The effect of a low continuous positive airway pressure on the reflex control of respiration in the preterm infant. The airway occlusion technique was used to measure the strength of the Hering-Breuer inflation reflex before and during the administration of low pressure CPAP. In five of 12 preterm infants studied in the first two weeks of life, CPAP did not alter the inflation reflex. In the other seven premature infants, shortened rather than lengthened inspiratory efforts were observed on occlusion 32 times of CPAP but only twice on CPAP. In seven term infants at 1 to 2.5 hours of age this shortening was noted only twice in 58 occlusions. In the preterm infants exhibiting short responses, the peak inspiratory pressure generated in response to occlusion rose on CPAP from 3.4 to 7.1 cm H2O (p less than 0.005), while respiratory rate fell from 61 to 49 breaths/minute (p less than 0.025). This data suggests that CPAP enhances these infants' ability to adjust to increased respiratory loads, possibly by the elimination of a Hering-Breuer deflation reflex.


Diagnosis of neonatal bacteremia by a microblood culture technique. A preliminary report. A method is described for obtaining blood by heel-stick from high-risk neonatal infants for bacteriologic studies. Results of culture of blood collected by heel-sick are compared to those of simultaneously drawn blood from a peripheral vein. The data obtained suggest that this method may be a useful adjunct in the close surveillance for bacteremia in high-risk neonates.


A comparison of the continuous and interrupted suturing techniques. This investigation compared the efficacy of interrupted and continuous suturing for primary closure of the apically positioned flap. Twenty-two flap procedures were performed on contralateral sites in 10 patients. The 11 sites where interrupted suturing was used had a degree of presurgical periodontal involvement which was similar to that in the 11 contralateral sites where continuous suturing was used. At postsurgical assessment visits, after 3 months and 6 months, gingival health status was evaluated for both groups. Recession, residual pocket depth and loss of attachment were also measured. Analysis of the data for each of these parameters indicated no statistically significant difference between the two groups. However, the overall clinical impression was that interrupted suturing provided better flap adaptation.


An in vivo comparison of chlorhexidine and picloxydine mouthrinses: a possible association between chemical structure and antiplaque activity. A double blind clinical trial was conducted in which both the plaque-inhibiting ability and the in vivo effects on the oral flora of chlorhexidine and picloxydine mouthwashes was compared. While picloxydine in higher concentration suppressed the oral flora more effectively than chlorhexidine, the latter agent inhibited plaque development to a much greater extent. This lack of correlation between antibacterial and antiplaque activity can be related to structural differences between these two bis-biguanides.


Adaptation of dental instruments for periodontal purposes. Modification of instruments used in general dentistry can make them useful in periodontal therapy. A periosteal elevator, a rongeur and instruments for cutting and carrying small particles of bone for grafting procedures have been described.


An unusual foreign body reaction - a case report. This case documents the course and treatment of a severe reaction to an unusual foreign body. A tooth brush bristle was lodged in the lower anterior areas between the cuspid and lateral incisor teeth. Although the patient noted some original discomfort, severe pain and bone destruction did not occur until 6 weeks after the original symptoms began. Treatment involved full thickness flap reflection of the involved area. The histologic examination showed a typical foreign body reaction to the bristle. All teeth remained vital throughout the disease process and healing phase. Healing was uneventful and the lost bone completely regenerated.


Foreign body-type reaction following crown cementation. 1. Hazards of the indirect impression techniques for crown fabrication are discussed. 2. A foreign body reaction caused by retained cotton fibers is substantiated. 3. Since the gingival retraction cord is a possible and likely source, placing the cord and choice of instruments is important.


Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects. The influence of various test meals and fluid volume on the relative bioavailability of ampicillin and amoxicillin was studied in healthy human subjects. Serum amoxicillin levels were somewhat, but not always, significantly higher than those of ampicillin from equivalent oral doses. Food ingested immediately before dosing reduced serum levels and urinary excretion of both antibiotics to a similar extent. Reduction of dosed water volume caused a marked decrease in serum amoxicillin levels in fasted subjects.


Role of central and peripheral mechanisms in the action of alpha-methyldopa on blood pressure and renin secretion. The mechanism by which alpha-methyldopa lowers arterial pressure and suppresses renin secretion was investigated in pentobarbital-anesthetized dogs in which changes in renal perfusion pressure were prevented by adjusting a suprarenal aortic clamp. After intravenous alpha-methyldopa (100 mg/kg) mean arterial pressure (MAP) decreased form 127+/-3 to a mean minimum of 107+/-4 mm Hg (P less than .01) and plasma renin activity (PRA) decreased from 20.6+/-4.8 to 10.9+/-1.7 ng/ml/3 hr (P less than .05). Blockade of peripheral dopa decarboxylase with intravenous carbidopa (20 mg/kg) significantly attenuated the hypotensive action of intravenous alpha-methyldopa but MAP still decreased from 145+/-6 to 130+/-5 mm Hg(P less than .001). Intravenous carbidopa completely abolished the fall in PRA produced by intravenous alpha-methyldopa (16.8+/-2.8 to 16.9+/-2.1 ng/ml/3 hr.) Intraventricular carbidopa (3 microng/kg/min) did not block the hypotensive (135+/-8 to 113+/-7 mm Hg, P less than .01) or renin-lowering effect (24.3+/-5 to 13.4+/-3.2 ng/ml/3 hr, P less than .01) of intravenous alpha-methyldopa (0.5 mg/kg decreased MAP from 118 +/- 5 to 104 +/- 5 mm Hg (P less than 0.001) but had no effect on PRA (23.4+/-6 TO 19.4+/-7 NG/ML/3 hr.) Intraventricular alpha-methylnorepinephrine (2 microng/kg) also decreased MAP from 127+/-5 to 112+/-3mm Hg (P less than .006) but again failed to significantly alter PRA (36.1+/-11.8 to 37.2+/-15 ng/ml/3 hr). These results indicate that there is both a central and peripheral component to the antihypertensive effect of alpha-methyldopa in the dog and that the suppression of renin secretion results from a peripheral action of the drug.


Biliary colic as a model for assessing analgesic activity in man. Acute pain from biliary colic is a model of pathological pain suitable for pharmacological investigations. It has been found useful for assaying analgesic effect of a narcotic-type agent (pentazocine) and a non-narcotic drug (indoprofen), both given intravenously in a single dose. Differences in pain intensity scores assessed on a five-point scale were taken as measurement of the pain-relieving effect. Distribution-free methods were used to estimate the potency ratio of the tested drugs. The analgesic potency of indoprofen based both on total and peak effect was roughly one-tenth that of pentazocine on a weight-for-weight basis. No adverse reactions were associated with indoprofen and a few were found after pentazocine.


Mechanism of protection from alloxan diabetes provided by n-butanol. Pretreatment with n-butanol (10 mmol/kg i.p.) 30 minutes before alloxan (100 mg/kg) protects mice from the permanent hyperglycemic effects (measured at 72 hours) of the diabetogenic agent. This dose of n-butanol caused an elevation of serum glucose at 30 minutes, the time of alloxan administration. Since glucose administration can protect animals from alloxan, the possibility that alcohol-induced hyperglycemia protected mice from alloxan was investigated. Mannoheptulose, an antagonist of glucose action at the pancreatic beta-cell, when given 24 minutes after n-butanol and 6 minutes before alloxan, eliminated the alcohol-induced protection. Fasted mice did not exhibit n-butanol-induced hyperglycemia at 30 minutes and alloxan given at that time produced diabetes. No protection was observed in fed animals when n-butanol was given 5 minutes before alloxan. The high serum levels of butanol and normal serum glucose which were observed at 5 minutes after alcohol administration indicated that the lack of protection was not due to a lack of circulating alcohol but resulted from an absence of hyperglycemia. The results indicate that pretreatment with n-butanol protects mice from alloxan-induced diabetes by the indirect mechanism of producing hyperglycemia at the time of alloxan administration.


