Hypersensitivity reactions in small intestine. I Thymus dependence of experimental 'partial villous atrophy'. Rats infected with the intestinal nematode Nippostrongylus brasiliensis have crypt hyperplasia with villous atrophy in affected areas of the small intestine. In thymus-deprived (B) rats the course of infection is prolonged but, despite the presence of many worms in the intestinal lumen, villi and crypts appear largely normal. This suggests that the tissue damaged associated with N. brasilliensis infection is caused, not by the worms, but by a local thymus-dependent immune reaction. There is some evidence to implicate lymphocytes rather than antibodies in this reaction. It is already know that T-cell-associated damage to the small intestine, such as occurs in allograft rejection, produces subtotal villous atrophy. The present findings suggest that when T cell react locally with helminth antigens a similar type of damage occurs. The presence of a local cell-mediated immune reaction may be the common factor which causes villous atrophy and crypt hyperplasia in many small intestinal diseases, eg, viral enteritis, giardiasis, cow's milk allergy, and coeliac disease.


A British family with herediatary pancreatitis. A family with hereditary pancreatitis is described. Nine family members definitely have had pancreatitis, whilst 15 more are suspected of having the disease. The condition presents as recurrent attacks of epigastric or central abdominal pain, sometimes radiating to the back, often associated with vomiting. The attacks of pain usually last three to four days. The inheritance fits well with an autosomal dominant pattern with limited penetrance, as it does in other families described in the literature. There is no aminoaciduria as has been described in some previously reported families. The attacks of pain start in childhood or young adult life (mean age of onset inthis family is 12-6 years) and appear to cease in this family by the age of 40 years. The diagnosis of pancreatitis in members of the family who have had confirmed pancreatitis was made by finding a raised serum amylase concentration in four cases, at laparotomy in four cases, and by pancreatic calcification seen on radiography in one case, The literature on the condition is reviewed, and it is speculated that the condition may have been underdiagnosed in Britain.


The immune response of mice to phiX174. The potentiation of B-cell immunity and the suppression of T-cell help by pertussis vaccine. The primary and secondary responses to phiX174 have been studied in T cell-deprived (T- minus) and control CBA mice including sham-operated (T+) and normal mice. The effect of pertussis on the immune response of these mice has been measured. It is concluded that: (1) the gammaG and memory responses to phiX are produced in T- minus mice even though greatly reduced in comparison with T+ and normal mice; (2) pertussis appears to enhance the gammaG response in T- minus mice while suppressing it in T+ and normal mice.


Permanent hapten-specific tolerance in B lymphocytes. Tolerance to the hapten TNP was induced in mice congenic with CBA but bearing the Ig-b allotype (Ig-b mice). To induce a high degree of tolerance it was necessary to give five injections of TNP-sulphonate followed by an immunogenic challenge (alum precipitate of TNP-BSA with pertussis adjuvant). Lymph node or spleen cells from these mice were transferred, with or without an equal number of non-tolerant CBA spleen cells, to irradiated CBA recipients and these were challenged with a different TNP-protein conjugate. Anti-TNP antibody bearing the Ig-b allotype was then assayed separately from total anti-TNP, as a measure of the contributions made by tolerant and non-tolerant B-cell populations respectively. Tolerant lymph node cell did not depress the response of normal cells, nor did the normal cells 'break' the tolerance of the Ig-b population even when the latter had been treated with anti-T-cell serum and complement. No response was obtained from tolerant lymph node cells when the recipients were challenged at different time up to 12 weeks after transfer. By this time the control non-tolerant lymph node cells had also lost the capacity to respond. It is concluded that: (1) effectively permanent tolerance, which is not maintained by afferent mechanisms, can be induced in lymph node B cells; (2) B-cell tolerance can be greatly enhanced by immunogenic challenge; (3) spleen may contain a distinct population of B cells which is less susceptible to tolerance; and (4) the life-span of virgin lymph node B cells is probably less than 12 weeks.


Subpopulations of mouse spleen lymphocytes. II. Immunological reactivity of spleen cells fractionated on BSA density gradients. We found in previous experiments that fractionation of non-immune mouse spleen cells on bovine serum albumin density gradients yields two subpopulations of T cells, one of high, the other of low density. Both subopopulations could be stimulated in corporate thymidine by the T cell-specific mitogen concanavalin A (con A). In the present investigation, spleen cells of mice immunized to sheep red cells (SRC) were similarly fractionated and the fractions recovered were assayed for: (a) reactivity to con A; (B) REACTIVITY TO SRC and (c) capacity to function as helper cells when stimulated with the homologous (SRC) or with a heterologous (donkey red cells) (DRC) antigen. Two subpopulations of cells reacting to con A were found in the spleens of the primed mice, corresponding to the subpopulations found in the non-immune mice. Both subpopulations contained cells responding to SRC (as measured by thymidine incorporation) and cells endowed with helper activity. The two subpopulations appeared to differ, however, in their specificity: while the denser cells could only exert their helper effect when stimulated by the specific antigen, the light cells could be effectively stimulated by both the specific (SRC) and the nonspecific (DRC) antigen.


Serologic evidence for cross-reacting antigens in two carcinogen-induced murine sarcomas. Serological evidence is presented that two chemically-induced (by methylcholanthrene and 3,4-benz(a)pyrene) sarcomas of C3HF mice contain cross-reacting tumor-associated cell-surface antigens. Xenogeneic and syngeneic antitumor antisera against the two sarcomas were studied with an isotopic, complement-dependent, antibody-mediated microcytotoxicity assay and an isotopic antiglobulin test for the detection of antibodies to tumor-associated antigens, in vitro. Absorportions with various tissues were performed which consistently revealed that the specific activity of the antitumor antisera could be removed by absorption with cells from either chemically-induced tumor, while absorption with syngeneic normal adult tissues, normal fetal tissues, or cells from a histogenetically unrelated tumor (spontaneous mammary carcinoma) failed to remove any specific activity. In view of the individual character of carcinogen-induced tumor antigens as detected by tumor transplantation techniques, our results suggest that chemically-induced murine sarcomas (even when induced by different carcinogens) contain both private and common cell-surface antigens, the latter detectable by serological methods. These common tumor-associated antigens may be related to a viral genome involved in the nalignant transformation of carcinogen-induced marine sarcomas.


In vitro immunological studies on East African cancer patients. II. Increased sensitivity of blood lymphocytes from untreated Burkitt lymphoma patients to inhibition of spontaneous rosette formation. Frozen aliquots of peripheral blood mononuclear cells from patients with Burkitt's lymphoma (BL) at various stages of the disease have been compared with samples from East African children who were healthy or who suffered from non-malinant disorders. Using the sheep-cell rosette test (which is believed to identify T-lymphocytes), we found a significant reduction in the proportion of rosette-forming cells (RFC) in the samples from untreated BL patients. After reduction of remission the difference between BL patients and controls was abolished. Rosette formation was more readily inhibited by anti-lymphocyte globulin (ALG) in samples from untreated BL patients than in controls. On induction of remission the rosette inhibition curve shifted towards the control values. The findings are compatible with the presence, in untreated BL, of a circulating factor which impairs the capacity of T-lymphocytes to form rosettes with sheep erythrocytes. It remains to be established whether the functional capacity of T-cells to protect the host against tumour proliferation is also impaired.


In vitro immunological studies on east african cancer patients. III. Spontaneous rosette formation by cells from Burkitt lymphoma biopsies. Spontaneous rosette formation was observed in eight out of nine Burkitt lymphoma biopsies. These were examined fresh and/or after culture in vitro for up to 48 h. The percentage of rosettes varied from 3.7% to 38%. There was a tendency for the percentage of rosettes to increase with time in tissue culture. It is suggested that the rosette-forming cells are T-lymphocytes infiltrating the tumour and functioning as a host defence mechanism against the proliferating tumour cells.


Immunological mechanisms in the pathogenesis of virus-induced murine leukemia. I. Autoreactivity. By an in vitro microcytotoxicity assay, thymocytes from mice infected with Moloney murine leukemia virus since birth (MuLV-M carriers) caused a dramatic reduction of normal, non-infected syngeneic target cells; they usually spared identically derived target cells infected with MuLV-M. Thymocytes from normal mice slightly stimulated the replication of the same target cells. This pattern of carrier thymocyte reactivity was evident at all ages tested during both preneoplastic and neoplastic periods. Transplantable lymphoma cells derived from a carrier mouse with overt thymic lymphoma behaved similarly. Lymphocytes from the spleens and lymph nodes of young preleukemic carriers (8-12 weeks old) usually were reactive against MuLV-M-infected tarted cells and not against non-infected target cells. In contrast, lymphocytes from older preleukemic carriers (16-17 weeks old) reacted in a manner similar to carrier thymocytes. These observations suggest that the thymic lymphoma induced by MuLV-M may result in part from an autoreactive process originating in the thymus, but eventually spreading to the peripheral lymphoid tissues.


The antigenicity of carcinoembryonic antigen in man. Binding of globulins to -125I CEA was detected in 10 of 24 sera from patients with cancer, 13 of 26 sera from blood donors, and 7 of 27 supernates of tumor-cell suspensions. Binding was predominantly by IgM in 10 of 14 sera tested by radioimmunoelectrophoresis. Binding was inhibited by 6 ng unlabelled CEA in one instance only, and by adsorption with blood group A erythrocytes in three cases. Binding was not increased in dialysed precipitates formed by ammonium sulfate at pH 2.5, while there was increased binding in precipitates of complexes of CEA and heterologous anti-CEA. These results confirm that human IgM binds to CEA, and in some cases binding appears to be mediated by antibodies to blood group A. However, the binding is weak and appears to be of low affinity. This suggests that binding of CEA by immunoglobulins represents cross-reactivity by antibodies to similar antigens, of which blood group A is one example.


Stimulation of Fracture Healing by Pacemaker in Rabbits.201S. An und-splaced fracture of each fibula was produced in 20 rabbits. Into the fracture of the right fibula, a cathode was inserted, which delivered 15 microamperes of galvanic current for more than one week. The source of current was 5v small transistor batteries which acted like a pacemaker. This stimulated healing of the fracture for 15 days. The left fibula fractures were used as controls. Both fibulae were studied roentgenographically and microscopically. This experiment suggested that galvanic current with a cathode placed in the fracture gap stimulated fracture healing.


