Canine leptospirosis: an immunopathological study of interstitial nephritis due to Leptospira canicola. In an attempt to define the pathogenetic mechanisms involved in acute interstitial nephritis due to Leptospira canicola the kidneys of 14 dogs were subjected to histological immunofluorescence and elution studies. Leptospiral antigen was found in three sites within the kidney; as discrete organisms in the proximal tubules, as granular deposits in the cytoplasm of macrophages and in large extracellular clumps in the interstitium. Deposits of IgG were also detected in the latter site and in plasma cells found in the surrounding cellular infiltrate. Anti-leptospiral antibody, mainly of the IgG class, was detected in renal eluates using both agglutination-lysis and indirect immunofluorescence. From these findings it was considered that the cellular infiltrates found in the kidneys of dogs suffering from acute leptospiral nephritis have two main functions; firstly, the local production of anti-leptospiral antibody and, secondly, phagocytosis.


Pathology of the cervical spine in rheumatoid arthritis: a controlled study of 44 spines. Cervical spines (with occiputs) of 44 patients with rheumatoid arthritis (RA) were compared with 44 control spines from patients without RA, matched for sex and age. There were six severe and seven slight atlanto-axial dislocations (both horizontal and vertical, two of which had been treated surgically) in the RA group and none in the control group. Ankylosis, synchondrosis, syndesmosis, bone erosions, and redness of synovial tissue in the atlanto-axial, atlanto-occipital and cervical intervertebral joints were more frequent in the RA group than in the control spines. The lesions permitting the best discrimination between the RA and control groups were used to calculate an overall score for the whole cervical spine. Sixteen of the 44 RA patients scored higher than the highest control value; only nine scored lower than the median control score. A higher score than the average value found for the RA spines was obtained by the male patients, the patients with seropositivity or subcutaneous nodules, the patients treated with corticosteroids, the patients who died in the Department of Rheumatology, and those whose death was related to the RA itself or to the treatment given.


Skin lesions, angioedema, eosinophilia, and hypocomplementemia. A six-year-old girl with recurrent urticaria and angioedema, vasculitis, and probable renal disease exhibited marked blood eosinophilia, increased levels of serum IgE, circulating Clq precipitins, and hypocomplementemia with evidence of activation of complement by the classic pathway. Biopsies of skin and muscle revealed heavy infiltrations of the vessel walls with eosinophils. Immunofluorescence studies revealed deposition of IgM, IgE, and C3 in the vessel walls. Exacerbations of the disease were associated with an increase in the eosinophil count and a decrease in the serum levels of C4 and C3. Remission was achieved with corticosteroid therapy. This patient has many features in common with the syndrome of skin lesions, angioedema, and hypocomplementemia recently described in adults.


Parathyroid function in uremic children during periods of renal insufficiency, hemodialysis, and transplantation. Function of the parathyroid gland was evaluated in children with renal insufficiency prior to and after imitation of hemodialysis, and again following renal transplantation. Serum levels of immunoreactive parathyroid hormone responded appropriately to increases or decreases of serum calcium concentrations in the three groups. Functional and histologic studies in the children with renal insufficiency demonstrated the cause of their elevated circulating levels of iPTH to be diffuse parathyroid hyperplasia. During hemodialysis, the serum concentration of calcium rose and that of iPTH decreased, when the calcium gradient between the dialysate and the blood favored movement of calcium into the body. During treatment with prednisolone (20 mg/kg intravenously) for reversal of renal transplant rejection, the serum concentration of calcium decreased and that of iPTH increased. These observations suggest that autonomy of the parathyroid gland rarely occurs in children with renal insufficiency, and that hemodialysis using a dialysate with a high concentration of calcium might assist in retarding the progression of renal osteodystrophy. Furthermore, if hyperparathyroidism contributes in part to growth failure in children with chronic renal disease, steroid-induced changes in cirulating iPTH following renal transplantation may inhibit growth.


A prolonged nursery epidemic associated with a newly recognized type of group A streptococcus. During a six-month period 69 infants in a newborn nursery were colonized with group A streptococci. Fifty-one had omphalitis, two infected circumcision wounds, and one each had meningitis, primary peritonitis, and conjunctivitis. Thirteen infants were asymptomatically colonized. Control of the epidemic was difficult. Benzathine penicillin prophylaxis to all infants suppressed active infection but did not eradicate asymptomatic colonization of the umbilical cord. Triple dye treatment of the umbilical cord plus benzathine penicillin prophylaxis eradicated the infection from the nursery. The epidemic streptococcus was a newly recognized ""skin strain,'' provisional type strain 5656-S, not previously known to cause epidemic disease or serious systemic infections.


Bactericidal capacity of monocytes of newborn infants. The peripheral leukocytes of newborn infants and of adult volunteers were studied after separation of polymorphonuclear and mononuclear cells. Monocytes were identified and quantitated with the aid of histochemical staining. The in vitro killing capacity of PMN and of monocytes was assayed against Staphylococcus aureus and Escherichia coli. The monocytes of both infants and adults were significantly less active than were their PMN, but the bactericidal capacity did not differ appreciably between newborn and adult cells of either type.


Beclomethasone dipropionate in long-term treatment of asthma in children. Beclomethasone dipropionate was found to be effective in reducing symptoms of asthma in children. There was no measurable influence on pulmonary function. An 18-month follow-up did not show untoward side effects on adrenal function, growth, serum electrolytes, and hepatic and renal functions with a dose of 100 mug three times daily. The treatment predisposes to the colonization with Candida albicans in the oropharynx.


Theophylline pharmacokinetics in premature infants with apnea. The pharmacokinetics of theophylline were examined in eight low-birth-weight infants (gestation: 26-32 weeks: birth-weight: 887-1,480 gm), who received the drug for treatment of primary apnea. The drug was assayed by high pressure liquid chromatography. The final dosage was 1 to 3 mg/kg/6 hour at 25 to 37 days of age. At the time, theophylline had a prolonged half-life ranging from 13 to 29 hours, a relatively large volume of distribution of 0.65 to 2.86 1/kg, and a small body clearance of 23 to 68 ml/hr/kg. The extremely slow and variable elimination of theophylline must be considered in treatment of apneic infants. The initial dosage regimen suggested is a loading dose of 6 mg/kg and a maintenance dose of 2 mg/kg/ 12 hours, with adjustments made based on monitoring of the serum concentration and on an increased biotransformation capability as maturation occurs.


Cultivation of the erythrocytic stages of Plasmodium berghei in primary bone marrow cells. Cultures of primary bone marrow cells, obtained from the tibiae and femora of hamsters (HBM), mice (MBM), or rats (RBM) were inoculated with red cells infected with Plasmodium berghei, P. vinckei vinckei, or P. knowlesi. Merozoites, rings, trophozoites, schizonts and a few gametocytes were seen in HBM and MBM cells inoculated with P. berghe-infected red cells. At 1 to 2 or 3 days after inoculation in HBM and MBM, the number of intracellular asexual stages decreased slightly or remained the same, whereas at 3 to 7 or 8 days a 4 to 7-fold increase occurred. Parasites then decreased in number from days 8 to 11 and no parasites were seen on day 12. Intracellular parasites were most numerous at 7 and 8 days in MBM and HBM cultures, respectively. Mice injected with supernatant or cells from control cultures (without cultured cells) or primary cultures inoculated 1 and 2 days earlier with P. berghei- or P. vinckei vinckei-infected red cells always became infected. Mice injected with material from 3-day-old control and experimental cultures usually became infected, and those injected with 4- to 12-day-old cultures never became infected.


Schizont-infected cell enrichment in rodent malaria. Mouse erythrocytes parasitized with Plasmodium berghei or Plasmodium yoelii were separated by ultracentrifugation using preformed isodensity gradients of the discontinuous type. Three fractions were obtained following centrifugation, the upper of which contained greater than 90% of all schizont-infected cells added to the gradient. The gradient material, Stractan II, is an arabinogalactan polysaccharide and appears to yield results similar to those available using gradients of bovine serum albumin. Cells are not altered morphologically or physiologically (as assessed by infectivity) by the treatment.


Stimulation of resistance in mice to sporozoite-induced Plasmodium berghei malaria by injections of avian exoerythrocytic forms. Mice received a series of injections of formalin-killed merozoites (FKM) of exoerythrocytic stages of Plasmodium fallax prior to challenge with sporozoites of P. berghei. In one study 4 of 16 FKM-immunized mice never exhibited parasitized erythrocytes after 2 challenges of 10(4) P. berghei sporozoites each, while all control animals died with high parasitemias. FKM-immunized mice were as susceptible as control mice to infections initiated with parasitized erythrocytes. In a second study, 14 of 16 mice immunized via the intravenous (i.v.) or combined intramuscular (i.m.) and i.v. routes were immune to an initial challenge with 10(4) sporozoites, but were susceptible to a second challenge. Three injections of FKM via the i.m. or intraperitoneal routes did not elicit a protective response against sporozoite challenge. Sera harvested from FKM-immunized and control mice prior to challenge produced no visible CSP reaction with P. berghei sporozoites, nor was infectivity of sporozoites altered after incubation in sera, showing that SNA was absent. In additional experiments results were less encouraging. An attempt to repeat the result of the second experiment failed. Each of 5 mice which received the same number of FKM by a similar schedule became infected after sporozoite challenge. In an additional study the immunization schedule was increased from 3 to 7 injections of FKM and 40% of FKM-immunized mice resisted challenge. However, mice which had received FKM prior to sporozoite challenge consistently displayed an increased prepatent period compared with control animals. A department from methods of the more successful studies was necessitated in these later studies in which FKM were harvested from cell cultures maintained for longer periods of time.


