antigen.


Phosphopyridoxal cyclic compounds with histamine and histidine. 6: The formation of phosphopyridoxal cyclic compounds with histamine and histidine in the presence of biological material. We have studied the dynamics of cyclic compound formation between histamine or histidine and pyridoxal 5'-phosphate (Hi-PLP or His-PLP) in incubates of rat gastric mucosa histidine decarboxylase (HD), rat intestinal diamine oxidase (DAO) or homogenates of either rat liver, intestine or gastric mucosa. For gastric mucosa HD, liver and gastric mucosa homogenates, the rate of cyclization was slightly decreased; however, the rate was significantly inhibited with intestinal DAO or intestinal homogenate. Binding of PLP by tissue components was measured; free PLP was bound abundantly by rat intestinal DAO and by rat intestinal homogenate. A possible mechanism by which intestinal tissues inhibit cyclic compound formation is discussed.


Possible involvement of endogenous histamine in the myotropic effect of clonidine on the isolated rabbit aorta. Clonidine has a contractile effect in the isolated rabbit aorta which can be blocked by alpha-adrenergic antagonist, phentolamine. Histamine H1-receptor blocker, mepyramine, partly antagonizes its myotropic effect and histamine H2-blocker, metiamide, potentiates it, implying a histaminergic component in the response. Inhibition of histamine synthesis by histidine decarboxylase inhibitor, GYKI 11.121, reduces clonidine-induced contraction in this preparation, while diamine oxidase inhibition by aminoguanidine potentiates it. This is indirect evidence of the possibility of de novo histamine synthesis by clonidine, which may take part on the contractile effect of the drug in the rabbit aorta.


A comparison of tissue gold levels in guinea-pigs after treatment with myocrisin injected intramuscularly and triethylphosphine gold chloride and myocrisin administered orally. A comparative study of tissue gold levels produced in guinea-pigs after the oral administration of either triethylphosphine gold chloride or Myocrisin (sodium aurothiomalate) or after the injection of Myocrisin intramuscularly is reported. Gold concentrations were determined 5, 24 and 168 hours after administration in stomach, small intestine, large intestine, kidney, liver and spleen and 5 and 24 hours after administration in skin, adrenals, heart, lung and brain. In gastrointestinal tissues, tissue gold concentrations were highest with triethylphosphine gold chloride. The stomach gold level 5 hours after oral administration of triethylphosphine gold chloride is particularly high and, taken in conjunction with the other gastrointestinal gold levels measured, suggests that a stomach rather than an intestinal absorption mechanism may predominate. A more extensive time-course study on kidney and liver is reported and the possible relationship between tissue concentration and toxicity is discussed.


The application and limitations of immunodiagnostic techniques in parasitic infections. The application of immunodiagnostic techniques in the diagnosis of parasitic infections has been discussed in relation to the conditions operating in developing countries where multiple parasitism is common and diagnostic facilities are often limited. The uses and limitations of the tests for individual diagnosis and epidemiological studies have been highlighted. The filter-paper plasma modification of the IFA test has been identified as a technique that has an advantage over all the others and could be universally used with great success in many developing countries.


Heterophile antibody to red cells in human trypanosomiasis. The heterophile red cell antibodies formed in human trypanosomiasis have been investigated. It has been shown that infection with Trypanosoma rhodesiense induces agglutinins reactive with sheep and rabbit red cells, whilst Trypanosoma gambiense induces agglutinins which react only with rabbit red cells. Both types of antibody can be distinguished from similar antibodies produced by infectious mononucleosis and Forssman antigen, and the detection and characterization of the antibodies therefore provides a basis for clinical diagnostic tests in human trypanosomiasis.


Jaundice and infectious mononucleosis in Ghana. A total of 715 sera from jaundiced cases were examined for Infectious Mononucleosis (IM) antibodies and 5.03% were found to be positive. It was further found that the incidence of IM antibodies in the study population increased with age, the incidence being most prevalent amongst the 11-20 year age-group. IM antibodies with jaundice were found to be most prevalent in the Volta and Eastern Regions, i.e. amongst populations of the coastal-lowland-swampy-shrubland zone of the country, particularly during the dry season which stretches from October through March. A preponderance of IM antibodies amongst females of the age-group 11-20 years was recorded. The possible mode of IM transmission in the tropical setting, with particular reference to Ghana, is proposed.


Prognostic value of histological grading of hydatidiform moles. Histological study of materials from 282 patients with hydratidiform moles showed no correlation between the degree of trophoblastic proliferation and the subsequent development of choriocarcinoma. A significant number of invasive moles, however, showed a marked degree of trophoblastic proliferation. All patients with molar pregnancy should continue to have adequate and mandatory clinical follow-up.


Coronary, ventricular, and pulmonary abnormalities associated with rupture of the interventricular septum complicating myocardial infarction. Left ventricular wall motion abnormalities, the extent and location of coronary artery stenoses, and the radiographic evidence of pulmonary venous hypertension were analyzed in a retrospective study of 40 patients who had surgically proven rupture of the interventricular septum after myocardial infarction. In 33 patients in whom chest films were available, interstitial or alveolar pulmonary edema was present in 78%, while left ventricular enlargement was present in 82%. Of 26 patients who had coronary angiography, complete occlusion of the right coronary artery, left anterior descending artery, or left circumflex artery was present in 92%, with few, if any, collateral vessels around the occlusion. The location of the rupture in the muscular septum was always in the region of akinesis or dyskinesis. Posterior defects were associated with posterobasal and diaphragmatic akinesis, and anterior defects with apical akinesis. Left ventricular aneurysms were adjacent to the septal rupture in 68%, and 74% had mitral regurgitation. The right ventricular diaphragmatic wall in posterior rupture was always akinetic, indicating right ventricular infarction. Thus ventricular septal defect after myocardial infarction (1) tends to occur with multiple coronary occlusions about which little collateral flow develops; (2) can accurately be localized anteriorly or posteriorly in the muscular septum by the location of the akinetic left ventricular wall segment; and (3) has an associated right ventricular infarct when rupture is posterior.


Bilateral pleural thickening: a manifestation of asbestos dust exposure. Bilateral pleural thickening in a relatively asymptomatic patient without evidence of pulmonary disease is frequently a manifestation of asbestos dust exposure, particularly when it is localized or in the form of a noncalcified pleural plaque. Bilateral pleural thickening will be discovered with increasing frequency if specifically searched for on every radiograph. This radiographic finding is suggested as a more realistic indication of asbestos dust exposure, particularly when correlated with a complete occupational history.


Pulmonary manifestations of acute aspiration of gastric contents. Radiographic manifestations of aspiration of gastric contents were reviewed in 60 patients. The findings were extremely variable, and there was no typical or characteristic appearance. Confluent and acinar infiltrates, as well as infiltrates composed of small irregular shadows, occurred singly or in a variety of combinations; the third pattern predominated in the majority of cases. Distribution was most commonly bilateral and multicentric and usually favored perihilar or basal regions, but localized or atypical densities were also observed. Patients with the most extensive radiographic abnormalities on initial studies tended to have the worst prognosis; however, mild early pulmonary infiltrates occasionally progressed to life-threatening abnormalities, and extensive initial involvement was frequently followed by a benign clinical and radiographic course. Radiographic changes often worsened for several days in uncomplicated cases, but improvement was generally manifested within the first week after aspiration. Worsening of infiltrates after initial improvement was associated with the development of bacterial pneumonia, the adult respiratory distress syndrome, and pulmonary embolism. In the appropriate clinical setting, aspiration of gastric contents should be an important diagnostic consideration in the presence of a wide variety of radiographic changes.


Accuracy of chest film screening by technologists in the New York early lung cancer detection program. A study of the feasibility of using specially trained radiologic technologists to screen chest radiographs was undertaken as part of an early lung cancer detection program. In their initial examination, 8,000 men had posteroanterior and lateral chest films which were prepared and evaluated by two specially trained technologists prior to interpretation by a radiologist. The technologists' accuracy in screening was subsequently assessed by comparison with the radiologist's interpretation and with clinical follow-up information. There were differences in the level of suspicion of the two technologists, but both were effective in selecting a subset of the screened population that contained the men with radiologically identifiable lung cancer.


The normal and abnormal left superior intercostal vein. A study of 500 normal erect posteroanterior chest radiographs was undertaken to determine the incidence of visualization and size of the left superior intercostal vein in normal individuals. The vein produces a small "nipple" lateral to the aortic knob on 1.4% of normal erect posteroanterior chest films; its diameter can be up to 4.5 mm in normal patients. Dilatation of the vein beyond 4.5 mm is a useful sign of a circulatory abnormality warranting further study. Dilatation may be due to absence of the inferior vena cava, hypoplasia of the left innominate vein, congestive failure, portal hypertension, Budd-Chiari syndrome, or superior or inferior vena caval obstruction. The differential diagnosis of an enlarged left superior intercostal vein includes mediastinal mass, especially lymphadenopathy, and aneurysm of the arch of the aorta.


Subglottic edema in acute epiglottitis in children. Analysis of airway radiographs of 20 children with proven acute epiglottitis revealed that five (25%) had, in addition to supraglottic edema, localized subglottic edema radiographically indistinguishable from that seen in croup. In all five patients the etiologic organism was Hemophilus influenzae type B.


Pneumopelvigraphy in childhood.

Pneumopelvigraphy in childhood. Pelvic pneumography was performed in 150 children, including those with precocious puberty, suspected pelvic masses, abdominal pain, virilization, ambiguous genitalia, gonadal dysgenesis, Stein-Leventhal syndrome, amenorrhea, and contralateral inguinal hernia detection. Pneumography proved safe, accurate, and easy to perform. However, advances in sonography have limited the use of pneumography primarily to the investigation of infant intersex problems and confirmation of idiopathic precocious puberty in the infant or very young girl.