Potentiation of antitumor drug action by centrophenoxine: specificity. The cytotoxic action of certain antitumor agents is potentiated by centrophenoxine although centrophenoxine itself is not an antitumor agent. Previous investigations have suggested that centrophenoxine might potentiate the cytotoxicity produced by antitumor drugs that alkylate, and other modalities that damage, DNA, but that it would not potentiate the cytotoxicity produced by antitumor drugs that inflict cellular damage in other ways. To test this hypothesis, the antitumor effects of X-irradiation UV-irradiation, alkylating agents and antitumor drugs that are not ordinarily considered to be alkylating agents were determined in the presence and absence of centrophenoxine. Mouse P388 lymphoma cells growing in static suspension culture were used as the experimental tumor. The cytotoxic action of most alkylating agents was found to be potentiated by centrophenoxine; Included in this group were several difunctional nitrogen mustards, two ethylenimines, a nitrosourea and mitomycin C. Greatest enhancement, 7-fold, was of chlorambucil antitumor activity. Centrophenoxine did not potentiate the lethality of X- or UV-irradiation or the cytotoxicity of several antineoplastic drugs that are not alkylating agents.


Gonadotrophin secretion in the ovariectomized guinea-pig: effects of electrical stimulation of the hypothalamus and of LH-RH. 1. Serial blood samples were collected from anaesthetized spayed guinea-pigs subjected to anterior hypothalamic stimulation or injected with luteinizing hormone-releasing hormone (LH-RH), and the effect on the secretion of follicle-stimulating hormone (FSH) and LH followed. 2. Hypothalamic stimulation enhanced LH secretion, although the response waned during the course of the 1 hr period of stimulation; the secretion of FSH was not increased. After stimulation, FSH and LH levels fell below control values. 3. The response to stimulation of the hypothalamus was greater 2 weeks after spaying than after 1 week. 4. Since repeated periods of hypothalamic stimulation induced repeated surges of LH secretion, the decline in LH secretion during stimulation was not likely to have resulted from hypothalamic damage, while the observation that the plasma concentration of FSH and LH declined below control values after brain stimulation implies the operation of inhibitory mechanisms. 5. Pre-treatment of spayed guinea-pigs with progesterone depressed the resting plasma concentration of LH but did not affect the immediate response to hypothalamic stimulation. After hypothalamic stimulation the plasma gonadotrophin levels did not fall below control values. 6. Pre-treatment with oestradiol benzoate depressed the resting plasma level of LH and slightly reduced the size of the LH surge produced by hypothalamic stimulation. However, the raised plasma LH concentration was sustained after stimulation ended. 7. The response to hypothalamic stimulation after pre-treatment with progesterone and oestradiol benzoate showed features of the reaction to each steroid given singly. 8. The I.V. injection of 0-5 microng LH-RH induced a surge of LH secretions without affecting FSH discharge. 9. Pre-treatment with progesterone did not greatly modify the response to LH-RH but after an injection of oestradiol the high level of LH produced by the releasing factor was sustained for about 2 hr. 10. Injections of LH-RH during the phase of depressed LH release after hypothalamic stimulation produced a surge of LH secretion which matched that seen in non-stimulated animals.


Thymidylate synthetase inhibitors. Synthesis of N-substituted 5-aminomethyl-2'-deoxyuridine 5'-phosphates. A series of substituted 5-aminomethyl-2'-deoxyuridines was synthesized as analogues of 5-thymidylyltetrahydrofolic acid, a proposed intermediate in the thymidylate synthetase catalyzed reaction. 1-(3,5-Di-O-p-toluoyl-2-deoxy-beta-D-ribofuranosyl)-5-chloromethyluracil (3) was treated with the appropriate amine to give the ester protected 5-aminomethyl nucleoside. Removal of the ester groups was accomplished with anhydrous potassium carbonate in methanol to afford the free beta-nucleoside. In this way 5-(2-dimethylaminoethylaminomethyl)-2'-deoxyuridine (5a), 5-dimethylaminomethyl-2'-deoxyuridine (5b), 5-N-mehtylpiperazinylmethyl-2'-deoxyuridine (5c), and 5-pyrrolidinylmethyl-2'-deoxyuridine (5d) were prepared. Compounds 5a,b,d were converted to the respective 5'-phosphates 6a,b,d. All three compounds were subtrate competitive inhibitors of thymidylate synthetase purified from Escherichia coli, calf thymus, and Ehrlich ascites tumor cells. The most active compound was 6a with KI's of 6,3.1, and 14 micronM observed for the respective enzymes.


Determination of antibacterial antibodies in serum by immunoradiometric assays. When used to determine immunopurified antibacterial globulins in saline-phosphate buffer, the detection sensitivities of direct competitive and indirect immunoradiometric assays were respectively 25 and 2 ng. Normal human and rabbit sera interfered in both types of assay, markedly decreasing sensitivity and precision. Various pre-treatments of sera and modifications of reaction conditions substantially decreased interference in the competitive assay without affecting the activity of added antibody, but they had only marginal effects in the indirect assay. When serum samples taken from rabbits after vaccination with the Live Vaccine strain of Francisella tularensis were tested with the two assays and agglutination tests, newly synthesised circulating antibody was usually detected earlier by the competitive assay than by the other methods.


Immunogenicity and characteristics of M protein released by phage-associated lysin from group-A streptococci types 1 and 23. A phage-associated lysin (PAL) was used to release M protein from goup-A streptococci of types 1 and 23. Much of the lysin-released-M protein (LYSIN-M) of both types was of high molecular weight, since LYSIN-M appeared just after the void volume on Sephadex G-200 gel-filtration. Some of the LYSIN-M appeared just after the void volume on Sephadex G-200 gel-filtration. Some of the LYSIN-M of both types was found to be firmly attached to group-A carbohydrate. Type-1 LYSIN-M was partially purified by ammonium-sulfate precipitation followed by absorption and elution from an immunoabsorbent column containing antibody for group-A carbohydrate. Type-23 LYSIN-M was partially purified by precipitation at its isoelectric point, pH 4-9. Rabbits immunised in the footpads with either type-1 or type-23 LYSIN-M responded by producing both precipitins and bactericidal (opsonising) antobodies. Some of the antiesera were absorbed and rendered specific for homologous acid extracts. The LYSIN-M preparations of both types 1 and 23 were originally contaminated with heat-labile antigen(s). Antibodies to these heat-labile antigen(s), which cross-react from type to type, were found in the type-specific antisera distributed by the Center for Disease Control. The specificity of Lancefield typing antisera depends on their being tested with extracts of streptococci prepared at pH 2 and 100 degree C for 10 min. Although LYSIN-M is more difficult to prepare and purify then acid-heat released M protein, it might prove useful for studying the nature of native streptococcal M protein.


The culture of clinical specimens for anaerobic bacteria: a comparison of three regimens. Three procedures for the anaerobic culture of clinical specimens are compared: (i) a conventional bench routine, (ii) a system whereby primary anaerobic plates were incubated for 48 h before examination, and (iii) an anaerobic chamber. It was shown that the anaerobic chamber was of no advantage over bench regimens when primary anaerobic plates were incubated for 48 h before being examined.


A protein factor associated with serum resistance in Escherichia coli. Immunogel-diffusion studies showed that 60 degree C LiCl extracts of the smooth serum-resistant mutant Escherichia coli strain 17 contained greater amounts of a protein antigen than did extracts of the parent strain LP729. An extract of strain 17 was fractionated on Sepharose 4B and the protein antigen was found as the only detectable antigen in a number of fractions; sodium dodecyl sulphate-polyacrylamide gel electrophoresis indicated that these fractions contained one major polypeptide band with a molecular weight of 46 000 daltons. We suggest that this protein antigen may be partly responsible for the serum resistance of strain 17 though its presence in other serum-sensitive strains suggests that additional factors are essential for full serum resistance.


Effects of biliary diversion on intestinal microflora in the rat. Certain bile acids inhibit the growth in vitro of organisms commonly found in the intestine and, in particular, anaerobic bacteria. As the importance of this effect in vivo has not been demonstrated, we investigated changes in intestinal flora in the rat after diversion of bile to the urinary bladder. Five days after operation there was an increase in numbers of Proteus sp. in the stomach, mid-jejunum and caecum and of coliform bacilli in the stomach and mid-jejunum. Lacto-bacilli were increased in the stomach. There was no change in numbers of anaerobic organisms. Similar changes in bacterial flora followed 5 days of pair feeding in control rats. Our results do not suggest a specific antibacterial effect of bile salts in the rat in vivo. The changes found are probably related to semi-starvation, because the food intake of the rats after operation was about half that of control rats having an unrestricted diet.


The effect of Treponema pallidum on mouse survival. Intraperitoneal infection with Treponema pallidum did not shorten the lives of inbred CBA mice. One hundred and fifty infected mice survived to a mean age of 41-24 months and 60 uninfected mice to a mean age of 41-38 months.