Familial occurrence of dot (microcystic), map, fingerprint dystrophy of the cornea. The clinical description of corneal microcysts, maplike changes, and fingerprints has led investigators to the conclusion that these changes may represent a corneal dystrophy. The familial or hereditary evidence which is usually necessary to label a corneal disease a dystrophy has been lacking. This paper describes a familial pattern of disease in two families where three generations were involved and in eight families with corneal changes in at least two generations.


[Lymphoreticular proliferations in the skin. Cytochemical and immunocytological studies in lymphadenosis benigna cutis]. In 8 patients with lymphadenosis benigna cutis (LABC) cytochemical and in 2 of them immunocytological studies have been performed. 1) In patients with LABC we find ectopic organoid proliferations of "lymphfollicle"-like structures within the dermis which predominately consist of small lymphocytes and large reticulum cells. Immunocytological differentiation of the lymphocytes leads to the characterization of B- and T-lymphocytes in a ration 2:1. 2) Large reticulum cells represent a peculiarly remarkable cell class in infiltrates of LABC. Because of their typical arrangement disseminated within the lymphocytic infiltrate they have been designated as "starry sky" cells. Cytochemically they are characterized by an unusual high content of nonspecific esterases and acid phosphatase, most of them show phagocytized basophilic bodies. Because of their shape, arrangement and enzymcytochemical behaviour these cells can be referred to as typical for the LABC disease. 3) Monocytes cannot be found within the "lymphfollicles". Mast cells and connective tissue cells are rarely observed. Polymorphonuclear granulocytes can be demonstrated in great numbers in any part of the involved cutis when there is an insect bite in history. 4) As a reaction of the ectopic proliferation of lymphoreticular tissue within the dermis there is an activation of the surrounding connective tissue with an increase of the alkaline phosphatase activity within these cells, new formation of collagen fibres and strong proliferation of alkaline phosphatase positive capillaries. 5) Etiopathologically it is stressed, that in LABC for example an insect bite induces stimulation of hematopoietic potentialities of undifferentiated mesenchymal germ centres within the cutis takes place, leading to the development of ectopic of "lymphfollicle" like structures.


Viridenomycin, a new antibiotic.

Viridenomycin, a new antibiotic. Viridenomycin, a new crystalline antibiotic, was isolated from the culture broth of Streptomyces viridochromogenes strain No. T-24146. Viridenomycin is a weakly acidic and lipophilic substance, which exhibits a strong absorption maximum at 310 nm and shows strong activity against Trichomonas vaginalis and gram-positive bacteria.


Alpha-1-antitrypsin content in the serum, alveolar macrophages, and alveolar lavage fluid of smoking and nonsmoking normal subjects. The content of alpha-1-antitrypsin in the serum, alveolar lavage fluid, and alveolar macrophages of smokers and nonsmokers was studied. Bronchoalveolar lavage was used to obtain alveolar fluid and macrophages from normal volunteers, and alpha-1-antitrypsin and albumin were measured using the electroimmunodiffusion technique. The serum level of inhibitor was not different between the two groups, while the total lavage fliud content of alpha-1-antitrypsin was increased in the smokers. The level of alpha-1-antitrypsin was also significantly greater (P less than 0.001) in the alveolar macrophages of the smokers suggesting the possibility of chronically increased alveolar levels in the cigarette smoker as a possible protective mechanism against proteolysis.


Scientific methodology applied.

Scientific methodology applied. The subject of this symposium is naproxen, a new drug that resulted from an investigation to find a superior anti-inflammatory agent. It was synthesized by Harrison et al. in 1970 at the Syntex Institute of Organic Chemistry and Biological Sciences. How can we chart the evolution of this or any other drug? Three steps are necessary: first, chemical studies (synthesis, analysis); second, animal pharmacology; third, human pharmacology. The last step can additionally be divided into four phases: metabolism and toxicology of the drug in normal volunteers; dose titration and initial clinical trials with sick subjects (pharmacometry); confirmatory clinical trials when the drug is accepted on the market and revaluation (familiarization trials). To discover the truth about naproxen, we must all participate actively with a critical mind, following the principles of scientific methodology. We shall find that the papers to be presented today all deal with the third step in the evaluation process--clinical pharmacology. It is quite evident that the final and most decisive test must be aimed at the most valuable target: the human being. The end product of this day's work for each of us should be the formation of an opinion based on solid scientific proofs. And let us hope that we will all enjoy fulfilling the symposium in its entire etymological meaning this evening. In vino veritas.


Effect of naproxen on gastrointestinal microbleeding following acetylsalicylate medication. This study was undertaken to determine if substitution of naproxen for ASA does influence salicylate-induced gastrointestinal bleeding. Twelve normal volunteers were selected and given increasing doses of salicylate until guaiac tests were consistently positive. Autologous labeling of their red blood cells with 51-Cr was used to quantitate the microbleeding. After two weeks on ASA, six subjects were double blindly switched to naproxen and six to placebo for another two weeks of observation. Two-way analysis of variance on the raw data shows a significant treatment effect associated with a significant interaction in both groups. Final analysis on a logarithmic scale permits orthogonal contrasts to be accurately made without any significant remaining interaction. It is concluded that substitution of naproxen for ASA at a dose of 500 mg daily is accompanied by a rapid reduction of microbleeding to "normal" levels.


Ascending afferents to the telencephalon of ranid frogs: an anterograde degeneration study. Sources of telencephalic afferents were examined in two species of frogs, Rana catesbeiana and Rana pipiens, by study of anterograde degeneration resulting from hemisection of the brain at the isthmus or at the caudal border of the thalamus and from electrolytic lesions in various portions of the diencephalon. The results indicate that some telencephalic afferents arise from levels caudal to the isthmus, that some striatal afferents arise from a level between the isthmus and the caudal border of the thalamus, and that a projection to the ipsilateral striatum arises from the anterior and/or middle portions of the dorsal thalamus. Diencephalic projections to pallial portions of the hemisphere were also observed. These results demonstrate substantial non-olfactory afferent projections to the telencephalon in ranid frogs.


Binding of poly (Glu-60 Ala-30 Tyr-10) by thymic lymphocytes from genetic responder and non-responder mice: effect of antihistocompatibility serum. The binding of 125-I-labeled GAT by murine thymocytes was studied by autoradiography. GAT binding was highly temperature dependent. Significantly more thymocytes bound GAT at 37 degrees C than at 4 degrees C. GAT bound at 37 degrees C was usually distributed in a "cap" over one pole of the cell. Preincubation of thymocytes with specific anti-H-2 serum markedly inhibited the subsequent binding of GAT. The frequency of antigen-binding thymocytes was not significantly affected by preincubation of thymocytes with anti-Thy-1 serum or a number of anti-immunoglobulin sera. The immune response to GAT is controlled by an H-2 linked immune response gene(s). Mice of strains that are H-2p, H-2q or H-2s (non-responders) fail to develop effective T cell helper function necessary for a humoral immune response to GAT under most conditions. However, both responder and non-responder strains had similar numbers of thymocytes capable of binding GAT in vitro, indicating that T cells from non-responder strains of mice do possess a recognition mechanism for GAT.


Migratory patterns of B lymphocytes. III. Inhibition of splenic follicular localization of transferred chicken bursa cells by preincubation with anti-Ig-1. Homing of 3-H-adenosine-labeled bursa cells to follicles in the chickens spleen was greatly reduced by prior incubation of the transferred cells with rabbit anti-chicken-immunoglobulin sera. This effect was transient, being present 6 hr after cell transfer but gone by 18 hr, when incubation was at 0 degreesC without complement. The inhibition persisted until at least 18 hr after incubation at 37 degrees C with complement.


Cell interactions between histoincompatible T and B lymphocytes. VIII. In vivo cooperative responses between lymphocytes are controlled by genes in the K-end of the H-2 complex. The genetic restrictions for successful carrier-primed T cell and hapten-primed B cell cooperative interactions were established in a totally in vivo double adoptive transfer system. In complementation experiments, we have demonstrated that genes localized in the K-end of the H-2 complex control successful T-B cell cooperative interactions. Thus, DBA/2 KLH-primed T cells cooperated with (C3H times C3H.OH)F1 and (C3H times C3H.OL)F1 DNP-primed B cells to make a secondary response to DNP-KLH, but not with (C3H times C3H.A)F1 DNP-PRImed cells. The presence of foreign histocompatibility determinants on the F1 B cells did not prevent successful physiologic cell cooperation provided the T and B cells shared common cell interaction genes coded for in the K-end of the H-2 complex.


Failure of pentamidine isethionate to provide chemoprophylaxis against Pneumocytis carinii infection in rats. Latent Pneumocystis carinii infections were exacerbated in 54 adult male Sprague-Dawley rats by administration of alternating subcutaneous doses of hydrocortisone-21-phosphate and of cortisone acetate three times a week, plus 0.5% chlortetracycline in their drinking water, until death or the termination of the experiment at 120 days. Twenty-eight of the rats were also given pentamidine isethionate (4mg/kg) intramuscularly daily for 14 days. Pentamidine-treated animals that died within the 120 days of the experiment survived longer than control animals. At necropsy, however, every animal in both groups had P. carinii in the lungs. The intensity of the infection was the same in the pentamidine-treated and control groups. Pentamidine isethionate administered in this standard regimen does not exert a significant chemoprophylactic effect against proliferation of P. carinii in rats. The study provides little encouragement for use of pentamidine as a prophylactic agent against P. carinii in high-risk patients.


Studies of immediate hypersensitivity in a patient with Acanthocheilonema perstans filarial infection. A 25-year-old white female returned from West Africa with a two-year history of epidosic swelling, pruritus, and pain in a wrist, associated with peripheral eosinophilia. Serologic and immediate skin tests with Dirofilaria immitis antigen were positive, and blood smears transiently showed microfilariae of Acanthocheilonema perstans after the patient had been treated with diethylcarbamazine. Before treatment, both the serum concentration of IgE and the eosinophil content of arylsulfatase, an enzyme that selectively inactivates slow-reacting substance of anaphylaxis, were elevated; the patient's peripheral leukocytes released histamine and eosinophil chemotactic factor of anaphylaxis when challenged with D. immitis antigen. After one course of diethylcarbamazine, the clinical manifestations and abnormal in vitro immunologic results resolved. Host response to A. perstans infection appears to involve both IgE-mediated hypersensitivity and alterations in an eosinophil enzyme.