Radiographic findings in ovarian teratomas in children. Twenty-one infants and children with ovarian teratomas are reported. Calcification or ossification occurred in 68%, a higher figure than quoted in prior series. Teeth were recognized in 29% of these. A lucent fat-containing mass was appreciated in only two patients. In younger children the tumor was more frequently abdominal rather than pelvic. In two patients the tumor was malignant. A patient with an amputated freely mobile teratoma is reported in detail and the differential diagnosis of mobile abdominal calcifications discussed.


Mailed thermoluminescent dosimeter determination of entrance skin exposure and half-value layer in mammography. A method of providing in vivo measurement of entrance skin exposure for mammography using mailed thermoluminescent dosimeters has been developed. The dosimeters are calibrated to 137Cs (662 keV), and a correction is applied to account for energy response. A mailed dosimeter packet which can be used to measure the half-value layer at mammography energies is also described. The results for both systems agree well (to within 10%) with careful ion chamber determinations. These dosimeter measurements provide a simple. Inexpensive means to reliably determine exposure and to monitor machine parameters on a periodic basis.


Radiographic features of ureteral endometriosis. The urographic findings in seven patients with ureteral endometriosis were reviewed. These consisted of short strictures (0.5-2.2 cm) located for the most part in that portion of the pelvic ureter projected within 3 cm of the inferior margin of the sacroiliac joint. Although the appearance is judged to be nonspecific, the diagnosis of ureteral endometriosis should be considered in any female patient of child-bearing age who has obstructive uropathy attributable to extrinsic obstruction of the pelvic portion of the ureter.


Inflammatory cysts of the pelvic peritoneum. Three young women with abdominal distension due to pelvic masses were investigated using ultrasound and conventional radiographic techniques. While the latter revealed masses of soft tissue density arising from the pelvis and displacing bowel, the sonogram indicated the morphologic features of thin-walled multiloculated cysts. They were located entirely within the peritoneal cavity and contained serous to serosanguineous fluid. The mesholelial lined walls were infiltrated with chronic inflammatory cells and were adherent to chronically inflamed fallopian tubes. Although these acquired cysts are familiar to pathologists and gynecologists, the literature contains little information about them.


Pitfalls of transhepatic portal venography and therapeutic coronary vein occlusion. Coronary vein occlusions via transhepatic portography for bleeding esophageal varices was attempted in 24 patients. Problems occurred that either prevented the attempt or resulted in less than adequate occlusion. These included blood flow in the left gastric (coronary) vein toward the liver due to occluded or stenotic splenorenal shunts, spontaneous left gastric vein to inferior vena cava shunts, and failure of powdered Gelfoam and heat-treated autogenous clot to cause permanent occlusion. Of 89 total transhepatic portographies, 65 for diagnosis and 24 for occlusion, major complications occurred in two.


Transcatheter gelfoam embolization of posttraumatic bleeding pseudoaneurysms. Diagnostic angiography combined with transcatheter therapeutic embolization is a simple and effective means of treating complex clinical situations associated with posttraumatic hemorrhage. Bleeding pseudoaneurysms, even when large, can be readily managed by this combined modality with resultant decrease in morbidity and hospital stay. Five patients with posttraumatic pseudoaneurysms are presented. All five were treated by transcatheter therapeutic embolization with Gelfoam. Of these five cases, three involved extremities, one involved the retroperitoneal space, and the last was of renal origin. Two of the five cases still required surgical intervention after initial successful therapeutic embolization, one for recurrent bleeding from collaterals and the other for evacuation of a massive pseudoaneurysm which was causing distraction of fracture fragments. The early use of angiography in suspected cases of posttraumatic hemorrhage, together with careful evaluation of potential collateral supply, is stressed. The use of transcatheter therapeutic embolization in the extremities as presented here is yet another example of the ever-broadening applicability of this technique.


Transcatheter embolization: prevention of embolic reflux using balloon catheters. Reflux of embolic material during therapeutic transcatheter embolization is a potential complication which can result in occlusion of distal vascular beds. The conditions under which reflux was demonstrated in laboratory animals include (1) low flow states, (2) overvigorous flushing, (3) selective contrast injections, and (4) placement of embolic material too proximally. Balloon occlusion of the orifice of the vessel undergoing embolization protects against reflux and allows more homogenous embolization. Because of experience gained in the laboratory, therapeutic transcatheter embolization is now performed in patients with balloon catheter protection. Preliminary clinical experience is described.


Bleeding simulated by the distal internal pudendal artery stain. A capillary and venous phase blush in the region of the distal branches of the internal pudendal artery that simulates bleeding can sometimes be seen on arteriograms of male patients who are not bleeding. We describe five such cases. Correct identification of this pooling of contrast material is important to avoid unnecessary treatment by transcatheter embolization or by infusion of vasoactive drugs.


Gas in the bile ducts (pneumobilia) in emphysematous cholecystitis. Gas in the biliary ducts (pneumobilia) was demonstrated in three cases of emphysematous cholecystitis. Pneumobilia is usually secondary to a spontaneous internal biliary fistula or incompetent sphincter of Oddi, and is rarely considered a manifestation of emphysematous cholecystitis. The presence of gas in the biliary ducts in these cases suggests that the cystic duct is patent, allowing gas to escape from the gallbladder lumen. The pathophysiology of emphysematous cholecystitis is discussed and an ischemic etiology considered.


Rheumatoid arthritis and its variants: analysis of scintiphotographic, radiographic, and clinical examinations. 99mTc pyrophosphate radionuclide scans of the axial and appendicular skeletons in 23 patients with rheumatoid arthritis and 15 patients with systemic arthritic conditions were compared to clinical and radiographic examinations. The nuclear scan was the most sensitive indicator of active disease and correlated extremely well with the other methods. A pattern of abnormal radionuclide activity in rheumatoid arthritis consisting of a symmetric peripheral joint process can be distinguished from that of the rheumatoid variants which tend to have more central skeletal involvement and asymmetric peripheral articular involvement. The nuclear scan is less specific than the radiograph in its ability to distinguish among the clinical entities. However, documentation of scintigraphic activity often antedated radiographic or clinical abnormalities.


Accuracy of CT in detecting intraabdominal and pelvic lymph node metastases from pelvic cancers. In 40 patients with pelvic cancers evaluated by computed tomography (CT), CT was less accurate in demonstrating lymph node metastasis compared to its high accuracy in detecting nodal involvement in lymphoma patients. This largely reflects the inability of CT to detect alterations in internal architecture in a normal-sized lymph node. While less sensitive, CT is a more specific method than lymphangiography in detecting nodal involvement by pelvic cancers. The role of CT in the staging of pelvic cancers is discussed.


Effect of CT noise on detectability of test objects. Three types of test objects were superimposed on noisy backgrounds and observed by 58 subjects: large low-contrast disks to simulate tumors, small disks to simulate calcifications, and bars to simulate blood vessels. Three types of noise were used: random noise, CT noise (reconstructed random noise), and an actual water scan taken with an EMI CT1010 scanner. In addition, each image was smoothed by a factor of two, giving six test patterns altogether. Photographic images were presented to 25 lay observers, while 25 other lay observers and eight radiologists used a viewing console. The photographs produced a slightly lower true positive rate than the console, although the degree of confidence in the identifications was slightly greater. The anticorrelation property of CT noise gives it a "lumpy" structure, which aided the identification of bars but impeded the identification of small disks. Smoothing did not significantly affect the detectability with random noise, but with CT noise, smoothing improved the detectability of bars and large disks.


Optimal contrast dosage in cranial computed tomography. Comparison of different contrast dosages in adult patients with malignant gliomas studied by computed tomography indicates that 28-42 g of iodine is required for clinically diagnostic results. This can be translated into a 10 min iodine blood level of 100 mg/100 ml. Contrast doses in the range of 14 g of iodine are not satisfactory.


Progress in radiology: colorectal tumors: pathology and detection. The prognosis in colorectal neoplasia has not improved in the past 20 years despite improved diagnostic techniques. The greatest promise lies in wider screening and earlier radiographic and endoscopic detection. To clarify the radiologist's role in finding large bowel tumors, the clinical, pathologic, and radiologic literature is reviewed. Since individuals over 40 years of age harbor the bulk of colon neoplasms, the most diligent efforts to detect these lesions should be made in this group. Controlled studies comparing single and double contrast barium enema techniques are lacking, but available data suggest that the double contrast examination is more sensitive for detection of the numerous small, but potentially malignant colon tumors. Careful radiographic technique, including a thoroughly clean colon, is critical for accurate detection regardless of which technique is used.


The Narangwal Nutrition Study: a summary review. Between April 1968 and May 1973 the department of International Health of The Johns Hopkins University carried out investigations into the interactions of malnutrition and infection and their effects on preschool child growth, morbidity and mortality in 10 villages of Punjab, North India. Base line surveys before the introduction of services revealed a high prevalence of malnutrition and undernutrition and infectious disease morbidity, as well as lack of accessibility, underutilization and poor population coverage of governmental health services. Study villages were selected in separate clusters and allocated to a control group and three service groups in which nutrition care and medical care were provided singly and in combination by auxiliary health workers resident in each village. Outcome effects were measured through means of longitudinal and cross-sectional surveys. Service inputs and service costs were similarly monitored. Results showed significant improvement of growth (weight and height) and hemoglobin levels of children. Perinatal mortality was reduced by nutrition supplementation to pregnant women. Medical care significantly reduced postneonatal and 1 to 3 mortality, and decreased illness duration of all six conditions examined in this paper. The auxiliary health worker capably managed more than 90% of health needs on her own and referred the rest safely to the physician. Analysis of cost per child death averted showed that cost-effectiveness declined with increasing age of the child. Prenatal nutrition care to pregnant women was most cost-effective in preventing perinatal deaths followed by medical care for infants, and then medical care for the 1 to 3 year age group. The relevance of the field research to national or international endeavors to solve present health problems of developing nations and the timeliness of projects such as the Narangwal Nutrition Study is also evaluated.


