Serum colony-stimulating and colony-inhibitory activity in response to neutropenia. Since sera from most species contain both colony-stimulating and column-inhibitory factors, the net CSA results from a balance between these opposing substances. Studies were performed to determine whether the increased CSA noted during neutropenia or endotoxemia is due to an increase in CSF or to a decline in serum inhibitors. Rats were treated with cyclophosphamide, total body irradiation, or endotoxin and bled during the peak CSA response. By separation studies using Sephadex G150, it was shown that serum levels of high-molecular-weight inhibitors were unchanged from control values. Minimal CSA was detected in normal serum fractions; increased activity was found in fractions from neutropenic animals. During a postcyclophosphamide rebound neutrophilia, serum CSA was undetectable; inhibitor levels were similar to those measured in untreated controls. These observations show that the increased serum CSA seen with neutropenia is due to a true increase in CSF and not to a decline in circulating inhibitors.


Intracranial lipoma. Report of a case and differentiation from other tumours of the cerebellopontine angle. Teratomata of the cerebellopontine angle are rare. A case of a lipoma of this localization occurring in a 50-year-old man with an interesting case history is reported. The differential diagnosis of tumours of the internal auditory meatus and the surrounding structures is discussed. In cases with an uncharacteristic clinical history suggesting involment of the VIIIth cranial nerve, it is important to focus attention on the existence of rare lesions of the internal acoustic porus. The diagnosis can only be established with operation and biopsy.


Estradiol-17 beta interference with meiotic maturation in Rana pipiens ovarian follicles: evidence for inhibition of 3 beta-hydroxysteroid dehydrogenase. Increasing doses of estradiol-17 beta added to in vitro incubations inhibited pregnenolone-induced germinal vesicle breakdown in Rana pipiens ovarian follicles. The inhibition was reversed with increasing concentrations or pregnenolone added to the medium. Because no evidence of estradiol-17 beta inhibition or interaction with progesterone-induced GVBD was observed, the effect of estradiol-17 beta on the conversion of 3H-pregnenolone to 3H-progesterone was investigated. Estradiol-17 beta in doses as low as 10(-7) M significantly inhibited the conversion of 3H-pregnenolone to 3H-progesterone in follicles incubated in vitro. It is suggested that estradiol-17 beta is a feedback inhibitor of 3 beta-hydroxysteroid dehydrogenase-isomerase, the enzyme complex that converts pregnenolone to progesterone, a necessary step in the initiation of GVBD.


The proteins of hepatitis B Dane particle cores. Although several studies have been done to analyze the peptides of purified 22-nm HbsAg particles, no information has been published about the peptides of the core of the Dane particle which bears the other hepatitis B viral antigen. HbcAg. Dane particles and Dane particle cores (produced by NP-40 treatment of Dane particles) were purified by equilibrium centrifugation in CsCl density gradients. Two populations of Dane particles were observed at densities 1.27 and 1.24 g/ml, respectively. The higher buoyant density Dane particles yielded exclusively cores of buoyant density 1.38 g/ml in CsCl, and the lower buoyant density Dane particles yielded two kinds of cores with buoyant densities of 1.38 and 1.325 g/ml, respectively. Only the higher density Dane particles and cores manifested endogenously primed DNA polymerase activity. The peptides of density 1.38 g/ml Dane particle cores purified by equilibrium CsCl density gradient centrifugation and HBcAg particles from HBV infected chimpanzee liver purified in the same way were analyzed by SDS-polyacrylamide gel electrophoresis. Both kinds of particles were found to consistently contain 3 Coomassie blue staining peptides with approximate molecular weights of 19,000, 70,000 and 80,000 daltons (designated P-19, P-70 and P-80 respectively). In addition, the HBcAg particles from infected liver regularly yielded a protein component with molecular weight greater than 200,000 daltons. This component was occasionally present in electrophoresis runs of core peptides from only one of two patients. Its irregular appearance after gel electrophoresis suggests it may have been an aggregate not completely dissociated under the conditions used. The lower density core component consistently contained P-19, P-70, and P-80, and infrequently additional minor peptides of uncertain origin. The irregular occurrence of the minor peptides in varying amounts suggests they were not intrinsic core proteins.


Cerebellar stimulation in man. Quantitative changes in spasticity. The effects of chronic anterior lobe cerebellar stimulation on patients with cerebral palsy have been investigated using a new method of quanitfying muscle rigidity and stretch reflexes. The ankle is oscillated sinusoidally, compliance is measured at several frequencies, and electromyographic activity of the extensor and flexor muscles is recorded. In some patients stimulation can reduce rigidity and coactivation of muscles immediately or slowly over days or months. In others no change is found.


Holoprosencephaly in neurosurgical practice. The clinical, angiographic, and pneumoencephalographic features of seven cases with holoprosencephaly are reported. Three of the alobar type in this series revealed  the facial dysmorphia characteristic of the anomaly. In the other four cases (one alobar, one semilobar, and two lobar), such facial anomaly was absent, and the diagnosis was achieved only after contrast studies. An azygous anterior cerebral artery running over the cerebral surface due to a defective interhemispheric fissure is pathognomonic for alobar and semilobar holoprosencephaly. Dysgenesis of the deep venous system was found in alobar, semilobar, and lobar holoprosencephaly, a finding helpful in diagnosis, especially of the lobar type. Air study and computerized tomography scan revealed incomplete separation of the ventricular system. The basic nature of holoprosencephalization and its differentiation from non-holoprosencephalic malformation are discussed. Six of the seven patients reported had hydrocephalus.


Diagnosis of exocrine pancreatic insufficiency in cystic fibrosis by the synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid. The synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid is specifically cleaved by chymotrypsin to Bz-Ty and PABA. The liberated PABA is absorbed and excreted in the urine. Accordingly, PABA recovery reflects intraluminal chymotrypsin activity and is an index of exocrine pancreatic function. This test was evaluated in 24 patients with cystic fibrosis to determine its role in the diagnosis of exocrine pancreatic insufficiency. Cumulative percent PABA recovery in six hours was significantly lower in CF patients compared with the control group. No overlap was noted between the two groups. There was good correlation between PABA recovery, fecal chymotrypsin activity, and coefficient of fat absorption. These findings indicate that PABA recovery is significantly reduced in patients with CF and steatorrhea and may prove a practical and reliable test of pancreatic insufficiency.


Pharmacological studies on N-demethylated carbachol. In attempts to find a drug more active than pilocarpine, the tertiary nitrogen derivative of carbachol, N-demethylated carbachol, was synthetized and tested on several autonomic nervous system preparations. N-Demethylated carbachol was active at muscarinic and nicotinic sites in vivo and in vitro. In superfusion studies, N-demethylated carbachol contracted the smooth muscle of the guinea pig ileum as well as skeletal muscles of frog recus abdominis and chick biventer cervicis. N-Demethylated carbachol decreased blood pressure in the rat, with an ED50 ("/- SEM) of 4.82 +/- 0.78 mg/kg. After close arterial injection to the cat superior cervical ganglion, N-demethylated carbachol elicited contractions of the nictitating membrane (ED50 of 1.68 +/- 0.24 mg/kg) that were not significantly affected by atropine. N-D-methylated carbachol stimulated salivation in dog Wharton duct preparations with an ED50 of 2.55 +/- 0.81 mg/kg. In contrast, pilocarpine had no effects on skeletal muscles in vitro, produced ganglionic effects blocked by atropine, had a prominent effect on salivation, and tended to elevate blood pressure.


[Massive digestive hemorrhage caused by arterial malformation of the jejunum. Diagnostic value of emergency arteriography]. A case of massive digestive bleeding due to an arterial abnormality of the jejunal wall is reported. Its interest is twofold: a) After a complete endoscopic and operative examination of the GI tract proved negative, an emergency superior mesenteric angiography was the only investigation which allowed to recognize the site and mechanism of the bleeding; b) from a nosologic point of view, the clinico-pathological picture was entirely similar to that of "Dieulafoy's erosion", a syndrome which has been only described, up to now, in the gastric mucosa.


Modification of oestrogen-induced uterine hyperaemia by drugs in the ovariectomized rat. Uterine blood flow in ovariectomized rats was measured by means of radioactive microspheres. Blood flow was increased from 55 ml min-1 100 g-1 by treatment (i.v.) with 0.5 microgram oestradiol kg-1 and reached 680 ml min-1 100 g-1 within 60 min. This oestrogen-induced increase of blood flow was reduced significantly by pretreatment with mepyramine (a histamine H1-receptor antagonist), cellulose sulphate (a kininogen-depleting agent) and aprotinin (a kininogenase inhibitor). Cimetidine (a histamine H2-receptor antagonist), kallikrein (kininogenase enzyme) and atropine (an anticholinergic drug) had no effect on the increased uterine blood flow. Indomethacin and AH 7170, which inhibit the formation of prostaglandins, also caused a lower increase in uterine blood flow. None of the pretreatments fully inhibited the oestrogen-induced increase in blood flow, suggesting that more than one mediator may be involved.


Suppression of C3 rosette formation by serum from patients with systemic lupus erythematosus. A corollary of disease activity. Many sera from patients with systemic lupus erythematosus (SLE) inhibit C3 rosette formation of normal human lymphocytes. Fractionation of SLE sera by Sephadex G-200 gel chromatography showed that the inhibition was present in low molecular weight serum fractions. A correlation was noted between inhibition of C3 rosette formation and disease activity. Inhibition of C3 rosette formation may be helpful and simple way to monitor clinical activity and complement activation in patients with SLE.


Education in rheumatology for the primary care physician. An international workshop considered rheumatological education of the primary care physician. All medical students need exposure to rheumatology. Emphasis should be on the musculoskeletal component and on the better defined diseases. During the postdoctoral years, principles of total health care need to be taught by well trained rheumatologists in tertiary care rheumatic disease units with comprehensive ambulatory care facilities. Continuing education of the generalist needs to be relevant to his professional competence. He needs to acquire and update the knowledge to manage common rheumatic diseases and to learn when to ask for help. General educational objectives are applicable to the field of rheumatology: cognitive skills bring knowledge of the scientific basis and clinical facts; motor skills--the ability to examine competently patients with rheumatic diseases; affective skills--the understanding of and capacity to deal with chronic illness.