Delayed culture of group-A streptococci: an evaluation of variables in methods of examining throat swabs. We studied the effects on the frequency of isolation of group-A streptococci from throat swabs of school children on three varibles: (1) plating the cultures within 4 h of collecting the swabs or after storage for 4 days at room temperature; (2) using a plain or a serum-coated cotton swab; and (3) including silica gel in the swab tube or omitting this. Under the conditions of our experiment, only delayed plating of the swab gave a statistically significant advantage. When the delayed-isolation technique was used, neither the swab type nor the presence or absence of silica gel significantly influenced the result. The least advantageous combination of variables was: plating within 4 h, a plain swab, and the absence of silica gel.


Continuous-culture studies of interactions among human skin-commensal bacteria. Chemostat studies were made of an antibiotic-producing Staphylococcus epidermidis strain (S6+), a similar, but antibiotic non-producing S. epidermidis strain (S6-), and a sensitive indicator strain of Micrococcus sp. (M7). Pure and mixed continous cultures were investigated at low population levels (in 0-1% peptone water) and at higher levels (in 0-5% peptone water). Strain S6+ antagonised the growth of strain M7 when its colony count was maintained above 10(7-0) per ml, while strain S6- remained unaffected.


Immunologic abnormalities in patients with malignant lymphoproliferative diseases. The B- and T-lymphocyte distribution was studied in 45 patients with malignant lymphoproliferative diseases. Eight patients with untreated Hodgkin's disease had normal mean percentages of complement receptor lymphocyte (CRL) cells and T-cells; however, the mean absolute number of T-cells was decreased. T-lymphocytes were also decreased in 3 patients with Hodgkin's disease treated 7-24 months previously. The number of T-lymphocytes increased markedly in all patients after treatment. Lymphocyte surface markers in non-Hodgkin's lymphoma showed distinctive patterns. Patients with leukemic reticuloendotheliosis or "hairy cell leukemia" characteristically had low percentages of CRL but normal or increased percentages of surface immunoglobulin-positive lymphocytes. The mean percentage and number of T-lymphocytes in this group were normal. Eight patients with nodular lymphocytic lymphoma and 2 patients with nodular lymphocytic-histiocytic lymphoma had normal mean numbers of CRL but decreased numbers of T-lymphocytes. Of 6 patients with diffuse lymphocytic lymphoma, 4 had elevated percentages and numbers of CRL. Despite low percentages, normal numbers of T-lymphocytes were found in 3 of these patients.


The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer. Sera from 134 selected patients with various types of cancer were tested for soluble antigen-antibody complexes by the C1q binding method. Sera from 85 healthy blood bank donors served as normal controls. C1q binding activity (C1q BA) values above the 95th percentile for healthy subjects were found in 83% of sera from patients with neoplastic diseases. The incidence of abnormal C1q BA values among patients with malignant melanoma was 83%, with breast cancer 74%, with colon cancer 75%, with lung cancer 88%, with leukemia and lymphoma 85%, and with miscellaneous tumors 94%. High C1q BA values were found most frequently in sera of patients who had been diagnosed relatively recently (within 5 mo) and who had evident residual disease after surgical treatment. Recurrence or progression of tumor growth occurred significantly more frequently in lung cancer patients with high C1q BA. DNA was not detected in cancer patients' sera and treatment with DNase did not decrease in C1q BA. C1q BA in sera could not be explained by the presence of antiglobulin antibodies. Sucrose density gradient ultracentrifugation studies of the serum C1q BA in 4 cancer patients showed that the major binding activity was found between 19S and 7S.


Inhibition and stimulation of the growth of Krebs-2 carcinoma by BCG vaccine. The effect of BCG vaccine on the growth of imtransplants of Krebs-2 carcinoma in mice was studied. The simultaneous injection of BCG and tumor cells either inhibited tumor growth (BCG given in admixture with tumor cells) or stimulated it (BCG injected contralateral to the tumor transplantation site). The BCG dose was directly related to the effect. Tumor growth was also stimulated by the ip injection of starch or liquid paraffin. In these experiments, the BCG effect was attributed to the redistribution of cells involved in nonspecific and specific tumor resistance. Shortly after BCG prevaccination, particularly when BCG doses were high and mice were susceptible to vaccine infection, BCG was either without effect or stimulated tumor growth; later, however, tumor growth was inhibited regardless of the BCG dose and the injection site of the BCG. The effect of BCG prevaccination was suggested to be due to: 1)the distraction of macrophages and T-lymphocytes to defend the host against the multiplying mycobacteria, and 2)the activation of the pool of these cells that become capable to participate in antitumor resistance after mycobacteria elimination.


Foreign-body tumors of mice: strain and sex differences in latency and incidence. Sarcomas were induced by sc implantation of unplasticized polyvinylchloride acetate films in female and male mice of strains AKR/J, BALB/cJ, BALB/cWat, CBA/H and CBA/H-T6, C3H/HeJ, C57BL/10ScSn, C57BL/6J-bgj, C57BL/cdJ, DBA/-1J l/LnJ, LP/J, SJL/J, X/Gf, 129/J, and hybrids (CBA/H-T6 X AKR/J)F1, (C57BL/10ScSn x CBA/H or CBA/H-T6)F1, (C57BL/6J-bgj x C57BL/6J)F1. The strains and sexes showed marked differences in incidence and mean latency of resulting tumors. Crucial information was provided for the selection of appropriate mouse strains for the study of interrelationships between genotypes, defined somatic properties, and the multifactorial process of foreign-body tumorigenesis.


Effect of systemic administration of BCG cell walls on bronchogenic carcinoma in hamsters. Systemic injection of BCG cell walls was evaluated for effects on the development of respiratory tract tumors induced by intratracheal instillation of benzo[a]pyrene plus Fe2O3 in Syrian hamsters. Only 74% of animals developed respiratory tract tumors at the dose level of benzo[a]pyrene used. Treatment with BCG cell walls reduced the incidence of respiratory tract tumors to 50%. A similar effect of treatment with BCG cell walls was found when only malignant tumors of the respiratory tract were considered. Both single and multiple injections of BCG cell walls effectively reduced the incidence of respiratory tract tumors.


Xenon-133 determination of muscle blood flow in electrical injury. Xe-133 washout determination of muscle blood flow (MBF) was used to detect muscle ischemia in electrical injury of an experimental animal model and three patients. The control MBF of rabbit hindlimbs, which averaged 11.29 +/- 1.07 cc/min/100 gm, was significantly reduced by electrical injury, to 5.82 +/- 1.49 cc/min/100 gm (p less than 0.001). An electrical injury of 4,000 watt-seconds or greater was associated with uniform MBF less than 1.00 cc/min/100 gm and with histopathologic alterations of muscle necrosis. Thenar MBF less than 1.00 cc/min/100 gm in two patients was associated with muscle necrosis requiring distal arm amputation. The remaining patient with sequential muscle blood flows above this level had uneventful healing of hand electrical injuries. Xe-133 determination of MBF may be a useful objective technique to determine the extent of electrical injury in muscle.


[Urological aspect of vesico-intestinal fistulas. Apropos of 14 cases]. This series of 14 cases of vesico-intestinal fistulae, together with a review of the literature, led to a certain number of remarks: From an aetiological standpoint, in addition to classical concepts with the predominance of diverticulosis of the colon accounting for 46% of cases, followed by carcinoma of the colon (14%) and Crohn's disease, we feel it to be of interest to stress the possible urinary origin of vesico intestinal fistulae (4 of our cases, and 4.5% of the total number collectedin the literature). From a diagnostic standpoint, we would emphasise that these fistulae present almost solely with urinary symptoms and signs and stress the clinical importance of what is now known, since J. Cibert, as "pre-fistulous cystitis" preceding the development of pathognomic signs--faecaluria and pneumatria. Radiological opacification of the colon and rectum is essential in patients with a syndrome of chronic urinary infection unexplained by a urological cause. From a therapeutic standpoint, the surgical treatment of vesico-intestinal fistulae is associated with a high operative mortality (2 deaths amongst our 14 patients) and which, independently of the aetiological factor (predominance of carcinomas) is explained above all by the septic nature of the lesions.


Inhibition of bacteriophage M13 and phix174 duplex DNA replication and single-strand synthesis in temperature-sensitive dnaZ mutants of Escherichia coli. A functional dnaZ product, known to be essential for host DNA polymerization and for the synthesis of M13 and phiX174 parental replicative-form (RF) DNA, is required also for RF replication and single-strand synthesis by both of these phages. All three stages of M13 and phiX174DNA replication (parental RF formation, RF replication, and single-strand synthesis) are inhibited in dnazts mutants at elevated temperatures. In addition, the thermolabile step in M13 parental RF formation appears to occur after RNA priming;i.e., the synthesis of M13 RF DNA proceeded when a dnaZts mutant, infected at a nonpermissive temperature, was transferred to a permissive temperature in the presence of rifampin.