Microhemagglutination test for detection of antibodies to nuclear Sm and ribonucleoprotein antigens in systemic lupus erythematosus and related diseases. A reproducible hemagglutination procedure to detect antibodies to Sm and ribonucleoprotein nuclear antigens is described. The application and interpretation is discussed. The hemagglutination test was found to be more sensitive than the immunodiffusion test; however, the hemagglutination test may not detect the presence of low titers of anti-ribonucleoprotein in the presence of a high level of anti-Sm antibody. Anti-ribonucleoprotein antibodies in the presence of high titers of anti-Sm antibodies are best identified by gel precipitation methods where precipitin lines can be characterized by their interaction with precipitin lines produced by known prototype antisera.


Increasing the predictive value positive of the precipitin test for the diagnosis of deep-seated candidiasis. Three hundred fifty human sera were tested by double immunodiffusion, crossed-line electrophoresis, and crossed immuno-affinoelectrophoresis with a concanavalin A intermediate gel for precipitating antibodies to antigens present in cytoplasmic extracts of Candida albicans. Sera from 48 of 287 hospitalized patients at risk of invasive candidiasis contained precipitating antibodies to Candida antigens. Of these 48 sera, 27 had precipitating antibodies only to cell-wall antigens present in the cytoplasmic extract, and 21 sera had precipitating antibodies to both cytoplasmic and cell-wall antigens. The latter sera came from patients who were 2.5 times as likely to have deep-seated candidiasis as those patients with precipitins exclusively to cell-wall antigens. Sera from seven of 22 patients with vaginal candidiasis and 10 of 41 patients with other fungal infections had precipitating antibodies to C. albicans cell-wall antigens; only two of these sera also contained precipitating antibodies to the cytoplasmic antigens. Crossed immunoaffinoelectrophoresis with concanavalin A reduced the number of false-positive results and increased the predictive value positive of the precipitin test for deep-seated candidiasis from 31% to 71%.


Allergic bronchopulmonary aspergillosis caused by Aspergillus ochraceus. A case with the characteristics of allergic bronchopulmonary aspergillosis is described. The species of Aspergillus involved, A. ochraceus, has not previously been found in this disorder. The organism had antigenic properties distinct from five other species of Aspergillus most commonly associated with allergic bronchopulmonary aspergillosis. The patient had immediate skin test, immunodiffusion, and radioallergosorbent reactivity to the species. Four per cent of 112 serum samples from others suspected of having allergic bronchopulmonary aspergillosis had precipitins to A. ochraceus only. It may be necessary in some cases to prepare and test extracts of the patient's Aspergillus isolate in order to confirm the diagnosis.


Abnormalities of in vitro lymphocyte response to mitogens in diabetic children during acute ketoacidosis. Cell-mediated immunity was evaluated in 11 children with diabetes mellitus; six children were evaluated during ketoacidosis and five were evaluated with ketonuria in the absence of acidosis. Five of the six ketoacidotic children had at least one positive delayed-hypersensitivity skin test. Lymphocytes from two ketoacidotic patients were unresponsive to phytohemagglutinin and pokeweed mitogen, and lymphocytes from these two patients plus a third patient were unresponsive to concanavalin A. Lymphocytes from all six patients responded to these three mitogens after one week of therapy. In the five diabetic children without ketoacidosis, lymphocyte responses were normal to all three mitogens. Similarly, the addition of glucose to normal plasma did not alter the lymphocyte transformations of three healthy nondiabetic controls. These data suggest that cell-mediated immunity may be transiently defective in children with acute diabetic ketoacidosis.


Studies in meconium. An approach to screening tests to detect cystic fibrosis. Screening for cystic fibrosis (CF) in newborns is desirable, and efforts should continue in establishing a system of easily available, reliable, simple, and inexpensive tests. In addition to the Boehringer-Mannheim (BM) test for the detection of albumin, we propose the assay for lactase and beta-D-fucosidase in meconium. These latter two enzymes are present in the meconium of babies with CF and absent in meconium of most healthy babies. In a mass screening program for CF involving 20,182 specimens of meconium using only the BM strip, we found 46 positive results. Twenty-nine specimens came from infants with CF, six of whom had meconium ileus. Seventeen specimens yielded false-positive results by the BM test. Eleven of these would have been excluded by the addition of the lactase and beta-D-fucoside assay, thus reducing the false-positive test results by nearly 61%. In a comparative study of the three methods, the lactase and beta-D-fucosidase yielded 1.2% false-positives when examined independently. Performance of these two assays may allow greater specificity in diagnosis when used in addition to the BM test.


A quarter Wheatstone bridge strain gage force transducer for recording gut motility. Quarter and half Wheatstone bridge extraluminal force transducers for recording of gastrointestinal motility are compared. Modification of the transducer to a quarter bridge is economical, simplifies construction, and improves longevity by eliminating the crossover wire which frequently short circuits. The quarter bridge transducer was found to be as accurate and sensitive as the half bridge transducer.


Trace metal and essential fatty acid deficiency during total parenteral nutrition. While deficiences of trace metals and essential fatty acids are rare in humans fed orally, the widespread use of total parenteral nutrition (TPN) has increased the likelihood of encountering these deficiences. A 14-year-old boy, with total villous atrophy of the small intestine, suffered from severe malnutrition and was placed on a conventional TPN regimen. Although not immediately recognized, he rapidly developed deficiencies of zinc, copper and essential fatty acids. Careful monitoring of the course of the illness and the responses to sequential treatments with zinc, lipid, and copper given intravenously allowed examination of the effects of the deficiencies on skin, intestine, liver, and hemopoietic systems and helped to establish normal requirements for the metals. The progress of the illness suggested that patients with intestinal malabsorption may be especially at risk of developing some of these lesser known complications of TPN.


Properties of beta-glucosidase in cultured skin fibroblasts from controls and patients with Gaucher disease. Membrane-bound beta-glucosidase from cultured skin fibroblasts can be solubilized in an active form by treatment of membrane preparations with a mixture of Triton X-100 and sodium taurocholate. Several properties of the solubilized enzyme have been studied in fibroblasts from normal, healthy individuals and from 14 patients with different clinical forms of Gaucher disease. The patients studied were classified as follows: group 1 consisted of 10 chronic patients, all (with one exception) of Ashkenazi Jewish origin; group 2 consisted of three black American patients with severe visceral symptoms, manifest from early childhood, but with no apparent neurological involvement; and group 3 consisted of a single white patient with the classical infantile form of the disease. Specific beta-glucosidase activity ranged from 6.6% to 16.5% mean control value in group 1 patients and from 4.1% to 5.8% in groups 2 and 3. When compared with the enzyme from control fibroblasts, the enzyme from chronic Gaucher patients (group 1) was more rapidly inactivated at 50 degrees C, had an altered pH curve, was less effectively inhibited by deoxycorticosterone-beta-glucoside, and was more effectively inhibited by deoxycorticosterone. The enzyme from patients in groups 2 and 3 was qualitatively indistinguishable from the control enzyme in terms of these parameters. No differences in Km (4-methylumbelliferyl-beta-glucoside) or sedimentation coefficient were found between the beta-glucosidases from control and Gaucher cells. The results demonstrate that cells from Ashkenazi Jewish patients with the chronic form of Gaucher disease contain a structurally altered form of beta-glucosidase. This enzyme differs both from normal beta-glucosidase and from the residual enzyme in patients of different ethnic origin and with clinically more severe forms of the disease.


Immunologically diagnosed malignancy in Sjögren's pseudolymphoma. Studies of lymphocyte markers in a patient with Sjögren's syndrome who exhibited histologically benign lymphoproliferation in the lung revealed a malignant cell clone. T and B cells were quantitated according to their ability to form spontaneous rosettes with sheep erythrocytes and to fluoresce with fluorescein-conjugated antiserums, respectively. Circulating lymphocytes were 66 percent T cells (N = 58 +/- 2 per cent) and 14 percent B cells (N = 22+/- 1 percent), the latter exhibiting normal polyclonal distribution of membrane immunoglobulins. However, lymphocyte suspensions obtained from fresh lymph node and from biopsy specimens from a lymphoid lung nodule revealed 95 percent and 88 percent B cells, with 1 percent and 2 percent T cells, respectively. Moreover, when cryostat-frozen sections from both tissues were reacted with each of the heavy and light chain-specific antiserums, most cells demonstrated the presence of intracytoplasmic mu kappa immunoglobulin exclusively. Twenty-two months later, a clinically and histologically classic lymphoma developed. Repeat marker studies performed on cells freshly isolated and on frozen sections from the histologically malignant lymph node revealed persistence of the monoclonal marker on most cells.