Suboccipital surgical approach to the cerebellopontine angle and internal auditory canal. The suboccipital craniectomy done with the patient in the prone position using modern microsurgical methods gives good anatomical exposure essential for efficient, accurate, total removal of cerebellopontine angle neoplasms and allows adjacent, uninvolved neurological structures to be spared. Modifying the anatomical exposure by varying the size and shape of the osseous craniectomy and placing the dural incision closer to the porus acousticus permits extradural retraction of the cerebellum. Thus large cerebellopontine angle neoplasms can be excised with less chance of damage to the cerebellum and smaller risk of hydrocephalus. The suboccipital craniectomy may be extended anteriorly to the facial nerve, thereby combining the suboccipital with the translabyrinthine approach, and providing a more direct angle to a large neoplasm involving the brain stem and cerebellum.


Linkage relations of a locus for congenital total nuclear cataract. A family with an autosomal dominant form of congenital cataract, total nuclear cataract, was examined for genetic linkage between the cataract locus and 30 marker loci. Close linkage was excluded for all of the 21 informative loci. There was no significant evidence for linkage of the cataract locus with any of the marker loci.


Effect of BCG on alloimmune cell-mediated cytotoxicity in (C57BL/6Jfemale x A/Jmale)F1 mice. I. Effect of different BCG treatments on cytotoxicity mediated by T-cells and macrophages. The effect of BCG on the development of cell-mediated cytotoxicity (CMC) in the spleens of allogeneic tumor-bearing female (C57BL/6Jfemale x A/Jmale)F1 mice was studied. BCG-treated tumor-bearing animals elicited a stronger CMC response than did the untreated tumor-bearing animals. Furthermore, the degree of activation was dependent on the time, route of injection, and dose of BCG. Therefore, if the BCG was administered at suboptimal conditions, a less marked stimulation of the CMC resulted. A combination of a high BCG dose given iv 12 days before implant of P815 tumor cells and a low, second dose given at the time of implant produced the most marked activation of the CMC response. By the use of in vitro technique, the specific CMC was mediated mostly by T-cells, with macrophages making a less significant contribution.


Effect of BCG on alloimmune cell-mediated cytotoxicity in (C57BL/6Jfemale x A/Jmale)F1 mice. II. Correlation with BCG activity in syngeneic tumor systems. The effectiveness of selected BCG regimens to produce an activation of cell-mediated cytotoxicity (CMC) in an allogeneic tumor system was compared with its ability to cause tumor regression in syngeneic tumor systems. In the tumor system selected in both inbred LEW rats and inbred C57BL/6J and (C57BL/6Jfemale x A/Jmale)F1 mice, a correlation was observed in that BCG treatments that caused marked CMC activation in the allogeneic tumor systems also effectively caused tumor regression and increased animal survival in syngeneic systems. It was concluded that the allogeneic CMC reaction can be used to predict the capacity of BCG to cause tumor rejection.


Expression of human T-lymphocyte antigens by natural killer cells. Rabbit antisera against human T-lymphocyte and B-lymphocyte antigens (anti-HTLA and anti-HBLA, respectively) were used to characterize natural killer (NK) cells mediating spontaneous cell-mediated cytotoxicity for myelogenous leukemia cell line K562 as measured in a 51Cr-release assay. NK activity of lymphocyte suspensions was abrogated by incubation of the suspensions in anti-HTLA plus complement but not by incubation in anti-HBLA plus complement. The effect of anti-HTLA was due to removal of NK cells rather than antigen-antibody complex inhibition of NK cells inasmuch as lytic complement was necessary. The results indicated that NK cells were HTLA+-HBLA- and thus supported the concept that NK cells are T-cells.


Aortic rupture into the esophagus during angiography. A 67-year-old woman was examined and found to have symptoms and chest roentgenogram suggesting acute aortic dissection. During emergency angiography, massive upper gastrointestinal bleeding developed, and the woman died. The angiogram showed a raised intimal flap of acute dissecting aneurysm. Postmortem examination showed extensive cystic medial necrosis, aortic dilation, and an unusual combination of anatomic abnormalities, which explained the previously unreported false-positive intimal flap. The site of aortic rupture was not localized, but a large tear was found in the esophagus.


[Local prophylactic measures to prevent postoperative infection after cataract operations (author's transl)]. The Allen procedure to prevent postoperative endophthalmitis has been applied in cataract operations since 1973. Postoperative endophthalmitis has been observed through the years 1965--1973 in 0.49% of registered cases, while the infection rate has now been lowered to 0.067%.


Lens structural disorders in the leopard frog (Rana pipiens) supplied to the laboratory from wild populations. Examination of lenses of 48 leopard frogs, Rana pipiens, from three commercial suppliers disclosed a high incidence of histologic aberrations. Only four of 17 lenses that appeared totally clear under the dissecting microscope were found to be free of discernible abnormalities on histologic examination. Deviations were most common in the area of elongation. Because of these findings, the applicability of frog lenses for cellular investigations was questioned.


Effect of surgery on granulocyte/macrophage colony-stimulating factor. Eighteen surgical patients were studied to determine the effect of anesthesia (general or spinal) and surgery on serum and urinary colony-stimulating factor(s) (CSF). CSF is a leukopoietin that stimulates proliferation of macrophages and granulocytes from bone marrow precursor cells. CSF was assayed by adding aliquots of serum or urine to semisolid agar cultures of bone marrow cells and scoring the number of colonies developing after 7 days of incubation. In all but 1 case, a 3- to 30-fold increase in the 24 hour excretion of urinary CSF was seen on the day of surgery and the first postoperative day. CSF urinary excretion began declining toward normal by the second postoperative day. A parallel increase in granulocyte count, a delayed rise in monocytes, and a decline in absolute lymphocyte counts were also observed. The data suggest that immediately postoperatively there may be a strong stimulus to granulocyte/macrophage proliferation. More rapidly proliferating cells would be anticipated to have increased vulnerability to toxicity from cell cycle-active chemotherapeutic agents.


Concomitant coronary artery bypass and major noncardiac surgery. Concomitant cardiac procedures performed in conjunction with coronary bypass have become commonplace, but not concomitant noncardiac procedures. Bernhard and associates were the first to report concomitant coronary bypass and carotid endarterectomy. This series, begun in 1971, consists of 71 noncardiac procedures performed concomitantly with coronary bypass on 68 patients. Thirty-seven procedures were performed for associated vascular disease, including carotid endarterectomy (25 patients) and resection of abdominal aortic aneurysm (three patients). Other concomitant problems included are thymoma, bronchogenic carcinoma, and hiatal hernia. The operative mortality rate of 2.9 percent compares very favorably with that of 1.7 percent in our group of patients having isolated coronary artery bypass. A plea is made for consideration of concomitant surgery in patients with operable coronary heart disease who have an additional serious noncardiac surgical disease.


[Immunological reactivity and the prognosis for allergic complications in the crew of the 2d Saliut-4 expedition]. Immunological reactivity of P. I. Klimuk and V. I. Sevastyanov was studied before and after their 63-day flight aboard the orbital station Salyut-4. The study used the methods to assay reactivity of T- and B-lymphocytes (PHA-blast-transformation, nonspecific formation of rosettes with sheep red blood cells, immunofluorescence to identify cells carrying immunoglobulin receptors on their surface, serum level of immunoglobulins as a function of Becells). Sensitization of the human body to allergenes of representatives of normal automicroflora of Staphylococcus, Streptococcus, Proteus and E. coli was examined. Specific immunological reactivity which was marked on the 2nd day and tended to return to normal on the 7th day postflight as well as a significant decrease of IgA were noted. Postflight P. I. Klimuk showed sensitization to allergens of Staphylococcus and Streptococcus. Results of immunological examinations of the first and second expeditions aboard the orbital station Salyut-4 were compared.


[Human visual functions during mild vestibular exposures]. Human experiments have shown that after mild stimulation of semi-circular receptors, which induces no motion sickness symptoms, the time of recovery of the central vision acuity shortens and after stimulation of otolith receptors tends to increase. Thresholds of color discrimination as applied to the red, green and violet colours as well as the course of back adaptation after mild stimulation of otolith receptors remain unchanged. The time of appearance of the Purkinje phenomenon after stimulation of receptors of semi-circular canals often remains unaltered and sometimes increases. It is assumed that the visual fixation of objects occurring with the time deficiency as related to the object display is accompanied by a compensatory-adaptive increase in the resolution capacity of the visual system.


The internal mammary bypass graft: a superior second coronary artery. In a study of the initial 1,004 consecutive patients who had direct coronary artery bypass at Ochsner Medical Institutions, computer methods of data processing were used to compare the clinical results between patients who had saphenous vein (SV) grafts and those who had internal mammary artery (IMA) grafts. The factors compared were the long-term mortality rates, nonfatal myocardial infarction rates, relief or persistence of angina, and the percentage of patients who acquired congestive heart failure. A simple comparison showed the patients with IMA grafts did better in all four categories; however, in a subsequent analysis in which maldistributed factors were removed, the rates of anginal relief and congestive heart failure were not significantly improved. The major benefit appears to be an increase in longevity among patients who had IMA bypasses.


Coronary bypass with Gore-Tex graft.

Coronary bypass with Gore-Tex graft. The case is presented of a 68-year-old man who previously had undergone aorta-coronary bypass. During a 3 year interval the coronary disease progressed, so that a once insignification lesion necessitated reoperation. A Gore-Tex vascular graft was chosen as a substitute because of the lack of saphenous vein. Three months posoperatively the patient's recatheterization study showed patency of the Gore-Tex graft placed in the distal righ coronary artery, and there was a satisfactory clinical result. No anticoagulants have been given to the patient after the operation.


Twisting of an aorta-coronary bypass conduit: a complication of coronary surgery. Twisting of an aorta-coronary bypass conduit was observed at necropsy in each of three patients. Three twists (540 degrees) just distal to the aortic anastomosis caused total obstruction of the bypass conduit to the left anterior descending coronary artery in one patient. A single twist (180 degrees) occurred in a bypass conduit in each of the othe two patients. Obviously, prevention of graft twisting is essential for successful bypass grafting.


Delayed cardiac tamponade associated with prophylactic anticoagulation in patients undergoing coronary bypass grafting. Early diagnosis with two-dimensional echocardiography. Pericardial tamponade occurring late in the hospitalization of a patient who has undergone a heart operation can be life threatening. Recognition of this insidious, but treatable, complication is difficult. Three patients experienced delayed tamponade while receiving warfarin prophylactically following coronary arter bypass. Two-dimensional echocardiography was useful in recognizing the effusion (and thus aided the diagnosis of tamponade) in each patients. The question of whether prophylactic antiocagulatin should be employed for patients undergoing coronary artery bypass procedures is also considered in light of both the present experience and collected reports from the literature.