Pyelolithotomy of a renal transplant.

Pyelolithotomy of a renal transplant. A large calculus developed in a renal transplant patient and was removed by pyelolithotomy. Hyperparathyroidism was not present. Important factors to consider before performing a nephrolithotomy in a transplanted kidney are whether the transplant was a right or left kidney and the timing of the operation in relation to renal function and infection. The etiology for renal stone formation in renal transplant recipients includes hyercalciuria, renal tubular acidosis, antacid administration and infection.


Prescribing of tetracycline to children less than 8 years old. A two-year epidemiologic study among ambulatory Tennessee medicaid recipients. The committee on Drugs of the American Academy of Pediatrics finds virtually no indications for administering tetracyclines to children less than 8 years old. This study analyzes tetracycline prescribing to ambulatory children less than 8 years of age in the Tennessee Medicaid program during a two-year period. Of the nearly 59,000 children in the study, 4,026 (7%) received 7,046 tetracycline prescriptions. Twenty-seven percent (527) of 1,947 participating physicians prescribed tetracycline; 26 physicians (5%) wrote 54% of the prescriptions for 45% of the children. Physicians in family practice prescribed the greatest quantity of tetracycline. Surgeons and internists prescribed more tetracycline to young children than did pediatricians. Rural location of practice was independently associated with increased tetracycline prescribing for all specialties. Recent graduates from medical school were less apt to prescribe tetracycline than were earlier graduates.


Crepitant cellulitis and myonecrosis caused by Klebsiella. A fatal case of crepitant cellulitis with myonecrosis, the first caused by Klebsiella pneumoniae, is reported. The infection started in the left thigh but progressed rapidly despite appropriate antibiotics and surgery, which included incision and drainage and later a left-hip disarticulation. This case emphasizes that nonclostridial crepitant cellulitis is potentially severe and that the presence of myonecrosis is an indication for early radical surgery.


Propranolol in the treatment of essential hypertension. In a series of 450 patients with mild essential hypertension, propranolol alone (P), propranolol plus hydrochlorothiazide (P+T), propranolol plus hydralazine (P+H), and propranolol plus hydrochlorothiazide plus hydralazine (P+T+H) were compared to reserpine plus hydrochlorothiazide (R+T). Comparison was based on reduction of diastolic blood pressures (BP) to below 90 mm Hg and at least 5 mm Hg less than initial BP after six months of treatment. This was achieved in 92% of patients who received P+T+H, 88% taking R+T, 81% receiving P+T, 72% on P+H and 52% taking P alone. The number of drop-outs, morbid events, and terminating side effects were insignificantly different among the various regimens. In this study, P and P+H were less effective, while P+T and P+T+H were as effective as the standard regimen.


Carotid sinus syncope. Report of two cases. In two cases of hyperactive carotid sinus with syncope, both patients had a history of syncopal attacks. Carotid sinus massage produced asystole lasting for four seconds with recurrent symptoms. Permanent demand pacemakers were implanted in both patients, causing a relief of symptoms.


Diffuse histiocytic lymphoma. The need for aggressive restaging. Fifteen patients with stage III and IV diffuse histiocytic lymphoma were treated with combination chemotherapy: cyclophosphamide, vincristine sulfate, prednisone, and procarbazine hydrochloride (COPP). Eight achieved a complete clinical remission. Of these, five relapsed, but remission was reinduced in three of these. Median survival of partial responders was 52 weeks compared to more than 129 weeks for complete responders. Complete clinical remission in diffuse histiocytic lymphomas did not presage a long disease-free interval as has been reported in biopsy proved remission series. Biopsy and staging by pathologic examination appear necessary to document remission in this disease.


Multiple myeloma with cutaneous involvement. A 49-year-old man with multiple myeloma, IgA type, contracted cutaneous plasmocytomas. No deposits of immunoglobulin were found in the cutaneous tumor by direct immunofluorescence. The case is an unusual manifestation occurring in multiple myeloma.


[Heart valve prosthesis in congenital heart defects]. The experience of 68 cases of prosthetic valve replacement for congenital heart diseases is presented. The majority of the cases were 57 patients with the Ebstein anomaly and tetralogy of Fallot. In the patients with the Ebstein anomaly the tricuspid valve was replaced, in those with the tetralogy of Fallot--a plastic enlargement of the pulmonary artery trunk and prosthetic replacement of the pulmonary valve with a ball valve or xeno-graft. Original techniques of radical correction of the Ebstein anomaly and tetralogy of Fallot are presented.


[Historical notes on the terms "glaucoma" and "cataract" (author's transl)]. The Greek term "glaucoma" has nothing to do with the disease we call glaucoma today and that we use to translate incorrectly with "grüner Star" throughout the German-speaking countries. The Greek adjective "glaucos" does not mean green but gleaming, sparkling. It signified the discolouring of the pupil in glaucoma. It was later replaced by the pathogenetic term hypochysis, Latin suffusio, denoting the supposed "trübe Feuchte" (opaque humour) that was taught to gather and congeal in front of the crystalline lens. Later on "glaukosis" was reserved for incurable cases, disease of the crystalline lens itself, which was looked at as the "organon visus" up to Felix Plater. The word "cataract"--waterfall--does not exist in Greek medicine. It appears in Salernitan medical science around the year 1000 as a synonym for hypochysis, the disease we call cataract today and which has been identified as opacity of the lens since Brisseau (1705). The nature of "incurable" glaucoma, later considered as a disease of the vitreous body, was clearly recognized as a consequence of intraocular increase of pressure only by v. Graefe.


[The monocyte-macrophage-system (author's transl)]. The importance of the monocyte-macrophage-system in specific and non-specific immune reactions is described. Macrophages are involved during both the afferent phase, e.g. antigen trapping, antigen processing, and the efferent phase, e.g. allograft rejection, tumour cell destruction, of the specific immune system. The monocyte-macrophage system can be activated by non-specific and - more important in vivo - by specific mechanisms via soluble factors produced by sensitized T-lymphocytes. Finally, some clinically important disorders of macrophage function are described.


Nuclear fluorescence of liver cells for IgG in viral hepatitis B: significance and relation to hepatitis B-core and anti-hepatitis B-core formation. The occurrence of anti-HBcAg antibodies in the blood as determined by indirect immunofluorescence  and its relation to the occurrence of HBsAg in the cytoplasm and of HBcAg and IgG in the nuclei of hepatocytes were studied in the following groups of patients (total of 123 biopsies): I. 64 HBAg-negative patients with various liver diseases; II. 51 HBAg-positive patients without therapeutical immunosuppression (6 acute hepatitis, 10 nonspecific reactive and 10 chronic persistent hepatitis, 19 chronic aggressive hepatitis, 6 "Hippie"-hepatitis); III. 8 kidney transplant recipients. It could be shown that nuclear IgG is found only if both parameters can be demonstrated at the same time: HBcAg in liver cell nuclei and anti-HBcAg antibodies in the serum in titers higher than 1:64. Accordingly, all types of hepatitis with excess formation of nuclear HBcAg (early phase of acute hepatitis, chronic aggressive hepatitis and chronic non-aggressive forms with generalized core formation, i.e. carrier state or chronic persistent hepatitis of the HBc type) may show nuclear fluorescence for IgG. All forms of hepatitis B without detectable core formation (acute hepatitis in the elimination phase, chronic non-aggressive hepatitis with isolated HBsAg expression, i.e. carrier state or chronic persistent hepatitis of the HBs type, posthepatitic phase) do not present nuclear IgG despite eventual anti-HBcAg formation. Finally, lack of anti-HBcAg or very low titers associated with lack of IgG in hepatocytic nuclei do not exclude generalized core formation in liver cell nuclei in chronic persistent hepatitis of effectively immunosuppressed patients. Although the demonstration of nuclear IgG has several diagnostic and prognostic consequences in common with the demonstration of HBcAg, a specific search for the core antigen in the tissue is needed for the correct appraisal of the HBcAg- and HBsAg tissue expression pattern and the associated disease.