Microsurgical approach to the cerebellopontine angle. Various sections of the IXth, Vth, vestibular and cochlear nerves have been performed on twenty patients. The technique we used was an 'a minima' approach to the cerebellopontine angle. This operation is atraumatic and quick to perform, and the postoperative period is always excellent. It seems very useful for patients with Ménière's disease or intractable pains in the glossopharyngeal or trigeminal fields. It can be used for diagnosis if a small neurinoma in the cerebellopontine angle is suspected.


Interactions of Fc receptors with antibodies against Ia antigens and other cell surface components. Two Fc receptor-dependent tests were investigated to study the question of a relationship between Fc receptors and known cell surface antigens, in particular I region-associated (Ia) antigens: (a) a rosette assay with antibody-coated erythrocytes (EA) as indicator cells and normal mouse lymphoid cells as source of rosette-forming cells, and (b) a cytotoxicity test with antibody-coated erythrocytes as target cells and normal mouse spleen cells as a source of cytotoxic cells (K cells). EA rosettes were specifically inhibited by antibodies reacting with Ia antigens. Various other antisera reacting with antigens on B lymphocytes, like anti-Ly 4.2 (raised in H-2 identical mice), rabbit antimouse B-cell serum, or rabbit antimouse immunoglobulin, also specifically inhibited the rosettes. No inhibition occurred in the presence of allogeneic or xenogeneic antisera reacting with T lymphocytes. K-cell cytotoxicity was specifically inhibited by each of the antisera (reacting with either B cells or T cells). F(ab')2 fragments of anti-Ia antibodies could still specifically inhibit EA rosettes but they could not inhibit K-cell cytotoxicity. Similar results were obtained with F(ab')2 fragments of anti-immunoglobulin antibodies. These results indicate that the mechanism of inhibition of Fc receptors in the two tests was different. In neither of the tests could we find any evidence for a unique association between the Fc receptors and Ia antigens. The Fc receptors on K cells did not seem to be associated at all with Ia antigens.


Acute abdominal pain in children.

Acute abdominal pain in children. Acute abdominal pain in children is a common and challenging problem for the family physician. The many causes of this problem require a systematic approach to making the diagnosis and planning specific therapy. A careful history and physical examination, together with a small number of selected laboratory studies, provide a rational basis for effective management in most cases. This paper reviews the more common causes of acute abdominal pain in children with special emphasis on their clinical differentiation.


The influence of thyroxine and acclimation temperature on glycogen reserves of the frog Rana pipiens. Leopard frogs were given daily injections of Na-l-thyroxine (2.0 mug/10 g body weight) for seven days, and control animals were given daily injections of the vehicle. During the period of treatment, half of the frogs were acclimated, in darkness and without food, at a constant temperature of 15 degrees C, whereas the remainder of the animals were acclimated at 25 degrees C. At the end of the seventh day, the frogs were killed by decapitation, and the glycogen concentration in samples of liver tissue and skeletal muscle was determined spectrophotometrically. Total hepatic glycogen of each frog subsequently was calculated from data on glycogen concentration and liver weight. Treatment of leopard frogs with thyroxine had no apparent effect on hepatic glycogen reserves of animals acclimated at 15 degrees C, but there was a striking reduction in glycogen content of livers from hyperthyroid frogs held at 25 degrees C. Mobilization of hepatic glycogen in thyroxine-treated animals held at 25 degrees C presumably was secondary to a general stimulation of oxidative metabolism. Treatment with thyroxine had no effect on the concentration of glycogen in skeletal muscle of leopard frogs held at either of the acclimation temperatures used in this study.


Single-unit responses to natural vestibular stimuli and eye movements in deep cerebellar nuclei of the alert rhesus monkey. To study the possible role of the cerebellum in the vestibular-ocular reflex, extracellular responses of cerebellar nuclear neurons were recorded in awake monkeys during natural vestibular stimulation; 115 neurons in the fastigial nucleus responded to horizontal sinusoidal accelerations applied to the head by means of whole-body rotation. More than 75% of these cells were located in a distinct layer, 500 mum thick, in the rostral part of the fastigial nucleus; they were excited by contralateral horizontal angular acceleration and inhibited by ipsilateral rotation (type IIf neurons). The remaining 25% of the population were scattered more caudally in the nucleus, and were excited by ipsilateral rotation and inhibited by contralateral rotation (type If). All showed fairly high resting discharges, averaging 50 spikes/s. Sinusoidal horizontal rotation (0.2--4.8 HZ) produced clear periodic modulation of the firing rate of fastigial neurons, which was approximately sinusoidal about the resting rate at low frequencies. As the frequency of oscillation (and the applied acceleration) increased, the sinusoidal modulation of unit firing increased in amplitude; at high stimulus frequencies the firing rate was usually driven to zero during the inhibitory part of stimulus cycle, but did not saturate in the excitatory half leading to an increase in the mean firing rate. The maximum firing rates of fastigial neurons were related to the peak acceleration by a power function. At all stimulus frequencies, the peak firing frequency of fastigial neurons lagged the input angular acceleration. Maximum firing of most units occurred just prior to the maximum velocity of the head. The gain and phase lag of the averaged unit discharge relative to head acceleration were calculated by Fourier analysis, using the fundamental as a first approximation of the response. Over a 20-fold stimulus range (0.2--4.0 HZ), mean phage lags of type IIf unit responses with respect to the applied acceleration remained relatively constant; the phase lag at 0.9 HZ measured 62 plus or minus 13 degrees. This phase lag is very similar to that recorded from vestibular nerve fibers (15), suggesting that type IIf fastigial neurons provide an excitatory signal to the ipsilateral vestibular nuclei which is in phase with direct vestibular afferent input, although functionally opposite in sign. Over the same frequency range, the gain decreased at minus- 18 dB/decade. Our data suggests that the majority of fastigial neurons work in parallel with flocculus Purkinje cells to functionally inhibit type Iv neurons in the ipsilateral vestibular nuclei.


Hemophilus influenzae type B susceptibility to 17 antibiotics. One hundred and one strains of Hemophilus influenzae type b isolated at the Children's Hospital Medical Center from blood or CSF and 18 strains known to be resistant to ampicillin of which 17 were supplied to us by others were tested for their sensitivity to 17 antibiotics. Two groups were defined according to their sensitivity to ampicillin. When 10-3 bacteria were applied, 18 strains isolated from patients with ampicillin treatment failures had a median minimum inhibitory concentrations of 3.1 mug/ml. At 10-6 bacteria the median MIC for the resistant strains increased 512-fold, whereas the sensitive strains increased two-fold. The most active antibiotics against sensitive and resistant strains were rifampin, chloramphenicol, gentamicin, rosamycin, and erythromycin with MICs ranging from 0.2-0.8 mug/ml at 10-3 bacteria and from 0.2-1.6 mug/ml at 10-6.


Childhood cirrhosis associated with alpha-1-antitrypsin deficiency. A genetic, biochemical, and morphologic study. A study of 27 relatives of a child with fatal hepatic cirrhosis due to homozygous Z variant alpha-1-antitrypsin deficiency revealed 15 members with heterozygous MZ phenotypes. Levels of circulating alpha-1-antitrypsin and trypsin-inhibiting capacity were shown to be unreliable in identifying the heterozygous state, Pi typing being necessary for definitive diagnosis. The morphologic evolution of the hepatic changes in this condition have been studied, and the importance of the PAS stain in identification of the characteristic cytoplasmic bodies is stressed.


Characterization of nucleoside transport in hymenolepidid cestodes. Three species of cestodes, Hymenolepis diminuta, H. citelli, and H. microstoma, were shown to transport nucleosides by a mediated process. In H. diminuta the Ki values of various competitive inhibitors led to the conclusion that at least 2 different loci are involved in the transport of nucleosides. One of these loci has greater specificity for the purine nucleosides, the other for pyrimidine nucleosides. No significant difference was observed in their affinity for ribo- or deoxyribonucleosides, although thymidine was slightly less effective as an inhibitor of ribonucleosides than was uridine. Transport by the pyrimidine nucleoside locus was stimulated by thymine, but not by hypoxanthine, whereas transport by the purine nucleoside locus was stimulated by hypoxanthine but not by thymine. Preloading the worms with thymine gave less stimulation of transport than did the presence of eoxgenous modulator. Efflux of previously accumulated nucleoside was not blocked by the presence of exogenous modulator. The presence of exgenous thymine enhanced the incorporation of uridine into the nonextractable pool. Thymine also stimulated uracil transport in H. citelli, but not in H. microstoma, and had no effect on uridine transport in either of these species. The results of transport and modulator studies on H. diminuta grown in hamsters were not different from the results with worms grown in rats indicating that the regulatory effects observed were an inherent function of the parasite and not the host.


Nitrogenous cations as probes of permeation channels. Nitrogenous cations may provide information-rich probes of cation-selective channels. Hence, for 52 nitrogenous cations we have used dilution potentials and biionic potentials to measure relative permeability coefficients (P's) across gallbladder epithelia of frog and rabbit, and have also determined the free-solution mobilities. Measured P's of most cations are uninfluenced by the presence of the netral form. The main permeation pathway for most hydrophilic cations is across the tight junctions. P's decrease with molecular size and increase with number of donor protons available for hydrogen-bond formation. Selectivity isotherms have been constructed from variation in P's due to pH or due to differences among individual animals. Both types of variation are consistent with the pattern expected from variation in electrostatic field strength of cation-binding sites. The isotherms permit P's to be re-expressed in a way that largely eliminates effects of species differences in field strength. Remaining species differences in P's are well fitted by a model of steric restriction, provided that one takes into account the effect of hydrogen bonding on molecular size. Rabbit gallbladder behaves as if it has narrower permeation channels than frog gallbladder. After correction for these steric effects, P is found to increase with number of donor protons nH up to four protons, with a steeper slope in rabbit than in frog gallbladder,  but is independent of nH from four to at least nine. Two groups of cations appear to permeate significantly via pathways other than tight junctions: oxycations, via polar pathways in epithelial cell membranes of rabbit but not frog gallbladder; and lipid-soluble cations, via membrane lipid. The results suggest that the cation-binding sites of gallbladder tight junction are acidic proton-acceptors that discriminate more sharply among proton donors than does water. Proton-rich solutes tend to be more permeant for two reasons: stronger binding energies to membrane proton-acceptor sites, and smaller effective size in a proton-acceptor environment. As deduced from comparisons of nitrogenous cation selectivity patterns, the permeation channel through gallbladder tight junction differs from nerve's sodium channel and artificial carriers and channels in its higher hydration and lower range of selectivity. Based on the steric analysis of nitrogenous cation permeation, one can correct alkali cation permeability coefficients for the effect of steric restriction.