Imaging platelet deposition with 111In-labeled platelets in coronary artery bypass grafts in dogs. At 8 and 32 hours after saphenous vein aortocoronary artery bypass graft surgery in four dogs, images of the grafts were obtained with a gamma camera after intravenous injection, 2 hours postoperatively, of autologous platelets labeled with indium-111. The location of platelet deposition could be accurately estimated from the scintiphotos. In vitro radioactivity counting of the segments of the isolated grafts showed 4 to 15 times greater activity in the grafts than in blood and 25 to 100 times greater activity than in normal myocardium. This was sufficient for delineating accurately the area of platelet deposition. This noninvasive technique may be a promising tool for a better understanding of the role played by platelets in the process of occlusion of saphenous vein bypass grafts in man.


[Whole gut irrigation for large bowel preparation (author's transl)]. In a controlled trial whole gut irrigation (w.g.i.) was compared with elemental diet for 4 days as large bowel preparation. Cleansing effect, caloric intake and preparation time were significantly better in the first group (w.g.i.). In addition w.g.i. was routinely used studying 42 patients in an open trial which showed also a reliable cleansing effect and good practicability. At present the experience refers to a total of 163 preparations by means of w.g.i. In a further study the efficacy of w.g.i. for removal of blood from the intestinal tract in patients with bleeding esophageal varices was investigated. In 8 out of 11 cases a complete removal of the blood masses was obtained, 3 of these patients showed an improvement of the preexisting coma-stage.


Initial adjuvant therapy in advanced squamous cell carcinoma of the head and neck employing weekly high dose methotrexate with leucovorin rescue. Our initial experience with weekly high dose methotrexate with leucovorin rescue (MTX-LCV), in advanced recurrent or metastatic squamous cell carcinoma of the head and neck with a 77% tumor response rate and high therapeutic index, prompted a trial of MTX-LCV as initial adjuvant therapy in high risk nonmetastatic patients. Results in 11 patients are presented and confirm the high response rate to MTX-LCV and the low incidence of myelotoxicity and mucositis, when concurrent urinary alkalinization is employed. Initial MTX-LCV administrations has not compromised subsequent optimum aggressive combinations of surgery and radiation therapy. Cytoreduction with MTX-LCV may be safely used initially in combined therapy for high risk squamous cell carcinoma of the head and neck.


The large vestibular aqueduct syndrome.

The large vestibular aqueduct syndrome. The radiographic observation of 50 patients, each having an enlarged (greater than 1.5 mm. diameter) vestibular aqueduct, are analyzed. In addition to the aqueduct other associated inner ear anomalies have been identified in 60% of this population including: enlarged vestibule (14); enlarged vestibule and lateral semicircular canal (7); enlarged vestibule and hypoplastic cochlea (4); and hypoplastic cochlea (4). The large equeduct then presumably represents an arrested phase of inner ear development common to all 50 cases. Only 8 of these cases may fall into the Mondini or Mondini-Alexander classification wherein cochlear abnormalities have been identified. The size of the aqueduct ranged from 1.5 to 8 mm. in the anteroposterior diameter; the clinical incidence is 50 in 3700 consecutive cases referred for inner ear tomography. Bilateral involvement is twice as common as unilateral with a female to male predominance of 3:2. Most cases are associated with congenital hearing losses.


Physicochemical properties of human middle ear effusions (mucus) and their relation to ciliary transport. Middle ear effusions were collected from 10 patients (14 ears) with secretory otitis media. Mucoid samples were pooled and reconstituted to various concentrations of nondialyzable solids. Viscoelasticity was studied using a magnetic microrheometer and compared with mucociliary transport rates measured on the frog palate. Results indicate that the viscoelastic properties of middle ear mucus correlate with mucociliary transport. A transport maximum was found at a 2% nondialyzable solids content. Implications relative to ineffective mucociliary transport in secretory otitis media are discussed.


Bell's palsy: a theory as to etiology. Observations in six patients. The etiology of Bell's palsy, like a number of other cranial nerve afflictions which consist of rapid or sudden loss of function, has never been satisfactorily explained despite extensive analysis by a number of investigators over the years. These entities may have a simple mechanical explanation in some patients. This consists of the sudden shift of an arterial loop in the cerebellopontine angle stretching the appropriate nerve. In Bell's palsy, the facial-acoustic nerve bundle appears to be stretched and compressed from the anterior aspect. Operative findings showing these abnormalities have been demonstrated in six patients and treated in five. A clinical-pathological analysis of the events of the history and findings in this modest series of patients with Bell's palsy appears to correlate clearly with such a cause.


[Treatment of malignant melanoma (author's transl)]. According to Clark there are three different types of melanoma: malignant melanoma which develops from the floor of a precancerous melanosis, the extensive superficial melanoma and nodular malignant melanoma. Therapeutically, surgery occupies the first place. Chemotherapeutically the combination of 3 or 4 different substances has given favorable results. Immunotherapeutically, immunization with BCG and mycobacteria, especially Cornyebacterium parvum, is considered the most reliable and least dangerous procedure. Altogether, a better prognosis for malignant melanoma can be expected in the future if diagnosis is made early and if treated with an optimum combination therapy.


[Circulating types of human glucagon (author's transl)]. In the plasma of healthy subjects, 4 fractions of immunoreactive glucagon are found. The first has a molecular weight of about 160000, the second of 9000, the third 3500 and the fourth about 2000. The third probably corresponds to the intact hormone glucagon. In cirrhosis of the liver and diabetes mellitus, a statistically significant rise in the third fraction has been found. In patients with tumors of the pancreatic A-cells, in addition to the third fraction the second in particular was also increased: it may be a precursor of the glucagon molecule. In chronic renal insufficiency, fractions 2 and 3 were as markedly increased as in glucagonoma, which suggests a role for the kidney in the decomposition of glucagon. The pathophysiologic significance of the four immunoreactive fractions of glucagon cannot yet be assessed with certainty.


[Detection of unrecognized hypertensives. A duty for longterm attendance (author's transl)]. The magnitude of the problem of hypertension is reflected in figures from the United States and Europe: with an incidence of about 15% of hypertensives in the adult population, about 1/3 of these individuals are unrecognized, a further third are indeed recognized but only inadequately treated or not at all, and only 1/3 are being satisfactorily treated. For this reason, not only the detection of unrecognized hypertensives must be dealt with, but also the problem of longterm supervision must be gone into at the same time. Were the adult population of the Federal Republic of Germany to be included in a "filter" investigation, about 3 million confirmed untreated hypertensives would have to be examined further and possibly treated. Also in an investigation of much smaller extent, the question of efficiency and tolerance must be raised.


[Assessment of blood pressure measurement for the diagnosis and therapeutic monitoring of hypertension (author's transl)]. Blood pressure readings are the central parameter in the diagnosis and therapeutic monitoring of arterial hypertension. Frequent measurements are therefore necessary because the blood pressures of healthy people, and in particular of patients with hypertension, are subject to considerable variability. Emotional factors, physical strain and diurnal differences have a modifying effect. Attempts to standardize a single measurement such as has been tried in the determination of the basic blood pressure or the diastolic levels have proved of little relevance for information on the daily blood pressure profile. The frequent determination of a random blood pressure after 2 to 3 minutes rest is a logical alternative. Regular monitoring is almost ideally obtained, especially under antihypertensive drug therapy, by the patient measuring his own blood pressure.


[Hypertension due to hormonal contraceptives and estrogens (author's transl)]. In over 95% of women who have for some time taken estrogen preparations or oral contraceptives containing estrogens there is no significant rise in blood pressure. Probably no more than 1 to 2% of young women treated develop clinically significant hypertension. In very rare instances, the preparations may induce potentially fatal malignant hypertension. Old age, a family history of hypertension and toxemia during earlier pregnancies seem to be predisposing factors for estrogen hypertension. Guide lines are given for the supervision of blood pressure in daily medical practice and circulatory contraindications to the prescription of these preparations are suggested.


[Hypertension in old age (author's transl)]. At the present time there are certain hints, but no definitive evidence, that hypertension in old age raises mortality and morbidity. No proof has yet been advanced that antihypertensive therapy improves the prognosis of senile hypertension. For this reason it is quite conceivable that hypertension in old age merely indicates arteriosclerotic changes but does not essentially cause them, so that senile hypertension is an indicator of risk but not a risk factor. Antihypertensive drug therapy for persons over the age of 65 is consequently only justifiable at present on the grounds of analogy. It is to be recommended if hypertensive complications are already present in organs, if additional risk factors are demonstrable or if additional risk factors are demonstrable or if there is a markedly increased blood pressure. A treatment already begun in earlier years which is effective and has few side effects should be continued. Antihypertensive treatment in old age must be initiated with low doses and carefully increased so that in patients who are often symptomless at first, the reduction in blood pressure does not create more problems in a short time than the untreated hypertension does in the course of years.


[Therapy of hypertension in general practice. Comments on the recommendations of the German Antihypertension League  (author's transl)]. The morbidity and mortality due to cardiovascular complications of chronic arterial hypertension are distinctly reduced by persistent and successful antihypertensive therapy. The principal emphasis is on drug therapy. Diet and psychotherapy should be used as supportive measures. Examples of antihypertensive drugs available for general practice: saluretics, beta-receptor blockers, dihydralazine (Nepresol), alpha-methyldopa, clonidine (Catapresan), reserpine and guanethidine (Ismelin). With mild hypertension (diastolic blood pressure up to 105 mm Hq), monotherapy with a beta-receptor blocker or a saluretic is indicated first. Contrary to the medical rule never to use a combination preparation if it can possibly be avoided fixed combinations have proved valuable in hypertensive therapy and facilitate therapy for the hypertensive patient and for the doctor.


[Side-effects on longterm treatment with antihypertensives (author's transl)]. Unspecific complaints as a result of lowering the blood pressure and substance-specific side-effects may occur during antihypertensive therapy. The frequency of the side-effects depends on the substance used (10 to 50%) and on the dose. An individual therapy, which in most cases involves the use of several substances, can reduce the frequency of side-effects decisively. With optimal therapy the ratio of benefits (= prevention of cardiovascular diseases) to side-effects (= sum of undesirable reactions) is completely acceptable in the treatment of high blood pressure.


[Results of conservative and operative treatment of urogenital tuberculosis (author's transl)]. In spite of the constant regression in newly notified Tbc patients, the percentage of extrapulmonary tuberculosis, especially of the urogenital region, remains unchanged at a high level. Modern therapy of urogenital tuberculosis is divisible into conservative, purely medicamentous treatment, possibly in combination with corticosteroids, and operative therapy, procedures preserving organs and rational eradication of tuberculous processes having to be carefully weighed against each other. The results of treatment are analyzed with reference to our own series of patients (n = 478).