Platelet antithrombin deficiency: a new clinical entity. A kindred with a history of multiple thromboses was studied for coagulant abnormalities. A deficiency of serum antithrombin III was found in approximately half of the 13 family members by either coagulant or immunologic assay. No clear relationship between antithrombin III deficiency and a history of thrombosis was present. Platelet antithrombin assays were also studied in the same subjects. Ten of the 13 members were deficient. None of the remaining three had a history of thrombosis. On the basis of these findings, the hypothesis is proposed that in some cases familial hypercoagulability may be due to a platelet antithrombin deficiency and that the serum antithrombin III deficiency in some cases is a secondary rather than a primary effect.


A modified processing and sectioning technique for hard tissues. A new procedure for embedding and sectioning hard tissues was developed to study bone regeneration in relation to carbon implants used in crown and bridge preparations of maxillas and mandibles of nonhuman primates. Tissues were fixed in 10 percent neutral buffered formalin, dehydrated in 95 percent and 100 percent ethyl alcohol, and embedded in a modified Spurr's low-viscosity embedding medium. Tissues were sectioned as thin as 50 to 100 micron with a Buehler Isomet Model 11-1180 low speed saw. Unstained sections, as well as tissue stained with hematoxylin and eosin and Gomori's trichrome, were examined with a light microscope. The sections were of high quality without distortion. This new procedure expedited experimental work because decalcification of tissues was not needed and implants did not fragment.


Evaluation of the Microcult-GC kit as a screening method for the detection of Neisseria gonorrhoeae. The Microcult-GC Kit was compared to the standard modified Thayer-Martin plate method for the isolation and presumptive identification of Neisseria gonorrhoeae. Two hundred and thirty specimens representing urethral, endocervical, rectal, and pharyngeal sites were inoculated to both media. If only genital and rectal cultures were compared, the overall agreement was 98 percent, with a false positive rate of 1/145 (0.7 percent) and a false negative rate of 2/145 (1.4 percent). However, in the pharyngeal cultures, 16 of 32 gave false positives, thus emphasizing the manufacturer's instructions to limit the kit's use to genital and rectal cultures. The kit system gives rapid presumptive results, has a long shelf life at room temperature, and needs little laboratory equipment for proper use.


New concept: a lab manual that withstands changing times. This paper describes the development of a laboratory manual that is concise, easily accessible, and most importantly can be updated with a minimal amount of time and effort. The manual is contained in a Rolodex card system which results in improved efficiency, more effective utilization of the laboratory, and improved relations between nurses, physicians, and laboratory personnel.


Experimental group B streptococcal infection in the rhesus monkey. I. Disease production in the neonate. Group B streptococci (GBS) are responsible for serious infections of newborn infants. An experimental model for GBS infection was developed in the newborn rhesus monkey in order to obtain more information concerning the pathogenesis of such infections. A series of 29 newborn monkeys were inoculated with either type Ic or type III GBS or sterile broth. Fatal neonatal meningitis without associated pneumonia was produced consistently following intracerebral inoculation with either type Ic or type III; intracerebral inoculation with sterile broth produced no apparent disease. Variable disease production followed intravenous or intra-amniotic GBS inoculation, and clinical manifestations ranged from no apparent disease to fatal meningitis and pneumonia. This monkey model may be useful for further investigation of treatment and prevention of neonatal GBS infection.


Investigation of mammalian ovulation with an in vitro perfused rabbit ovary preparation. An in vitro perfused rabbit ovary preparation has been developed to study local factors responsible for the ovulatory process. This preparation enables: (1) isolation of the ovary from systemic influences, (2) direct serial observations of follicle development and ovulation, (3) addition to the perfusing medium of substances that may influence ovulation acting at the level of the ovary, and (4) correlation of the times of individual follicle rupture with ovarian contractile patterns. With this model the temporal requirements for human chorionic gonadotropin in the process of ovulation have been studied. The direct effects on ovulation of prostaglandin F3 alpha (PGF 2 alpha), the antihistamine chlorpheniramine, and calcium deprivation were also investigated. Chlorpheniramine and EDTA each led to inhibition of ovulation and depressed ovarian contractility. The use of the isolated in vitro ovary preparation permits characterization of the local requirements for ovulation.


Neural control of gonadotropin secretion in primates. In the rhesus monkey, there is abundant evidence to indicate that ovarian secretions, mainly estradiol-17beta, control "tonic" as well as "cyclic" secretion of gonadotropins during the menstrual cycle. This mechanism of control ensures coordination of ovarian morphology and anterior pituitary secretory patterns. The primary site of action of estradiol in controlling both "tonic" and "cyclic" secretion of gonadotropins has been circumscribed to the medial basal hypothalamic-pituitary unit. A modulatory role in "cyclic" secretion by neural structures situated within the anterior hypothalamic-preoptic area or by efferent fibers in passage through this region also has been postulated. However, the accrued evidence indicates that in the primate, contrary to the rodent, the role of these rostral neural structures is not essential for menstrual cyclicity. Strong evidence also indicates that the isolated pituitary gland can respond to estrogen signals as well. Secretion of gonadotropin-releasing hormone, the hypothalamic decapeptide, into the long portal vessels is, however, essential to maintain function of the gonadotroph. Further, pulsatile release of luteinizing hormone is distinctly under the control of a similarly paced hypothalamic clock.


Analysis of corneal crystalline deposits in multiple myeloma. A 46-year old woman and a 59-year-old man had corneal crystals, multiple myeloma, and IgG kappa hypergammaglobulinemia. In one case, crystalline deposits were also present in the lens. In both patients there was a marked decrease in the amount of crystals during chemotherapy. The crystals within the cornea of one case were identified by light and electron microscopy in material obtained during a lamellar keratoplasty. The crystalline deposits were located only in the corneal epithelium, and their regular repeating internal arrangement was confirmed by monochromatic optical diffraction of electron micrographs of sections through them. By immunofluorescent and immunoperoxidase techniques, the crystals reacted positively for immunoglobulin and particularly IgG kappa chains.


Retinal ganglion cell degeneration in experimental optic atrophy. By ophthalmoscopic and histopathologic examinations at various intervals after retinal injury, we studied progressive ganglion cell atrophy following retinal photocoagulation in 25 owl monkey eyes. A reduced ganglion cell population was apparent within three to four weeks after the photocoagulation and was maximal by six weeks.


Malignant melanoma of the choroid in neurofibromatosis. A 60-year-old white woman with generalized neurofibromatosis and multiple melanocytic hamartomas of the iris developed an unusual choroidal mass, with secondary sensory retinal separation in the left eye. Ophthalmoscopically the tumor had a peculiar donut configuration that was caused by a large focus of central necrosis within a spindle B melanoma.


Listeria monocytogenes endophthalmitis with a black hypopyon. A 68-year-old woman had a marked decrease in visual acuity, increased intraocular pressure, and acute iridocyclitis. She developed a pigmented hypopyon simulating an occult intraocular melanoma. Two anterior chamber paracenteses showed growth of Listeria monocytogenes. The patient received systemic intravenous penicillin, topical fortified gentamicin sulfate drops, and intraocular injections of cephaloridine. On discharge from the hospital after a two-week stay, visual acuity had improved and intraocular pressure had decreased.


Pathologic changes induced in respiratory tract mucosa by polycyclic hydrocarbons of differing carcinogenic activity. Seven aromatic polycyclic hydrocarbons (PCHs) were investigated for their toxic effects on respiratory mucosa: benzo(e)pyrene (BeP), pyrene, anthracene, benz(a)anthracene(BaA), dibenz(a,c)anthracene(DBacA), benzo (a)pyrene (BaP), and dimethylbenz(a)anthracene (DMBA). The compounds were chosen because they comprise a spectrum of PCHs ranging from noncarcinogens, to initiators, to weak and strong carcinogens. All of them except DMBA are environmentally relevant chemicals. The chemicals were tested over an 8-week period. Heterotopic tracheal transplants were continously exposed and the histopathologic effects induced by the various PCHs were periodically assessed semiquantitatively. All PCHs exhibited varying degrees of toxicity for respiratory epithelium and submucosa. BeP clearly showed the least toxicity followed by pyrene and anthracene. BaA and DBacA caused marked epithelial and submucosal changes. In addition to epithelial hyperplasia, undifferentiated epithelium and squamous metaplasia developed. Marked mononuclear infiltration occurred in the subepithelial connective tissue. With BaP the epithelial and submucosal changes were similar but were much stronger. DMBA was the most toxic substance, causing epithelial necrosis followed by generalized keratinizing squamous metaplasia; the subepithelial changes consisted of an early acellular exudate and, later (at 8 weeks), marked condensation and hyalinization of the lamina propria. The toxic response pattern of the tracheal mucosa to carcinogenic agents was characterized by the chronicity of epithelial and connective tissue damage, as opposed to the short-lived hyperplastic and inflammatory response elicited by the noncarcinogens and weak initiators.


Genetic control of resistance to tumors. Hybrid resistance to a BALB/c plasmacytoma, MPC-11, has been investigated. The results indicate that heterozygosity within the H-2 complex is neither necessary nor sufficient for resistance to be observed. However, in the presence of a single gene or gene complex which segregates independently of H-2, differential effects of various H-2 haplotypes can be seen. Resistance is radiation-sensitive and silica-insensitive and probably depends on active immune responses. The data also suggest that production by a hybrid of endogenous viral antigens with certain type-specific determinants shared with viral antigens expressed on the tumor may interfere with resistance. The mechanism for this is not understood but might involve tolerance, suppression, or enhancing antibody.


Tumor-induced immunosuppression.

Tumor-induced immunosuppression. Three tumor systems, including a mastocytoma, plasmacytomas, and a leukemia-lymphoma were studied for their ability to modify humoral immunity to sheep erythrocytes both in vivo and in vitro. All tumors resulted in a depression of the hemolytic antibody plaque-forming cell response in susceptible mice. These studies indicated that the mechanism(s) of suppression, although not fully defined, were different for each model system investigated.