Quantitative relationship between active sodium transport, expansion of endoplasmic reticulum and specialized vacuoles ("scalloped sacs") in the outermost living cell layer of the frog skin epithelium (Rana temporaria). When an isolated frog skin (Rana temporaria) is exposed to a hydrostatic pressure difference between inside and outside bathing solutions (inside pressure higher than outside) of 20-50 cm of H2O and if under these conditions the skin is short-circuited electrically, small "vacuoles" appear light-microscopically in the outermost living cell layer in the epithelium. The number of such "vacuoles" shows a linear dependency on the rate of active sodium transport as measured by the short-circuit current. Electron-microscopically, the "vacuoles" are interpreted as previously undescribed organelles, the "scalloped sacs" which are about 0.5 mu in diameter, with a wrinkled surface and bounded by a unit membrane. This organelle is in intimate contact with sacs and tubules of smooth endoplasmic reticulum. The observed increase in the number of scalloped sacs usually is accompanied by a significant expansion of the whole system of endoplasmic reticulum. Some of the "vacuoles" seen light-microscopically must indeed be expanded cisternae of endoplasmic reticulum. The findings are discussed in light of the possibility that the scalloped sacs and the endoplasmic reticulum may be involved in active transport of sodium ions.


Acute renal failure in combat injuries.

Acute renal failure in combat injuries. The mortality in 25 patients suffering from post-combat injury acute renal failure (ARF) was 64%. Abdominal injuries were present in 17 patients with a mortality rate of 64.7%. Respiratory insufficiency occurred in 14 patients, jaundice occurred in 13, and septicemia in 10. The mean period of oliguria was high, 24.1 days per survivor, and the number of hemodialyses averaged 21.6 per survivor. It is concluded that the high mortality is primary due to the severity of the underlying injury itself and not due to the renal failure, that the ARF is more severe than in civilian injuries, as evidenced by a prolonged oliguric phase, and that frequent and intensive hemodialysis regimen is necessary for the elimination of deaths from uremia per se.


Lumbosacral nerve root avulsion: report of a case and review of the literature. The 14th myelographically demonstrated case of lumbosacral nerve root avulsion is presented with a summary of the previously reported cases. In most cases lumbosacral nerve root avulsion is associated with pelvic fractures and sacroiliac dislocation, which cause a stretching force to be applied to the nerves of the lumbar and sacral plexuses, and in turn to the nerve roots intradurally. This force causes nerve root avulsion in the intradural course of the nerve root. The myelographic defect is a pseudomeningocele or diverticulum-like outpouching created by the tearing of the arachnoid covering of the nerve roots. Myelography clearly indicates nerve root avulsion and surgical exploration is not indicated.


Cell-detaching activity mediated by an enzyme(s) obtained from human leukocyte granules. Granule proteins have been isolated from human peripheral blood leukocytes and their effects on intact tissue culture cells have been determined. Three hours after the addition of the mixture of granule hydrolases, both HeLa cells and human newborn fibroblasts were detached from one another and from their growth surface, but they seemed to remain viable, since cell-bound -51Cr was retained. Further studies with HeLa cells indicated that after as long as 24 hours in the presence of these enzymes the cells remained viable as judged by several independent criteria. The enzyme activity responsible for cell detachment was subject to inhibition by various protease inhibitors. Its molecular size, as determined by gel filtration, was approximately 20,000 daltons. In addition, the naturally occurring serum inhibitor of this enzyme activity was characterized as either alpha(1)-antitrypsin or another protein with similar properties.


Risk of coronary surgery. Two hundred consecutive patients with no hospital deaths. Revascularization surgery must carry a low morbidity and mortality rate to be a valid alternative treatment of obstructive coronary disease. A consecutive series of 200 patients underwent coronary bypasses at LIJ-HMC. The average age was 53.9 years (33 to 77) with 81.5 per cent of the patients men. Clinical presentation was as follows: 28 per cent were in New York Heart Association Class III and 72 per cent in Class IV (or unstable). Previous infarctions were documented in 37 per cent. Sixteen patients (8 per cent) had disease of the main left coronary artery. Single bypasses were placed in 37.5 per cent, double in 40.5 per cent, and triple or quadruple in 22 per cent. The rate of vein graft patency was 95.3 per cent (245 of 257 studied grafts). There were no hospital deaths in this consecutive group of 200 patients. There have been two late deaths after an average follow-up period of 16 months.


Postperfusion stenosis of the common left coronary artery. Late stenosis is a rare but potentially lethal complication of coronary perfusion. In 3 patients, anginal pain appeared 2 to 6 months after aortic valve surgery. Coronary angiography was performed because of rapid evolution of symptoms. Severe stenosis of the common left coronary artery was shown in all 3 cases. Immediate aorto-coronary bypass was undertaken with good results. Graft patency was demonstrated in 2 cases, 6 and 7 months after the operations.


A comparison of membrane and bubble oxygenation as used in cardiopulmonary bypass in patients. The importance of pericardial blood as a source of hemolysis. A prospective clinical study involving more than 500 patients was designed to compare the Landé-Edwards membrane oxygenator and the Bentley bubble oxygenator. First, the importance of exposure of blood to the pericardium as the major source of hemolysis during open-heart surgery was confirmed. Because of this finding, we included in this study only those patients in whom the blood spilled into the pericardium was not returned to the pump. Under these circumstances, we found that hemolysis was relatively low in patients oxygenated with the membrane oxygenator.


Maternal deaths in Australia compared with England and Wales from 1967 to 1969. A comparison of the main causes of maternal death in Australia and in England and Wales over the same three-year period from 1967 to 1969 was undertaken, based on the trienneal reports from the two countires. In this triennium the maternal mortality rates (maternal deaths due to pregnancy and childbirth and not including associated maternal deaths) of the two countries were very similar, that of Australia being 0.23 per 1,000 and that of England and Wales being 0.21 per 1,000. These figures include death due to abortion, and both show an improvement from the previous triennium. Comparison of the figures still reveals higher death rates from haemorrhage, pulmonary embolism and preeclampsia in Australia than in England and Wales, but this is largely balanced by the higher death rate from abortion in England and Wales. In 1972 Neil and Townsend compared the first report on maternal deaths in the Commonwealth of Australia with the fifth report on maternal deaths in England and Wales, covering the triennium 1964 to 1966. The purpose of this article is to compare the reports on the triennium 1967 to 1969 (Beischer et alii, 1972); Report on Confidential Enquiries into Maternal Deaths in England and Wales, 1967-1969) and to comment on the improvements which have occurred in this triennium.


Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal-change nephrotic syndrome. To assess immunologic factors in the pathogenesis of idiopathic minimal-change nephrotic syndrome (INS), serum immunoglobulin concentrations were measured in 37 children with this syndrome and compared with those found in 36 with nephrotic syndrome secondary to chronic glomerulonephritis (CGN). Serum IgG and IgA levels were significantly reduced in nephrotic patients with either INS or CGN, IgG averaging 18.5 and 25.9 per cent of normal (P less than 0.001) and IgA 59.8 and 44.1 per cent of normal (P less than 0.01) respectively. Values increased after treatment of INS with prednisone, but mean values remained low. Serum IgM concentrations in INS averaged more than twice normal before, during, and after successful treatment with steroids. Patients with CGN did not have equivalent elevations of serum IgM. Thus, the primary defect in INS may be immunologic and could consist of deficiency in the T-cell function that mediates conversion of IgM synthesis to IgG synthesis.


T-lymphocytes and serum inhibitors of cell-mediated immunity in renal insufficiency. In acute as well as chronic renal insufficiency significant immunological abnormalities were found: diminution of delayed hypersensitivity skin reactions, lymphopenia, reduction of the absolute but not relative number of peripheral blood T-lymphocytes. Responses of lymphocytes from uremic patients to PHA, allogeneic cells, or antigens were normal when lymphocyte cultures were preformed in allologous serum from a healthy individual. Sera from uremic patients had an inhibitory or toxic effect on stimulation of normal lymphocytes. Such an in vitro inhibitory activity was found not only in the whole serum but also when certain substances retained in renal failure (methylguanidine, larger molecules, etc.) were added in the lymphocyte cultures.


[Data obtained in more than 20 years of extensive use of Salvioli's diffusing anti-tuberculosis killed vaccine in Bologna]. V.D.S. (Killed T.B. vaccine, Salvioli disperdent) has been administered intradermally to the newborn in Bologna for over 20 yr. It causes a distinct reaction, lasting several weeks, in the injection site and its associated tissues. The alllergy thus constituted is evidence of a highly effective, timely and lasting defence reaction, accompanied by a marked increase in paraspecific reactivity directed to various other sources of infection. These features have been observed and recorded over the long period in which V.D.S. has been widely employed in voluntary vaccination of the newborn in Bologna.


Vagal responses to vestibular stimulation in the cat. The effects of vestibular stimuli on the vagal efferent complex were examined in cats under chloralose anasthesia. The results showed that two functionally distinct groups of vagal efferent fibres are excited by vestibular stimuli. The neural complex involved in the delayed vestibulo-vagal response (latency of 15-22 msec) lies at the orbital surface of the cerebral cortex. The early response (latency of 3-5 msec) originates in the medulla oblongata. The reaction of some vagal units to vestibular polarization is quite similar to that of vestibular units and suggests that primary vestibular fibres reach the ipsilateral vagal efferent neurons. The present experiments give further evidence that the vestibular complex exerts a controlling influence on the cardiovascular system.


Hemophilus meningitis: comparison of H. influenzae and H. parainfluenzae. Eleven cases of Hemophilus meningitis seen in the last year are reported. Three were H. parainfluenzae and eight were H. influenzae. The number of patients is small but probably indicates that there is little difference in the clinical or laboratory data in meningitis caused by these two organisms. The children with H. parainfluenzae tended to be less anemic and had more normal admission spinal fluid sugars and proteins, but this was probably because these patients were older and had shorter prodromes. As more cases of H. parainfluenzae meningitis are noted, it seems likely that there will not be any difference in the clinical or laboratory data. Two of the three cases of H. parainfluenzae meningitis had the complication of ataxia secondary to severe bilateral vestibular deficits. Finally, it should be noted that these two organisms will not be distinguished by routine bacteriological studies, and that differentiation must be carried out by an experimental laboratory.