[Surgical treatment of gastric stump carcinoma. Causes of the poorer results compared with primary gastric carcinoma (author's transl)]. In 3183 gastric operations during the past 13 1/4 years, 40 gastric stump carcinomas were observed after B II resection for benign ulcer. Eight of these underwent radical subtotal resection; 14 had total gastrectomy. Early and late follow-up prognosis of total gastrectomy for gastric stump carcinoma is significantly (p less than 0,05) worse than that for total gastrectomy for primary carcinoma of the stomach (n = 112). To improve the prognosis of gastric stump carcinoma, periodic follow-up of all patients with resected stomach to confirm an early diagnosis is necessary. Radical subtotal resection must be given priority because of its significantly lower lethality compared with a total gastrectomy.


[Metabolic and surgical aspects of total gastrectomy (author's transl)]. A follow-up examination was possible in 63 patients from a total of 323 with a total gastrectomy. All patients gained weight. The laboratory findings are in the normal range except for the low level of serum carotene and vitamin A. Carotene is greatly reduced by duodenal bypass or a short interposition of a small intestine loop. Radiological, endoscopic and histological findings correlate closely. Also, a reflux into the lower third of the esophagus causes clinical discomfort in 2/3 of all patients after esophagojejunostomy with end-to-side anastomosis. The interpretation of the negative points in conjunction with follow-up findings demonstrates the advantage of Longmire's interposition of a long small intestine loop for post-gastrectomy reconstruction.


[Epidemiology of rabies (author's transl)]. Rabies is widespread in all continents except Australia. As an anthropozoonosis its main importance is in areas with uncontrolled dog rabies, nowadays principally topical and subtropical regions. The greatest economic losses however are encountered in the cattle herds of South and Central America, where paralyssa prevails. In the northern hemisphere particularly rabies is enzootic among wildlife. Under the given ecological conditions only one or two species act as primary vectors of the infection. In Europe and parts of North America the red fox, in the arctic regions the arctic fox; in the middle West of the USA the skunk and in smaller foci the raccoon and mongoose are the reservoirs of rabies.


[Epidemiology of rabies in the German Federal Republic (author's transl)]. Rabies has spread from east to west with an annual advance of about 40 km. By 1960, the silvatic type of rabies had reached the Rhein. The principal carrier is the fox which is involved in 70% of epidemic occurences. The danger of infection of other wild and domestic animals and of humans starts with foxes. From 1974-76 the number of rabies findings in wild animals had increased by almost 100%. Cattle in the fields are particularly endangered by rabies from game. Rodents, like rats and mice have no epizootic importance in such epidemics. Since the first appearance of rabies in the Federal Republic of Germany, 15 humans have died from it, 7 of them had been infected abroad.


[Indications for rabies vaccination and prophylactic immunization in man (author's transl)]. Since therapy of an overt attack of rabies fails, we are completely dependent on prophylaxis. This must be carried out with extreme care. A careful detailed history is the most important, the fundamental question being: was this a provoked or unprovoked attack by the animal? In addition some knowledge of the behavior of different animals towards man is essential. Before every treatment, the question whether it is really necessary must be settled. The help of a veterinary colleague should be called upon in taking the history. A rapid diagnosis can be obtained by fluorescence serology of the dead animal.


[A purified rabies vaccine from human diploid cell cultures (author's transl)]. In order to improve the tolerance of rabies vaccine from human diploid cell cultures, the rabies virus antigen is purified in the sucrose density gradient by means of a flow ultracentrifuge. The purified virus has a specific infectiosity of 10(9) LD50 and a speicific activity of 250 units "relative activity" per 1 mg protein. The purified vaccine has been shown to be well tolerated, effective and stable.


[Experience in man with a purified rabies vaccine from huamn diploid cell (HDC) cultures (author's transl)]. A rabies HDC vaccine purified by density gradient centrifugation was used before and after exposure and the antigenic activity and tolerance investigated. Three injections on days 0, 7 and 21 induced neutralizing antibodies between 1:100 and 1: less than 1000 with 100% conversion rate, while one injection is sufficient for a booster. Vaccination after exposure is described; simultaneous passive immunization does not imply inhibition of the active immune response. Quantifiable local and general reactions seldom occur and serious neurological complications are not to be expected.


[Experience with new vaccines in rabies vaccination treatment (author's transl)]. As a result of our experience in 266 persons vaccinated with HDC vaccine we consider this type of vaccine to be a great advance. In spite of our very positive judgement we are of the opinion that vaccination should not be done without adequate indication. This type of vaccine contains certain imponderables which argue against widespread vaccination. At any rate, complications occurred in one of our patients vaccinated with HDC vaccine Mérieux. Nevertheless we consider vaccination before exposure of persons who are genuinely at risk, such as veterinarians, laboratory staff in rabies laboratories and possibly also hunters and agriculturalists in infected areas to be acceptable.


Evidence against the reversion of mutation in the Haemophilus influenzae phage HP1c1 by preinfection treatment of host cells or phage with MNNG. N-Methyl-N'-nitrosoguanidine (MNNG) causes reversion of a temperature-sensitive mutation in a bacteriophage of Haemophilus influenzae if exposure to the mutagen takes place after infection but before lysis. However, neither pre-infection treatment of the phage DNA, host cells, or both will cause reversion. The reasons for this are discussed in relation to the somewhat different results in the Escherichia coli lambda phage system and in relation to error-prone repair and replication processes.


Acquired von Willebrand's disease. Evidence for a quantitative and qualitative  factor VIII disorder. To define further the factor VIII abnormality in acquired von Willebrand's disease, we performed immunoelectrophoresis of factor VIII antigen, as well as quantitative measurements of the antigen, factor VIII procoagulant activity and von Willebrand factor activity on plasma from an affected 57-year-old man who also had a poorly differentiated lymphocytic lymphoma. No evidence for an inhibitor against factor VIII procoagulant activity or von Willebrand factor activity was detected, but immunoelectrophoresis showed none of the less anodic forms of factor VIII antigen. There were concomitant decreases in total antigen (0.19 U per milliliter) and von Willebrand factor levels (0.12 U per milliliter). Factor VIII-procoagulant activity was borderline low (0.45 U per milliliter). Correction of both the abnormal immunoelectrophoresis pattern and the quantitative abnormalities followed radiotherapy of the lymphoma. The factor VIII abnormalities might have resulted from binding or destruction of theless anodic forms of factor VIII antigen by the malignant lymphocytes.


Normal erythropoietic helper T cells in congenital hypoplastic (Diamond-Blackfan) anemia. To examine the erythropoietic function of T and null cells in congenital hypoplastic (Diamond-Blackfan) anemia, we fractionated the peripheral blood of three normal subjects and three affected patients into subclasses of null, T and B cells. Mixtures of these cells were co-cultured in plasma clots in the presence of erythropoietin. Erythroid colonies grew in cultures of normal null cells if either normal or patient T cells were co-cultured with them. Null cells of patients with hypoplastic anemia did not produce erythroid colonies under any culture conditions. We conclude that in this disorder, T cells function normally as helper cells in erythropoiesis and do not suppress colony formation, whereas the erythroid progenitor cells in the peripheral blood null-cell fractions are deficient in either number of function.


Treatment of solid Gardner lymphosarcoma with methotrexate sorbed on 2-hydroxyethylmethacrylate polymer in combination with leukovorin. Implantation of 2-hydroxyethylmethacrylate microporous carrier with sorbed methotrexate (Hema-Hex-MTX) proved more toxic on C3H strain mice with a solid Gardner lymphosarcoma than on tumor-free mice of the same strain. If, during the first week of the experimental disease, the Hema-Hex-MTX implantation was followed by administration of leukovorin in course of next 24 hours the toxicity of MTX was abolished and the treated mice survived significantly longer than control animals.


Abnormal T cell subpopulations and circulating immune complexes in the Guillain-Barré syndrome and multiple sclerosis. Immunologic studies were performed in 21 patients with multiple sclerosis (MS) and 16 with the Guillain-Barré syndrome (GBS). Levels of thymus-derived (T) cells measured by "total" and "active" rosette formation between sheep erythrocytes and peripheral blood mononuclear cells (TEt, TEa) were within normal limits in all the patients, with the exception of four GBS patients, including one who also had received chemotherapy for lymphoma and three who were receiving steroids. When lymphocytes from the 21 patients were incubated with the bone-marrow-derived (B) lymphoblastoid cell line PGLC-33H, there were, for 12 of 18 MS patients and 11 of 16 GBS patients, significant decreases in a subpopulation of peripheral blood T lymphocytes that form "PGLC rosettes" (PGR) with the PGLC-33H cells. (Peripheral blood T cells from normal individuals formed PGR with 23.9 +/- 3.8 percent of PGLC-33H cells.) Using the 125l-C1q binding assay, immune complexes were detected in the serum of 14 of 19 MS patients and 15 of 16 GBS patients. An association between increased C1q binding and decreased PGR values was found in 10 of 18 MS patients and 12 of 17 GBS patients. The results suggest that in both diseases the etiology may involve a decrease in the subset of T cells that bind to the IgM-producing cell line PGLC-33H, in association with the appearance of circulating immune complexes containing the infectious viral agent.


Complement-dependent serum: neuroelectric blocking activity in multiple sclerosis. In attempting to discover a relationship between the neurologic and immunologic abnormalities in multiple sclerosis, we found a serum factor that inhibits the ventral root response in isolated, perfused frog spinal cords. This effect is correlated with disease activity. Blocking activity of the serum was lost by heating to 56 degrees C, restored by adding complement, and was found in the serum IgG fraction. There was no correlation of neuroelectric blocking activity with measles complement-fixing antibody. An antibody other than that to measles virus may thus have a role in the pathogenesis of multiple sclerosis.


Pentylenetetrazol and reflex activity of isolated frog spinal cord. The superfused in vitro frog spinal cord preparation was used to investigate the effects of pentylenetetrazol (PTZ) on the spinal cord. PTZ depressed monosynaptic, but augmented polysynaptic reflexes, and decreased primary afferent deplorization. Concurrently, in Ringer's solution containing sufficient magnesium or cobalt ions to block synaptic transmission, PTZ antagonized the hyperpolarizing effects on motoneurons and the depolarizing effects on primary afferent fibers of the inhibitory amino acids GABA, beta-alanine, taurine, and glycine. PTZ did not affect responses to the excitatory amino acids glutamic acid and aspartic acid. Furthermore, PTZ did not alter high affinity uptake by cord slices, K+ -evoked release of [3H]GABA from them, or the spinal concentration of GABA. These data suggest that PTZ may produce its excitatory effects by postsynaptic blockade of inhibitory processes mediated by GABA (and possibly by other amino acids).