[Biology of lectins and their application in clinical biochemistry (author's transl)]. Lectins are proteins or glycoproteins, originally isolated from plant seeds. Characteristics are their ability to bind glycoproteins or glycolipids depending on the carbohydrate residues. The present review describes the structure of the lectins, their binding specificity and their functions with respect to precipitation of glycoproteins, agglutination of cells, transformation of lymphocytes and toxic action. Recently, lectin-analogs have been described in rabbit liver, which are responsible for hepatic uptake of circulating glycoproteins. The regulation of this process is intimately linked to the terminal N-Acetylneuraminic acid (NA-NA). Moreover, its significance is shown during fetal development, oncogenic transformation, immunologic recognition as well as homostasis. Due to the different terminal carbohydrate residues, glycoproteins of adult, fetal or transformed cells can be separated using affinity chromatography. Besides the purification of glycoproteins, lectins are also used for the separation of intact cells. Therefore the use of lectins is recommended for preparative and analytical methods, for the measurements of glycoprotein-turnover and for clinical diagnostics.


Diagnosis of encephalitozoonosis in experimentally infected rabbits by intradermal and immunofluorescence tests. The indirect immunofluorescence antibody test was performed on serial blood samples from eight young New Zealand White rabbits with experimental encephalitozoonosis. The test showed seroconversion in six of the eight infected rabbits by the 8th day after inoculation and in all rabbits by the 15th day. Antibody titers reached a peak by about the 36th day after inoculation and remained significantly elevated until the termination of the experiment at 84 days after inoculation. None of four sham-inoculated rabbits showed an immunofluorescence response by the 60th day after inoculation. Immunofluorescence and intradermal test responses were compared before infection and at the 60th day after inoculation in a total of 32 experimentally infected rabbits. Both tests were equally effective (100%) in detecting infected animals. Six of eight (first group) and 22 of 24 (second group) experimentally infected rabbits were confirmed histologically to have lesions compatible with encephalitozoonosis. No cross reactions were observed between Encephalitozoon cuniculi and Toxoplasma gondii, Eimeria perforans, or Eimeria stiedai by intradermal test or immunofluorescence test.


Electrophysiologic response audiometry: state of the art. Electrophysiologic response audiometry (ERA) is based upon recording neuroelectric potentials from sites extending from the cochlea to the cortex. These recordings rely on the use of averaging computers to extricate desired neuroelectric responses from the ongoing background electrical activity of the human auditory system and brain. The different neuroelectric responses are distinguished by response latency, response waveform, and probable site of origin. Responses which occur within the latency range of 1 to 5 msec originate from the cochlea and auditory nerve. Responses in the 4- to 8-msec latency range have the brain stem as their origin. Responses with latencies from about 8 to 50 msec presumably arise from the upper brain stem and primary projection areas. Responses with a fast waveform include those with latencies between 1 and 50 msec. Slow wave responses from about 50 to 300 msec originate as a secondary discharge from the primary cortical projection areas and surrounding secondary and association areas. The longest latency potentials (300 msec) are slow shifts that appear to arise from the prefrontal and secondary or association areas of the cortex. These response classes are discussed in terms of their clinical utility for threshold estimation and diagnostic value.


Evacuation of pericardial, anterior mediastinal, and peripleural air collections in neonatal respiratory distress. Alveolar rupture in the neonate can result in the dissection of air along vascular sheaths and the formation of abnormal collections within the mediastinal, pleural, pericardial, or peripleural spaces or elsewhere. Intercostal tube placement for pneumothorax is frequently required. A method is presented for the placement of Intracath catheters into pericardial, anterior mediastinal, and peripleural collections of air when other adjustments in treatment have not allevaited clinical distress.


Morphology of canine hearts after 24 hours' preservation and orthotopic transplantation. Ten dogs underwent orthotopic cardiac transplantation after preservation of the donor heart for 24 hours in an oxygenated hypothermic, hypertonic, intracellular solution, either with (five dogs) or without (five dogs) continuous, oxygenated, low-pressure perfusion. Eight dogs survived for 24 hours after transplantation, at which time they were put to death. The two nonsurvivors were among the five with nonperfused hearts. Examination of all 10 donor hearts showed differences between the two groups: Four of five nonperfused hearts showed severe transmural myocardial coagulation necrosis but only small foci of contraction band necrosis (myofibrillar degeneration). The perfused hearts, however, showed more extensive subendocardial areas of contraction-band necrosis, but only minimal and focal coagulation necrosis, indicating less severe hypoxic damage. These results indicate that oxygenated perfusion with a hypothermic, hypertonic, intracellular solution may permit improved transplant survival after extended cardiac preservation.


Hemoglobinopathies.

Hemoglobinopathies. The determination of the structure of hemoglobin is one of the milestones of molecular biology. This information has provided an intimate understanding of the way in which the molecule functions physiologically; Study of hemoglobin has proved relevant to a number of biomedical disciplines. This protein is a prototype of a general class of allosteric enzymes whose function depends upon transition from one conformation to another. Recently, attention has been focused on environmental factors, including 2,3-DPG, hydrogen ion concentration, and CO2, which can modify and perhaps regulate the behavior of hemoglobin within the red cell. Comparisons of primary amino acid sequences of animal hemoglobins have provided new and independent phylogenetic insights. Furthermore, surveys of human hemoglobin phenotypes have been of considerable utility in the study of population genetics. Finally, certain variants are responsible for specific clinical syndromes. As we shall discuss in detail, in most cases the clinical features can be directly attributed to lesions at a submolecular level. This chapter will first present a detailed account of interrelationships between hemoglobin structure and function. Secondly, we will consider the various factors in health and disease which can modify hemoglobin's physiologic role. This background information will be useful in the consideration of inherited and acquired disorders of hemoglobin structure and function.


End-stage renal failure in juvenile diabetes mellitus: a 5-year follow-up of treatment. A group of 43 juvenile diabetic patients accepted for renal transplantation and followed up for as long as 5 years was studied. The cumulative survivial of the group was 66% at 1 year and 58% at 5 years. The 1-year survival of those receiving cadaveric renal allografts (65%) or of those on dialysis alone (55%) was less than the survival of those after living related donor transplantation (88%). The major morbid sequelae included retinopathy, neuropathy, and peripheral vascular disease. While patients were on dialysis, blindness increased, with 44% of the bilateral blindness and 27% of the unilateral blindness representing new cases. After transplantation, permanent unilateral or bilateral blindness developed in an additional 12% of the patients. Severe neuropathy progressed rapidly in patients on dialysis and improved after transplantation in all. Fifty percent of the patients who survived transplantation 1 year or more required amputation of one or more extremities. Only 25% of the patients who survived 1 year after transplantation were without blindness, severe peripheral vascular problems, or both.


Are there unknown mineralocorticoids in low-renin essential hypertension? The blood pressure elevation of primary aldosteronism is caused by excessive production of the known mineralocorticoid, aldosterone. The blood pressure elevation of low-renin essential hypertension may also be caused by mineralocorticoid excess, but which which mineralocorticoid is responsible is uncertain. Normal levels of aldosterone, found in this disorder despite suppressed plasma renin, and the presence of an unknown mineralocorticoid have been hypothesized to explain low-renin essential hypertension. We contrasted the blood pressure responses and changes in aldosterone seen in patients with low-renin essential hypertension and primary aldosteronism during treatment with two adrenal enzyme inhibitors. The results demonstrate the similarity between decrease in blood pressure and in aldosterone during early adrenal inhibition in both primary aldosteronism and in low-renin essential hypertension. During treatment with a distal adrenal blocker, patients with primary aldosteronism demonstrated decreases in both aldosterone and blood pressure, whereas patients with low-renin essential hypertension showed a decrease in aldosterone without significant change in blood pressure. This suggested that aldosterone was not the major mineralocorticoid responsible for low-renin essential hypertension. Unknown mineralocorticoid excretion decreased (along with blood pressure) during early inhibition but failed to decrease (along with blood pressure) during late inhibition at a time when aldosterone excretion decreased. This suggests that unknown mineralocorticoids play significant roles in the blood pressure elevation of low-renin essential hypertension.