A fluidic-controlled, miniature respirator with a new positive airway pressure device. A simple and miniature respirator was developed providing controlled ventilation and application of a positive airway pressure. The positive airway pressure is achieved by an airflow through a canula into the airways. During expiration the direction of this insufflated air-flow is changed and the dynamic pressure necessary for it manifests itself as a positive airway pressure. Mechanical ventilation functions according to the principle of the Ayre-T-Piece: flow direction and, therefore ventilation, is controlled by occlusion of the expiratory limb. Occlusion is brought about by inflating a balloon. The inflation of the balloon is controlled by fluidic-circuits. They allow setting of frequency, duration of inspiration and pressure limit. As the above mentioned system for creating a positive airway pressure is integrated, mechanical ventilation with PEEP is achieved. Tests on a lung model were performed to establish the variables which influence the amount of positive pressure produced by an air-flow through a canula into a tube. Results indicate that the positive pressure obtained is inversely correlated to the diameter of tube and canula and varies with the angle of inflow (Tab. I, II, Fig. 4). The pressure-rise-velocity depicted in Fig. 5 suggests that sighing is possible in an open system. On an anencephalic newborn pressure-flow-ratios were established (Fig. 6). Pressure-time curves during spontaneous breathing, CPAP assisted breathing and sighing combined with CPAP were recorded in a 3 month old baby (Fig. 7, 8, 9). The discussion states the technical performance of the respirator (frequency 100/min-1/3 min., tidal volume 5-100 ml, controlled ventilation with pressure limitation, application of PEEP) and additional advantages (no apparatus deadspace, disposable i.e. sterile air supply-system, the miniature dimensions 10 x 10 x 5 cm, versatility and simple therefore technically reliable construction).


The effect of folic acid on gingival health. On days 0 and 30 of a double blind study, two groups of 15 subjects each were evaluated using a plaque index, a gingival index, a gingival exudate flow and fasting plasma folic acid levels. Group I received 2 mg of folic acid twice daily for 30 days while Group II received a placebo. Results of the study seem to indicate that folic acid supplemented to the diet may increase the resistance of the gingiva to local irritants and thus lead to a reduction in inflammation.


Microbial contamination of dental units and ultrasonic scalers. Microbial contamination of the water system in 12 dental units and nine ultrasonic scalers was investigated. Water samples from ultrasonic scalers, high-speed handpieces and water syringe lines showed microbial concentrations of up to 2.6 million, 3.3 million and 190,000 colony forming units/ml respectively. Flushing the lines for 2 minutes reduced the microbial levels, but complete elimination of all bacteria was not achieved. The infectious potential of contaminated water, to the dentists and patients, particularly the compromised host is discussed.


Synthesis and properties of mesoionic pyrimido[1,2-b-a1pyridazine-2,4-diones and mesoionic pyridazino[2,3-a-a1-s-trizine-2,4-diones: mesoionic analogs structurally related to fervenulin. Derivatives of two new and unusual classes of heterocycles, possessing structural similarities to the broad spectrum antibiotic fervenulin, were synthesized and examined for in vitro antimicrobial activity. Only three of 17 mesoionic pyrimido[1,2-b]pyridazine-2,4-diones exhibited evidence of antimicrobial activity while seven of eight mesoionic pyridazino[2,3-a]-s-triazine-2,4-diones were active against one or more microorganisms. Susceptibility toward attack by nucleophiles of both mesoionic pyridazino[2,3-a]-s-triazine-2,4-diones and fervenulin was observed.


Pharmacokinetics and plasma binding of diazepam in man, dog, rabbit, guinea pig and rat. The pharmacokinetics and plasma binding of diazepam were compared in man, dog, rabbit, guinea pig and rat. Diazepam (D) and its major metabolite, desmethyl-diazepam, were measured in blood and plasma by a specific and sensitive gas-liquid chromatography assay with an electron capture detector. After an intravenous bolus injection plasma levels of D declined biexponentially in all species examined and the data were analyzed according to the two-compartment open model. The binding of D and desmethyldiazepam has been determined at therapeutic concentrations by equilibrium dialysis in man (96.8 and 96.6%, respectively), dog (96.0 and 95.9%), rabbit (89.9 and 94.7%), guinea pig (91.3 and 78.6%) and rat (86.3 and 90.5%). In man, the elimination half-life, T1/2(beta), increased significantly (P less than .01) with decreasing total plasma clearance (Cl). Plasma binding affected Vd and Cl, but only Cl increased significantly (P less than .05), if more free D was available. This indicates that unbound drug is rate-determining for clearance by the liver, and that D fits into the restrictive elimination class in man. In the four animal species tested, Cl was a direct linear function of the body surface area. T1/2(beta) and the rates of drug clearance were characteristic figures for each species: from 1.1 hours and 81.6 ml/min/kg in the rat to 32.9 hours and 0.35 ml/min/kg in man, whereas T1/2(alpha), the half-life of distribution, varied only approximately 3-fold (0.3-1.0 hours) in the different species. A considerably higher extraction ratio than the unbound fraction of diazepam exists in these animal species, and blood clearance exceeds liver blood flow, giving reason to assume a much higher ability of the liver to metabolize D, and a species-dependent extrahepatic metabolism. The large variations described suggest that pharmacokinetic data or plasma binding results cannot simply be extrapolated to man.


Pepsin secretion in the anaesthetized cat and the effect of sympathetic nerve stimulation. 1. Experiments were performed on chloralose anaesthetized cats and gastric mucosal blood flow, acid and pepsin secretions were measured. Gastric mucosal pepsin and protein contents were measured at the end of the experiments which were done in three groups: gastrin (A), vagal (B), vagal and sympathetic nerve (C) stimulations. 2. Vagal stimulation significantly reduced (76%) the pepsin content of gastric mucosa compared with gastrin stimulated animals, none of which secreted pepsin. 3. The sum of the secreted and extracted pepsins for all the three groups was not significantly different. There was no significant difference in the extracted protein from any of the groups. 4. Gastric mucosal blood flow, acid and pepsin outputs all had significant correlations with time during the first 70 min of vagal stimulation. During the period 80-160 min of vagal stimulation acid secretion and mucosal blood flow were not correlated with time but pepsin output declined significantly. From 170 to 220 min of vagal stimulation, acid and pepsin outputs and mucosal blood flow were not correlated with time. 5. The assumed pepsin store during each period was calculated and after 40 min of vagal stimulation there is a constant percentage pepsin output from this assumed store. 6. There is some data to suggest that pepsinogen synthesis was occurring during the period 170-220 min of vagal stimulation. 7. Sympathetic nerve stimulation which started at 160 min after the beginning of sustained vagal stimulation, significantly inhibited gastric acid secretion and mucosal blood flow, and in addition it significantly inhibited pepsin secretion. This is consistent with the hypothesis that sympathetic nerve inhibition of gastric mucosal function is mediated by a vasoconstrictor mechanism.


Adrenal and pancreatic endocrine responses to hypoxia in the conscious calf. 1. Pancreatic and adrenal responses to intense hypoxia have been examined in conscious unrestrained calves 3-5 weeks after birth. 2. The outputs of both cortisol and corticosterone from the right adrenal gland rose steadily in response to hypoxia and this cortical secretory response was accompanied by a pronounced increase in blood flow through the gland. The changes in both steroid output and adrenal blood flow corresponded with those which occur in response to supramaximal doses of corticotrophin in calves of the same age. 3. Neither adrenaline nor noradrenaline were released in significant amounts from the adrenal medulla until the arterial PO2 had fallen below 15 mmHg. Such severe hypoxia caused secretion of catecholamines at rates comparable with those recorded during maximal stimulation of the sympathetic innervation to the gland in anaesthetized calves. The response to intense hypoxia in these conscious calves differed from that which occurs under anaesthesia in that the amount of adrenaline released was invariably greater than that of noradrenaline. 4. Severe hypoxia produced a rapid but transient increase in plasma glucagon concentration, followed by a pronounced rise in plasma glucose concentration in animals with abundant liver glycogen. No change in plasma insulin concentration was observed during hypoxia although it rose subsequently in response to hyperglycaemia. 5. Bilateral section of the splanchnic nerves virtually abolished the release of catecholamines in response to hypoxia but the adrenal cortical and pancreatic responses did not appear to be affected.


Controlling anomalies of vertical dimension and speech. In this article, definite ways and means have been discussed for controlling the the verticale dimension of occlusion by using certain tooth-to-tooth and tooth-to-tissue relations that exist in normal speech. The primary emphasis is placed on managing the problems encountered in the most troublesome types of patients--those with Class II occlusions, the tongue thrusters, and those who lisp. It is not easy to identify those patients in whom these problems previously existed after they become edentulous. An Analytical Control Chart has been introduced which can be used to separate these problem patients from the normal ones, and a step-by-step procedure for their management can be followed. Also the phases of this approach which are beneficial in restorative dentistry are reviewed.


The residual ridge in partially edentulous patients. The residual ridge which forms after the extraction of teeth is characterized by a loss of substance when compared with the dentulous ridge. The residual ridge shrinks in an apical direction and shifts lingually. This remodeling pattern takes place mainly at the expense of the bony crest, the buccal plate of the alveolar process, and the gingival tissues covering it. The lingual positioning of the residual ridge crest was observed in maxillary and mandibular specimens in all the regions of the jaws and regardless of the number of teeth missing. Cross sections of the residual ridge were square, parabolic, or tapered. The base of the pontic for a fixed partial denture should be made buccolingually as the mirror image of the crest of the residual ridge it is to contact, and it should follow mesiodistally the contour and length of the clinical crowns of the adjacent abutment teeth.


A stent for a split-thickness skin graft vestibuloplasty. Accepting the requirement that there must be intimate contact between a split-thickness skin graft and the underlying periosteum in a vestibuloplasty, a method of forming a stent to meet this.criterion is presented. The procedure uses an overextended impression and a custom-made acrylic resin base. Two methods of modifying the base with a secondary impression to form a stent at the time of the operation are described.


Relationship of investing medium to occlusal changes and vertical opening during denture construction. Four groups of 20 dentures with nonanatomic teeth were processed using four different investing techniques. The incisal guide pin was measured and recorded before processing and again after processing and remounting of each denture on the articulator. The difference between the two readings indicated vertical changes during processing. The least vertical opening and a complete absence of occlusal changes occurred in the dentures invested in the plaster of paris core with an artificial stone cap. The following conclusions were made: (1) Vertical opening in denture processing can be minimized by investing in plaster of paris molds with a stone occlusal matrix. (2) Tooth movement is minimized by the use of this investment combination. (3) Inadequate investing procedures contribute to vertical opening and occlusal discrepancies. (4) Vertical opening of dentures processed by compression molding technique may be due to other factors. This can only be determined by further investigation.