[Clinical study and course of 102 cases of chronic pancreatitis]. Symptomatology, signs and clinical course were studied in 102 cases of chronic pancreatics (CP), confirmed on the basis of strict criteria. Calcifications were present in 72 cases and chronic alcoholism in 81 cases. In seven patients acute pancreatitis, confirmed at surgery, appeared to have preceeded the development of CP. The only clinical difference between calcifying and non-calcifying forms was a higher incidence of steatorrhea in the first group. Cholelithiasis was present in 17 p.cent, alcoholic cirrhosis in 17 p.cent and a peptic ulcer in 24 p.cent of the whole series. Seventy two patients underwent surgery either for a complication in their course (attack of acute pancreatitis, pancreatic pseudo-cyst, cholestatic jaundice, segmental portal hypertension or antro-pyloroduodenal stenosis) or for cholelithiasis. Course assessed in 70 patients studied for more than 2 years was regressive in almost 60 p.cent of cases. There was no difference in the frequency of regression in those patients undergoing surgery and those treated medically only. In all cases, abstention from alcohol is an essential factor to a favourable result.


Thymus-derived rat lymphocyte receptor for cell surface antigens is a nonserologically defined product of the major histocompatibility gene complex. Recognition of cell surface antigens by nonsensitized thymus-derived rat lymphocytes is not affected by antisera against immunoglobulin, yet can be effectively blocked by treatment of the lymphocytes with alloantisera raised against lymphoid cells. However, allo antisera induced by nonlymphoid cells do not inhibit recognition. Adsorption of blocking antisera on immunoglobulin-Sepharose columns does not decrease their blocking activity. Absorption of blocking alloantisera with liver and kidney homogenates removes the cytotoxic alloantibodies, yet does not affect the capacity of the antisera to block recognition. Anti-H1-1 alloantisera block antigen recognition only of lymphocytes of strains that share the H1-1 locus. These results suggest that the constant part of the thymus-derived lymphocyte receptor for cell-surface antigens is a product of the rat major histocompatibility locus, which is not identical with the serologically defined antigens.


Differentiation of population of peripheral blood lymphocytes into cells bearing sheep erythrocyte receptors in vitro by human thymic extract. A small population of human marrow cells has been shown to be differentiated in vitro by thymic extract into cells bearing T-lymphocyte (thymus-derived lymphocyte) characteristics. By a similar method, the differentiation of human peripheral blood lymphocytes has been studied. A discontinuous gradient of bovine serum albumin was used to isolate lymphocytes into four layers and cells from layers I and III demonstrated the greatest potential for differentiation by human thymic extract. Appearance of T-lymphocyte characteristics was recognized by the spontaneous E-rosette technique with sheep erythrocytes. Ability of human marrow cells to be differentiated under the influence of human thymic extract was abolished by specific inhibitors of nucleic acid synthesis, however, had no inhibitory effect on the maturation of peripheral blood lymphocytes during a 2 hr incubation with human thymic extract but puromycin, an inhibitor of protein synthesis, abolished this differentiative step in cells of layer I. It is suggested from these studies that many of the cells in peripheral blood that are differentiable by thymic extract are at a stage of maturation more advanced than those in human marrow that are also differentiable by thymic extract.


Repair of ultraviolet irradiation damage to a cytoplasmic component required for neural induction in the amphibian egg. Localized ultraviolet irradiation of the amphibian egg destroys a cytoplasmic component that is required for neural induction. Destruction of that component severely diminishes the inducing capacity of the dorsal lip at gastrulation, as determined by embryological assays. Repair of the ultraviolet lesion can be achieved by replacing the dorsal lip of the irradiated embyro with a lip from an unirradiated embryo.


Presynaptic action of barbiturates in the frog spinal cord. The action of pentobarbital on primary afferents of the isolated frog spinal cord was analyzed with sucrose gap and intracellular recordings techniques. Pentobarbital in concentrations generally considered to be in the anesthetic range greatly prolonged presynaptic inhibition and also depolarized primary afferents. The depolarization was accompanied by an increase in excitability and resulted from activation of gamma-aminobutyric acid receptors, possibly by a direct action on these receptors, since the depolarization was reversibly blocked by gamma-aminobutyric acid, but not by glycine, antagonists, and magnesium ions. Furthermore, dorsal root ganglion cells exhibited a reduced sensitivity to both gamma-aminobutyric acid and pentobarbital after a "desensitizing" dose of gamma aminobutyric acid. The prolongation of presynaptic inhibition and the activation of gamma-aminobutyric acid receptors on primary afferents by pentobarbital should act to reduce the amount of transmitter released from the first synapse in sensory pathways.


Cross-reactivity between human thymus and mouse lymphoid tissues, as revealed by rabbit antiserum against human brain. Rabbit anti-human brain antisera were found cytotoxic for mouse thymus, lymph node, and spleen cells. Absorption with human thymus cells removed some of the cytotoxic antibodies. Cross-reactions were also detected among human brain and thymus and mouse brain, liver, and erythrocytes.


Transcatheter arterial embolization in the management of bleeding in the cancer patient. Selective transcatheter arterial embolization was performed in 7 cancer patients with gastrointestinal or uterine bleeding. Most were bleeding from neoplastic tissue and were refractory to conservative management. Complete and permanent cessation of bleeding was obtained in 5 patients, including 3 with gastric bleeding, 1 with colonic bleeding, and in 1 with uterine bleeding. Successful arterial embolization allowed further treatment of the underlying disease which was particularly critical as these patients were poor surgical candidates. No significant or prolonged side effects were noted.


[Value of HL-A groups in diagnosis in rheumatology]. Since 1972, several relations have been demonstrated between some HL-A antigens and some articular diseases. The W27 antigen frequency is highly increased in ankylosing spondylitis (88%) and in Reiter disease (78%) compared with controls (5%). In peripheral forms of psoriatic rheumatism, the W17 and HL-A13 antigens are more frequent (24% and 15%) than in healthy subjects (4% and 5%). In central forms of psoriatic rheumatism, there is a relation with W27 (48%) and still, we do not know if this association concerns only spondylitis or also sacro-iletis. The HL-A typing may be useful for the diagnosis of some rheumatologic diseases, when for the diagnosis of ankylosing spondylitis. The relation between W27 and ankylosing spondylitis is cleanly stronger than that between Waaler-Rose reaction and rheumatoid arthritis.


[W27 HL-A antigen. Diagnostic value in rheumatology]. The authors studied the tissue groups in a first series of patients with properly diagnosed rheumatic disorders. They found HL-A W27 antigen in 84 percent of 50 cases of primitive ankylosing spondylarthritis in adults, in 33 percent of the 50 cases of Fiessinger-Leroy-Reiter syndrome, in 20 percent of the 40 cases of psoriatic polyarthritis (50 percent of the 12 cases with radiological sacroiliac involvement) and in 66 percent of the 6 cases of spondylarthritis associated with haemorrhagic rectocolitis. In a second series of 45 patients with unclassifiable inflammatory rheumatism, only the W27 antigen tested for and it was found in 33 percent of the patients. On the basis of these observations, which were compared with those in other publications, the authors confirm the absence of a clear correlation between the pathological picture and the presence of the W27 antigen. They discuss the significance of the association between the W27 antigen and the disease, and underline the diagnostic and sometimes the prognostic value of the W27 test in rheumatology.


Rapid changes in shape and cell architecture of isolated fragments of amphibian embryonic tissues as an experimental model of morphogenesis. Changes in the shape and cell architecture of pieces of epithelial and neural ectoderm, mesoderm, neural tube, and combined ectomesodermal fragments from embryos of Rana temporaria 0-60 min after isolation were studied. The fragments were capable of changing their shape quickly (actually during separation) or after a latent period of several minutes. Rapid deformations were not prevented by cooling or by moderate doses of cyanide; as a rule they were connected with contraction of the surface area of the cells of the fragment and they can be regarded as relaxation to forms with lower mechanical energy. The direction of the deformation usually coincides with the subsequent normal morphogenesis of the particular anlage. Deformations with a latent period are suppressed by cooling and by the addition of cyanide, which lead to an increase in the surface area of individual cells, but they reduce the total surface area of the fragment. The shape of the fragments becomes more complex: they become irregularly twisted, they form folds, and they separate into spherical regions with stretched surfaces ("drops"). These processes are connected with the performance of positive mechanical work by the intracellular contractile systems. The reasons why the fragments become more complex in shape are discussed.


Behavior of sperm nuclei injected into intact ripening and ripe toad oocytes and into oocytes ripening after removal of the germinal vesicle. The behavior of frog sperm nuclei (obtained by treating a sperm suspension with pronase) in the cytoplasm of intact ripening and ripe toad oocytes and in the cytoplasm of oocytes ripening after removal of the germinal vesicle was studied. Sperm nuclei treated with pronase in the cytoplasm of intact ripe oocytes behave like the nuclei of sperm cells penetrating during normal fertilization: they increase in volume, synthesize DNA, and start to divide. They undergo no changes in the cytoplasm of oocytes ripening in the absence of karyoplasm. Transformations of sperm nuclei into pronuclei and DNA synthesis in them are found initially at the metaphase stage of the second maturation division.


Prophylactic anticoagulation in total hip replacement. In the prevention of thromboembolic complications following elective total hip operations, warfarin is a safe and effective agent which causes minimal bleeding complications, if the drug is first administered on the first postoperative day and thereafter continued in various dosages to maintain a prothrombin time between one and one and one-half and two times that of the control. Dextran also is effective in preventing thromboembolic complications but causes more bleeding problems, especially when administered intraoperatively.


Transmyocardial left-to-right shunt complicating acute inferior wall myocardial infarction after aortocoronary bypass. A 61-year-old woman suffered an inferior wall myocardial infarction on the third day following aortocoronary bypass surgery. Her condition subsequently deteriorated and she was not responsive to vigorous conventional therapy. On the twenty-first postoperative day, selective coronary arteriography revealed a patent circumflex bypass graft and an occluded right coronary artery bypass graft. Left ventricular injection showed slight dilation of the ventricle and a reduced ejection fraction. A dissection from the left ventricular cavity into the myocardium, across the septum near the apex of the left ventricle with rupture into the right ventricle, was seen functioning as a left-to-right shunt with a step-up in oxygen saturation at that level. This was corrected by operation on the twenty-ninth postoperative day and, 9 months after operation, the patient remains asymptomatic and has normal exercise tolerance.