Mineralocorticoid hypertension in childhood. Evidence for the existence of a hormone that is stimulable by adrenocorticotropic hormone (ACTH) and capable of causing hypertension has been collected in several patients. This hormone is not a known mineralocorticoid or glucocorticoid. The hypothesis that a steroid can produce hypertension was tested in an 18-year-old man with dexamethasone-suppressible hypertension. During dexamethasone treatment, when aldosterone secretion was suppressed, less than normal and the patient was normotensive, steroids were given by constant infusion in an attempt to reproduce the hypertension of the dexamethasone-free state. Hypertension was not caused by 5 days of administration of aldosterone, 18-hydroxydeoxycorticosterone (18-OH-DOC) at 1 mg/day, or deoxycorticosterone (DOC) at 30 mg/day. However, sodium retention and potassium loss were observed during infusion of aldosterone and DOC. Hypertension was produced within 5 days during infusion of ACTH or oral metyrapone. The hypertensive effect of the metyrapone was eliminated by the additional treatment with aminoglutethimide. These studies suggest that an ACTH-dependent steroid rather than aldosterone, 18-OH-DOC, or DOC may be the cause of the hypertension in this patient. Study of a 3-year-old child who presented with short stature, hypertension, hypokalemic alkalosis, suppressed renin and ACTH, and decreased excretion of all known steroids suggested excessive secretion of a pressor hormone. Reversal of the hypertension and hypokalemic alkalosis occurred when spironolactone was administered. ACTH exacerbated the clinical and biochemical abnormalities, suggesting that the secretion of the unknown factor was dependent on ACTH. A study of the urinary steroids revealed remarkably low excretion of aldosterone and cortisol. Plasma levels of ACTH were low. The low production of aldosterone was not associated with the increased excretion of precursor metabolites. These finding suggest the secretion of an unknown hypertensive  factor of remarkably high potency, with the ability to suppress the secretion of both renin and ACTH.


Mechanisms of spontaneous hypertension in rats. Studies on the Kyoto (SHR) and the New Zealand (GHR) strains of genetically predisposed hypertensive rats have shown that in the SHR neurogenic influences, primarily of higher central origin, play an important role in the initiation of hypertension. Studies on human essential hypertension indicate that this may also be true for man, although it is far from being the sole explanation. Brookhaven hypertension-prone rats illustrate the interaction between genetic and exogenous factors since they require an overload of salt for the development of high blood pressure. The Milan hypertensive rats (MHS), on the other hand, illustrate a genetic deviation of renal function with imbalance between glomerular filtration and tubular resorption of sodium and water, which may simulate at least some variants of the relatively mild forms of low renin hypertension in man. Structural adaptive vascular changes have been demonstrated in SHR and GHR and in nongenetic renal hypertension in rats, and there are several indications of their presence in MHS. Thus, regardless of the nature of the initiating factors, these secondary but rapidly established changes occur and greatly contribute to the maintenance and acceleration of the hypertensive state. The vascular changes can even be regarded as a common denominator for chronic hypertension and serve as an element which, in fact, reinforces the initiating mechanisms. The progress of the vascular changes can be interfered with by reducing the pressure load. Lowering the blood pressure by pharmacologic treatment is most effective when the treatment is initiated as such an early age when the cardiovascular structural adaptation is still minimal. Treatment in later phases is less successful since the adaptive increases in cardiac and vessel wall thickness can then no longer be fully normalized by pressure reduction because of increased amounts of collagen and other connective tissue elements in the vessel wall, which regress poorly. An increased wall thickness of the resistance vessels implies a vascular hyperreactivity to constricting influences which, in turn, rapidly brings the blood pressure back to supranormal levels as soon as therapy is stopped.


[Tumors of the small intestine - clinical signs and symptoms, diagnosis and therapy (author's transl)]. 66 patients suffering from tumors of the small intestine were operated upon between 1963 and 1976 in the Surgical Department of the University of Mainz Medical School. In 16 cases benign tumors were found (6 neurinoma, 4 leiomyoma, 4 lipoma, 2 polyps), in 50 cases the tumors were malignant (24 carcinoma, 20 sarcoma, 2 malignant schwannoma, 4 carcinoids). Only in 12 patients surgery was radical and no metastases found. In more than one third of the patients surgery had to be done as an emergency operation because of life threatening complications. The correct diagnosis was established preoperatively only in 57.5% of all cases. Only 5 out of 15 patients still living have survived more than 5 years. Correct interpretation of early clinical symptoms, repeated X-ray studies and additional chemotherapy may improve the prognosis of malignant tumors of the small intestine.


[Circumfusion chamber for microscopic examination of living single cells and other particles]. A new circumfusion chamber is described for microscopic or micrometric investigations on living single cells and similar particles. The chamber allows to collect rare single cells. Cells are fixed within the optical field or measuring field in spite of relative high velocity of the medium. Rapid changes of the cells milieu are possible, reactions of the cell are individually visible or measureable. The chamber is temperated and allows application of different special microscopic techniques.


Gram-negative bacillary pneumonia in the compromised host. The clinical and radiological characteristics of 217 consecutive episodes of gram-negative bacillary pneumonia occurring  in 189 adult cancer patients between November 1968 and December 1974 were analyzed. The majority of patients had acute leukemia (54%). Fever larger than or equal to 101 degrees F was the single most common symptom and sign of the presence of infection (90%). Next in frequency were crepitant rales (65%), cough (41%), dyspnea (19%) and chest pain (18%). Radiographic evidence of pneumonia was found in 83% of cases and it consisted mainly of alveolar infiltrates involving both lung fields and predominantly the bases. Up to one-third of the patients had normal chestx-ray examinations at the onset of infection, though they subsequently became abnormal in 42% of them. The majority of patients (81%) whose initial chest x-rays did not reveal the presence of pneumonia were neutropenic (less than 1000 circumlating neutrophils/mm3). Klebsiella sp. and Pseudomonas sp. were the most common infecting organisms. The overall cure rate was 61%; 70% for Klebsiella sp. infections and 64% for Pseudomonas sp. infections. Pulmonary abscesses  occurred in 14% of the cases. Cures were related to the antibiotic sensitivity of the infecting organisms and to the number of circulating neutrophils during the period of infection. Best results were obtained with the administration of gentamicin, the newer aminoglycoside antibiotic sisomicin, tobramycin and amikacin, or the combination of gentamicin with carbenicillin or with cephalosporins. Early and vigorous therapy of gram-negative bacillary pneumonia with appropriate antibiotics has improved the prognosis of this infection at our institution.


A simple apparatus for controlled pressure perfusion fixation. An apparatus is described for vascular perfusion of small animals with fixative solutions which while simple and inexpensive allows quantitative and reproducible pressure control. Direct measurement of outflow pressure demonstrated that a sphygmomanometer used to supply external pressure to a plastic blood transfer pack achieved these features. Reproducibility of pressure was maintained by filling the bag with air between perfusions, or when smaller volumes of fixative solution were needed. Rodent brains from fetal to adult ages, and other animals of similar size, have been reliably well fixed by this method.


Immunological properties of Propionibacterium acnes. I. Potentiation and Suppression on antibody response to sheep and hamster erythrocytes in mice. Adjuvant activity of phenol-treated cells of Propionibacterium acnes C-7 in antibody response was investigated in ICR mice. Simultaneous administration (day 0) of P. acnes (i.p.) and sheep red blood cells (SRBC) (i.v.) enhanced the formation of direct plaque-forming cells (PFC) on days 2, and the formation of indirect PFC response on day 7 and thereafter. Conversely, pretreatment from 11 to 14 days before antigen injection suppressed markedly the antibody response. The potentiation and the suppression of immune response depended on doses of antigen and of P. acnes, the timing of adjuvant injection and the time of assay. The two opposite phenomena caused by P. acnes were also confirmed in antibody response against hamster red blood cells (HRBC). Pretreatment with P. acnes 1 to 14 days before antigen injection suppressed markedly anti-HRBC antibody response, whereas P. acnes injected simultaneously with HRBC or one day after injection of the antigen induced prolongation of antibody response and the production of 2-mercaptoethanol-resistant antibody.


Detection of R plasmids in naturally occurring fish-pathogenic bacteria, Edwardsiella tarda. The conjugative R plasmids were detected from fish-pathogenic Edwardsiella tarda isolated from cultured eels. These R plasmids were resistant to sulfonamide and tetracycline, or sulfonamide, streptomycin, chloramphenicol, tetracycline and kanamycin. There were no inhibitions in growth of phages W-31, P1, T1, T3, T7, and lambda. They were classified into incompatibility group A.


[Problems in the diagnosis of intrauterine viral infections, applicable methods and our current studies]. In this review article the authors summarize the prevelance and diagnosis of "intra uterin viral infections", including their studies in this field.