The bond strengths of resin systems to etched enamel. This study was undertaken to compare the resin-enamel bond strengths of seven anterior restorative resins using the acid-etch technique. Six of the materials (Restodent, Enamelite, Smile, Nuva-System, Concise, and Adaptic) were composite resins. Only one, Sevriton, was an unfilled resin. Of the seven, only Sevriton and Smile were not designed for the acid-etch technique. Of the materials tested, Sevriton and Enamelite had the weakest bonds. There was no significant difference in the bond strength among Nuva-System, Smile, and Restodent; the bonds of all these were stronger than those of Sevriton and Enamelite. Concise showed a significantly greater bond strength than all the other materials in the study except Adaptic and the Nuva-System. The resin-enamel bond strength of Adaptic was of a greater magnitude than that of all other test materials.


Porcelain shoulder adaptation using direct refractory dies. Eleven direct refractory dies were made from separate polysulfide rubber impressions of two Dentoform teeth which had been prepared for porcelain-fused-to-gold veneer crowns with labial porcelain shoulders. Porcelain veneer crowns were built and fired directly on the dies, following the manufacturer's instructions and using a common laboratory technique. The finished crowns were seated on the Dentoform teeth, and the porcelain-tooth adaptation was measured with a micrometer eyepiece in a dissecting microscope. In general, the study indicated that by use of a direct refractory die, the porcelain adaptation of an average porcelain shoulder veneer crown could be made to fall within the tolerances of a clinically acceptable gold margin (39 mu).21 The crown could likewise be made to adapt closer than the normal thickness of cement film may allow (20 to 40 mu).22 However the adaptation of many crowns was more uneven than the above statements would tend to indicate. The study also showed that with great care and a limited number of firings, margins of a lesser thickness than a piece of 0.001 inch (25.4 mu) platinum foil could be attained. There appears to be promise in the use of a direct refractory die material. However, more studies are needed to overcome some of the problems in the technique described.


Midline granuloma and Wegener's granulomatosis: clinical & therapeutic considerations. Midline granuloma (MG), limited Wegener's granulomatosis (LWG), and generalized Wegener's granulomatosis (WG) have been viewed by some investigators as representing an interrelated disease spectrum. Others believe that MG and WG are two distinct clinicopathologic entities. A series of cases is presented suggesting that therapy of MG should be individualized. Treatment may include corticosteroids, high-dose irradiation, and/or immunosuppressive drugs. LWG may be treated initially with corticosteroids alone, but lack of response requires the addition of an immunosuppressive agent. WG should be treated with an immunosuppressive drug and, at times, corticosteroids as well. None of the cases of MG described in this report progressed to WG. This may be interpreted as supporting the contention that MG and WG are separate diseases. Alternatively, aggressive treatment of MG with irradiation or immunosuppressives may prevent its transition to more generalized disease.


Renal damage in systemic lupus erythematosus with normal renal function. Renal biopsies were performed on 12 patients with definite systemic lupus erythematosus (SLE) with normal renal function. Three had had previous nephropathy which responded to treatment, with return of urinalysis and function to normal. Specimens were studied using light microscopy (LM), immunofluorescence (IF), and electron microscopy (EM). Mild to moderate abnormalities were found in all patients. Changes by LM (primarily hypercellularity) were found in 11 specimens (no glomeruli were obtained in one) and classified as inactive. IF studies were positive in eight of the 12 biopsies with either focal or diffuse distribution of IgG, IgM, and/or C3. EM changes were observed in all cases and were of mild to moderate severity. They included focal to multifocal glomerular hypercellularity, basement membrane thickening, foot process fusion, and mesangial and intramembranous electron dense deposits. No subepithelial or subendothelial deposits were found. Microtubular structures were present in three specimens. These data suggest that careful study of renal biopsy specimens may reveal evidence of kidney involvement in all patients with SLE.


Phosphorus-nitrogen compounds. 20. Thiophosphorus hydrazones. Six pyridine-2-carboxaldehyde, one pyridine N-oxide 2-carboxaldehyde, and five diketone thiophosphoric hydrazones, three thiophosphoric hydrazides, and two cupric chelates were synthesized. The chelates and nine of the hydrazones were tested against Ehrlich ascites carcinoma. Seven of these latter  agents were administered concurrently with either cupric and/or ferrous salts to mice bearing this tumor. The greatest activity was found with the chelate, cimethyl pyridine-2-carboxyaldehyde phosphorothioic hydrazone-copper (1:1). The hydrazone portion of this chelate also formed a ligand-copper (2:1) complex. Although all of the hydrazones but one were inactive when evaluated alone, the concurrent injection of cupric ion increased survival times by an avoli alkaline phosphatase was found to be inhibited by two thiosemicarbazones in a manner similar to that previously reported by these agents against alkaline phosphatase derived from Sarcoma 180-6-thiopurine resistant ascites cells. None of the 14 hydrazides or hydrazones tested against E. coli enzyme displayed significant inhibition.


Family medicine: an historical perspective. The relatively new specialty, family practice, has stimulated a renewed interest in personal, comprehensive care of the entire family. This approach to patient care is derived from the general practice tradition. The development of family practice as a specialty occurred at the end of a long period of decline in general practice. Understandably, the founders of family practice sought to identify and change or eliminate factors contributing to this decline. Organized efforts to effect these changes began with the establishment of the American Medical Association Section on General Practice in 1946 and the American Academy of General Practice in 1947 and culminated with the final approval of the new discipline as a medical specialty in 1969. The success of this new specialty is a tribute to the efforts and careful planning of its founders.


Ca++ fluxes in isolated cells of rat pancreas. effect of secretagogues and different Ca++ concentrations. Secretagogues of pancreatic enzyme secretion, the hormones pancreozymin, carbamylcholine, gastrin I, the octapeptide of pancreozymin, and caerulein as well as the Ca++ -ionophore A 23187 stimulate 45Ca efflux from isolated pancreatic cells. The non-secretagogic hormones adrenaline, isoproterenol, secretion, as well as dibutyryl cyclic adenosine 3',5'-monophosphate and dibutyryl cyclic guanosine 3',5'-monophosphate have no effect on 45Ca efflux. Atropine blocks the stimulatory effect of carbamylcholine on 45Ca efflux complately, but not that of pancreozymin. A graphical analysis of the Ca++ efflux curves reveals at least three phases: a first phase, probably derived from Ca++ bound to the plasma membrane; a second phase, possibly representing Ca++ efflux from cytosol of the cells; and a third phase, probably from mitochondria or other cellular particles. The Ca++ efflux of all phases is stimulated by pancreozymin and carbamylcholine. Ca++ efflux is not significantly effected by the presence or absence of Ca++ in the incubation medium. Metabolic inhibitors of ATP production. Antimycin A and dinitrophenol, which inhibit Ca++ uptake into mitochondria, stimulate Ca++ efflux from the isolated cells remarkably, but inhibit the slow phase of Ca++ influx, indicating the role of mitochondria as an intracellular Ca++ compartment. Measurements of the 45Ca++ influx at different Ca++ concentrations in the medium reveal saturation type kinetics, which are compatible with a carrier or channel model. The hormones mentioned above stimulate the rate of Ca++ translocation. The data suggest that secretagogues of pancreatic enzyme secretion act by increasing the rate of Ca++ transport most likely at the level of the cell membrane and that Ca++ exchange diffusion does not contribute to the 45Ca++ fluxes.


Errors in area measurement in thick sections, with special reference to trabecular bone. A formula is derived for the errors caused by section thickness in the measurement of the mean cross-sectional areas of opaque material embedded in a transparent medium. There are some simplifying assumptions which can only be justified by limiting the maximum thickness of the section, but no restriction whatever is placed upon the shape of the opaque material. For isotropic materials a very simple formula is found, relating the relative error in cross-sectional area to measurements of area and boundary profile length on the section surface. The effect of anisotropy in the material may be very large. To illustrate this, numerical calculations are made for two particular classes of simple anisotropic material, those which might be made from isotropic materials by linear distortions.


Superconductivity--a possible mechanism for non-thermal biological effects of microwaves. Recent evidence for high temperature superconductivity in lipids and in a protein and for a role for superconductivity in growth and nerve processes, combined with experimental demonstration of microwave effects on probable superconductive tunneling in carbon films at room temperature, suggest the possibility that non-thermal effects of microwaves on biological systems may occur by a superconductive mechanism.


Properties and synthesis of tubulin in neuroblastoma cells. Cloned neuroblastoma cell lines derived from the spontaneous mouse tumor C-1300 were used to study nerve cell differentiation. Our findings included a) morphologic and electrical differentiation was induced by the addition of dimethyl sulfoxide to the culture medium of some of the neuroblastoma clonal lines; b) a contrasting difference existed between the percentage of the phenylalanine-specific, tRNA species deficient in the peroxy Y-nucleoside in the mouse embryo or rat brain (6-10%) and that of mouse neuroblastoma cells (85%); c) the assembly of neuroblastoma microtubules and neurofilaments that are necessary for neurite outgrowth proceeded from preexisting pools of tubulin and actin, but a sustained level of phosphorylated tubulin was not required for this regulation; and d) the in vitro translation of tubulin and actin was accomplished with mRNA from rat brains in a wheat-germ cellfree system.


Control of expression of differentiated functions in neuroblastoma cell hybrids. Cell hybrids have been extensively utilized for gene mapping; more than 50 enzymes and nonenzyme proteins have been assigned to individual human chromosomes. Hybrids have also been used in the study of differentiation; fusions involving mouse or human neuroblastoma cells and various nonneuronal lines resulted in hybrid cells that continued to express neuronspecific functions. The expression of the differentiated state is, however, not an all-or-none phenomenon: One neuronal trait may be evident in such hybrids, in the absence of others. The potential usefulness of the human neuroblastoma hybrids for the assignment of genes involved in the expression of differentiated functions to specific chromosomes is discussed.


Interaction between Trypanosoma brucei and Plasmodium berghei in concurrent infections in mice. In conccurrent infection of Trypanosoma brucei rhodesiense and Plasmodium berghei yoelii in mice, potentiation of one parasite by the other was observed, especially the malaria by the trypanosome infection. The effect appeared early in the infection. It is suggested that the mutual potentiation of the two infections was probably due to immuno-suppression which both organisms are capable of inducing in the host.