Investigating the child with frequent infections. Children frequently present with a history of repeated infections. When these infections are serious and respond poorly to normally successful treatment programs, suspicion of a basic defect in one or more host defense mechanisms may be raised. In such cases defects in humoral or cell-mediated immunity, phagocytic cell functions or the complement system must be sought. Much of our knowledge about the development and functions of these cooperating but independent systems allows clinical observations to provide a generally accurate prediction of the nature of the defect involved. The degree of sophistication with which the systems can be evaluated and the possibilities for therapeutic manipulation are rapidly increasing. In this article are outlined the basic pathophysiological mechanisms needed to approach these increasingly recognized problems.


[Indication for coronary surgery with special reference to hemodynamic results]. An analysis is made whether and how far the aims of coronary artery bypass surgery improvement or relief of angina, improvement of the physical working capacity, improvement of the oxygen supply of ischemic myocardium, improvement of the myocardial function, improvement of longevity, can be attained. 48 percent of 87 patients had complete subsidance of angina pectoris after operation. There was a considerable improvement in 32 percent, no change in 14 percent, and a deterioration in 6 percent. After operation, the working capacity was improved in 73 percent of our patients significantly, in some cases nearly unlimited. By a comparison between loss of complaints and bypass function (open or closed) we found a good correlation between functioning bypasses and complaints. But there are some cases without complaints in spite of a closure of the bypass. Also the reverse, unchanged complaints in spite of an open bypass, was seen. A normalisation of preoperative disturbed myocardial function can be attained. Significant improvements, but also deteriorations can be found. Generally, there is a good correlation between improved myocardial function and improvement of the working capacity. Yet there is not rarely a discrepancy between a significant improvement of the working capacity and the left ventricular function. The explanation may be a loss or a postoperative augmented threshold for anging pectoris. Comparing the groups of patients with conservative and surgical treatment, the superiority of surgical treatment cannot be proved as yet. An exception seems to be the stenosis of the left main coronary artery. With this exception, prognostic considerations cannot play a role for the indication of a coronary bypass operation. Aspects for the indication of coronary surgery are untractable or disabling angina pectoris and the consideration how impending complications can be prevented.


Relation of intraoperative or early postoperative transmural myocardial infarction to patency of aortocoronary bypass grafts and to diseased ungrafted coronary arteries. Serial preoperative and postoperative electrocardiograms and vectorcardiograms were obtained in 500 patients undergoing saphenous vein aortocoronary artery bypass graft surgery. Evidence of transmural myocardial infarction was found early postoperatively in 67 patients (13 percent). Age and sex distributions, number of vessels diseased or vessels grafted, and preoperative and postoperative New York Heart Association functional classification (mean follow-up, 26 months) did not differ in the groups with and without infarction. Increased duration of cardiopulmonary bypass time (more than 120 minutes) was slightly greater in the group with infarction (P smaller than 0.05). Multivariate analysis revealed that 60 percent of patients in the group with infarction were identified by a 1st day serum glutamic oxaloacetic transaminase value greater than 100 U/liter; however, for each such patient identified, there was approximately one false positive result. Use of other values (creatine phosphokinase, cardiopulmonary bypass time and total anoxic rest time) did not improve discrimination. Twenty-five percent of all transmural infarctions occurred within the zone of myocardium supplied by a diseased ungrafted artery. In 32 patients with early evidence of transmural mycardial infarction in a zone of myocardium supplied by a grafted artery, postoperative angiography showed as many with patent as with occluded grafts. Of 154 patients in the group without infarction who had early postoperative graft angiograms, 30 (19 percent) had one graft occluded and yet no evidence of transmural infarction by our criteria. Therefore, early postoperative evidence of transmural myocardial infarction as defined in this study is an unreliable indicator of the status of the graft supplying the zone of infarction.


Aortocoronary bypass in the diabetic patient. ONe hundred twelve patients undergoing aortocoronary bypass--35 with diabetes of adult onset and 77 without diabetes--were studied to determine whether diabetic patients have additional operative risks and greater operative mortality and whether their coronary disease differs from that of nondiabetic patients. Among the diabetic patients there was a greater prevalence of preoperative unstable angina, prior myocardial infarction and class IV functional disability (New York Heart Association criteria). The major coronary arteries angiographically and at operation appeared similar in both groups. The blood flow rates measured in aortocoronary bypass vein grafts were similar in both groups, raising doubt about the presence of microvascular disease in the myocardium of the diabetic patient. Preliminary follow-up results demonstrated relief of anginal symptoms in 76 percent of diabetic and 78 percent of nondiabetic patients. The operative mortality rate of 9 percent in diabetic and 4 percent in nondiabetic patients occurred among the first 40 patients in the series; no patient in either group has died in the immediate postoperative period during the last 18 months of the study. Aortocoronary bypass should be recommended to diabetic patients with symptomatic coronary arteriosclerosis using the same criteria for operability applied to the nondiabetic population.


Surgical versus medical treatment of occlusive disease confined to the left anterior descending coronary artery. The results of saphenous vein bypass grafting and medical treatment were compared in 53 patients with stable angina pectoris, high grade occlusive disease confined to the left anterior descending coronary artery and normal or minimally impaired left ventricular function. Survival, incidence of myocardial infarction, relief of angina and response to exercise testing were evaluated. In the 29 surgically treated patients, followed up a mean of 24 months, there were two late deaths (7 percent) and five myocardial infarctions (17 percent). Twelve patients (41 percent) were free of angina and the majority had increased exercise performance when tested up to 18 months postoperatively. In the 24 medically treated patients, there were no deaths and one myocardial infarction (4 percent) in a mean follow-up period of 37 months. Six patients (25 percent) were free of angina. Less improvement in exercise performance was observed than in the surgically treated group. This subset of patients with isolated left anterior descending coronary artery disease has a favorable prognosis that is not enhanced by bypass grafting. Surgical treatment is more effective than medical treatment in relieving angina and improving exercise performance in the early years after coronary arteriography.


Cellular recognition and activation within the lymphoid system. The present study is concerned with cellular recognition and activation within the lymphoid system. Data presented indicate that in human peripheral blood phagocytes recognize and preferentially bind phagocytes, and thymus-derived (T) lymphocytes recognize and preferentially bind other T lymphocytes rather than thymus-indepedent (B) lymphocytes. Recognition of non-self results in activation of lymphoid cells; recent data using a calcium ionophore, A23 187, suggest that calcium may act as an intracellular messenger by which signals for cellular activation are transmitted from the cell surface to the nucleus.


Neonatal Haemophilus influenzae infection. Report of eight cases and review of the literature. Eight cases of neonatal Haemophilus influenzae infection occurred at Colorado General Hospital during a 3 1/2-year period. Four of the cases were due to nontypable organisms and four to type b organisms. Four were bacteremic, only two of which were type b. None of the patients had meningitis. In all instances, maternal genital tract cultures yielded H infleuzae that, when tested, was of the same serotype as the infant isolate. A survey of cervical cultures among normal and pregnant women yielded H influenzae in less than 1%. There are several possible reasons for the disparity between the apparent high incidence of neonatal infection and low prevalence of maternal carriage.


Hereditary telangiectasia manifested as gastrointestinal bleeding without external visible telangiectasia. Gastrointestinal bleeding is one of the most common problems confronting the physician. In most instances, the source of the bleeding is easily identified, e.g., peptic ulcer disease, bleeding esophageal varices or a colonic lesion. Recurrent gastrointestinal bleeding, however, represents one of the major enigmas confronting the practicing physician. The patient experiences intermittent episodes of weakness, easy fatigability and anemia with occult blood in the stool. Multiple barium radiographic examinations and often endoscopy and exploratory laparotomy are unrevealing as to the etiology of the bleeding. We have had occasion to investigate three such patients. Multiple evaluations of these individuals did not reveal the source of the bleeding until many years later--Rendu-Osler-Weber Disease (ROW). At the time of their evaluations these patients did not reveal the usual telangiectatic areas present on the skin and oral mucous membrane. The diagnosis was suggested by the presence of multiple gastric mucosal telangiectasia identified by gastroscopic examination. This report emphasizes the need for thorough endoscopic evaluation of patients with gastrointestinal bleeding and describes the gastroscopic findings that indicated hereditary telangiectasia as the probable source of bleeding from the gastrointestinal tract.


Color vision testing in young children: a review. It is often recommended that children be screened for possible color vision deficiencies as early as possible. This paper examines the validity of commercially-available color vision tests when used with young children (age three to seven years). It is concluded that with the possible exception of the anomaloscope, no test is entirely suited for children, in most cases because the test makes cognitive demands beyond the capability of the young child.


The Titmus Pediatric Color Perception Test as a color vision screener: a comparative study. The Titmus Pediatric Color Perception Test was compared to three other standard tests of color vision (Ishihara, Dvorine, Farnsworth D-15) with a population of adults. It is concluded that the results of the Titmus test are consistent with those of the other tests if certain specific scoring methods, described in the text, are used.


Prolonged bleeding times with factor IX and XI deficiency von Willebrand's syndromes. This report describes three patients with a prolonged bleeding time and reduced platelet retention on glass beads, two of the three established criteria for conventional von Willebrand's disease (vWd). However, the third standard, the diminution of factor VIII, was replaced by a decrease of factor IX or XI in the first two instances, respectively, and combined factor VII and IX deficiency was present in the last patient. These associations suggest that the vW (bleeding time/platelet retention) factor is not necessarily homogeneous, may not be dependent on a single genetic determinant, and may be present in a molecular complex composed not only of factor VIII but of other blood clotting proteins as well. Although simulating classic vW, these homologues may more appropriately be called von Willebrand syndromes. Finally, unusual as they may be, their clinical recognition is important to insure that such patients receive not only factor VIII concentrates in treatment since these materials do not contain factors IX and XI and may not even be a suitable source of platelet retention factor under these modified circumstances.