Metric characteristics of the canine dental complex in prenatally androgenized female rhesus monkeys (Macaca mulatta). Permanent maxillary canine teeth (C1) are appreciably larger in males than in females in most nonhominid Anthropoidea. Mandibular canines (C1) and mandibular first premolars (P3), against which C1 are sharpened in honing behavior, reflect commensurate sexual dimorphism. These three teeth constitute the canine dental complex. The canine complex crown metrics of seven mature genetically female rhesus Macaques, androgenized by prenatal exposure to testosterone propionate, were compared with a control sample (N = 12) for evidence of masculinization. The C1 and C1 were measured for clinical crown lengths (L) and mesiodistal and buccolingual widths. The functionally significant and highly dimorphic honing dimensions (HD), which approximate the honing surfaces of P3, were noted. In t-test comparisons, the C1 L and P3 HD in androgenized monkeys were significantly larger than those of the control group (P less than 0.05). Identical results were obtained with White's nonparametric ranking technique. Standardized lateral skull radiographs showing earlier dental formative stages were available for five of the seven animals, and these were compared with radiographs of control skulls. The developing C1 were longer and wider than in the controls. This was not reflected in the crown metrics of mature animals because of marked dental attrition. We concluded that androgens can masculinize the female rhesus canine complex, if given during critical periods of prenatal development. We hypothesize that genes encoding the male canine complex are normally activated by endogenous fetal androgens during such critical periods.


A proposed selective cell carcinogenesis in mammary tumors. The present study was done to ascertain whether a specific carcinogenic agent has a causal effect on the initial proliferation of only one cell type or whether it acts indiscriminately on all cells in the breast secretory unit. Enzymes histochemistry and electron microscopy were performed on DMBA-induced mammary tumors in female Sprague-Dawley rats and on virus-associated spontaneous mammary tumors in C3H/HEJ mice. The results showed that the chemical carcinogen DMBA affects initial myoepithelial cell proliferation, while virus-associated mammary carcinoma originated from ductular epithelial cell proliferation. To determine whether a specific tumor is composed of a single cell type, tumors were grown in tissue culture. The monolayer was fixed in the usual manner for electron microscopy while in Falcon tissue culture plates. The plates were dissolved in xylene and the monolayer was cut into small pieces and embedded in the plastic media. Electron microscopy performed on the tissue culture and the original tissue from the virus-induced tumors showed the presence of viruses in large numbers. It also suggested the differentiation of basal membrane to form basal lamina and apical plasma membrane into microvilli. This study strongly suggests the presence of selective cell carcinogenesis in the mammary gland.


Is the concept of "control group" valid? A quantitative comparison of behavior of caged baboon groups. Behavioral comparisons between six caged baboon groups indicate that the groups have consistent and similar behavioral attributes. At the same time it is possible to distinguish between classes of animals in each group such as males versus females and high status versus low status rank. Comparable results are obtained in both ANOVA and Kruskal-Wallis one-way analysis of variance by ranks. This investigation supports the assumption that baboon groups exhibit behaviors that are both consistent and predictable where environment and group composition are controlled. Thus there appears to be a strong species-appropriate set of behaviors. Behavioral plasticity and group variability might be due largely to a combination of environmental stimuli and the particular history of that group. Differential individual histories or idiosyncracies do not invalidate experimental designs which rely on randomization to structure control groups.


Palm trees and Chagas' disease in Panama. An ecological survey of triatomines in the sylvan ecosystem of the Canal Zone and selected sites in Panama disclosed for the first time a close association of Rhodnius pullescens and Triatoma dimidiata, the two most important vector species of Chagas' disease in Panama, with a single species of a widely distributed palm tree, Scheelea zonensis. This association may explain why Chagas' disease is prevalent in certain rural communities in Central Panama and rare in others. An immense focus of zoonotic Trypanosoma cruzi infection exists in the forests of the Canal Zone with presence of large populations of triatomines, associated with scheelea zonensis and other yet undescribed microhabitats, and high (50--60%) trypanosome infections in all of the major triatomine species. Common opossums, anteaters, and spiny rats seem to be the principal animal reservoirs of T. cruzi in this complex and relatively undisturbed ecosystem.


Renal amyloidosis with nephrotic syndrome in two patients with schistosomiasis mansoni and chronic salmonellosis. This report describes two Egyptian patients who presented with the nephrotic syndrome and concurrent infections with Schistosoma mansoni and Salmonella paratyphi A. Unlike similar cases previously reported from this unit, these patients did not respond to antimicrobial and antischistosomal therapy, and their renal biopsies demonstrated amyloidosis. These two case reports and several experimental observations suggest that chronic schistosomiasis and salmonellosis may lead to secondary amyloidosis in susceptible individuals.


Inflammatory carcinoma of the breast. A therapeutic approach followed by improved survival. Disappointing results of radical mastectomy for treatment of inflammatory breast carcinoma led to its abandonment and the use of alternative therapeutic methods without improvement of survival rates. Results of radical mastectomy combined with other therapeutic modalities have not been fully evaluated so far. In a series of nine patients with proven inflammatory breast carcinoma and no distant metastases, two underwent radiotherapy, oophorectomy, and adrenalectomy (group A) and seven underwent preoperative irradiation, radical mastectomy, postoperative irradiation, and chemotherapy (group B). There were no local recurrences in either group. Group A patients survived five and eight months (mean, 6.6+/-2.1) and patients of group B survived 45.5+/-26.2 months (p less than 0.05). Results show no rational basis for withholding radical mastectomy, but suggest that improved survival may be obtained when radical mastectomy is an integral part of a rational sequential therapeutic schedule.


Intensive care--a medical audit.

Intensive care--a medical audit. A 4-year audit of one Intensive Care Unit, during which time 1718 patients were admitted, shows that allocating 1% of all acute beds for intensive care purposes is not adequate. This is reflected by the high mortality among the patients discharged from the unit. Sophisticated monitoring equipment led to a marked improvement in mortality rates in each group to which it was applied. Simple to use, automated, biochemical equipment was very cost effective for blood gas measurement but less so for electrolyte determinations. Intensive care is very labour intensive, but the cost benefit in terms of lives saved is large. It is suggested that audits of this type help to identify the consequences, including adverse consequences, of decisions by administrators.


A quantitative estimation of the depletion of the granules of argyrophile cells in the gastrointestinal tract of reserpine treated Rhesus monkeys. The depletion of the granules of argyrophile cells following administration of reserpine has been studied at various levels of the gastrointestinal tract of the Rhesus monkey. Granulation of the cells has been estimated by the photometric method of SINGH(1976). The argyrophile cells that persist after reserpine administration show a statistically significant reduction in their granulation as compared to cells of untreated controls (P less than 0.001).


Concentration of immunreactive FSH, LH and prolactin in seminal fluid following i.v. application of LH-RH and TRH. Immunreactive FSH, LH and Prolactin are measured in seminal fluid and serum following i.v. injection of LH-RH and TRH. Levels of hormone levels in serum and seminal fluid are not correlated. Only LH levels, but not those of FSH and PRL depend on the interval between injection of releasing factors and ejaculation. Dilution curves and column chromatography of seminal fluid LH point that it might not be identical to serum LH. Since in the testis a HCG immunreactive substance has been described it is likely that it forms part of the LH concentrations measured in seminal fluid.


Spermatophagy in the seminiferous tubules and excurrent ducts of the testis in Rhesus monkey and in man. The fine structure of cells capable of phagocytosing spermatozoa in the testes and epididymes of monkeys and men was studied by means of transmission and scanning electron microscopy. Both resident cells, such as Sertoli cells and epithelia of the rete testis, and free cells, such as macrophages (spermatophages) were found to phagocytose spermatozoa or fragments of spermatozoa in the seminiferous tubules and excurrent ducts. The spermatophages develop from precursor cells which invade the seminiferous tubules. After phagocytosis of spermatozoa they increase in size and sometimes possess more than one nucleus. Large spherically shaped spermatophages are found in the epididymis. In the rete spaces of Macaca fascicularis spermatophages are able to penetrate the rete epithelia and reside in the subepithelial connective tissue layers. Spermatophagy is frequently seen in the gonads of older men and in certain cases of oligozoospermia. In Macaca an increased number of spermatophages occurs at the end of the spermatogenetic season.


Long-term therapy with sodium cromoglycate (intal, lomudal or aarane): effects and side effects. Review of 72 atopic asthmatic children from the age of three years demonstrated that the long-term use of sodium cromoglycate (Intal, Lomudal or Aarane) produced no serious side effects clinically or on pathological testing. Almost all the children improved, especially in their heights and weights. There is some evidence that girls showed a better response than boys. A possible explanation of growth improvement is discussed and it is concluded that SCG not only prevents asthmatic symptoms but it gives asthmatic children the best chance of maturing normally.


Distribution of tissue water and electrolytes in normal rhesus macaques. Techniques for the determination of water and electrolytes in individual tissues of normal rhesus macaques (Macaca mulatta) are described. Base-line values are presented for intracellular and extracellular distributions of water and electrolytes in 14 tissues, including skin, skeletal muscle (gastrocnemius), cardiac muscle (left ventricle), lung, diaphragm, liver, renal cortex, outer medulla and inner medulla, cerebral cortex, cerebellum, thalamus-hypothalamus complex, medulla oblongata, and spinal cord.