Replicative bacteriophage DNA synthesis in plasmolyzed T4-infected cells: evidence for two independent pathways to DNA. Bacteriophage T4-infected Escherichia coli rendered permeable to nucleotides by sucrose plasmolysis exhibited two apparently separate pathways or channels to T4 DNA with respect to the utilization of exogenously supplied substrates. By one pathway, individual labeled ribonucleotides, thymidine (tdR), and 5-hydroxymethyl-dCMP could be incorporated into phage DNA. Incorporation of each of these labeled compounds was not dependent upon the addition of the other deoxyribonucleotide precursors, suggesting that a functioning de novo pathway to deoxyribonucleotides was being monitored. The second pathway or reaction required all four deoxyribonucleoside triphosphates or the deoxyribonucleoside monophosphates together with ATP. However, in this reaction, dTTP was not replaced by TdR. The two pathways were also distinguished on the basis of their apparent Mg2+ requirements and responses to N-ethylmaleimide, micrococcal nuclease, and to hydroxyurea, which is a specific inhibitor of ribonucleoside diphosphate reductase. Separate products were synthesized by the two channels, as shown by density-gradient experiments and velocity sedimentation analysis. Each of the pathways required the products of the T4 DNA synthesis genes. Furthermore, DNA synthesis by each pathway appeared to be coupled to the functioning of several of the phage-induced enzymes involved in deoxyribonucleotide biosynthesis. Both systems represent replicative phage DNA synthesis as determined by CsCl density-gradient analysis. Autoradiographic and other studies provided evidence that both pathways occur in the same cell. Further studies were carried out on the direct role of dCMP hydroxymethylase in T4 DNA replication. Temperature-shift experiments in plasmolyzed cells using a temperature-sensitive mutant furnished strong evidence that this gene product is necessary in DNA replication and is not functioning by allowing preinitiation of DNA before plasmolysis.


DNA of minute virus of mice: self-priming, nonpermuted, single-stranded genome with a 5'-terminal hairpin duplex. The genome of the nondefective parvovirus minute virus of mice (MVM) is a linear DNA molecular weight 1.48 x 10(6), which is single stranded for approximately 94% of its length. In contrast to the genomes from defective parvoviruses MVM DNA does not contain a detectable inverted terminal redundancy. A combination of enzymatic and physical techniques has shown that the molecule contains a stable hairpin duplex of approximately 130 base pairs located at the 5' terminus of the genome. MVM DNA is efficiently utilized as a template-primer by a number of DNA polymerases, including reverse transcriptases. Polymerases lacking 5' to 3' exonuclease activity yield a duplex DNA product with a molecular weight 1.96 times that of the viral genome, in which the newly synthesized complementary strand is covalently attached to the template. This duplex contains an internal "nick" that can be sealed by DNA ligase to produce a self-complementary single-strand circle. The MVM DNA duplex is cleaved twice by EcoR-RI restriction endonuclease to yield three distinct fragments in molar amounts. These results suggest that the initiation of DNA synthesis in vitro occurs at a point within 100 bases of the 3' end of the genome, using the 3' terminus of viral DNA as a primer, and that the sequence of nucleotides in the genome is not permuted.


Bacteriophage-specific DNA-binding proteins in P22-lysogenic and in P22-infected Salmonella typhimurium. Crude extracts of Salmonella typhimurium lysogenic for phages P22 or L contain proteins that specifically retain phage DNA on nitrocellulose filters. Three DNA-binding activities were found after infection with P22. One is P22 specific, accounts for the largest proportion of DNA-binding proteins, and corresponds most likely to the c2 repressor. An early transient binding activity measured with both P22 and L DNA was found to be directly related to the expression of genes c1 and c3. A third, late binding activity for P22 and L DNA is related to phage production.


Some limitations and pitfalls of excretory urography. A review of some of the more important limitations and pitfalls in the interpretation of excretory urograms is presented. Although there is no infallible method of avoiding interpretive errors it is suggested that the development of good viewing habits, including an orderly and systematic appraisal of each film, coupled with a physiologically oriented approach to film interpretation will reduce mistakes significantly. Similarly, many pitfalls may be circumvented by the simple expedient of close collaboration between urologist and radiologist, and by the reluctance of either to accept urography that is suboptimal by current standards.


Bacterial rep- mutations that block development of small DNA bacteriophages late in infection. Several related mutants of Escherichia coli C have been isolated that block the growth of the small icosahedral DNA phages phiX174 and S13 late in infection. Phage G6 is also blocked, at a stage not yet known. Growth of the filamentous phage M13, though not blocked, is affected in these strains. These host mutations co-transduce with ilv at high frequency, as do rep- mutations. However, the new mutants, designated groL-, differ from previously studied rep- mutants in that they permit synthesis of progeny replicative-form DNA. The groL- mutants are blocked in synthesis of stable single-stranded DNA of phiX174 and related phages. They are gro+ for P2. Evidence that groL- mutations and rep- mutations are in the same gene is presented. Spontaneous mutants (ogr) of phiX174, S13, and the G phages can grow on groL- strains. The ogr mutations are located in the phage's major capsid gene, F, as determined by complementation tests. There are numerous sites for mutation to ogr. Some mutations in genes A and F interfere with the ogr property when combined with an ogr mutation on the same genome. The ogr mutations are cis acting in a groL- cell; i.e., an ogr mutant gives very poor rescue of a non-ogr mutant. The wild-type form of each G phage appears to be naturally in the ogr mutant state for one or more groL- strains. It is suggested that a complex between F and rep proteins is involved in phage maturation. The A protein appears to interact with this complex.


The urographic findings in acute pyelonephritis: non-obstructive hydronephrosis. Excretory urography was performed on 4 patients early in the course of acute pyelonephritis. These studies showed dilatation of the involved collecting system without obstruction. The dilatation resolved after therapy in 3 patients and was not present on a previous excretory urogram in the fourth. Although previous studies have shown that the excretory urogram is usually normal in cases of acute pyleonephritis these cases demonstrate that this disease can produce dilatation of the collecting system and mimic obstruction.


Scintiphotography in the early diagnosis of urine leakage following renal transplantation. The use of radionuclides in the evaluation of postoperative renal transplantation patients has proved to be an effective technique for the early diagnosis of urinary extravasation. It has the advantage of demonstrating the existence of urine leakage prior to visualization of extravasation on conventional cystograms and excretory urograms. It has the additional advantage of requiring no urological instrumentation and can be repeated as often as clinically indicated.


Serratia marcescens and the urologist.

Serratia marcescens and the urologist. Serratia marcescens, long considered a non-pathogen, is now found to be responsible for outbreaks of nosocomial infections. An outbreak of Serratia infection at 2 institutions is reported, in which 253 cultures of Serratia were grown and 115 patients were involved. The 3 most important conditions that preceded isolation of Serratia were the use of indwelling urethral catheters, antibiotic therapy and operation. All infections were acquired in the hospital. An epidemiological survey showed that the organism is present in the environment, even in the absence of active infection.


The control of postoperative wound pain with the use of bupivacaine injections. In a study of 50 operative cases 0.5% bupivacaine hydrochloride solution was injected in the area of the subcostal nerves at the time of closure of the wound except in 2 with previously noted infection. In the latter 2 cases the solution was injected when the wound was opened. No untoward results were noted from these injections and a definite decrease in the use of analgesics was required. In addition, there is preliminary evidence that peristalsis and flatus occur much earlier in cases in which the solution was used compared to a control group. Respiration was enhanced, earlier patient mobility was noted and the general depression from injectable analgesics was avoided.


Use of defunctionalized bladders in pediatric renal transplantation. Congenital urinary tract anomalies are common causes of renal insufficiency and failure in children. Frequently, the hydroureteronephrosis and/or bladder damage from previous reconstructive procedures is so severe that supravesical diversion is required. Renal transplantation in these cases is sometimes avoided because of implied urologic and infectious complications, and the early loss of the homograft. Nevertheless, newer techniques have been developed for transplantation in patients with end stage renal disease and defunctionalized bladders. Herein is described the use of defunctionalized bladders as receptors of renal homografts in 5 of 42 transplant recipients seen during the last 4 years.


Pseudorejection: the Page kidney phenomenon in renal allografts. A case of renal allograft pseudorejection owing to perinephric hematoma is presented and the Page kidney phenomenon is discussed as the pathophysiologic mechanism. The term pseudorejection is introduced and defined as a remediable form of graft dysfunction resulting from renal parenchymal compression. Sonography was helpful, in addition to the standard diagnostic modalities in making the diagnosis. Early recognition and decompression of a peritransplant hematoma or lymphocele may decrease graft loss from this insidious entity.


Idiopathic ureterolithiasis in a renal transplant patient. Only 9 cases of ureteral stone formation in renal transplant recipients have been reported previously. The majority of these occurred in association with hyperparathyroidism. We herein describe a case in which a ureteral calculus caused partial obstruction within 3 months in a euparathyroid recipient of a living related renal transplant.


Foreign body in bladder and perivesicular inflammation masquerading as pelvic lipomatosis. Inverted teardrop-shaped bladder deformity ofetn is caused by pelvic lipomatosis or perivesical accumulation of extravasated blood or urine, or both. A foreign body (toothpick) lodged in the bladder and resulting in urinary infection and perivesical inflammation also was found to be capable of causing this unusual bladder deformity. The bladder contour returned to normal after removal of the foreign body and treatment of infection.


Reduction perineoplasty for scrotal elephantiasis: a method of surgical reconstruction of the penis and scrotum. Scrotal elephantiasis can be insidious in onset, idiopathic as to cause and debilitating in progress. The massive scrotal enlargement results in a sac-like structure that first envelopes and then completely covers the penis, testes and the regional spermatic cord structures, causing loss of topographic identification. The urethra leads into a stratified, squamous epithelial-lined canal, which traverses the edematous subcutaneous tissue to open irregularly at the inferior aspect of the scrotal bag. The difficulty of acquiring sustained periods of cleanliness, the incontinence of urine despite an intact urethral sphincter, the unesthetic gross appearance and the loss of libido and mechanical copulation function are the significant symptoms and signs that indicate the extent of the debility. A form of treatment that would alleviate this distressful state and would be feasibly applicable should be worthy of critical consideration. Therefore, a case of a reduction scrotoplasty (reduction perineoplasty) for idiopathic lymphedema of the penis and scrotum is presented.