[Immunological determination of various blood proteins in clinical nephrology]. The serum levels of certain proteins were determined in 130 nephropathics collected into 8 different diagnostic groups, and in 20 normal subjects considered as a control group. The purpose was mainly to assess the clinico-diagnostic interest of such a measurement in nephrological practice. The results point to its clinical usefulness, particularly in differential diagnosis. It is possible to formulate interesting physiopathological interpretations notwithstanding the limitations of the eminently clinical features of the research.


Treatment of hypertension with labetalol. Labetalol, a new antihypertensive drug which combines alpha- and beta-blocking properties, was used in an open clinical trial in a mixed group of 47 adult patients with mainly essential hypertension, many of whom had been poorly controlled on other drugs. Labetalol lowered lying and standing blood pressures significantly when given alone or when combined with other antihypertensive drugs and it was generally well tolerated. It is easy to use, and in some severe cases has been dramatically effective. Mean daily dose was 767 mg. A postural hypotensive effect was seen especially in patients taking concomitant diuretics but was not troublesome. Labetalol reduced heart rate in patients who were not on previous or concomitant beta-blocker therapy. Side effects were few and did not cause major problems. A transiently or persistently weakly positive ANF was noted in nine patients; the significance of this is uncertain at this stage and needs further assessment. Raynaud's phenomenon, which had complicated previous beta-blocker therapy in some patients, improved with labetalol.


[Formation and cellular structure of the lines of tension in the axial rudimenta of amphibian embryos]. The lines of mechanical tension (cross-lines) in axial rudiments of the amphibian embryo represent bands of polarized cells. They form in the inner layers of the rudiments as separate bundles of polarized cell which, then, merge, attain the external surface and gather in lengthy planes (cross-planes) and, later, degrade. The primary inductor induces the formation of cross-lines in the ventral ectoderm of the early gastrula. The growth of cross-lines in considered as one of the types of contact cells polarization. The morphogenetic role of contact polarization is discussed. The connection between the subsequent tension patterns is based on the fact that the lines of exit of the cross-planes on the surface of the embryo coincide with the direction of the previously established tensions.


[Effect of sera against aggregated mouse immunoglobulins on a population of lymphoid and hematopoietic cells]. The in vitro treatment of the mouse spleen cells immunized by the ram erythrocytes with the rabbit and mouse sera against the thermoaggregated mouse immunoglobulins resulted in the inhibition of antigen binding receptors of rosette forming cells. The mouse serum, unlike the rabbit one, induced the inactivation of receptors in rosette forming lymphocytes both in the non-immune and immune mice on the 8th day after the antigenic stimulation. The treatment of bone marrow cells from the intact mice with these sera increased insignificantly the number of hemopoietic colonies in the spleens of lethally irradiated syngenic recipients and stimulated markedly the migration of spleen cells. This may be due both to the direct effect of these sera and to their mediated (through the humoral factor) influence. The inactivation of antigen binding receptors in the spleen rosette forming cells suggests the presence of immunoglobulins on the membrane of B-lymphocytes in the aggregated state or in the form of antigen--antibody complexes.


Inflammatory response, endophthalmitis, corneal dystrophy, glaucoma, retinal detachment, dislocation, refractive error, lens removal, and enucleation. This paper provides a synopis of published data on most of the major complications of the implantation of currently used intraocular lenses. With one exception, these studies lack controls, and the results show the variations expected when a variety of lens implants, techniques, and surgeons are compared. The author's personal data are also included.


Management of surgically dislocated intravitreal lens fragments by pars plana vitrectomy. We examined 26 eyes (19 of them following phacoemulsification) with surgically dislocated intravitreal lens fragments; 24 eyes were subsequently operated on using pars plana vitrectomy for removal of lens fragments. From this select group of patients we found moderate to severe uveitis, glaucoma, and vitreous opacification present in virtually all cases. Less common complications were retinal detachments (six cases) and bullous keratopathy; the latter problem was found most commonly in eyes subjected to anterior segment maneuvers such as the use of lens loops or vitreous irrigation for removal of the lens material. Pars plana vitrectomy proved an excellent method for removal of lens fragments. A simultaneous two-instrument technique using the Wilson foreign-body forceps and the vitrectomy machine facilitated removal of the denser sclerotic lens fragments. This procedure resulted in resolution of the uveitis and glaucoma with improvement in visual acuity in 20 of the 24 eyes. However, only 10 of the 24 patients operated on obtained 20/40 or better visual acuity. A relatively prompt pars plana vitrectomy in eyes subjected to a minimum of surgical trauma yielded the best visual results.


[Exceptional clinical courses of granulomatous colitis in children and adolescents (author's transl)]. Acute complications are known in chronic ulcerative colitis as well as in Crohn's colitis. They can rarely be seen also in childhood and adolescence. Massive rectal bleeding, particularly acute toxic dilatation of the large bowel should be treated surgically after a short-term medical therapy. The procedure of choice is the one stage proctocolectomy. Alternatively the method described by TURNBULL performing a loop ileostomy and several colostomies can be used. Besides the clinical symptoms and signs more than 8 stools and a temperature of more than 38 degrees C in the first 24 hours of hospitalisation can predict a severe clinical course.


Immunologic parameters in childhood Hodgkin's disease II. T and B lymphocytes in the peripheral blood of normal children and in the spleen and peripheral blood of children with Hodgkin's disease. A study of peripheral blood lymphocyte populations in 27 children with Hodgkin's disease (HD) and 13 age-matched control subjects is presented. The absolute numbers and percentages of T and B lymphocytes identified by their surface marker characteristics were determined. In addition, in 13 HD children the percentages of T and B lymphocytes were estimated in the spleens removed at staging laparotomy. No differences were observed between the total peripheral blood lymphocyte counts of HD and control children, and we found no evidence of progressive lymphopenia with advancing stages of the disease. No decrease in the numbers of peripheral blood T lymphocytes was seen in this group of HD children. In contrast, the proportions and absolute numbers of B lymphocytes tended to be significantly lower in the children with HD than in the control subjects. In 9 of the 13 spleens studied high percentages of T lymphocytes were seen; low percentage of B lymphocytes were found in all spleens examined.


Effect of ampicillin and chloramphenicol against Haemophilus influenzae. Synergy, determined by isobolograms constructed from the minimal inhibitory concentrations of combinations of ampicillin and chloramphenicol, was observed against six of 13 ampicillin-susceptible Haemophilus influenzae type b isolates and against five of eight ampicillin-resistant strains by using a small inoculum of 10(4) colony forming units (CFU) per milliliter. Synergy occurred against nine of 13 ampicillin-susceptible and against two of eight ampicillin-resistant strains using a large inoculum of 10(7) CFU/ml. When synergy was not observed, additive effects occurred against the remainder of isolates. Additive effects were also observed against single strains of chloramphenicol-resistant, nontypeable H. influenzae and H. parainfluenzae. No antagonism was observed. These data indicate that ampicillin and chloramphenicol may be synergistic against a significant number of H. influenzae strains depending on inoculum size, but the effect is unpredictable for a given isolate. These data support the recommendation that ampicillin and chloramphenicol both be used as initial therapy for patients with suspected bacterial meningitis.


[Familial immune deficit and genetic deficiency of adenosine deaminase or of nucleoside phosphorylase (author's transl)]. Two familial enzymopathies, always related to the combined immune deficit, are reviewed. Both are clinically characterized by repeated infections since the birth, leading to fatal issue before age of 4 years. The hereditary deficiency of adenosine deaminase is associated to the deficient functions of T and B lymphocytes. The activity of the enzyme is non detectable in the erythrocytes, strongly reduced in the lymphocytes and in several organs. In hereditary deficiency of nucleoside phosphorylase the functional anomalies of T lymphocytes are observed. The biochemical mechanism of the relation between the two enzymopathies and the deficient function of the immune system is centered on the metabolic pathway of purine nucleosides ans nucleotides.


Dexamethasone modulates binding and action of epidermal growth factor in serum-free cell culture. Experiments probing the mechanism by which glucocorticoids modulate cell proliferation were carried out on serum-free cell cultures of quiescent human diploid foreskin (HF) cells. Added alone, the synthetic glucocorticoid dexamethasone had no effect on cell number. However, dexamethasone enhanced the mitogenic response of HF cells to epidermal growth factor (EGF) by 50% at all EGF concentrations. The mitogenic action of EGF was maximally promoted by a dexamethasone concentration of 100 ng/ml (0.25 muM). Binding studies with (125)I-labeled EGF ((125)I-EGF) suggested that dexamethasone caused this "permissive" effect by modulating cell surface receptors for EGF. Paralleling their increased responsiveness to EGF growth stimulation, dexamethasone-treated cells exhibited a 50-100% increased ability to bind physiological concentrations of (125)I-EGF. A binding increase was apparent after a 4-hr dexamethasone treatment. The dexamethasone-treated cells maintained an increased ability to bind (125)I-EGF during the prolonged exposure to EGF that was required to stimulate cell division. Moreover, the increase in (125)I-EGF binding exhibited a dexamethasone dose-dependence similar to that for the enhancement of EGF mitogenesis, suggesting a relationship between the dexamethasone effects on binding and growth. An investigation of the binding increase showed that it was specific for glucocorticoids, and required protein synthesis. The enhancement of (125)I-EGF binding diminished with increasing concentrations of (125)I-EGF, indicating that dexamethasone caused a qualitative change in the EGF receptors (possibly a change in receptor affinity or cooperativity). The alteration in (125)I-EGF binding may occur as part of a far-reaching dexamethasone-mediated change in the cell surface, because dexamethasone treatment slightly increased the ability of HF cells to bind (125)I-insulin, and decreased by half their ability to bind (125)I-thrombin.


RNA content in human lymphocyte subpopulations. Human peripheral blood lymphocytes are stained with the metachromatic dye acridine orange and the fluorescence of individual cells is measured by flow cytometry. The relative content of stainable RNA per cell is estimated by comparison with RNase-treated cells. Non-T and T lymphocytes have different mean quantities of RNA per cell, and these classes exhibit different distributions of RNA content. Non-T cells have a unimodal distribution with a sharp peak and exponential distribution towards higher RNA values. T cells have a bimodal distribution with two separate peaks. When T cells having receptors for IgG (Tgamma cells) and IgM (Tmu cells) are separated, each of these cell populations displays a unimodal distribution. Of these three lymphocyte subpopulations, Tgamma cells have the lowest content of RNA per cell. Non-T cells have slightly higher RNA content than Tgamma, and Tmu cells have twice as much RNA as Tgamma cells. The RNA content, which surely relates to the different functions of these lymphocyte subpopulations, may also be a useful marker for rapidly distinguishing the lymphocyte subpopulations.