[Study of preliminary irradiation with wave-lengths 366 and 405 nm on lethal UV-damage to yeast cells]. The protective action of irradiation with wavelengths of 366 and 405 nm on the cells of Saccharomyces cerevisiae, XI race, against lethal lesions caused by short-wavelength UV was studied. Among the total number of the cells with lethal lesions caused by UV, 25--30% of the cells were protected by light with the wavelength of 405 nm, and 50--55% of the cells were protected by light with the wavelength of 366 nm. Lethal UV lesions of the cells are supposed to be of different nature.


[Cytomorphologic characteristics of Saccharomyces cerevisiae and Candida utilis as an index of the physiologic state of the culture]. The dimensions of daughter cells without scars, and of mother cells with 1--4 scars, of Saccharomyces cerevisiae and Candida utilis were studied in the one-stage chemostat at D equal to 0.05, 0.1, 0.25, and 0.35 hr-1. The average dimensions of the cells increased with the specific growth rate. At low values of the specific growth rate, "immature" daughter cells separate and attain reproductive ability as independent individual organisms. A twofold increase in the biomass of yeast cells occurs at the account of growth of the buds and small daughter cells.


[Ergosterol synthesis by hybrids and strains of yeasts of the genus saccharomyces with different ploidies]. Numerous hybrid and polyploid strains of the Saccharomyces genus were obtained by hybridization. The activity of ergosterol synthesis was assayed in hybrids, several industrial races, and in haploid and diploid cultures produced from the spores of these races. The content of ergosterol was determined in 160 strains and hybrids. Ergosterol synthesis is controlled by recessive genes, and accumulation of ergosterol in the cell depends on the interaction between genes. During growth in semiindustrial conditions, triploid hybrids accumulated more biomass than diploid, and particularly haploid, strains. Polyploid hybrids valuable for food industry have been selected, according to several characteristics, from active hybrid strains. One of them, the triploid 262, is characterized by a high rate of ergosterol synthesis, good baking quality, and resistance to dehydration.


A controlled intrauterine contraceptive device trial. Three intrauterine contraceptive devices (IUCD) the Lippes Loop, the Dalkon Shield and the Inhiband, were prospectively compared after their random allocation to patients. Over a 12-month period after insertion, the Dalkon Shield was shown to be significantly superior to the Inhiband. Significant differences were not demonstrated between Shield and Loop or Loop and Inhiband in the duuration of this trial. It is submitted that the methodology detailed could, and probably should be used for future IUCD assessments.


Reflections on the development of valvular prostheses. Surgical attempts to open obstructed heart valves in the 1940s led to the eventual development of valvular prostheses, accompanied by the parallel development of methods of sustaining extracorporeal circulation; biocompatible materials; and engineering designs. Early problems encountered included the incidence of thrombotic phenomena, audibility of valvular noise, impaired flow dynamics, and hemo-incapability. These problems have been solved with increasing success with the creation of new plastics, the ball valve design, and improved manufacturing processes.


Neonatal meningitis and circumcision.

Neonatal meningitis and circumcision. This paper presents four cases of fulminating neonatal sepsis with meningitis. In each infant, there was evidence of an infected circumcision wound. Two infants had Escherichia coli and two had Group B haemolytic streptococcus cultured from the cerebrospinal fluid. One infant died. The risk of introducing infection through iatrogenic portals of entry is a definite problem in the neonate. Circumcision is an unnecessary routine procedure, which puts the infant at risk.


Aortic valve replacement with a subcoronary ball valve--early experiments. Between the years 1954 and 1958, the combined effort of a surgeon and an engineer allowed the development of some of the principles of aortic valve construction that proved clinically successful several years later. It was demonstrated for the first time that there was adequate room in the area of the sinuses of Valsalva below the coronary arteries for a prosthetic ball valve, and that such a ball valve did not obstruct flow. Aortic pulse tracings with such a ball valve in place were indistinguishable from those with the natural valve. Finally, the principle of the cloth sewing ring was utilized for suturing the valve in place.


The history of the Björk-Shiley tilting disc valve. After observing a high residual gradient and a high mortality in patients with a narrow aortic root undergoing aortic valve replacement with a small ball valve during the period 1962-1965, it was most gratifying to find a much smaller gradient in similar patients with the Wada-Cutter valve in 1968. A tilting disc valve seemed a solution, particularly for patients with narrow aortic root, but the disc had to rotate to eliminate localized wear in a hinge mechanism. Together with Donald P. Shiley, I tested a tilting disc valve with a rotating disc of Delrin, for wear and also in a pulse duplicator in 1968. Because the function was much better than that of the clinically popular Starr-Edwards ball valve prosthesis, the Björk-Shiley valve was first inserted in a patient on January 19, 1969. My clinical experience and judgement justified the omission of animal trial; such trial would have been irrelevant.


The effect of tri-potassium di-citrato bismuthate (De-Nol) on the healing of chronic duodenal ulcers. Forty-six patients suffering from chronic duodenal ulcer, proven endoscopically, were treated in a randomized double-blind cross-over trial with either tri-potassium di-citrato bismuthate (De-Nol) or placebo for four weeks and assessed symptomatically and endoscopically. Those patients who failed to heal after treatment with either agent were crossed over to the alternative preparation and reassessed after a further 28 days. Forty-two patients completed the study involving 57 patient treatments. A highly significant improvement in both symptomatic response (P less than 0.01) and endoscopic healing (P less than 0.01) was seen in those patients receiving tri-potassium di-citrato bismuthate (De-Nol) as against placebo therapy.


Heart valve replacement with the pivoting disc prosthesis: appraisal of results and description of a new all-carbon model. The Lillehei-Kaster pivoting disc (LKPD) valve has a free-floating pyrolite carbon disc suspended within a unibody titanium housing. A brief history of its development beginning in 1964 illustrates the origin of the concepts of central flow, lifetime durability, laminar flow, and low profile with lightness of weight. Clinical evidence indicating that this prosthesis has lifetime wearability is confirmed by complete freedom from mechanical failure in widespread clinical usage. Postoperative studies for abnormal hemolysis disclosed a striking improvement over lateral flow prostheses. The hemodynamic performance has been evaluated in both early and late postoperative studies and showed excellent results in all but the smallest sizes in the aortic position. The incidence of thromboembolism was found to be very low. In a total of 1610 patients at risk, the overall incidence of embolism was only 1.1 percent, and fatal embolism occurred in only one patient. These results with use of the LKPD valve have confirmed substantial progress in resolving the problems of prosthesis-related complications. Performance parameters still in need of improvement have also been identified, and these considerations have been incorporated into the design of a new all-carbon prosthesis with bioengineering refinements to meet these needs.


[Diagnosis of candidid colpitis by Microstix -Candida (author's transl)]. The increase in the clinical significance of candida albicans in gynecology, particularly the high incidence (candidiasis) in the pregnant woman, demand an easy, efficient and rapid method for the routine diagnosis of candida albicans. Microstix -Candida, a specially developed dry culture medium in miniature form, has been studied in comparison to the conventional Nickerson's Medium. Good agreement of the data was obtained in 425 patients. The main advantages are the ease of handling and the 24 hour incubation period. The observed difference in data obtained from the phase microscope examinations and the Microstix Candida cultured specimens are discussed in detail.


Genetic determination of the mitochondrial adenine nucleotide translocation system and its role in the eukaryotic cell. On integrating experimental data published previously, the following picture of the mitochondrial adenine nucleotide (AdN) translocation system is being presented: 1. The AdN translocation system serves not only to transport ATP synthesized within mitochondria into the cytosol but also to transport cytosolic ATP into the mitochondria when oxidative phosphorylation is not functioning. 2. The AdN translocator is coded for by nuclear genes and the mitochondrial protein synthesis is not involved in its formation. 3. The AdN translocation system must be preserved and functioning even in cells which could dispense with oxidative phosphorylation. It assures appropriate concentrations of intramitochondrial ATP. 4. The intramitochondrial ATP is required for normal replication of mitochondrial DNA. Tis supports the view that the mitochondrion is a self-replicating semi-autonomous organelle. 5. The appropriate concentration of ATP must be present in mitochondria to make possible cell growth or multiplication. This points to a direct or indirect role of mitochondria in the control of cell proliferation.


Gene expression in mitochondria and bacteria. Mitochondria and bacteria possess protein synthesizing machineries which are similar in many respects; The regulation of gene expression in mitochondria is unknown. We, therefore, tried to use a well-established prokaryotic regulatory system for the exploration of mitochondrial gene regulation. DNA of the bacterial virus can be used as a template for gene expression in a mitochondrial in vitro system. The gene directed enzyme synthesis in the mitochondrial system is the basis for a study of regulation in mitochondrial protein synthesis.