Rehabilitation after cardiac transplantation. The physical, occupational, and social status of 56 patients who survived six or more months after cardiac transplantation at Stanford University Medical Center was reviewed. Fifty-one (91%) were classified as successfully rehabilitated. Four (7%) retained substantial physical disability, and one (2%) experienced psychiatric disability. These results demonstrate the therapeutic usefulness of cardiac transplantation in carefully selected recipients.


Pancreatic abscess with Haemophilus influenzae and Eikenella corrodens. An infected pancreatic pseudocyst was caused in part by Haemophilus influenzae and Eikenella corrodens. To my knowledge, neither organism has been isolated previously from pancreatic abscesses. I believe that the infecting bacteria originated in the oropharynx and descended through the duodenum.


Persistence of Treponema pallidum following penicillin G therapy. Report of two cases. The isolation of Treponema pallidum from cerebrospinal fluid (CSF) obtained from two adult patients, both of whom had normal CSF values except for positive fluorescent treponemal antibody-absorption (FTA-ABS) tests and both of whom had received currently recommended courses of penicillin, raises important considerations in the treatment of neurosyphilis in adults.


Transition in the character of immunological memory in mice after immunization. I. Memory for IgM and IgG antibody responses. The immunological memory in antibody response of mice to bovine serum albumin was investigated at the level of IgM and IgG antibody-forming cells, The antigen at a dose much lower than required for eliciting a detectable level of the primary antibody response could latently activate the immune machinery to an extent adquate for specific recall, whereas higher doses of antigen were effective in evoking strong anamnestic response. The potentiality to develop the anamnestic response was found even in the latent phase of the primary antibody response and was maintained for more than 2 months. The immunological memory acquired in an early phase after the primary immunization mainly involved IgM antibody response and late memory concerned IgG response.


Clinical study of second kidney transplantation. During the period from November 1972 to February 1975, 39 patients received second renal grafts in our institution. The clinical course of the patients was analyzed and compared with 121 patients who received only one graft during the same period. The graft survival either from living related or cadaveric sources was inferior in the second graft group. However, mortality was not increased by re-transplantation. Major differences were noted in the occurrence of hyperacute or accelerated type rejections. There was a high incidence of this type of rejection in the second graft group, especially in the simultaneous retransplant group.


[ECG changes during a stenocardia attack caused by physical loading]. ECG was examined during anginal attacks caused by dosaged bicycle tests in 200 patients with chronic coronary insufficiency of varying degree. In 79.5% of the patients the anginal attack was accompanied by ECG changes. The ECG changes preceeded the appearance of anginal attack precursors. Half of the patients, mainly those with infrequent attacks of retrosternal pains recurring not daily, and only under extreme physical exercises, could continue the test for 2 min. and longer despite the appearance of transitory ECG changes, and do on with it until the development of anginal attack precursors. Proper attention to this fact seems to be of importance for the evaluation of the reserve of coronary circulation in patients with chronic coronary insufficiency.


[Cardiac insufficiency in ischemic heart disease]. The presented analysis deals with the physiopathological mechanisms of the debelopment of postinfarction cardiac insufficiency and the clinical peculiarities of its manifestations. It is emphasized that the leading cause of cardiac insufficiency consists in a reduction of the contractile function of the left ventricular myocardium due to the development of asynergy in the cicatrical zone. The addition of several accompanying factors, such as heart mitralization, tachysystolic form of ventricular fibrillation, repeated infarction with a growing asynergic zone, aggravate the course of cardiac insufficiency providing for the development of hypertension in the general circulation system.


[Effect of hydrocortisone on some indices of cardiac activity and of the greater circulation in acquired heart defects]. The catheterization technique was used to study the effect of 100 mg of water soluble hydrocortisone "Russel" upon the cardiac activity and greater circulation in patients with acquired heart diseases. Hydrocortisone was found to produce different effects upon the cardiac output and tonicity of the greater circulation vessels--increases or decreases them, or does not change at all. The varying dynamics of these indices serves as a manifestation of the optimizing effect of hydrocortisone on the cardiovascular system, depends on the initial values of the parameters in question, and is directed towards normalizing the oxygen consumption in the body (its blood flow). No direct correlation was found between the cardiac output and the pressure in the ventricles in patients with acquired heart diseases prior to and following hydrocortisone administration.


[Daniel Bernoulli (author's transl)].

[Daniel Bernoulli (author's transl)]. History in medicine receives life only from personalities. This is a report on the physician and mathematician Daniel Bernoulli which considers also his relationship to his father Johann Bernoulli and also his ambivalent relationship to his mothertown Basel. Very interesting parallels to the life of Hermann Helmholtz are demonstrated. Daniel Bernoulli, later professor of physics, lectured a mathematically based functional anatomy; in this connection he dealt profoundly with the eye and its function. The author deals with Bernoulli's work on muscle contraction (demonstrated on the abducens muscle) and on the elementary perimetric determination of the blind spot.


[Julius Hirschberg (1843-1925), ophthalmologist and medical historian (author's transl)]. Julius Hirschberg of Berlin was one of the most brilliant ophthalmologists of his time. As a surgeon and as the editor of the "Centralblatt für praktische Augenheilkunde" (1877-1919) he enjoyed a world-wide reputation. He devised an electrical hand magnet for the extraction of intraocular foreign bodies (1879 - see Duke-Elder, System of ophthalmology, vol. 14/I, p.616) and investigated, among many other aspects of clinical ophthalmology, the ocular manifestations of general disease (e.g. diabetes). Hirschberg's greatest achievement is his History of ophthalmology, from the ancient Egyptians down to 1900 AD ("Geschichte der Augenheikunde" 1899-1919, 9 vols., 4700 p.). Because Hirschberg mastered not only several modern languages, but also Greek, Latin and Arabic, he was able to familiarize his readers with the original thoughts or even words of the earlier authors. Belonging himself to a positivistic and optimistic generation, he based his narratian on men, facts and tangible progress. Many problems which are discussed by modern historians of science have already been masterly treated by Hirschberg; reading his "Geschichte" is still worthwhile, even for English speaking scholars.


[Excentric lamellar graft in cases of recurrent pterygium (author's transl)]. A description is given of a technique using a lamellar graft for the treatment of recurrent pterygium. The rate of recurrence is smaller than when compared to the results obtained by treatment with simple lamellar keratectomy.


[The treatment of candida-albicans-endophthalmitis (author's transl)]. A widespread septicaemia with candida albicans, which occurs most commonly after excessive therapy with antibiotics and steroids or after immunsuppressive therapy, may produce an endogenous endophthalmitis. We observed 7 such cases treated with 5-fluorocytosine (Ancotil, Roche). The treatment was successful in 5 cases. There were no serious side-effects observed from this drug.


[The development of the hydrophilic contact lens and the optical and therapeutical significance (author's transl)]. The development of soft lenses is recent compared to the history of hard lenses. In cooperation with chemists an appropriate material was developed which was found more suitable than all previously used hard material for close contact with the cornea. The development of the soft lens from the modest start up to the most advanced soft lens is shown in tables demonstrating the therapeutic results in young children with unilateral aphakia. During the development the scepticism of many experts had to be overcome. To day the soft lens is a contact optical and thereapeutic aid of great significance.


[Simple repairs for loss of eyelid substance (author's transl)]. The authors present the simple technics of eye lid repair. The loss of skin and possibly of M. orbicularis oculi, is differentiated from that of the complete thickness of the eye-lid. The first can be treated by free Thiersch or Wolfe-Krause-split-skin graft or full thickness skin grafts, the second by direct suture or by various local advancement flaps according to the "quarter" rule of Mustardé.


[Complex repairs for loss of eyelid substance (author's transl)]. The repair of large defects of the lid region may require complex reconstruction using skin, tarsus and conjunctival grafts or flaps. The authors have classified the lesions in three groups: inner canthus, lower lid and upper lid. For each group, the more applicable technics are described.


[Two-stage full-thickness skin grafts to cover extensive lid defects (author's transl)]. Delayed full-thickness skin grafts present an alternative means of treatment to flaps for the closure of deep defects in the lid region. They are indicated wherever there is a risk of recurrence of the causative process which might lead to the loss of the transposed skin.


[Recurring, infiltrative and destructive lipo-granuloma of the lid following treatment of relative stenosis of the lower canaliculus (author's transl)]. The application of fat-containing ointment to the horizontal part of the lower canaliculus produced within 12 weeks a rapidly growing Lipoid-Granuloma of the whole lower lid. A recurrence shortly after surgical removal of the tumor necessitated surgical reconstruction of the lid.


[Advances in the automation of perimetry (author's transl)]. The most important improvements and innovations since 1973 in the automatic perimeter Octopus are described. On the one hand, they include instrumental modifications, namely spatial separation of the perimeter from its control panel, the introduction of step motors in order to increase the accuracy of setting of the stimulus coordinates, the tilting of the perimeter cupola and patient in order to increase stability and comfort of the latter, a fully automated fixation control system, the use of a magnetic-tape recording system, providing analytical programs for the computer and recording computer-answers at the same time. On the other hand, progress has been made in the optimisation of threshold determination methods in the visual field and in the design of methods for the graphical display of the sensitivity distribution across the visual field.


[Reconstruction of the medical canthal area (author's transl)]. Defects of the medial canthal area with partial full-thickness loss of the upper and lower eye-lid can be repaired by the following technique: closure of the larger lid defect by a free transplant of tarsus and lid margin from the opposite lower lid and a sliding skin flap. The minor lid defect is closed by a pedicled tarso-conjunctival flap and a free or sliding skin graft.


[Sexchromatin determination in a corneal graft in adult cystinosis (author's transl)]. On the basis of the distribution of F-bodies (Y-Chromatin) and Barr-bodies (X-Chromatin) in a lamellar keratoplasty from a female donor and in the surrounding male corneal tissue of a 55-year-old male patient with adult cystinosis a few female corneal epithelial cells could be identified 7 years after corneal tissue-graft had been performed. It was concluded that after keratoplasty epithelial cells grow into each other, i.e. from the graft to the host tissue and vice versa. The fact that even after 7 years female epithelial cells from the donor can still be detected is put down to the metabolic condition resulting in cystinosis.