Clonal dominance: loss and restoration in adoptive transfer. An adoptive transfer system was used to study the mechanism responsible for clonal dominance of the anti-phosphorylcholine response in BALB/c mice. The adult spleen contains phosphorylcholine-specific precursor cells that are capable of developing into antibody-producing cells after transfer into lethally irradiated animals. The neonatal liver of the BALB/c mouse lacks precursor cells specific for phosphorylcholine but contains immature cells that differentiate into specific precursors during the normal course of ontogeny. The transfer of fetal or neonatal liver cells into lethally irradiated recipients prevents the appearance of the dominant H8 clone which constitutes the majority of the clones responding to phosphorylcholine in adult BALB/c mice. However, if these cells are transferred into neonatally suppressed recipients that lack the H8 idiotype, dominance of the H8 clone can develop. The conversion of the committed immature progenitor cell into a responsive B lymphocyte precursor is a regulated event. Regulation at the level of progenitor cells determines the eventual clonal profile of the immune response to phosphorylcholine. It is suggested that selection of the dominant clone occurs at this level.


Effect of alloxan-diabetes on alpha-amylase and sialic acid levels in the parotid and submandibular glands of rats. The relationship of diabetes to salivary gland metabolism has been investigated by comparing the levels of alpha-amylase, sialic acid and total protein in the parotid and submandibular glands, plasma and kidneys of control and alloxan-diabetic rats. A significant decrease in alpha-amylase activity was found in both the parotid and submandibular glands of the diabetic rats by use of both a chemical and an electrophoretic assay. Plasma and kidney levels of the enzyme were not altered in the diabetic rats. Sialic acid levels were not affected by the alloxan-induced diabetes. Although the total protein concentration was significantly altered only in the kidneys of the alloxan-diabetic rats, the electrophoretic patterns of both the parotid and submandibular gland soluble proteins were markedly different between the control and alloxan-diabetic rats. The electrophoretic data indicate that protein metabolism in general, and the alpha-amylase concentration specifically, are altered in the salivary glands of alloxan-diabetic rats.


A radiotelemetry pill for the measurement of ionising radiation using a mercuric iodide detector. A small radiation measuring pill is briefly described which utilises the principles of radiotelemetry and the properties of a room temperature semiconductor radiation detector such as mercuric iodide. By transmitting a radio signal to a remote receiver the pill could be an effective tool in localising bleeding sites along the gastrointestinal tract and also possibly in the diagnosis of gastrointestinal carcinoma. Other uses of the radiopill are suggested. The size of the pill is 27 mm x 10 mm diameter and consists of a mercuric iodide crystal, an amplifier, a frequency modulated transmitter and one battery. The radiotransmitter operates at about 106 MHz and has a range of about 10m, and the sensitivity of the pill has been found for 99Tcm, 131I and 32P.


[Correlation of encephalotomography and computer tomography in space occupying lesions in the midline and cerebellopontine angle (author's transl)]. The diagnostic value of encephalotomography and computer tomography in neuroradiology of midline tumors is discussed. Characteristic differences of both methods are summarized. The following conclusions of clinical importance are derived from our experiences: 1. Computer tomography is the most valuable method in the diagnostic procedure of midline tumors. Encephalography is not necessary is cases with density differences of tumor and surrounding brain tissue or contrast enhancement. 2. Encephalotomography should be performed in cases with dislocation of cisternes and ventricles without density differences or contrast enhancement. 3. Encephalotomography is the method of choice in patients with unclear computer tomography and contradictory clincial symptomatology.


Transcatheter embolization for lower gastrointestinal bleeding. Transcatheter embolization was performed in 7 patients with lower gastrointestinal bleeding. Hemorrhage was controlled in each of the 5 actively and massively bleeding patients but recurred after several months in 2 patients who had bled intermittently from vascular dysplasias. The authors recommend preoperative angiographic localization of the bleeding site in almost all cases of major lower gastrointestinal bleeding. When the cause and bleeding site have been identified, it seems reasonable to exploit the therapeutic potential of the angiographic catheter already in place: indeed, surgery may be obviated. If embolism fails or ischemic sequelae develop, partial colectomy can still be performed. Further long-term follow-up will be necessary before the role of transcatheter embolization can be definitively assessed.


Decrease in ventricular and sulcal size after death. Fifty-one intact corpses were examined with the EMI head scanner from 1 1/2-52 hours after death; 15 of these had antemortem CT scans. Seven had sequential postmortem CT scans. CT scans and autopsy findings for lateral ventricular size and sulcal width were compared. The lateral ventricular size generally, and the sulcal width occasionally, became smaller after death, though the decrease was usually mild. This decrease was demonstrated not only on antemortem and postmortem sequential CT scans, but on postmortem sequential CT scans alone as well.


Abnormal gallium scintigraphy in Pneumocystis carinii pneumonia with a normal chest radiograph. The authors describe a patient with malignant lymphoma in whom the use of a 67Ga citrate lung scan assisted in the diagnosis of P. carinii pneumonia. In immunodeficient patients presenting with unexplained fever, abnormal pulmonary function tests, a normal chest radiograph, and few chest symptoms, the 67Ga citrate scan may lead to the early detection and successful treatment of this potentially lethal infection.


Haemostatic effect of triglycylvasopressin on bleeding from gastric mucosal lesions in the rat. The haemostatic effect of triglycylvasopressin (TGLVP) on the gastric mucosa was evaluated in an experimental model in the rat. TGLVP was found to reduce the bleeding significantly compared with the untreated controls. The haemostatic effect was most prounounced and prolonged when 200 microgram/kg b.w. was given intravenously. The clinical application of this finding is discussed.


Traffic of T and B lymphocytes in the normal spleen. The occurrence of C3b and C3d complement receptors and of Fc and E receptors in normal splenic tissue was studied in cryostat sections incubated with specific marker cells. Thereby the topographic distribution of T and B lymphocytes in the splenic tissue was mapped: Te lymphocytes are found especially in the periateriolar sheaths, B lymphocytes in eccentric zones around the arterioles. The cells in the splenic pulp carry especially Fc, but also C3b receptors, whereas C3d receptors appear to be specific of lymphocytes. The basic lymphocyte traffic behind the mapped distribution of the lymphocyte subpopulations in the spleen was elucidated by lymphocyte kinetic studies using autologous 51Cr-labelled reinfused lymphocytes. These studies were performed partly on normal persons and partly on splenectomized persons without immune defects. The results indicate the presence of an exchangeable pool of T as well as of B lymphocytes in the spleen, the T cell pool being larger and making up in normals about 30% of the total exchangeable T lymphocyte mass. The matrix for the T lymphocyte pool in the spleen is the periateriolar sheaths. The difference in structure between the lymph nodes and the lymphoid tissue of the spleen, including differences in the distribution of lymphocyte subpopulations, are explained by the special vascular arrangement in the spleen.


Gastrointestinal hemorrhage in long-lasting traumatic coma. Sixteen cases, aged 19 to 61 years and suffering from traumatic coma were studied for periods varying from 7 to 20 months. Obvious or occult gastrointestinal hemorrhage appeared in every case, the earliest presentation being after a few weeks and the latest at 20 months. Gastric acidity was normal in 15 cases. Five patients had duodenal ulceration in repeated roentgenological examination. Concomitant clinical findings included clubbing and paraarticular new bone formation in 9 patients. In addition, hypoxia with repeated values between 63 and 88 mm was observed in 13 of the 16 patients. The latter observation strongly suggests that hypoxia of gastrointestinal mucosa may, indeed, play a pathogenetic role in gastrointestinal hemorrhage of patients with C.C.I.


Value of fiberoptic gastrointestinal endoscopy in infants and children. Fiberoptic gastrointestinal endoscopy was performed on 52 patients between the ages of 2 months and 16 years. The procedures were safely and easily done with premedications consisting of meperidine, promethazine, and chlorpromazine, and atropine, with diazepam given at the time of the procedure. Fiberoptic endoscopy was particularly helpful in localizing the site of upper gastrointestinal hemorrhage, in retrieving foreign objects, and in removing colonic polyps. In contrast, endoscopy added little to the clinical history and roentgenographic studies in children with recurrent abdominal pain or vomiting, in whom we believe fiberoptic endoscopy is not indicated unless the symptoms or history appear inconsistent with the diagnosis of functional bowel disease.


Effects of contrast media on the canine subarachnoid space. This study reports an investigation of the canine arachnoid membrane using the scanning electronmicroscope (SEM) regarding the effects of contrast material on these structures. In the normal arachnoid membrane, two basic surface patterns were observed; one fenestrated and the other embossed with parallel fibers. Ventriculography was performed on 30 mongrel dogs divided into five groups: control, air, iophendylate, meglumine iothalamate, and Metrizamide. SEM study of the arachnoid membrane from basal cisterns showed no change after air ventriculography. After contrast agents were used, macrophages appeared and fenestrations became closed with fibrin-like substance.


Haemophilus vaginalis (Corynebacterium vaginale) vaginitis in women attending public health clinics: response to treatment with ampicillin. Haemophilus vaginalis (Corynebacterium vaginale) was isolated from genital specimens from 150 women who came to a public health venereal disease clinic. Forty-six patients returned to the clinic for at least one follow-up examination. Of the returnees, 22 of 24 who initially had received adequate therapy (14 g ampicillin in seven days) were cured, compared with three of 22 who did not received adequate therapy (X2 = 25.11; P less than 0.00005). These data included significant cure rates with adequate therapy among the 46 returnees, of whom 25 had vaginitis due to H. vaginalis only (X2 = 16.67;  P less than 0.00005) and 21 had vaginitis caused by a mixture of pathogens (X2 = 5.86; P less than 0.0156). Specimens obtained from 24 of the 46 returnees were cultured for H. vaginalis on the second visit; 19 were negative, and only five were positive. Clinical responses of the patients correlated closely with the results of culture in both treated and untreated groups (X2 = 14.23; P less than 0.00016).