Human infections: economic implications and prevention. Morbidity and mortality from infectious diseases clearly remain high. Economic assessments should not be based soley on the costs of existing disease but should incorporate costs saved by preventive efforts as well as savings likely to be attained within several years by improved preventive measures. These factors can be used to assess the relative needs for research for specific infections and to compare the economic importance of infections with that of other health problems. Preventive activities for individuals and for larger groups are outlined, and the relation of research to prevention and control of infections is presented.


Antimicrobial drug usage in general hospitals in Pennsylvania. The Inter-Society Committee on Antimicrobial Drug Usage has conducted a survey of 20 randomly selected general hospitals in Pennsylvania. Records studied were of 5288 patients who either died or were discharged on 10 random days throughout 1974. About 28% of these patients received at least one antimicrobial drug during hospitalization. In 60% of the patients the drugs were given for treatment of infectious disease; in 30% they were given as prophylaxis for surgical or nonsurgical procedures. Prophylactic treatment was given for more than 2 days after a procedure in most cases, even though it is not considered effective after 48 h. Discontinuing prophylaxis after 48 h would reduce by 20% the use of antimicrobial drugs in hospitals. Overall, ampicillin and the cephalosporins were the most commonly prescribed drugs, with the more toxic drugs being used infrequently; over half of the patients given antimicrobial drugs had cultures taken. Both of these findings are consistent with accepted standards for antimicrobial drug usage.


Increased risk of lymphoma in sicca syndrome. The risk of cancer was ascertained in 136 women with sicca syndrome followed at the National Institutes of Health (NIH). Seven patients developed non-Hodgkin's lymphoma from 6 months to 13 years after their first admission to NIH. This was 43.8 times (P less than 0.01) the incidence expected from the rates of cancer prevailing among women of the same age range in the general population during this time. In addition, three cases of Waldenström's macroglobulinemia occurred in this study group. Eight patients developed cancers other than lymphoma, similar to the number expected based on the rates prevailing in the general population. Patients with a history of parotid enlargement, splenomegaly, and lymphadenopahy had an increased risk of lymphoma. These clinical conditions did not appear to be early manifestations of undiagnosed lymphoma but rather seemed to identify a subgroup of patients with sicca syndrome with marked lymphoid reactivity, who had a particularly high risk of subsequently developing lymphoma.


Hyperchloremic acidosis during the recovery phase of diabetic ketosis. We have studied 35 patients to find the occurrence of hyperchloremic acidosis during the recovery phase of diabetic ketoacidosis. At admission the patients had typical normochloremic acidosis, with increased anion gap exactly balancing decreased serum bicarbonate. In contrast, in 18 patients with phenformin-induced lactic acidosis, the increase in anion gap at admission was much greater than the decrease in bicarbonate. The difference between lactic acidosis and ketoacidosis may be explained by a slower rate of excretion of lactate than of ketone anions. After the patients with ketoacidosis were treated, the acidosis became predominantly hyperchloremic with normal anion gap. Failure to normalize serum bicarbonate is attributed to excretion of ketone anions in the urine.


Treatment of severe hypophosphatemia.

Treatment of severe hypophosphatemia. Aspects of phosphate biochemistry pertinent to therapy, the distribution of phosphorus in body compartments, therapeutic phosphorus preparations, prevention of hypophosphatemia, therapeutic guidelines, and side-effects of phosphorus therapy are reviewed. Severe hypophosphatemia (less than 0.32 mmol/litre or less than 1 mg/dl) can occur with normal or depleted body stores. Because a large amount of phosphorus may shift rapidly between the extracellular and intracellular or bone compartments, the size of a possible total body deficit cannot be estimated from the serum phosphorus level. Similar shifts may occur unpredictably during repair of hypophosphatemia. Therefore, correction of hypophosphatemia in any patient must be empiric and the response of serum levels to therapy should be followed closely. We discuss a method likely to correct hypophosphatemia while minimizing side-effects.


Meningococcal polysaccharide vaccines: recommendation of the Public Health Service Advisory Committee on Immunization Practices. Meningococcal disease is endemic in the United States, and sulfonamide-sensitive serogroup B strains currently cause most cases. More than two thirds of all cases occur in persons less than 20 years old. Three meningococcal polysaccharide vaccines are licensed for selective use in the United States: monovalent A, monovalent C, and bivalent A-C. This recommendation describes indications for their use, with particular attention to primary immunization, and use in pregnancy and in epidemic control.


Influence of some factors on protein A production by human strains of Staphylococcus aureus. (author's transl). Using passive haemagglutination test, 48 human strains of Staphylococcus aureus cultivated on trypticase soya have been shown to be non-producers, but after subcultures especially on gelified "Oxoid broth n 2", 46 strains (95%) produced protein A. This observation points out the troubles encountered during protein A detection on the field of routine work.


Effect of progestins on glucose and lipid metabolism. Gestamimetic amounts of progesterone enhance basal and glucose-stimulated insulin production. Contraceptive doses of synthetic progestins cause a moderate increase or no change in glucose-stimulated insulin production, depending on route of administration and species tested. Estrogens potentiate the insulinotropic effects of progesterone and the synthetic progestins. Basal serum triglyceride concentrations are generally unaffected by progesterone or 17 alpha-acetoxyprogesterone treatment but may decrease during 19-nortestosterone administration. Glucose tolerance does not change during treatment with gestamimetic doses of progesterone alone but may improve in rats and monkeys during concurrent estrogen administration. By contrast, deterioration of glucose tolerance is observed in women treated concurrently with synthetic estrogen plus 19-nortestosterone derivatives and, occasionally, with 19-nortestosterone derivatives alone. No consistent changes in glucose metabolism have been observed after treatment with 17 alpha-acetoxyprogesterone derivatives alone. The cause of the species-related differences in glucose metabolism during 19-nortestosterone treatment is obscure.


Endogenous endophthalmitis associated with bacillus cereus bacteremia in a cocaine addict. A 22-year-old black female intravenous cocaine addict presented with an endophthalmitis of the right eye. Diagnostic evaluation included an immediate anterior chamber paracentesis and a delayed vitreous aspiration. Although cultures from the involved eye were negative, all 7 blood cultures grew Bacillus cereus suggesting that this organism was the responsible agent of an endogenous endophthalmitis. The patient was treated with appropriate systemic and local antibiotics with resolution of the acute inflammatory signs. However, a phthisical eye has been noted on follow-up examinations.


Acute measles encephalitis of the delayed type. An acute measles encephalitis with epilepsia partialis continua occurred three months after measles in a previously healthy child with no detectable immunological defect. Levels of measles antibodies in serum and cerebrospinal fluid were high, and tubular inclusions of the type seen in subacute sclerosing panencephalitis were found in nerve cell nuclei. A communicating high-pressure hydrocephalus developed in the later stage of the disease. This case demonstrates that measles encephalitis of the delayed type should systematically be considered in children with acute encephalitis.


Epileptogenic mineralization: pathological variants with good prognosis. Four examples of grossly mineralized lesions of the brain, causing seizures, are described; they include 2 hamartomas, a choristoma (novel associations), and an idiopathic "brain stone." Each was detectable with routine roentgenograms, and the seizures were ameliorated by surgical therapy.


A behavioral analysis of complete unilateral section of the pyramidal tract at the medullary level in Macaca mulatta. Ten Macaca mulatta monkeys were operantly conditioned to perform three motor paradigms designed to evaluate single and combination finger movements. Eight of these monkeys were retested after left medullary pyramidotomy; 2 monkeys underwent left medullary pyramidotomy prior to conditioning. All animals were tested for three years after operation. Monkeys with a completely sectioned medullary pyramid could, with time, perform difficult motor paradigms that required: (1) both individual and combination finger movements; (2) proximal upper extremity motor control; (3) thumb and index finger pincer grasp; and (4) the ability to preprogram and then execute a precision hand movement. The greater the extent of pyramidal tract destruction, the longer the time necessary for recovery of both discrete finger movement and pincer grasp, the greater the effort needed to attain recovery of hand function, and the weaker the affected musculature. The 2 animals in which pyramidotomy of at least 70% of the tract preceded efforts at operant conditioning learned and performed difficult motor paradigms. In all animals, neurological examination revealed that the most enduring and functionally most important deficit that interferes with hand function following pyramidotomy is loss of contactual hand orienting responses and failure of reflex sensorimotor adjustments.


[Use of protein-free potato juice concentrates in the production of tetracycline]. The study on the use of potato juice concentrate in tetracycline production showed that the tetracycline-producing strain 3-NK of Actinomyces aureofaciens grown on seed and fermentation media containing 2--2.5 and 0.35--0.45 per cent (by dry substance) of the concentrate produced the same antibiotic yield as that on the media with corn steep liquor.


[Simple qualitative methods of detecting beta-lactamase-producing strains of microorganisms]. Modifications of two microbiological qualitative methods for detection of beta-lactamase-producing microbial strains are described. The methods are based on the principle of Goths. One of the methods named "contact" significantly differs from the prototype and is more simple, convenient, easily reproducible and does not require the use of special equipment and special training of the staff.


Amoxicillin entry into human cerebrospinal fluid: comparison with ampicillin. The entry of amoxicillin and ampicillin into cerebrospinal fluid (CSF) of humans was studied in the absence of meningeal inflammation. Twelve volunteers received 33 mg of amoxicillin per kg intravenously over 30 min and nine volunteers received 33 mg of ampicillin per kg. The CSF specimens were sampled at 1, 2, and 4 h after the beginning of the infusion. Blood samples were obtained at the end of the infusion and at 45, 60, 90, 120, 180, and 240 min after the beginning of the infusion. Amoxicillin and ampicillin were both detected in the CSF. Ampicillin tended to give higher CSF levels than amoxicillin, although the difference was small. Serum concentrations of ampicillin equaled those of amoxicillin.