[Determination of cardiac output by means of an automatized thermal dilution technique (author's transl)]. Cardiac output was measured in 55 patients by the direct Fick method and an automatized thermodilution method. The results showed a good correlation (correlation factor r = 0.87, regression equation y = 0.91 x + 0.59). For the thermodilution method ice-cold normal saline solution as indicator substance was injected into the right atrium. The temperature-time-curve was measured by a thermistor located in the pulmonary artery. The area of indicator dilution was determined by electronic integration, the calculated cardiac output appeared as 1/min in digital display.


Immunological characterization of lymphoproliferative disorders by membrane markers. The characterization of lymphocyte subpopulations by means of surface markers improved our understanding of the immunopathology of lymphoproliferative disorders. In chronic lymphocytic leukemia an accumulation of B-lymphocytes have been documented. The antibody deficiency syndrome in these patients might well reflect a maturation defect of the leukemic B-lymphocytes. In patients with Hodgkin's disease the relative number of B- and T-lymphocytes in the blood was not markedly altered in comparison to normal controls. An increased proliferation primarily of T-lymphocytes however, might suggest their accelerated turnover as an indication of the host response. In most patients with "Non-Hodgkin" lymphomas high numbers of B-lymphocytes were found in affected lymph nodes, and these appear occasionally in the peripheral blood. Differences in immunopathological manifestations of the various subgroups of the "Non-Hodgkin" lymphomas are emphasized and the rare occurrence of lymphomas of T-lymphocytes (mainly observed in lymphoblastic lymphomas and in Sézary syndrome) is discussed. Immunopathological alterations in immunocytomas and the myelomas are considered in respect to the involvement of B-lymphocytes at different stages of maturation.


The effect of minoxidil on blood pressure and plasma renin activity in patients with essential and renal hypertension. The effect of the new vasodilator, minoxidil, on blood pressure and plasma renin activity was studied in 21 hypertensive patients: 12 patients with essential and 9 with renal hypertension. The average maximum dosage of minoxidil was 27.9 +/- 6.0 mg/day (M +/- SD). Average duration of treatment was 84.5 days. During the observation period the average systolic blood pressure fell from 195 +/- 18 to 159 +/- 7 mm Hg (M +/- SD), and the mean diastolic blood pressure fell from 120 +/- 8.3 to 92.5 +/- 8 mm Hg (p less than 0.01). These patients had been treated earlier with other antihypertensive agents, such as reserpine, saluretics, hydralazine, alpha-methyldopa, and clonidine, without any significant reduction in blood pressure. Before treatment, plasma renin activity after resting was 59 +/- 6.4 ng/ml/16 h (M +/- SE) and after saluretics and orthostasis 89 +/- 12.7 ng/ml/16 h. After treatment, the decline in renin value after resting was statistically significant: 42.7 +/- 3.3 ng/ml/16 h (p less than 0.05), and the stimulated renin had fallen to 70 +/- 3.4 ng/ml/16 h (p greater than 0.1). A comparison of the renin stimulation values of patients with renal hypertension also revealed a significant reduction (p less than 0.01). Side effects which appeared at a daily dose of 15 to 30 mg consisted mainly of tachycardia and fluid retention and could be controlled by the administration of propranolol and chlorthalidone. In 5 women and in 1 man was observed a cosmetically disturbing, reversible hypertrichosis. Orthostatic hypotension was observed in one patient. Minoxidil is an effective antihypertensive agent. However, because of its side effects, it generally must be administered with beta-receptor blocking agents and saluretics. It is possible that its blood pressure lowering effect is due, at least in part, to a suppression of the plasma renin activity.


Medical treatment of gastric and duodenal ulcer. Antacids prove ready if only temporary relief of the symptoms of ulcers. Physicians have been able to increase the rate of healing of gastric ulcers by advising patients to stop smoking and then either admit them to hospital for bed-rest, or use carbenoxolone sodium as an outpatient therapy. The early trials of some other drugs have shown increase in rate of healing of gastric ulcer, but there is no medical treatment which will prevent the high recurrence rate of benign gastric ulcer. The limited data indicate that adequate medical reduction in acid secretion and enhancement of mucosal resistance may benefit patients with duodenal ulcer.


Marburg experiment on surgical research: a five-years' experience on the cooperation between clinical and theoretical surgeons. The organisation of surgical research in Marburg is an experiment which has run for five-years and war carried out in attempt to establish a cooperation between clinical and theoretical surgeons (scientists in basic research). The experiment was started 1970 by creating a Division of Experimental Surgery and Pathological Biochemistry at the Surgery Clinic of the University. Structures and functions in this experiment were 6 small working teams, special services for the teams and for the whole Department of Surgery as well as a training programme in surgical research for theoretical surgeons. Success and failure in the experiment were evaluated by criteria testing three principal functions of surgical research: Training of clinical and theoretical surgeons in methods and techniques of surgical research, performance of controlled clinical trials and basic research in surgery. The early results of the Marburg experiment seem to be promising.


Changing trends in the surgical treatment of duodenal ulcer. On the basis of fully or partly controlled clinical trials the long term results of several standard operations for duodenal ulcer have been compared--subtotal gastrectomy, truncal vagotomy and antrectomy, truncal vagotomy and gastro-enterostomy, truncal vagotomy and pyloroplasty, selective vagotomy and pyloroplasty and proximal gastric vagotomy without drainage. Few statistically significant differences emerge but the following observations seems to be justified: (a) Subtotal gastrectomy and vagotomy and antrectomy probably offer better protection against recurrent ulceration than any of the other operations examined, but the greater intrinsic operative risks of these two resection procedures is emphasized. (b) Disturbances of alimentary function occur to a variable extent after all operations but appear to be least troublesome after proximal gastric vagotomy without drainage. In particular this operation is followed by a negligible incidence of diarrhoea compared with truncal vagotomy procedures. (c) On overall (Visick) grading the two resection operations and proximal gastric vagotomy without drainage do better than truncal vagotomy with drainage, proximal gastric vagotomy being specially notable for the relatively small proportion of patients in category 3 after its use. Surgical strategy in the choice of elevtive operation for duodenal ulcer is discussed.


Immunohistological study on collagen in cartilage-bone metamorphosis and degenerative osteoarthrosis. Synthesis of collagen by chondrocytes was studied by immunofluorescence using antibodies specific for type I, II and III collagen. The following tissues and culture conditions were chosen for this immunohistological study: normal articular cartilage, epiphyseal growth cartilage, cartilage undergoing osteoarthrotic degeneration, suspension culture and monolayer culture. While type II collagen is the unique collagen all over hyaline cartilage, type I collagen is produced by hypertrophic chondrocytes in the growth plate. In addition, chondrocytes in osteoarthrotic areas of articular cartilage synthesize type I collagen. Under in vitro culture conditions, chondrocytes initially product type II collagen and synthesize later on type I collagen. The change of synthesis from type II to type I collagen is more rapid in monolayer than in suspension culture. It is concluded that the presence of matrix compounds and the cellmatrix interaction as well are necessary to maintain synthesis of type II collagen in chondrocytes. Alterations in the cell-matrix interactions are shown to occur in the hypertrophic zone of the epiphyseal growth plate, in cartilage undergoing osteoarthrotic degeneration as well as in chondrocytes grown in culture. Thus, change in the control of gene activity may subsequently lead to change in collagen synthesis. It is possible that the synthesis of type I collagen, which cannot fulfil the physiological function of a structural element in cartilageneous tissue, is a crucial factor in the process of osteoarthrosis.


Dienes typing of Proteus strains isolated from barrier-maintained animals. The possible use of Dienes' phenomenon for typing proteus strains as an aid to bacteriological monitoring of barrier-maintained animal units was investigated. It was rare for more than 1 Dienes' type to be isolated from an individual animal. A persistent relationship between 1 or 2 Diene's types and each strain of animal was demonstrated, although these same types were shown to be capable of causing clinical disease in their normal host. The findings suggest that Dienes' phenomenon may be of value in detecting outside contamination of barrier-maintained animals and also might usefully be applied to experimental epidemiological studies.


Assessment of nasalization in the speech of deaf children. Nasality is widely recognized as a problem in the speech of many deaf people. This paper describes one approach to the assessment of nasalization and to the development of visual aids to assist in training of velopharyngeal control. The approach involves detection of the velopharyngeal opening during voiced sounds by means of a small accelerometer attached to the nose, and presentation of the accelerometer output on a computer-controlled visual display. The display may be used as a training aid, or for the purpose of analyzing either recorded or live speech. Objective data are presented on some of the properties of the accelerometer output for the speech of people with normal hearing and of a number of children whose hearing is severely impaired. These data show inadequate velopharyngeal control, particularly improper nasalization of certain vowels, for a significant number of the deaf children. For a group of the hearing-impaired children, subjective judgments of the adequacy of velopharyngeal control and of other speech attributes were obtained. Correlations among these judgments and relations between judgments of adequacy of velopharyngeal control and the objective measures of nasalization are shown. Some comments are made on the development of procedures for the training of velopharyngeal control using the display as an aid.


The changing face of peptic ulcer in the elderly. The elderly patient presents a challenge to the physician both in recognition of peptic ulcer disease and in long term management. Only with close observation and an awareness of the higher complication rate can a successful therapeutic approach be developed.


Host factors and infectious diseases in the elderly. Because of declining function of their immunologic and other organ systems, elderly individuals are more susceptible to certain types of infections of their heart valves, meninges, urinary tract, and skin. They may develop serious sepsis with subtle clinical signs and symptoms, which makes accurate diagnosis difficult. The antimicrobial agents of choice for use against the organisms most commonly responsible for these septic symdromes are listed in Tables 2, 3, and 4. Some methods of preventing these infections are discussed, but further studies to verify old techniques and establish new ones are needed.


[Direct immunofluorescence in cutaneous lupus erythematosus]. A study of the Direct Immunofluorescence Method in skin biopsies of 62 patients with discoid lupus erythematosus is presented. All the specimens were examined to determine the presence of immunoglobulins (IgG, IgM, IgA) and complement (C3) on the different histological structures of the skin. The presence of immunoglobulins and complement was detected not only in the basement membrane of the lesion but also on the hyaline bodies, collagen fibres, dermal capillaries, basal membrane of hair follicles, dermal inflammatory cells, sweat glands and arrector pili muscles. The significance of these findings is discussed.