Abnormal left renal vein. No barrier to Warren shunt. The purpose of the distal splenorenal shunt is to provide decompression of gastroesophageal varices while avoiding insult to the diseased liver. However, the technical difficulty of the operation has prevented widespread application of the procedure. It is important, therefore, that the technical problems an hazards of the operation continue to undergo analysis. This report has described successful establishment of a Warren shunt in three patients with abnormalities of the left renal vein. Previous left nephrectomy or an anomaly of the left renal vein does not preclude the use of the distal splenorenal shunt in the treatment of variceal hemorrhage.


Fiberoptic endoscopy. Precise definition of upper gastrointestinal disease. When properly employed, endoscopic examination of the upper gastrointestinal tract with the flexible maneuverable-tip fiberoptic instruments is the most accurate method of diagnosing any upper gastrointestinal tract disease. Two hundred consecutive endoscopic procedures in the upper gastrointestinal tract were performed without significant morbidity or mortality; the results were reviewed to ascertain the overall diagnostic value of this modality. Although the overall numbers in each subgroup are still small, the experience indicates that: (1) thorough endoscopic examination of the upper gastrointestinal tract can be carried out expeditiously in most patients without morbidity; (2) upper gastrointestinal tract disease can be precisely defined in the majority of patients; and (3) endoscopic examination frequently alters the initial clinical diagnosis. The precise cause of upper gastrointestinal tract hemorrhage can be diagnosed in at least three of four cases. Some unnecessary operations can be avoided and proper therapy for specific sources of bleeding can be initiated promptly.


Meckel's diverticulum: should it be excised incidentally at operation? Meckel's diverticulum is the most common congenital abnormality of the small intestine, occurring in about 2 per cent of the population. Complications of a Meckel's diverticulum, including hemorrhage, inflammation, bowel obstruction, and neoplasms, occur in 15 to 33 per cent of cases and invariably demand operative treatment. When signs or symptoms arise from a Meckel's diverticulum, morbidity and mortality are high. Incidental Meckel's diverticulectomy should be performed at any age when the morbidity and mortality of the primary procedure will not be increased substantially.


Pancreatic pseudocyst with hemorrhage into the gastrointestinal tract through the duct of Wirsung. A case of massive upper gastrointestinal hemorrhage is presented in which a pancreatic pseudocyst eroded into the splenic artery resulting in intracystic hemorrhage through the duct of Wirsung. Total excision of the pseudocyst, spleen, and tail of the pancreas is recommended.


Treatment of Eales' disease with photocoagulation. 224 eyes with Eales' disease were subjected to photocoagulation. In 205 (=91%) the disease could be brought to a morphological standstill over a mean observation time of 5 years after completion of treatment. Visual acuity remained unchanged or improved in 185 eyes (=87%). Postcoagulative macular puckering occured in 6 eyes (=3%).


Ultrastructural changes of the capillaries of the cat iris in experimental neuroparalytic keratitis. In order to study the morphological basis of the increased permeability of the capillaries of the iris in neuroparalytic keratitis the ophthalmic division of the trigeminal nerve in the cat was denervated using a stereotactic method. The homolateral iris was studied by electron microscopy three days after denervation. Abnormally large pinocytotic vacuoles were observed in the endothelial cells of the iris capillaries and the intercellular junctions of the endothelial cells showed widened inter-cellular space and macula occludens. These ultrastructural changes may explain the protein leakage into the anterior chamber in neuroparalytic keratitis.


[Objective determination of accommodation in eyes with permanent central scotoma due to amblyopia (author's transl)]. Objective determination of accommodation in 38 children with permanent central scotoma due to amblyopia on one side (with central and eccentric fixation) revealed: 1. The physiological adaptation of refraction for far and near distances did not serve its purpose. 2. There was either no or an irregular response on hyperopia, which was produced by placing concave lenses in front of the eye while fixing a far object, or on myopia produced by placing convex lenses in front of the eye while fixing a near object. 3. On hindering clear vision which could not be compensated by accommodation there was contrary to normal eyes no reactive change of refraction at all or only a poor one. The accommodation behavior in eyes with permanent central scotoma due to amblyopia does not differ from that in eyes with permanent central scotoma due to organic lesions when using the same test methods.


The influence of moistening fluids on the measuring results of applanations-tonometry (author's transl). The applanation tonometry is influenced by several factors not considered by the law of Imbert-Fick. For instance, a change in the conditions of moistening the cornea may falsify the result of measuring. This has been proved clinically and experimentally with Polyvinylpyrrolidon. The fault in measuring is larger with applanation tonometers producing variable applanation areas along with constant pressure than with those flattening small invariable corneal area. Aside of the difficulty of exact measurement of the applanation areas the latter tonometers are superior to the former ones because of this reason, too.


[The influence of the eye prominence on the EOG potential level (author's transl)]. The influence of globe prominence on the electro-oculogram potential level was measured in patients with unilateral protrusio bulbi, myopia or hyperopia. The EOG potential level on the side with the more prominent globe was lower if the prominence was due to protrusion. If the prominence was due to myopia, the EOG potential was higher compared to the contralateral non-myopic eye. In hyperopic eyes the potential level was lower.


Fluorescein in the human optic disc,.

Fluorescein in the human optic disc,. 1. Compressing the globe to intraocular pressure values even higher than the systolic ophthalmica pressure does not totally empty the capillaries of the disc. 2. Almost only the plasma layer at the wall of the retinal and papillary vessels is the source of vessel fluorescence seen after intravenous fluorescein injection. Therefore small vessels fluoresce almost as much as big ones and extravasates appear as very brilliant patches. 3. Fluorescein diffuses into the disc tissue mostly from the surrounding tissues (uvea, ev. sclera). 4. The blood circulation in the disc diminishes more than that of the retinal vessels if the eye is compressed, 5. Fluorescein is not especially appropriate for the measurement of the circulation in the disc.


Retinal pigment epithelial degeneration, partial retinal atrophy and macular hole in acute lymphocytic leukemia. A seven year old child with acute lymphocytic leukemia presented at autopsy with a macular hole, and degeneration of the retinal pigment epithelium and its overlying photoreceptors. She had been treated with cobalt 60, methotrexate, vincristine cyclophosphamide and prednisone. A review of the literature of similar findings as well as pigment epithelial degenerations from other causes is presented.


The significance of tears' lactate dehydrogenase in health, and external eye diseases. The normal values of the lactate dehydrogenase contents of tears in the presence of pyruvate and lactate as substrates were determined. The quotients of the LDH values measured in the presence of the two different substrates, and also the ratio of the subunits (H and M) of the isoenzymes, differ from the corresponding data of blood serum. In the event of external inflammatory diseases of the eye, LDHp/LDHl decreases in the tears; this deviation is enhanced by treatment with drugs inhibiting protein synthesis, primarily iododeoxyuridine. Conversely, in trachoma the ratio of the LDH isoenzymes containing mainly M (muscle) subunits are increasing. In diabetes mellitus the shift of metabolism toward the citrate cycle is reflected to a larger extent by the LDH values in the blood serum than by those in tears.


[The influence of riboflavin on vitreous homogenate (author's transl)]. Sunlight causes a decrease of viscosity of a mixture of riboflavin and ox vitreous homogenate while without riboflavin no reaction can be observed. The mechanism of this reaction is not yet clarified. It is possible that the reaction is closely related with the degradation of the viscosity of a hyaluronic acid solution by ascorbic acid cause of the production of H2O2 in both reactions. As an other mechanism the transfer of light energy on hyaluronic acid by riboflavin can be assumed.


[The diagnosis of pseudotumours of the macula by means of ultrasonography (author's transl)]. The echograms of 35 patients affected with pseudotumours of the macula were analysed in detail. Pseudotumours and malignant melanomas can be distinguished by means of ultrasound with high probability if the minimal prominence of the tumour is not lower than 1.1 mm, and with certainty if the minimal prominence is not less than 1.5 mm. The echogram of pseudotumours is mainly characterized by its extraordinary irregularity.


Protease inhibitors in chronic obstructive pulmonary disease. Quantification of the major plasma protease inhibitors and genetic typing of alpha1-antirypsin were done in 107 patients with chronic obstructive pulmonary disease and in 91 control subjects with normal ventilatory function who were similar with respect to age, race, and sex. There was a significant increase in frequency of the PiZ gene and the Pi MZ phenotype of alpha1-antitrypsin among the patients when compared with the control subjects. No evidence for a primary deficiency of any other antiprotease was found; however, the mean concentration of inter-alpha-trypsin inhibitor was significantly lower in the patients than the control subjects, and moderate deficiency of alpha1-antichymotrypsin was noted in a few patients. These data indicate an increased risk of developing chronic obstructive pulmonary disease in persons with the Pi MZ phenotype of alpha1-antirypsin and suggest a possible relationship between these diseases and low serum concentrations of inter-alpha-trypsin inhibitor.


Gastrointestinal bleeding: treatment with intra-arterial vasopressin. Seventeen patients with upper and lower gastrointestinal hemorrhage were treated with selective intra-arterial continuous vasopressin infusion. 62.5 per cent of variceal and 60 per cent of nonvariceal episodes of hemorrhages were permanently controlled by vasopressin. The initial total success rate was 76.5 per cent. No major complications occurred. Early success with this technique has encouraged its continued use under a controlled setting for indications for its use to be evaluated.


The role of the thymus in spontaneous autoimmune thyroiditis. In two models of genetically determined, spontaneous autoimmune thyroiditis, neonatal thymectomy increases the incidience and severity of disease. The simpliest explanation is that the thymus, or thymus-derived cells, normally exert a suppressive effect on the autoimmune response to thyroglobulin in addition to the helper function that is necessary to initiate the autoimmune reaction.


The mitogenic activity of polyadenylic-polyuridyclic acid complexes. Polyadenylic-polyuridylic acid complexes (poly A:U) at the 1-5 mu g level, were mitogenic for spleen cells when given intravenously to normal Balb or cortisone-treated mice. Similarly, mitogenicity was evident when poly A:U was added to tissue culture fluids containing spleen cells from normal or cortisone-treated mice, or bone marrow cells from normal mice. Under these conditions, this adjuvant was not mitogenic for thymus cells or mesenteric lymph node cells, either in vivo or in vitro.