Comparison of the in vitro activity of Bay k 4999 and piperacillin, two new antipseudomonal broad-spectrum penicillins, with other beta-lactam drugs. Bay k 4999 and piperacillin, two new substituted ampicillins, were compared with other beta-lactam antibiotics, including carbenicillin, azlocillin, mezlocillin, benzylpenicillin, ampicillin, and cefoxitin, against a wide range of gram-positive and -negative organisms. Bay k 4999 and piperacillin were extremely active against Pseudomonas aeruginosa (50% inhibited by 2 mug/ml), being about 16-fold more active than carbenicillin. Bay k 4999 was the most active drug against Escherichia coli (50% inhibited by 0.5 mug/ml) and Klebsiella spp. (50% inhibited by 2 mug/ml). Piperacillin and Bay k 4999 were equally active against Proteus spp., and piperacillin had high activity against Bacteroides fragilis (50% inhibited by between 1 and 2 mug/ml).


Quantitative assessment of bactericidal activities of beta-lactam antibiotics by agar plate method. Quantitative bactericidal activities of beta-lactam antibiotics were determined by the agar plate method. Broth cultures, of which the colony-forming units were counted before the study, were inoculated on antibiotic-containing agar plates, utilizing a 10(-3), 10(-2), or 10(-1) dilution or undiluted culture plated with each 0.001-ml calibrated loop. These plates were incubated at 37 degrees C overnight, and the minimal drug concentration at which no bacterial growth was observed on the plates was defined as minimal inhibitory concentration. After this procedure, the agar surface was treated with beta-lactamase spray to inactivate the antibiotic. These plates were incubated again at 37 degrees C overnight. The minimal drug concentration at which no evidence of bacterial growth was visible on the plates (resulting in a 100% kill) was defined as minimal bactericidal concentration. The lowest concentration which reduced the number of colony-forming units to 1/1,000 that in the original inoculum (resulting in a 99.9% kill) was defined as minimal lethal concentration. When compared for Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Serratia marcescens, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, alpha-hemolytic streptococcus (non-enterococcal), beta-hemolytic streptococcus, and enterococcus, the minimal bactericidal concentrations were generally several fold higher than the minimal inhibitory concentrations. Minimal lethal concentrations were virtually the same as minimal inhibitory concentrations for gram-negative strains; however, for some gram-positive strains, minimal lethal concentrations were higher than minimal inhibitory concentrations.


New antipseudomonal penicillin, PC-904: affinity to penicillin-binding proteins and inhibition of the enzyme cross-linking peptidoglycan. The mechanism of action of a new antipseudomonal penicillin, PC-904, was studied with respect to its binding affinities to penicillin-binding proteins (PBPs) and its inhibitory activities on cross-linking enzymes of peptidoglycan synthesis in vitro. PC-904 showed especially high affinity (compared with that of penicillin G) to Escherichia coli PBP-3. It also had high affinities to PBP-2 and -1Bs and low affinities to PBP-1A, -4, -5, and -6. Similar results were obtained with Pseudomonas aeruginosa, in which this antibiotic showed very high affinity (compared with that of penicillin G) to PBP-3, -1A (presumably corresponding to E. coli PBP-1Bs), and -2; there was especially high affinity to PBP-3 and much less affinity to PBP-1B (presumably corresponding to E. coli PBP-1A). These results are compatible with morphological observations that at concentrations near its minimal inhibitory concentration or less, this antibiotic induced the formation of filamentous cells of E. coli and P. aeruginosa. At higher concentrations or after prolonged incubation, it induced lysis of the cells. The remarkably high affinity of PC-904 to pseudomonal PBP-3, -1A, and -2 may partly explain the potent antipseudomonal activity of this antibiotic. In E. coli, the concentration of PC-904 required to inhibit the cross-linking reaction in enzymatic peptidoglycan synthesis, presumably carried out by PBP-1Bs, was as low as the inhibitory concentrations of penicillin G, ampicillin, and carbenicillin.


Effect of beta-lactam antibiotics on in vitro peptidoglycan cross-linking by a particulate fraction from Escherichia coli K-12 and Bacillus megaterium KM. The binding constants of several beta-lactam antibiotics towards penicillin-binding components in Escherichia coli K-12 (Spratt, Eur. J. Biochem. 72:341-352, 1977) and the antibiotic concentrations required to inhibit the peptidoglycan transpeptidase of E. coli 50% were compared. Penicillin-binding component 1B may have been the transpeptidase working in vitro. The structure-activity relationships of beta-lactam antibiotics and the mechanisms of action in E. coli and Bacillus megaterium are discussed.


Anthracene with near ultraviolet light inhibiting epidermal proliferation. Anthracene plus near ultraviolet (UV) light (UV-A, 320 to 400 nm) suppresses DNA synthesis and mitosis in mouse epidermis. Ultraviolet-A light or anthracene alone does not have any effect. There is no photoactivation of anthracene to enhance depression of DNA synthesis by either UV-B (290 to 320 nm) or UV-C (254 nm) light. While methoxsalen with UV-A light inhibits DNA synthesis, the phototoxic drugs chlorpromazine hydrochloride and demethylchlortetracycline do not. The combination of anthracene plus UV-A light may have therapeutic effectiveness for psoriasis with less potential for photocarcinogenesis than psoralens plus UV-A light.


[Restriction of washing and its effect to the normal human skin flora. Quantitative and qualitative investigations of the aerobic skin flora (author's transl)]. The behaviour of the aerobic skin flora of the flexor sides of the forearms, under a three-week restriction of washing, was investigated in twenty-four patients for its quantitative and qualitative aspects. The combined scrabbing-washing method was used as described by Burtenshaw with Ringer's solution. After a three-week restriction of washing, using the Wilcoxon Test, statistically no significant changes in the total number of microorganisms were found in areas investigated in the intermittent sampling of the skin flora. A three-week restriction of washing in the region of the flexor sides of the forearms does not induce significant changes in the composition of the normal aerobic skin flora. The percentage of differences in the total number of bacteria fluctuates up to the mark in wide limits; statements about standard deviations are not permitted because of the technical and experimental conditions. There was no shifting of the Resident flora to other groups of bacteria in the patients under study. Pathogenic microorganisms could not be found in higher numbers after the second sampling.


[Viral acanthomas and specialized forms of keratinosome "membrane coating granules" (author's transl)]. In the case of viral acanthomas, the stratum spinosum and granulosum presents ballooned cells which contain all transitional stages from multivesicular bodies (MVB) to keratinosomes. A particularity in condylomata acuminata are the "wagon-wheel" bodies. These structures are typical for the non keratinazed squamous epithelium. The participation of intercellular extruded "wagon-wheel" bodies, MVB and atypical keratinosomes on an irregular baso-apical diffusion-barrier in the epidermis of cases with viral acanthomas has been discussed. On the basis of the relation seen between MVB and the Golgi-apparatus, their transition to partially atypical keratinosomes in cases of viral acanthomas and their "expulsion" into the intercellular space could indicate that in keratinozytes the enzymatically regulated feed-back between the cellular surface and the capability to synthesize is changed by viral agents. The interference appears to manifest itself in the Golgi-apparatus and also appears to be "specified" by the terrain present.


Thyroid-stimulating hormone and prolactin levels in breast cancer. Serum thyroid-stimulating hormone (TSH) and prolactin (PRL) levels were measured before and after intravenous administration of protirelin to 148 patients with breast carcinoma. There was a high prevalence (36%) of elevated basal TSH; however, most of the patients were euthyroid and had normal serum thyroxine and T3 resin uptake. The PRL level was elevated in 22% of the cases. Both the mean PRL and the mean TSH levels for the breast cancer patients were significantly elevated above the respective means in a control group. We could find no correlation between serum TSH and PRL levels, suggesting that the purported association between a decreased thyroid state and breast cancer is probably not mediated through an increased PRL level. The mean survival and mean disease-free interval were shorter for patients with either elevated TSH or elevated PRL levels, but in neither case was the difference statistically significant.


Non-group D streptococcal meningitis misidentified as enterococcal meningitis. Diagnostic and therapeutic implications of misdiagnosis by screening microbiology. Two patients had nonhemolytic Gram-positive coccal meningitis. Both pathogens were initially misidentified as a group D enterococcus by growth in "selective" media, which led to the use of inappropriate and potentially toxic systemic and intrathecal aminoglycosides. Careful evaluation of the antibiotic sensitivity data and additional microbiological studies allowed correct identification of the organism. The important diagnostic and therapeutic considerations in differentiating true enterococcal infections, especially meningitis, from those caused by other alpha-hemolytic or nonhemolytic streptococci are emphasized. A simple laboratory schema for rapid recognition of such pathogens is reviewed.


[Calyceal ectopic diverticulum].

[Calyceal ectopic diverticulum]. The authors present 15 cases of calicial ectopias. They then review some of the names frequently given to this illness and discuss certain theories which link this anomaly with other kidney cystoses, taking special care to point out the difficulties involved in the correct performing of a differential diagnosis with calculous hollows, particularly those situated in lower calices.