[Congenital psoriasiform erythroderma with bullous eruptions]. A 39 years old female patient with congenital erythroderma is reported. The condition was considered as the non bullous type of Brocq's congenital ichthyosiform erythroderma until recently. The patient was admitted as she had generalized erythema, desquamation and oedema, pyrexia and oliguria. The scales were fine and small, quite different from those of lamellar ichthyosis. The patient developed a recidivant pustular eruption on palms, face and trunk. So the diagnosis was changed to congenital psoriasiform erythroderma and this was supported by histopathological examination of both scaling and pustular lesions. There was a remarkable improvement on amethopterin therapy. The case is discussed and the relevant litterature is reviewed.


[Spontaneous rupture of the allografted kidney (author's transl)]. Spontaneous rupture of allografted kidneys occurred in 6 cases after 95 renal transplantations performed in the Department of General Surgery at the University Clinic in Essen. An analysis of this complication after renal transplantation is presented considering our own experience and 60 cases from the literature. The characteristic symptoms which were found in all cases consisted of oliguria, pain and swelling of the graft site and signs of hemorrhage. In 90% transplant rupture occurred within 3 weeks postoperatively. The surgical therapy should preserve the ruptured organ whenever possible. In 5 of our 6 cases we were successful in preserving the graft by suturing the tear. The analysis of the etiologic factors of 66 cases shows that oedema of the renal graft is the most common finding. A possible etiological factor seems to be the method of organ preservation.


Horizontal tongue flap in repair of tonsillar palatal defect. Local tissue, when available, seems superior to utilizing distant tissue for reconstruction of the tonsillar fossa region. Repair of the defect employing a horizontal posteriorly based tongue flap has been useful. It has the advantage of minimal decrease in the remaining tongue bulk and mobility, requires only 90 degrees rotation, and can be used after radiation therapy or ligation of the ipsilateral lingual artery.


Rhomboid flap principles and common variations. The rhomboid flap was initially popularized by a Russian, Alexander Limberg, and modified by Claude Dufourmentel of Paris. Numerous variations on the flap have been proposed more recently by Webster and Gunter. This flap has found its way into the practice of most surgeons doing head and neck surgery, with its primary advantage being that it is an extremely simple flap operation to learn, with great versatility. The general principles and their clinical application are presented in order to increase proper utilization of the flap.


Dermal grafts: an alternative technique. The drum dermatome technique for obtaining dermal grafts is described. Results using this technique are equivalent to conventional methods using a mechanical dermatome.


LH and FSH responses to luteinizing releasing hormone in normal fertile women. These studies were designed to permit calculation of bioassay dose-response curves for luteinizing releasing hormone (LRH) during three phases of the menstrual cycle in normal women. No previous data permit such estimations. Synthetic LRH was administered as a single i.v. bolus injection to 18 normal women. The dose levels were 30, 100, and 300 mug administered in the follicular, preovulary, or luteal phase of the menstrual cycle in a 3(2) factorial design. Each subject was injected with the same dose in two different phases of the same cycle. The total number of injections given to the entire group of women was 36. For comparative purposes, the same doses (30, 100, and 300 mug) were administered to eugonadal men. In absolute as well as in relative terms, the highest maximal responses were observed in the preovulatory phase, and the lowest in the follicular phase. Measured as the area under the time-response curve, the highest maximal responses were observed in the luteal phase. The duration of the elevation in LH and FSH in response to LRH showed no significant relation to the phases of the cycle but, for both hormones, was related to the dose of LRH administered. Dose-response curves were established for both LH and FSH in all three phases of the cycle, but only in the preovulatory and luteal phases were the F ratios significant for LH. For FSH, the F ratio was only significant in the luteal phase. The potency of LRH was found to increase throughout the cycle, culminating in the luteal phase. The potency in the early follicular phase was similar to that in normal, adult, human males. Throughout these studies the FSH:LH ratio remained less than one. During the normal menstrual cycle follicle growth is initiated by FSH secretion and the FSH:LH ratio is greater than one. These findings indicate that a factor other than the decapeptide, LRH, must stimulate FSH secretion during the follicular phase. Since any modulating hormonal factors (e.g., gonadal steroids) would be present during our studies, modulation of pituitary response to endogenous LRH can not explain the relative increase in FSH (compared to LH) seen in the early follicular phase of women. Lastly, the slopes of the dose-response curves for LRH stimulation of LH vary with phase of the menstrual cycle. The slope was least in follicular phase, greater with ovulatory phase, and greatest for luteal phase (when LH-FSH secretion is lowest). These data indicate that the differences in response to LRH are not simply alteration of potency (or quantitative differences) but differences in a qualitative response. Furthermore, endogenous LRH secretion must be lowest during the luteal phase, when response to exogenous LRH is greatest. It is common to test pituitary LH-FSH secretory ability by administering 100 mug of LRH intravenously. The 95% confidence intervals for the relative maximal responses to 100 mug LRH in normal, fertile women on the third day of the menstrual cycle were 200%-700% for LH, and 150-200% for FSH.


Metabolism of branched-chain amino acids in altered nutrition. Plasma concentrations of the branched-chain amino acids (leucine, isoleucine, and valine) are more prominently affected than the concentrations of other amino acids by changes in dietary-caloric, protein, fat, and carbohydrate-intake in man. For example, within a day of starvation or protein deprivation, there are increases or decreases, respectively, in concentrations of these amino acids in the plasma of healthy human volunteers. The cellular mechanisms of these changes have been investigated in rats, since the changes in the plasma branched-chain amino acid concentrations in response to the previously stated dietary alterations are similar to those found in man. Among the tissues studied (liver, skeletal muscle, heart, kidney, and intestine) only liver and the skeletal muscle exhibit changes in branched-chain amino acid concentrations in response to dietary alteation. Changes in plasma concentrations appear to reflect more intimately those of the muscle than theliver. After 8 days of starvation, there is a 25% decrease in the muscle protein, but after 8 days of protein deprivation, there is no significant change in the muscle mass. Increases in concentrations of branched-chain amino acids in the muscle are much smaller than the amounts of these amino acids lost as protein constituents form the muscle during fasting. Changes in tissue transport, transamination, oxidation, or metabolic conversions of branched-chain amino acids in tissues. It is concluded that increased muscle protein breakdown, which provides substrates for enhanced gluconeogenesis in the liver and enhanced branched-chain amino acid oxidation in the muscle, is the major mechanism of hyperbranched-chain aminoacdemia in starvation. On the other hand, the principal factors in the development of hypobranched-chain aminoacidemia during protein deprivation are absence of exogenous amino acids as well as curtailed muscle protein breakdown.


Structure-function relationship: immunologic. It is suggested that the antigenic site of glucagon for the specific sera is located within the 24-29 section of the molecule and within the 2-23 section for the fully cross-reacting sera. Biologically inactivated glucagon may retain immunoreactivity in spite of the loss of receptor-binding activity.


[Induced filament formation in S. enteritidis by means of different sodium and chloride salts and different carbohydrates]. We have previously observed filament formation in S. enteritidis which grew on media containing different salts and carbohydrates. In this study, sodium citrate, sod. carbonate, sod. molybdate, sod. acetate, sod. sulfate, potassium chloride, calcium chloride, saccharose and glucose were used as inducing agents. Different concentrations of most of the above substances were effective in filament formation in S. enteritidis. Temperature (37 degrees C and room temperature), pH of media and state of media (liquid and solid) are also found to be effective in filament formation in some levels.


[106 cases of infantile diarrhea caused by enteropathogenic E. coli 0111:B4 serotype in a 1974 epidemic in Ankara]. 106 Enteropathogenic E. coli (E.P.E.C.) 0111 : B4 were isolated from the stools of children with gastro enteritis. 101 of these came from different pediatric wards, 5. from outpatient clinics with no history of previous hospital contact. In 16 months different E.P.E.C. serotypes were isolated, these are shown table VI. In spite of the uniformity of the serotype isolated during 1974 epidemic various serotypes were isolated in subsequent years. Among these serotypes 0111 : B4 was most prevalent, consisting of 47.3% of all isolations.


[The isolation of two of yersina pseudotuberculosis from wild animals in different regions of Turkey]. Two strains of Yersinia pseudotuberculosis were isolated from wild animals collected from different regions in Anatolia. Skin test with Y. pseudotuberculosis antigen on human subjects in various parts of Turkey gave a high percentage of positive results. It seems probable that this microorganism can cause infections in man transmitted by wild animals.


[Oxidation of aliphatic alcohols and acids by yeasts capable and incapable of growth on n-alkanes]. Yeast cultures, capable and incapable fo growth on hydrocarbons, were tested for their ability to oxidize aliphatic alcohols and acids, intermediate products of n-alkane degradation. The cultures belonging to 7 genera and 13 species did not grow on liquid paraffins and tetradecane. However, they grew on tetradecanol and oxidized aliphatic alcohols and fatty acids, the pattern of oxidation of the substrates being the same as in the case of alkane-oxidizing yeast cultures grown on glucose. None of 45 yeast strains (12 genera and 36 species) which did not grow on paraffin was able to oxidize tetradecane. As follows from this and earlier evidence (Lozinov et al., 1976a), the only reaction typical of yeasts capable of growth on n-alkanes is the oxigenase reaction of their oxidation to alcohols.


[Comparison of various aspects of normal and filament forms of S. enteritidis IV]. Induced filament formation of S. enteritidis by means of sodium chloride was previously reported. In this study various aspects of normal and filament forms of S. enteritidis are compared. Filament forms had lost some of their biochemical activities when compared with the normal forms of S. enteritidis. There was no serological difference between the two forms. We were unable to show any difference in antibiotic sensitivity, because concentrated sodium chloride inhibited cell growth. No difference was observed between the two forms in pathogenity against mice. The resistance to heat was decreased in filament forms. In addition to these, staining and spreading of nuclear elements showed some variations in the young and old filaments.


[Change in the composition of Candida albicans cells during development of resistance to polyene antibiotics]. The composition of lipid and protein components of the membrane structures was studied in the strains of Candida albicans susceptible and resistant to polyene antibiotics. The content of sterols was lower and the content of free fatty acids was higher in the cells of resistant strains cf. susceptible strains. The composition of sterols was also different in the resistant strains: analysis of absorption spectra of sterol extracts in heptane in UV revealed complete absence of ergosterol, the main component of the susceptible strain, and appearance of a heterogenous peak at 215--240 nm.