Effect of fistulae on endolymphatic hydrops. An experiment was performed on 31 guinea pigs to study the effect of fistulae of the horizontal canal, superior canal, common crus, and utricle on the course of experimentally induced endolymphatic hydrops. The effect of fistulae on corresponding parts of normal ears was also studied in an additional 17 animals. The results indicated a remarkable consistency of healing of the fistulae in both groups of animals. Fistulae had no significant effect on the course of endolymphatic hydrops, irrespective of whether the fistulae were made immediately before or several months after obliteration of the endolymphatic duct or whether a polyethylene strut was introduced into the membranous labyrinth. Once again, the functional significance of the endolymphatic sac was clearly apparent, for ablation of the sac consistently produced severe hydrops and atrophic changes in sensory and neural structures. Assuming that the mechanisms of labyrinth repair in the guinea pig are comparable to the higher mammalian ear, it is apparent that procedures designed to surgically fistulize the membranous labyrinth are of questionable value and are probably not rational therapeutic approaches to the management of Ménière's disease.


Osteogenesis imperfecta congenita and tarda: a temporal bone report. The temporal bone report of an operated case of osteogenesis imperfecta tarda is presented. Histological examination confirmed the presence of bilateral fixation of the footplate by otosclerosis as the cause of the conductive hearing loss. Fragility of bony septae in the mastoid and of the stapedial crura were observed. Sensorineural impairment in later years with a reduction in neural elements in the cochlea appear related to the extent and activity of the otosclerotic foci. Additional temporal bone reports of three cases of osteogenesis imperfecta congenita show lack of deposition of the skein-like bone in the endochondral layer, sparse bony septae in marrow spaces and deficiency of the perosteal layer. The stapedial crura were thin and in two cases both were deformed and fractured.


Diagnosis of an enteric duplication with pertechnetate 99mTc scanning. A case of enteric duplication is reported in which preoperative pertechnetate (99m)Tc scanning demonstrated localized uptake in the region of the anatomic abnormality. This test is recommended for use in the evaluation of lower gastrointestinal bleeding in infants and children.


Electronystagmographic findings in central nervous system disease. A helpful central sign on electronystagmography with eyes closed is hyper-excitability on a caloric test. Another sign is consistent nystagmus in the presence of normal calorics. With eyes open, calibration overshoot, gaze nystagmus, pendulum tracking, failure of tracking a pendulum were by far the most common central abnormality in the experience of the author.


Localization of tissue plasminogen activator in relation to morphologic changes in human saphenous veins used as coronary artery bypass autografts. Employing the histochemical fibrin slide technique, we studied the localization of fibrinolytically active sites in relation to morphologic changes in saphenous veins used as coronary artery bypass autografts. Of veins from 100 patients undergoing surgery for coronary heart disease, 63 samples revealed well-demarcated intimal fibrinolytic activity. Distinct foci of lysis were present in the media and adventitia of all vein samples corresponding to the distribution of the vasa vasorum. Graft specimens obtained by autopsy from 13 patients surviving from 30 minutes to 13 days revealed considerable intimal damage with loss of fibrinolytic activity. Medial fibrinolytic activity disappeared early concomitant with disorganization of the medial muscle fibers, followed by necrosis, atrophy and fibrous transformation of the muscular structures. Adventitial activity disappeared later. One reoperation sample obtained after 8 weeks in situ showed moderate proliferative intimal fibrosis without an apparent neo-intima and without fibrinolytic activity, and one section showed evidence of valve cusp fibrosis, while most of the media had been replaced by fibrous tissue. Numerous foci of "medial" -adventitial fibrinolytic activity indicated presence of vascular structures in the venous wall. The fibrin slide technique is a convenient tool for studying the process of revascularization.


Current management of upper gastrointestinal bleeding. Over a four-year period, 585 patients were hospitalized for massive upper gastrointestinal bleeding. Endoscopy diagnosed the cause of bleeding in 80% of 200 patients so studied. Selective angiography localized the bleeding site in 12 of 20 patients, and infusion of vasopressor stopped hemorrhage in six. Barium studies was 90% accurate in diagnosing ulcer disease but failed to detect gastritis. One hundred thirty (22%) patients were operated upon for medically uncontrolled bleeding. The proportion of patients requiring surgery fell from 33% in year one to 13% in year four. Benign ulcer disease caused bleeding in 51% of surgical patients, while gastritis was found in 20%, esophageal varices in 15% and stress ulcer in 8%. Overall operative mortality was 29%. Among 38 duodenal ulcer patients, mortality was 18%. Vagotomy and pyloroplasty were more effective than resection in this group. Resection for distal gastric ulcers in 22 patients resulted in a mortality of 14% and no rebleeding. While V&P controlled bleeding in 12 alcoholics with gastritis, five (42%) died postoperatively. Mortality among 20 patients with esophageal varices was 35%, although all five survived who had porto-caval shunts. Eight of 10 patients operated upon for stress ulcer bleeding died. Postoperative rebleeding occurred in 14 patients, eight of whom were again operated upon. In all but one a new lesion was found to be responsible for hemorrhage. Increasing use of gastroscopy and selective angiography can be expected to improve diagnostic capabilities in patients with upper gastrointestinal bleeding. Infusing vasopressor into selected arteries should reduce the need for surgical control of gastritis, variceal and stress ulcer bleeding, conditions poorly managed by current operative techniques.


Giant horseshoe intra-abdominal abscess. A study of 12 patients with giant horseshoe abscess of the abdominal and pelvic cavities seen at the Surgical Services of the University of Cincinnati Medical Center has emphasized the complexity and bizarre nature of these lesions. These infections represented a huge abscess or series of communicating abscesses extending from one subphrenic space along the corresponding paracolic gutter into the pelvis, up and along the opposite paracolic space, and into the other subphrenic space. Since these lesions occurred infrequently, they were often not recognized until they had become far advanced and had produced profound effects on the patients. The diagnosis was difficult and obscured by various factors including the postoperative state after laparotomy for complex diseases or serious injuries of the biliary tract, the genitourinary tract, or the alimentary tract. An important etiologic component of the formation of these giant abscesses was the continuing escape and collection of large volumes of fluid resulting from lesions of the biliary tract, postoperative hemorrhage, or an unrecognized large perforated peptic ulcer. Nine patients were treated successfully and 3 died. The many diagnostic and therapeutic problems presented by the patients with this interesting and complex lesion have emphasized the importance of earlier and more accurate diagnosis, early and adequate surgical drainage, intelligently applied antibiotic therapy and appropriate supportive treatment. Failure to recognize and drain effectively each of the component sections of this lesion led to continuing sepsis with prolonged morbidity, progressive debility, and death.


Membrane vs bubble oxygenator: clinical comparison. Numerous studies have demonstrated the superiority of membrane oxygenators (MO) over the bubble oxygenators (BO) when used for prolonged cardiopulmonary support. However, there is little information available evaluating the MO for routine, short-term cardiopulmonary bypass. In this study the 5MO314 Modulung-Teflo (MO) was compared to 5M30314 Miniprime Variflo (BO). The data of 91 patients (46 MO and 45 BO) were analyzed according to the duration of cardiopulmonary bypass (Group I less than 60 min., Group II 60-90 min. and Group III greater than 90 min.). Hemodynamic parameters, fluid and blood balance, as well as hematologic and blood gas studies were used for comparing the two oxygentors. The hemodynamic parameters were better, and the arterial blood gases were more physilogic with the MO. The postoperative blood loss was significantly less when using the MO. The other measurements documented the stability of the MO. All statements were based on statistical analysis with a DEC PDP-9 computer, using the MIIS language and operating system. Consequently, we are now using this MO for routine cardiopulmonary bypass.


The surgical treatment of unstable angina pectoris. Since the advent of saphenous vein bypass grafting as successful means of myocardial revascularization, a variety of coronary artery disease syndrome have come under surgical attack. The proper role of surgery in many of these coronary syndromes remains ill-defined. However, clear indications for surgical revascularization exist in patients with unstable angina pectoris, i.e., progressive angina and onset of rest pain and noctural angina in spite of adequate medical therapy. An analysis has been made of 100 consecutive patients with unstable angina pectoris who underwent myocardial revascularization over the past 2 years at the Woodruff Medical Center of Emory University. Included in this group are the following subgroups: 1) Emergency cases with pre-infarction angina (including Printzmetal angina); 2) Cases of combined valvular heart disease and coronary artery disease; and 3) Advanced coronary artery disease with certain complications of previous myocardial infarction. A discussion of the relative merits of saphenous vein grafts and internal mammary artery anastomoses is presented and indicates that the technique selected should be determined by the quality of the distal native coronary circulation. Surgical mortality and morbidity figures, patency rates of saphenous vein grafts and internal mammary artery anastomoses visualized postoperatively, and the number of patients wiht dramatic relief of angina pectoris in this series support current enthusiasms for available surgical techniques for myocardial revascularization.


Conventional splenorenal shunts. A reconsideration. From 1961 to 1971, 73 central splenorenal and 66 portacaval shunts were done for cirrhotic patients who had bled from esophageal varices. Comparative analysis revealed low (3% and 2%, respectively) operative mortality for elective operations, equal (93%) effectiveness in control of variceal bleeding, but substantial diferences in the incidence of postshunt encephalopathy. For patients who had mimal hepatic dysfunction before operation, disabling disorders in mentation developed in 5% of patients who had splenorenal shunts, in contrast to 50% of patients who had portacaval shunts. Survival rates after the two shunts were nearly identical. Thus, the advantages of splenorenal shunts concern the quality of life but not the length of survival. These observations are considered in relation to available therapeutic alternatives.


Occult gastrointestinal bleeding. An evaluation of available diagnostic methods. Occult gastrointestinal bleeding was defined as continued bleeding in spite of a normal series of roentgenorgrams of the upper part of the gastrointestinal tract, barium enema, and sigmoidoscopy. Twenty-six such patients were treated. A thorough systematic evaluation, including gastroscopy, colonoscopy, visceral angiography, and isotopic scanning, was done preoperatively. Using colonoscopy and arteriography, nearly 60% of the bleeding sites were identified. Seventy-six percent of the lesions identified were in the terminal part of the ileum or the ascending colon. Exploratory laparotomy should be performed for life-threatening hemorrhage or as a diagnostic test only after a thorough preoperative evaluation. If results of a complete preoperative evaluation including arteriography were normal, then the likelihood of finding a discrete cause of bleeding at laparotomy was high (80%). A systematic evaluation and diligence of both physcian and patient in localizing the site of bleeding are essential.