[A simplified arteriographic analysis of systolic pressure and of the pressure-time index]. Systolic stress has been measured in 20 ms periods during ventricular ejection by monoplanar angiographic method, both under basal conditions and after infusion of trinitro-glycerine (TNG) in 8 coronary patients. None of them showed significant segmental contraction abnormality. No correlation was found between the corresponding values of mean systolic stress sigma and mean systolic pressure P, either under basal conditions (r=0.48) or after reduction of the load (r=0.24). On the other hand, values of sigma correlated closely with the corresponding values of the stress sigmas at the end of the isovolumic contraction phase, both under basal conditions (r=0.95) and after TNG (r=0.98. A similar correlation was found between the corresponding values of the peak of systolic stress and of sigmas both under basal conditions (r=0.94) and after TNG (r=0.96). Determination of sigmas is technically simple, and only requires the calculation of ventricular end-diastolic volume, together with measurement of end-diastolic thickness and aortic diastolic pressure. This simplified angiographic method is useful to express the determinants of myocardial energy using parietal stress values instead of intracavitary pressure values.


[Auricular and left ventricular compliance in acute and chronic mitral insufficiency]. Left atrial and ventricular compliance has been studied in 25 cases of chronic mitral incompetence (CMI) and 9 cases of acute mitrale incompetence (AMI). Left atrial compliance was evaluated by the ratio between maximal variation in volume and corresponding maximal variation in pressure; it was found to be higher in cases of CMI than in cases of AMI. Left ventricular compliance was evaluated by various indices (Diamond, Mirsky, Gaasch, Laird), and was found to be increased equally in the chronic and acute types. It is possible that an explanation of this increase incompliance is to be found in the rearrangement of myocardial fibres which follows the dilatation. It constitutes a fundamental means of chronic adaptation, and shows that the diastolic elastic properties of the cavities of the atrium and ventricle are as important in the evaluation of mitral incompetence as the properties of systolic contraction.


[Mitral commissurotomy under direct vision. 37 cases]. 1 188 mitral commissurotomies were carried out between 1962 and 1976, 37 of them (3.1%) being under direct vision. The two operative deaths (5.4%) occurred early in the series. Longer term follow-up showed that 3 cases died secondarily, and 3 had revision surgery. The main complication was mitral incompetence (51% of operated cases had a systolic murmur). The varying indications and results are presented; these justify a prospective study, but not a recommendation for the systematic adoption of mitral commissurotomy by an open heart technique.


[Rupture of the mitral valve chordae. Electrocardiographic, clinical and angiographic findings]. This report concerns 9 patients in whom rupture of the cordae of the mitral valve was suspected from the echocardiogram. The authors recall the clinical, echocardiographic, arteriographic, haemodynamic and anatomical findings in patients with rupture of the chordae; they emphasise the importance of echocardiograpy in the pre-operative diagnosis of this condition. In this series, the most frequent clinical sign was a loud pan-systolic murmur at the apex. The electrocardiographic abnormalities were nonspecific. Cardiomegaly was present in most cases. The main echocardiographic findings were those of additional echoes between the two cusps of the mitral valve during diastole, or an abnormally posterior or anterior position of the posterior cusp during diastole, or the presence of mitral prolapse. Other nonspecific signs were frequently present. Left cineangioventriculography showed a significant degree of mitral leakage during diastole in all patients. All 9 patients had an operation or came to post mortem; rupture of the chordae was confirmed in 6 of them. As far as the other 3 cases were concerned, two of them had lengthening of the mitral cordae, and the last had mitral prolapse associated with endocardial vegetation. A further group of 60 patients undergoing surgery for mitral incompetence without rupture of the chordae allowed us to establish that there were no false negative results on the echocardiogram.


[A treatable condition: parietal rupture of the heart during the acute phase of myocardial infarct. Apropos of a further case treated successfully with surgery]. A man aged 62 had an unexpected anterior myocardial infarction, complicated during the thirteenth hour after onset by parietal rupture and consequent acute tamponnade. The diagnosis was confirmed by echocardiography and then by pericardial puncture which allowed enough time for an operation to be undertaken under extra-corporeal circulation. The infarct was resected together with the weakened area of rupture, and the quality of the patient's life has been maintained at an excellent level after one year.


[Myocardial infarct before the age of 36: 20 cases]. Twenty cases of myocardial infarction in 16 males and 4 females and less than 36 are reported. The number of heavy smokers was greater than in other age groups (86%), and an association between tobacco consumption and lipid abnormalities was found in 3/4 of cases. All the females were on contraceptive treatment, one recurring during pregnancy. The clinical features of the infarctions were an onset which was usually unexpected (n=14), ar attack which was sometimes precipitated by exercise (n=3), and the infrequency of residual angina. The exercise test (n=16) showed up an associated abnormality in only one case out of four, but the fact that the rate-pressure product was normal suggests that the coronary artery networks were in a satisfactory state of function. Ventriculography (n=14) was normal in 35% of cases. Coronary arteriography (n=18) showed significant lesions in 12 cases, one trunk being affected in 6, two trunks in 5, and 3 trunks in one; the lesion index was 1.6. In 6 cases there were few changes in the coronary arteries, and the probable mechanism of the infarct is discussed: besides the possibility of a recanalised thrombus, which appears to be the likely one in two of our patients, spasm played a possible role even though the ergonovine provocation test was negative. The mortality during the first month was zero; as a secondary event over a follow-up period of 38 months, there were two deaths and four recurrences, one of which occurred in a healthy coronary vascular tree.


[Analysis of factors which can influence results of aortocoronary bypass surgery]. The various factors influencing the result of treatment have been studied in a series of 100 consecutive patients undergoing aorto-coronary bypass graft surgery. There were three operative deaths and twelve cases of post-operative infarction. Longterm, 85% of them were three year survivors, clinical improvement being maintained in 84% of them. Post-operative tests showed that 70% of patients have no pain on the maximal exercise test, but 48% had ischaemic depression of the ST segment. From among the 47 patients who had follow-up arteriography, 78% of the grafts were patent, but no improvement of the contractility of the left ventricle could be demonstrated (pre-operative ejection fraction 47 +/- 3%, post-operative 49+/- 3%). The pre-operative clinical features rarely give any indication of the prognosis. The same is true in the present series of the condition of the left ventricle, bearing in mind the fact that patients with grossly impaired ventricular contractility (ejection fraction below 30%) were routinely excluded from surgery. It is essentially the state of the coronary arterial network, as assessed by a score made up from the degree and number of stenoses, the quality of the distal bed, and the anatomical distribution, which will pick out those patients more at risk both from the surgery and from post-operative death and in whom the longterm result is likely to be disappointing with no improvement in function, with obstruction of the grafts, or with secondary death.


[Hyperventilation test in coronary disease: a comparison with a bicycle ergometer exercise test. Report of 100 cases]. A hundred cases have been studied and divided into three categories:--60 normal subjects;--30 coronary subjects with a positive exercise test;--10 subjects with defective nervous control of the circulation; using the exercise test, we studied the effects of hyperventilation on repolarisation of the ventricle. In the normal subjects there was no ischaemic depression of the ST segment, but there were minor changes in repolarisation which affected the T wave in 73% of subjects and were essentially posterior in distribution. In the coronary subjects, we found three with ischaemic depression of the ST segment and one with ST elevation of 2.5 mm (6.7% of the coronary subjects). This last finding is evidence against the commonly held hypothesis that reproduction of ST depression by hyperventilation during the exercise test indicates a false positive test. In the patients with defective nervous control of the circulation, 9 had an ischaemic type of ST depression, either as a new feature or as a more severe one compared with that found at rest. The mechanism by which these depressions are produced has not been totally explained:--in the cases with defective nervous control of the circulation, it appears that latent increased sympathetic activity is increased by the hyperventilation;--in the coronary subjects, it may be caused by true ischaemia or by an associated defect in nervous control of the circulation.


[Recording of His potentials from surface chest leads using a computer]. Under certain circumstances it is possible to record His potentials using surface chest leads. These potentials have a very low intensity over the thorax, and must be separated from the "background noise" by an averaging technique. The desired activity occurs before the R wave and has a constant relationship to it; the potentials picked up by the chest leads are amplified, coded numerically, and presented to the memory store which accepts only those potentials which precede the R wave. It then summates the successive cycles, using a synchronising signal to ensure that they coincide. All this is carried out with an averager. In the 80 patients studied, a signal which seems very likely to reflect His activity was obtained in slightly more than a third of cases. The findings were correlated in 14 cases with those produced by invasive techniques, and showed that the main source of error was the after-potential of the P wave after a short PR interval--this occurred in one case; in the other 13 cases, the correlation was good. This method needs to be refined before it can be used clinically. It seems unlikely that it will replace the invasive technique which is so important for stimulation tests, and so necessary for studies of dynamic pharmacology.


[Isolated left anterior hemiblock during attacks of angina pectoris]. The clinical significance and mechanism for changes in the axis of the QRS complex during attacks of angina pectoris (excluding cases of Prinzmetal's angina) are unknown. Previous work has suggested that left anterior hemiblock under these circumstances is a sign of unstable angina indicating a lesion in the anterior descending artery. Two cases with left anterior hemiblock associated with frequent attacks of angina have been the subject of careful study. In case one, atrial stimulation tests showed that the left axis deviation was not related to tachycardia. It only occurred when atrial stimulation was carried out for long enough to induce myocardial ischaemia as witnessed by precordial pain and disorders of repolarisation. In case two, the left anterior hemiblock came on at first at the same time as the attacks of angina, and then became permanent. Bypass graft of the anterior descending artery restored the QRS axis to normal, and corrected the repolarisation disorders which were of ischaemic origin. These findings argue in favour of an ischaemic origin of this conduction defect. Unlike ischaemia of the left anterosuperior subbranch, anterior left hemiblock is indicative of extensive ischaemia of the anterior wall of the left ventricle relative to an obstruction in the anterior descending artery or in the main trunk of the left coronary artery.