[ 771 Shigella strains isolated in a 15-year period from Americans living in Ankara. Comparisons with Shigella strains isolated from Turkish natives]. The author had worked as a bacteriologist in Ankara American Air Force Hospital from 1958 to 1972. During this period of time he was able to isolate 771 shigella strains from the American patients of the hospital. The amounts and the percentages of the subgroups are listed below together with the two other Ankara City Pediatric hospital results (see article). american community lived in Ankara for 15 years and shared many aspects which were important in shigella epidemiology like using city's tap water, shopping from the same green groceries to by fruits and vegetables so on. For shigella cases Ankara had seasonal alterations in July and August being the peak months. Americans, disease followed that course exactly. The big difference was being the local people of the city had those epidemics with the flexneri strains but Americans had them with the sonnei strains. To show the possible sources which could infect the community time to time and make sonnei predominant yielded negative result. All the patients stools were cultured. Sensitivity studies employing "plate disk diffusion" techniques were done. All patients treated accordingly. Stools checked for routine carriership exams. None become a chronic carrier. American installations had their shops, clubs, mess halls.  The food handlers of these places had checked routinely by the preventive medicine office. None found infected. Only at 1963 the amount of flexneri isolations were higher than sonnei. All the remaining years sonnei were predominant. Antibiotic sensitivity studies showed no differences between subtypes. Except streptomycin and sulphamide strains stayed fairly sensitive to other antibiotics. Resistance factors contained maximum 6 markers. The little Americans community in Ankara consisted a unique and highly socioeconomic-wise developed group of the city. Many attempts to find the answer for the question is "who is infecting who" was always fruitless. That gives the impression as if the Americans were more sensitive to the shigella infections caused by sonnei strains for some reason. In another words Americans were more resistant to the infections other than sonnei.


[Use of ultrasound in the quantitative estimation of soil and rhizospheric microorganisms]. Ultrasonic treatment of soil, though being very effective for desorption of cells and deaggregation of microcolonies, may damage and kill microorganisms. Possible application and effectiveness of ultrasonic treatment was studied in this work with chernozem (dry and wet samples), rhizosphere and rhizoplane of pea. An ultrasonic disintegrator of low frequency is recommended for dry soils. Ultrasound cannot be recommended for treating rhizosphere and rhizoplane of plants without checking its effectiveness in each case.


[Enteropathogenic E. coli strains isolated in our laboratory within the last 8 months]. 63 E. coli strains were isolated and typed seriologically from feces samples sent to our laboratory from infants suffering from diarrhea in March-October 1975. 5 out of these strains were typed as 0111 : B4, one as 055 : B5 and another one as 0125 : B15, which are generally regarded as enteropathogenic E. coli. Also sensitivity test were carried out and many of these strains were found to be multiple antibiotic resistant.


[Antigenic relationships between various strains of Candida albicans]. In this short communication the results of cross agglutination and absorption tests among seven standard Candida albicans strains (C. albicans CBS - 562, C. albicans CBS - 1899 (C. truncata), C. albicans CBS - 2695, C. albicans CBS - 5144 (C. intestinals), C., albicans CBS - 5145 (C. biliaria) are given. It showed that these microrganisms have the same antigenic structure.


Controlled evaluation of the beta adrenoceptor blocking drug oxprenolol in anxiety. An investigation of the effectiveness of the beta adrenoceptor blocking drug oxprenolol in the treatment of primary clinical anxiety is reported. A controlled double-blind evaluation of oxprenolol versus diazepam and placebo was carried out. The results of the trial showed diazepam to be generally more effective and to produce a more rapid onset of symptom reduction than oxprenolol. The role of beta adrenergic blocking drugs in the treatment of clinical anxiety and related syndromes is discussed.


Beclomethasone dipropionate aerosol for asthmatic children requiring maintenance oral steroid therapy. A single-blind crossover trial comparing beclomethasone dipropionate by inhalation with prednisolone by mouth in the treatment of asthmatic children over a period of 10 months is reported. Fourteen children aged between nine and 16 years entered the trial. All had severe chronic asthma requiring maintenance oral prednisolone therapy in doses ranging from 2 to 7-5 mg/day. Beclomethasone dipropionate given by inhalation in a dose of 400 mug/day was found to be a satisfactory alternative to prednisolone by mouth for controlling the symptoms of asthma. During the course of this trial, three of the children died suddenly during acute exacerbations of asthma. All three had evidence of extensive inflammation of the tracheobronchial tree.


Effect of 15 (R) 15 methyl prostaglandin E2 on the healing of gastric ulcers: a double-blind endoscopic study. A double-blind trial was carried out to assess the effect of 15 (R) 15 methyl prostaglandin E2 on the healing of gastric ulcers. The prostaglandin preparation was given orally in doses of 150 mug every 6 hours for two weeks to 10 subjects with proven gastric ulcer. The control group consisted of 10 subjects with proven gastric ulcer, who did not receive prostaglandin treatment. All were in hospital, and at rest in bed. Ulcer healing was assessed endoscopically with a duodenofibrescope. The maximum diameter of the ulcer crater was determined endoscopically just before and after two weeks of treatment. In the prostaglandin group, complete healing was seen in three cases and considerable healing (50% and more) in five cases, and the overall mean healing rate was 63-3%. In the control group, complete healing was seen in no case and considerable healing in one case, and the overall mean healing rate was 17-1%. The difference was highly significant. The results confirm the belief that 15 (R) 15 methyl prostaglandin E2 is effective in promoting the healing of gastric ulcers.20


[Evidence for the action of raubasine from a new formulation of Lamuran tablets]. It was possible in a controlled double-blind study to demonstrate by means of dynamographic measurements the action of raubasine in patients with cerebrovascular disorders. A new formulation of Lamuran tablets (MF706d) was used for the investigation. This formulation has an improved in-vitro dissolution rate for raubasine that is largely independent of pH. In the raubasine group (10 patients aged 47 to 81 years, including 6 cases of anacidity) there was after one and two weeks treatment with dialy doses of 90 mg raubasine a significant reduction of the raised vascular resistance and pulsewave velocity and systolic blood pressure in the internal carotid artery which indicate an improvement in cerebral haemodynamics. In contrast, no significant changes in these parameters could be found in the placebo group (9 patients aged 52 to 83 years). The therapeutic relevance of the haemodynamic effects was supported by a simultaneous clinical improvement.


[Action of raubasine (new formulation) in arterial occlusive diseases (author's transl)]. A double blind cross-over study under acute experimental conditions was carried out in 26 patients with angiographically confirmed occlusion in one or two limbs in order to see whether a change in the formulation of raubasine preparations improves the circulation in diseased limbs. Either 100mg raubasine or placebo tablets were administered in a randomized order. Blood flow at rest and "peak-flow" after total arterial occlusion for 3 min showed a significant improvement under raubasine compared with the pre-occlusion period whilst these parameters were not affected by placebo. Systolic blood pressure and heart rate remained almost constant under raubasine whilst they were reduced under placebo. A similar response was seen in a subgroup of 19 patients with occlusion of the femoral artery. It can thus be said that in the present investigation the new formulation of raubasine preparation (MF 706d) has been shown in a double blind study to improve both the blood flow at rest and the "peak-flow" to a significant degree in patients with arterial occlusions.


[Bencyclan (Fludilat) in the treatment of patients with ischaemic cerebral infarction (author's transl)]. In 50 patients suffering from local cerebral circulation disturbances the effects of bencyclan--administered intravenously in a dosis of 500 mg per day--were evaluated under double-blind conditions. At the same time all patients received digitalis and physiotherapy. Besides a detailed recording of the neurological and psychopathological status a number of psychological tests were applied in order to get objective data about psychomotor function, cerebro-organic capacity and mood. The control recordings after a three weeks' treatment demonstrated an improvement of the clinical as well as the psychological parameters in either group. There were no marked, statistically significant differences in the extent of improvement between the bencyclan and the placebo group; that means bencyclan has no effect on the signs of ischaemic cerebrovascular disease, which exceeds the effects of digitalis and physiotherapy.


Template properties of human DNA-dependent RNA polymerase II. DNA-dependent RNA polymerase II has been purified from lymphocytes of patients with chronic lymphocytic leukemia (CLL). Form II polymerase and Escherichia coli RNA polymerase have been used to study the transcription of human DNA and chromatin. The hybridization kinetics of the transcripts of DNA and chromatin by the human polymerase are quite different; chromatin transcripts hybridized to DNA at a much slower rate than DNA transcripts, whereas the transcripts of DNA and chromatin by bacterial polymerase have similar hybridization kinetics.


Early consolidation chemotherapy for adults with acute leukemia in remission. Three courses of intensive consolidation therapy were administered to 13 patients with acute leukemia after they achieved complete remission. The patients were randomly allocated to receive their therapy in or out of a protected environment unit and with or without antibiotic prophylaxis. The results suggest that the protected-environment-prophylactic-antibiotic program may have protected the patients from infection, although the numbers in each group are too small for meaningful comparison. However, early consolidation therapy was not beneficial, since the duration of remission and survival of these patients was less than that of a group of comparable patients who received only conventional maintenance therapy.


Polarity and the regulation of the ilv gene cluster in Escherichia coli strain K-12. A series of Mu-1 induced isoleucine and valine auxotrophs derived from the wild type K-12 strain of Escherichia coli and from a valine resistant (ilvO-) mutant were examined. It was concluded that the genes ilvE, ilvD and ilvA constitute a single operon and are transcribed from E to A. Furthermore, the ilvG gene, expressed only in ilvO- strains, does not lie between ilvE and ilvD as previously assumed. A mutation in rho was examined for its effect on the ilvEDA operon. One effect of the rho- mutation was a mimicking of an isoleucine limitation signal. A model for the regulation of the ilvEDA operon is discussed. The model involves multiple attentuation sites and a possible role for the ilvO locus which lies at the distal end of the ilvEDA operon (but is not part of it). Supportive evidence for the proposed direction of transcription was obtained by examination of a series of gammailv transducing phages.