Synthesis of 1alpha-hydroxyergocalciferol. A synthesis of 1alpha-hydroxyergocalciferol (1alpha-hydroxyvitamin D2, a potent analog of vitamin D2, is described. The preparation route involves conversion of ergosterol in two steps (60%) to the known ergosta-4, 6, 22-trien-3-one and dehydrogenation of the triene with SeO2 to ergosta-1,4,6,22-tetraen-3-one (30%). Epoxidation of the tetraenone to the corresponding 1alpha, 2alpha-epoxide followed by Li/NH3 reduction gave ergosta-5,22-diene-1alpha, 3beta-diol in 26% yield from the tetranone. After conversion to the corresponding diacetate and allylic bromination/dehydrobromination 1alpha-acetoxyergosteryl acetate was obtained. Irradiation of this intermediate gave the previtamin which was converted to the new vitamin analog by thermal equilibration and hydrolysis of the acetates. Charcteristic uv, nmr and mass spectral patterns confirmed the structure of the product.


The multicellular spheroid as a model tumor allograft. II. Characterization of spheroid-infiltrating cytotoxic cells. Alloimmune lymphoid cells infiltrating multicellular spheroids of EMT6 mammary sarcoma cells (a solid tumor allograft model) have been characterized according to their morphological and functional properties. Both lymphocytes and macrophages were found within spheroids at the time of peak tumor cell damage. Cytotoxic cells specific for allograft antigens were also present. Using a short-term 51-Cr release assay, the cells responsible for cytotoxicity were characterized as a nonadherent, nonphagocytic T cell population. Velocity sedimentation cell separation further demonstrated that these cytotoxic cells had the physical properties of small lymphocytes. Some evidence for selective spheroid infiltration by specifically alloimmune cells was also obtained. The possible relationship of this cellular infiltrate to graft damage is discussed.


In vivo and in vitro induction of cytotoxic lymphocytes by alloantigen-reactive lymphocytes fractionated on spleen cell monolayers. The generation of cytotoxic T cells by normal and primed lymphocytes fractionated on spleen cell monolayers was examined by two methods. In the first method, sublethally irradiated recipients were inoculated with the fractionated cells, and 5 to 6 days later the spleens were tested for cytotoxicity against 51Cr tumor target cells syngeneic to the host. Significant reduction of cytotoxic activity was observed in one-half of the experiments. In the second method, the fractionated cells were cultured with mitomycin C-treated stimulated cells and tested 6 days later for cytotoxicity. A slight reduction of cytotoxic activity was observed. In both methods, the cytotoxic response generated by the fractionated alloantigen-primed lymphocytes was similar to the response obtained with unprimed cells.


[Dynamics of immunologic reactivity in the acute phase of virus hepatitis B]. In 15 patients with acute icteric viral hepatitis B the immunological reactivity was tested. The examinations were performed on the 1st, 7th, and 14th day of hospitalization. They consisted of the determination of the HBsAg and its antibodies in the serum, of the percentage of the B- and T-lymphocytes, of the lymphocyte transformation test under the influence of phytohaemagglutinin, of the lymphocyte migration inhibitory test when the HBsAg is present as well as of the determination of the IgG, IgA and the IgM-level. A decreased percentage of the T-lymphocytes, a decreased blastic transformation and an inhibition of the lymphocyte migration was proved. After a transient increase in the first and second examination the IgG-level returned to the normal in the third examination, whereas the IgM-level increased. Finally dynamics and importance of the cellular reactivity in the pathogenesis of viral hepatitis B are discussed.


Characteristics and in vitro growth influencing effects of the spleen cell population in a methylcholanthrene induced mouse sarcoma system. Effects of immunization on the growth of the early passages of two methylcholanthrene induced mouse tumors, MC57 X and MC57 Y, were different. For tumor X, immunization resulted in complete protection, while tumor Y was enhanced. The enhancing effect was individual tumor specific. The spleens of tumor bearing animals were enlarged and the proportion of blasts, EAC- and EA-rosettes were increased. This was the case for the T cell enriched population also. In lesser extent, such findings were also obtained in the lymph nodes. The spleens of control and tumor bearer animals were tested for effect on the in vitro growth of tumor cells. From both sources non-adherent subpopulations enriched in C3 receptor bearing cells substantially reduced the number of tumor cells. Using the T cell fractions, only those derived from tumor bearer spleens were active. The in vitro effects on the growth of the two tumors were cross-reactive. T cells exhibiting growth inhibition in vitro were detectable 13 days after subcutaneous inoculation, when the tumor was already measurable, while earlier the T cells enhanced the growth. The outcome of the in vitro tests reflected only the tumorous status of the animal and did not relate to preimmunization.


Human blood lymphocyte fractionation with special attention to their cytotoxic potential. In studies concerning the natural cytotoxic activity of human blood lymphocytes we have found that: 1. T cell, which rosette with sheep erythrocytes can be separated by centrifuging on Ficoll the lymphocyte and erythrocyte mixture without previously pelleting and incubating in the cold. 2. Lysis of marker erythrocytes with ammonium chloride impairs the cytotoxic activity of lymphocytes. Incubation at 37 degrees C for 12 hr prior to the test restores the activity to some extent. 3. A high proportion of the so call "null" fraction i.e. cells remaining in the interface after removal of B cells (passage on nylon column) and sedimentation of E rosettes, sediments as rosettes with sheep EAC'indicating that these cells carry low density E and C3 receptors. Rosetting with SRBC or ox EAC' gave significantly lowr values. On a per cell basis the "null" fraction was the most efficient one in natural cytotoxicity. Depletion of cells with low affinity E or E and C3 receptors left highly active subfractions.


No development of experimental autoimmune thyroiditis in nude mice. Homozygeous nu/nu mice do not develop experimental autoimmune thyroiditis and circulating thyroglobulin autoantibodies after two immunizations with murine thyroid extract and fortified complete Freund's adjuvant. However, heterozygeous nu/+ mice are perfectly apt for the induction of both thyroiditis and thyroglobulin autoantibodies. These results provide further evidence for the assumption that the development of experimentally induced autoimmune thyroiditis depends on the presence of T-cells as opposed to the spontaneously occurring autoimmune thyroiditis in Obese strain (OS) chickens which is mediated by B-effector cells. The present data further show that thyroglobulin is a T-dependent antigen in the mouse.


Developmental biology of Pneumocystis carinii, and alternative view on the life cycle of the parasite. In this paper we present, based on elaborate ultrastructural studies, data on the existence of both intracellular and extracellular stages of Pneumocystis carinii, which result in a proposal of a new life cycle of the parasite. Up to now the formation of daughter cells in thick-walled pneumocysts is supposed to be the only way of multiplication. The present study shows that in rats treated with cortisone acetate the formation of daughter cells also takes place within thin-walled pneumocysts. In our opinion this way of multiplication is important for the understanding of the rapid increase in number of the parasites in an infected lung. The presence of pneumocysts inside the alveolar epithelial cells suggests that intracellular development of the parasites can occur, but the method of cell penetration, intracellular multiplication and parasite liberation is still unknown. Moreover our observations for the first time indicate a direct pathogenicity of the parasites in host cells.


[Endoscopic sclerosing of oesphageal varices (author's transl)]. Due to unsatisfactory results of porto-systematic shunts in oesophageal varices as prophylaxis or as therapy in haemorrhagic states local therapeutic measures have attracted attention, especially sclerosing the wall of the oesophagus by an endoscopic technique.


[Influence of homologous n-alcanoic acids on the function properties of isolated skeletal muscles. III. Contractures by fatty acids and relations to the effects of caffeine]. The influences of octanoic, decanoic, and hexadencanoic acid were tested on the contracture capability of isolated skeletal muscle of frogs and rats. 1. 100 mM octanoic or 10mM decanoic acid induce contractures in skeletal mucles after 20-30 min of exposure. 2. The time of exposure necessary for induction of contractures is shortened by an increase of bath temperature, electrical stimulation or KCl-depolarization of muscles. 3. Simultaneous addition of fatty acid and caffeine (10 mM) effects a depression and a delay of the caffeine contracture. The contractures evoked by 5 mM caffeine are inhibited by lower concentrations of fatty acids (1 mM octaonoic acid, 0,1 mM hexadecanoic acid). 4. After the complete development of a caffeine (or fatty acid) contracture the muscle is not able to develop an identical contracture by a second application of the same drug, even after intermediate treatment during one or two hours in Ringer solution. If the contracture is interrupted one minute after the caffeine application by changing the solution, the tension returns quickly to the resting level. A subsequent addition of caffeine (10 mM) after about 10 minutes effects an identical contracture. Thus the effect of fatty acids on caffeine contracture may be studied on the same muscle which served as its own control. 5. As mechanisms involved in the development of fatty acid contractures and in the inhibition of caffeine contractures, interactions of free fatty acids and lipids of biological membranes are disucssed. Especially, there may be changes of the calcium affinity of cellular membranes.


Regeneration of ankylosed teeth in the adult frog premaxilla. The relationship between the ankylosed amphibian tooth and regeneration of a jaw segment was studied. A section of the premaxilla was removed in 95 young leopard frogs. Subsequent would healing was observed at intervals of 0-180 days. The dental lamina formed new teeth and by 90 days, teeth in varying stages of development could be seen extending across the wound segment. Teeth within the wound grew to normal size and shape and were replaced by their successors without support of underlying jaw bone which grew in later and often was incomplete.


Biogenic amine and amine precursor uptake by mast cells. The mast cell population is heterogeneous concerning its amine precursor and amine uptake. The immature cells incorporate amine precursors, but in more advanced stages of their maturation they take up only 5-HTP. The mature cells do not take up precursors only 5-HT. The thyroid gland and heart muscle mast cells take up the highest amount of 5-HT; this may be related with some specific function of the mast cells in these two organs. Neither of the mast cells would take up histamine, the compound is synthetised by the cells.


Nucleus isthmi of the frog: structure and tecto-isthmic projection. The morphology of neurons in the isthmic nucleus was studied with the Golgi technique. Most of the neurons have thick dendrites covered with lamelliform dendritic processes. The tecto-isthmic projection was investigated with the Fink--Heimer technique after partial tectal lesions. The anteromedial part of the tectum projects on the dorsal and anterior part, the caudomedial tectal region on the dorsal and posterior part of the nucleus. The posterolateral tectal area projects on the anterolateral part of the nucleus, and the axons originating in the anterolateral tectal quadrant terminate in its ventral and caudal part.


Fascicular conduction distrubances after coronary bypass surgery. Two hundred patients underogoing coronary bypass graft surgery were studied to determine the frequency and significance fo new fascicular conduction distrubances. The follow-up period ranged from 13 to 39 months. New disturbances developed in 39 patients (20 percent). Isolated right bundle branch block (6 percent) and left anterior hemiblock (6 percent) were the most common disturbances. Righ bundle branch block was usually transient and was not associated with further complications in the follow-up period. However, patients with either transient or persistent left bundle branch block or left anterior hemiblock, or both, had (1) increased later mortality compared with patients without new fascicular conduction disturbances (5 of 26 versus 11 of 161; P less than 0.02), and (2) increased late myocardial infarction (2 of 26 versus 2 of 161; P less than 0.05). New left fascicular conduction disturbances after coronary surgery identified a subset of patients with more extensive ischemic heart disease, suggesting that these patients require close follow-up care.


Haemophilus influenzae type b osteomyelitis. Three children had osteomyelitis due to Haemophilus influenzae type b. They were seen with signs and symptoms indistinguishable from infection caused by other organisms. One child was initially misdiagnosed as having septic arthritis because of failure to appreciate that Hemophilus may also cause bone infection. In the second patient osteomyelitis and arthritis developed during ampicillin sodium therapy for treatment of Hemophilus meningitis. His initial infection was caused by an ampicillin-sensitive isolate but his orthopedic infection subsequently responded to therapy only after changing to a regimen of chloramphenicol. In the third patient, bone scintigraphy was helpful in diagnosis since serial roentgenograms were not diagnostic of osteomyelitis. The anticapsular antibody responses of these patients were measured by radioimmune assay. The levels found were low but comparable to age-matched control children with H influenzae type b meningitis.


Drug therapy reviews: clinical use of hemostatic agents. Systemic hemostatic agents are reviewed. Among the agents discussed are vitamin K preparations (phytonadione, menadione, menadione sodium bisulfite, menadiol sodium diphosphate); and blood products (whole blood, plasma, cryoprecipitate, factor VIII concentrates, factor IX concentrates and fibrinogen concentrates). Normal and abnormal hemostasis and fibrinolysis are discussed, as is the general management of systemic hemostatic defects. Specific disorders covered are clotting factor deficiencies, hemophilia A, factor VIII inhibitors, von Willebrand disease, hemophilia B (Christmas disease), other congenital coagulation disorders, acquired deficiency of factors II, VII, IX and X, and defibrination syndrome.


T cell acute lymphocytic leukemia terminating as malignant histiocytosis. Less than 200 cases of malignant histiocytosis (histiocytic medullary reticulosis) have been reported in the literature. Five previously reported cases and the case reported in this article have been preceded by acute lymphocytic leukemia. All of these cases have had similar courses characterized by prompt response of the leukemia to chemotherapy followed in three to six months by the onset of rapidly fatal malignant histiocytosis. The leukemic lymphoblasts in the two cases studied for lymphocyte surface markers had T cell markers. No residual leukemia was identified at autopsy in four of the six cases.


A new observation in the clinical spectrums of erythroleukemia. A report of 46 cases. Erythroleukemia is a disease manifested by an abnormal proliferation of erythroid and myeloid precursors, generally consisting of a primary erythroid phase (chronic erythemic myelosis), a transition phase involving erythroid and myeloid precursors (erythroleukemia) and, finally, the purely myeloblastic (acute myeloblastic leukemia) phase. The experience at Memorial Sloan-Kettering Cancer Center is reported. Presenting signs and symptoms are consistent with prior reports. The chemotherapy results in the past have been poor; because of the poor results, chemotherapy is started only if one of the following criteria are present: (1) frequent transfusion requirements; (2) rapidly increasing peripheral white blood cell count or percentage of leukemic blast forms; (3) frequent recurrent infectious and/or hemorrhagic complications. A hitherto unrecognized association of erythroleukemia and symptomatic rheumatic disease and numerous immunologic abberations are reported. The symptoms related to this rheumatic disorder do not seem to be relieved by therapy directed at the leukemic process, but rather by the use of simple anti-inflammatory agents.


Circulatory effects on osmotic water exchange in Rana pipiens. Tritiated water (3H2O) exchange was shown to be more sensitive to circulatory changes than to arginine vasopressin (ADH)-induced permeability changes. Reducing the circulation (sciatic artery ligation) and increasing the circulation (severing the sciatic nerve) caused the 3H2O exchange in frog legs to decrease from 6.0 +/- 1.3 (5) to 3.5 +/- 0.5 and increase from 6.0 +/- 0.7 (10) to 8.6 +/- 0.6 ml.h-1, respectively. In contrast injection of ADH caused a negligible increase in 3H2O exchange from whole frogs, while at the same time causing a significant increase in osmotic water exchange from 0.22 +/- 0.08 (6) to 0.63 +/- 0.13 (6) g.100 cm-2.h-1.200 mosM-1. Circulatory changes in whole frogs were produced by inducing a diving bradycardia that was less pronounced in a bath aerated with oxygen than with air. The bradycardia caused a reduction in skin circulation, as measured by 3H2O exchange, from 0.210 +/- 0.007 (16) to 0.17 +/- 0.006 (16) ml.h-1.cm-2 in air mixed media and from 0.149 +/- 0.009 (16) to 0.135 +/- 0.011 (16) in oxygen mixed media. Diving bradycardia was also found to affect osmotic water uptake which decreased from 0.61 +/- 0.05 (16) to 0.39 +/- 0.03 (16) g.100 cm-2.h-1.200 mosM-1 in air mixed media and from 0.61 +/- 0.05 (16) to 0.51 +/- 0.04 (16) in oxygen mixed media. The results indicate that circulation affects osmotic water exchange.


Chylous ascites after a Warren shunt.

Chylous ascites after a Warren shunt. A patient with intractable chylous ascites after a successful Warren shunt procedures is presented. The general incidence, etiology, pathophysiology, and treatment modalities of chylous ascites are discussed. Chylous ascites is a serious postoperative complication of the Warren shunt and should be considered in the differential diagnosis of a patient with ascites subsequent to this procedure.


Studies on the cytodifferentiation of the neuroblasts and visual cells in the chick embryo retina, using the electron-microscopic autoradiography of 3H-thymidine. Studies on the histogenetic analysis of cytodifferentiation of the neuroblast and visual cell in the chick embryo retina were made using the autoradiography of 3H-thymidine. The posterior pole region of the eyeball was observed in all the animals used. The retina in a 4-day-old chick embryo consists exclusively of matrix cells forming the matrix layer. In a 5-day-old chick embryo retina, neuroblasts first differentiated from the matrix cells migrate into the outer part of the matrix layer, forming mantle layer. The matrix cell is a homogeneous epithelial cell containing abundant free ribosomes and a poorly developed cytoplasmic membrane system in the cytoplasm. The characteristic sign of differentiation of the neuroblast is an appearance of elements of rough-surfaced endoplasmic reticulum and an indentation of the nucleus. The primitive visual cell having just lost its ability to synthesize DNA appears just beneath the pigment epithelium in a 7-day-old chick embryo, and all the cells lying beneath the pigment epithelium lose the ability to synthesize DNA at 10 days of incubation. The cytoplasmic process of the matrix cell is in contact with the adjacent one, making an apicolateral junction. When the matrix cell loses its ability to synthesize DNA, a big tentlike process extending over the level of the apicolateral junction appears. This phenomenon is considered to be a sign of differentiation from matrix cell to primitive visual cell, and this big tentlike process containing 2 centrioles is a primordium of the inner segment of the visual cell.


Automatic computerized perimetry in the detection of neurological visual field defects. A pilot study. Forty-seven eyes from 25 patients with neurological disease were examined with an automatic computerized perimeter primarily intended for glaucoma. Manual kinetic and static perimetry with Goldmann's instrument was used for comparison. In 32 fields, the automatic method disclosed all defects that had been found by manual perimetry. Furthermore, it detected three small defects that had been missed in the initial manual examination. The remaining 12 fields were normally using both methods. Consequently, in detecting field defects, the automatic perimeter was superior to the manual method.


Iris fluorescein angiography in diabetic vitrectomy patients. Preoperative iris fluorescein angiograms (IFA) and ophthalmic records of 34 diabetic patients who underwent vitrectomy were reviewed. Of 2 patients without clinically apparent rubeosis, 23 showed evidence of iris microvascular abnormalities or rubeosis on IFA. Patients with rubeosis (Grades III and IV) on IFA had a 63% incidence of postoperative neovascular glaucoma, thus isolating them as a high risk group. The visual outcome of patients developing neovascular glaucoma was poor.


[Photocoagulation and vitreous growth. Experiments on development of the vitreous (author's transl)]. The examination in optical section of sheep eyes, photocoagulated several months previously, shows a disturbed vitreous growth above the destroyed retinal areas (Figs. 2-4). The shape of the resulting deficiencies of vitreous structure (holes) suggests that the vitreous is produced by retinal elements and develops by appositional growth. Holes above lesions due to photocoagulation in an early developmental stage are longer (Fig. 1a; Fig. 2) than those above photocoagulations in later stages (Fig. 1b; Fig. 4). Holes above lesions with intensive retinal destruction (Fig. 2a; Fig. 4a) produce more important vitreous deficienceis than do weaker coagulations (Fig. 2b). Structural deficiencies, though extensive at first, become less important during further growth (Fig. 1c; Fig. 2c; Fig. 3 shows transverse sections at a deep and superficial level through the holes of Figure 2c), which is a sign that in the retinal scars a regeneration of elements producing vitreous occurs. Apart from the theoretical implications concerning the development of the vitreous, the results of our experiments should be considered when photocoagulating children.


Q-switched ruby laser induced damage of the adult rabbit lens capsule. The technique of Q-switched ruby laser induced mechanical destruction of the lens capsule was used to study the reactions of the adult rabbit lens. The defect produced in the anterior lens capsule was larger than the 40-60 micrometer focus, which was due to rolled-up edges of the capsule. Long-term observations revealed some decrease in size of developing localized opacification and a healing of the defect by outgrowing lens epithelium with the formation of a new capsule. The rupture of the posterior capsule led to a slowly progressive opacification with little intraocular macrophage reaction.


Corneal preservation at -4 degrees C in a modified tissue culture medium. Addition of 6% PVP (polyvinylpyrrolidone, mol wt 40,000) to tissue culture medium No. 199 prevents it from freezing at -4 degrees C. Forty donor corneas stored for five and ten days in this medium had a mean thickness of 0.61 and 0.67 mm, respectively. By means of specular microscopy, intact endothelium was found after these storage periods. Epithelial cell layers were histologically present. Electronmicroscopic studies revealed only slight changes in the subcellular endothelial structures. During perfusion with modified Ringer's solution at +34 degrees C, the thickness of stored corneas decreased.