Cytoduction as a new tool in studying the cytoplasmic heredity in yeast. When crossing the haploid cells of genetically marked yeast strains we observed the appearance of both normal diploid zygotes and haploid nuclear cytoplasmic hybrids. The latter had the nuclear markers of one and the cytoplasmic marker (rho+) of the other parent. The autonomous cytoplasmic factor transfer was termed as cytoduction. Cytoduction is supposed to be the abortive form of yeast cell mating. Only about 1% of cytoductants in usually observed. Cytoduction can be used as a simple test on cytoplasmic determination of some characters. We observed the transfer into cytoductant cells of not only rho+ marker but of resistance factors to antibiotics (erythromycin, neomycin) and killer factor as well. Cytoduction can be applied towards constructing strains having the identical nucleus genotype with mitochondria and other cytoplasmic factors of different origin. In crossing strains with doubly marked mitochondria recombination of mitochondrial markers in cytoductant haploid cells was observed, the pattern of which was similar to that of mitochondrial recombination in normal zygotes.


Determinant for multiple drug resistance possessing features of a mitochondrial episome in Saccharomyces cerevisiae. A mutation for multiple resistance to tetracycline, cycloheximide and oligomycin appears to be followed by reconstruction of the mitochondrial genome resulting in the formation of independent nucleotide sequences that determine different resistant phenotypes. Heterozygotes for the cross resistance factor lack locus T responsible for relation tetracycline which comes from the alpha-parent. The nuclear recessive gene-suppresor i induces deletion of the whole determinant for multiple resistance. The loss of mt-DNA on ethidium bromide treatment does not lead to the loss of this determinant which remains in the cells either in an active or in a passive state.


Mitochondrial recombination in crosses of iso- and anisomitochondrial Saccharomyces cerevisiae. Mitochondrial mutants resistant to erythromycin, neomycin and monomycin were isolated. Mitochondria were transmitted from different natural strains to the cells of the same nuclear genotype. In bifactorial crosses of such isochromosomal and anisomitochondrial yeasts we tested random samples of diploid colonies. The distribution of mitochondrial markers in parent and recombinant classes has been shown to occur unequally. The asymmetry of parent and the polarity of recombinant classes were observed to differ in different mitochondrial mutants. Anisomitochondrial strain crosses proved that mitochondrial origin essentially influenced both the parent and recombinant classes distribution and the susceptibility of the transmission to the effect of mating type locus. One can distinguish between 'homo- and heterosexual' cross combinations in terms of recombination polarity. The new type of mitochondria was found to occur with high frequency of transmission to the zygote progeny of markers resistant to erythromycin but not of markers resistant to neomycin. The problem of 'sex' in mitochondria is discussed.


The structure of animal mitochondrial DNA (base composition, pyrimidine clusters, character of methylation). Base composition, content of pyrimidine isopliths and the degree of methylation of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) from various vertebrates and protozoon Crithidia oncopelti have been studied. MtDNAs from mammals (ox, rat) do not differ in fact in the GC content from the respective nDNA. The GC content in mtDNA from fishes (sheat fish) and birds (duck, chicken) is 1.5-2.5 mole % higher than in the respective nDNA. Kinetoplast DNA (kDNA) from Crithidia oncopelti (GC = 42.9 mole %) differs significantly in base composition from nDNA (GC = 51.3 mole %). All the mtDNA and kDNA studied differ from the respective nDNA by a lower degree of pyrimidine clustering. The amount of mono and dipyrimidine fragments in mtDNA is more than 30 mole %, whereas in nDNA it does not exceed 23 mole %. The quantity of long pyrimidine clusters (hexa and others) is 2-4 times lower in mtDNA than in nDNA. The lower degree of clustering of pyrimidine nucleotides seems to be a specific feature of all the mtDNA studied. This may be indicative of common traits in the organization and origin of mtDNA. All mtDNA of vertebrates contain 5-methylcytosine as a 'minor' base (1.5- 3.15 mole %) and surpass by 1.5-2 times the respective nDNA in the methylation degree. It has been found that in animals mtDNA is species specific as far as the 5-methyl-cytosine content is concerned. In mitochondria and nuclei of rat liver certain DNA methylase activity has been detected, which provides in vitro the methylation of cytosine residues both in homologous DNA and various heterologous DNAs. The specificity of methylation in vitro of cytosine residues in the same heterologous DNA from E. coli B varies with the source of enzymes. The mitochondrial enzyme methylates cytosine as the lone monopyrimidine residue, whereas the nuclear enzyme methylase cytosine in the di- and tripyrimidine fragments.


The character of protein-nucleic interaction in relation to the mtDNA-membrane complex. Specific sites that interact with structural proteins of the mitochondrial inner membrane were found in mitochondrial DNA (mtDNA) of rat liver. Analysis of the isolated DNA fragments revealed their capacity to form a complex with membrane proteins in vitro and allowed the detection of a protein with a molecular weight 40,000. The size of the fragments was found to be 12-18 nucleotide pairs with an average molecular weight 10,000 MtDNA sites recognized by membrane protein proved to be quite unique in having a secondary structure, a high content of AT sequences (82%) and oligopyrimidine blocks. It was shown that the light mtDNA strand, rich in adenine, is 60% more active in the binding with membrane mitochondria than the heavy one.


The genetic system of kinetoplasts in trypanosomatides. In the present report, the genetic system of Crithidia oncopelti kinetoplast is used as a model for investigation of kinetoplast DNA (kDNA) structure, its transcription, protein synthesizing apparatus of the kinetoplast and the protein synthesis controlled genetically by kDNA. It was shown that kDNA of C. oncopelti can be isolated from cells or from kinetoplast fraction in the form of a network complex structure consisting of a lot of circular molecules. These minicircles have a contour length of about 0.83 micronm and molecular weight of 1.6 X 10(6). The kDNA was demonstrated to be of higher AT content type than nuclear DNA. Besides, kDNA is characterized by a lesser degree of clustering of pyrimidines as compared with the nuclear one. The isolated kinetoplasts of C. oncopelti were shown to exhibit activity of DNA dependent RNA polymerase. The effect of some antibiotics and intercalating substances on RNA synthesis in kinetoplasts and mitochondria appears to be identical. Kinetoplasts of C. oncopelti have their own protein synthesizing system, whose components (ribosomes, rRNA, proteins, factors of incorporation) differ from those of the cytoplasm. Inhibition of translation by some antibiotics and of transcription by acriflavin allowed the suggestion that several proteins of kinetoplast ribosomes may be synthesized within this organoid. It was shown then that kDNA may be involved in the formation of the protein synthesizing apparatus in the kinetoplast.


Mitochondrial genes and cell heredity.

Mitochondrial genes and cell heredity. It is well known that mitochondria are only partly an autonomous system since they are subjected to nuclear control. For this reason, in studying mitochondrial genes one has to consider constantly the integration of mitochondrial and nuclear genetic systems. This fact makes experimental approaches still more sophisticated, especially, when one turns from individual genetic structures to mitochondrial heredity on the level of cells and multicellular organisms. Here we shall discuss some theoretical aspects of mitochondrial heredity that have been comparatively rarely dealt with in the literature.


Specific features of the structural organization of the mitochondrial genome in rat liver. The nature of intramolecular heterogeneity of mtDNA in the liver of white rats has been studied. The peculiarities of the melting curve, and the possibility of DNA fractionation of nucleotide compounds with hydroxylapatite (HA) column chromatography has shown the presence of sequences differing in the mean nucleotide content. A section of about 350 pairs in size repeated four times was found in the reassociation of most thermolabile fraction with a mean composition of 28% GC. These sections are well seen on the denaturation map of the recorded molecules formed in the range of temperature transition 'helix-coil'. The distance between the centers of fusible sections (in percentage of total length) is 32.5, 32, 14.0 and 21.5.


Intramitochondrial synthesis of membrane proteins in yeast: differential inhibition by ethidium. Yeast cells (Saccharomyces cerevisiae) were grown in the presence of [14C]phenylalanine and pulse-labelled with [3H]phenylalanine in the presence of cycloheximide. The proteins extractable into chroloform: methanol (2:1) were isolated from mitochondria and analysed by SDS gel filtration. Four protein fractions varying in molecular weight were separated. In order to identify the transcriptional origin and the site of protein synthesis ethidium bromide was used. Different sensitivity of protein syntheses to various concentrations of ethidium was shown. These data are discussed in relation to the possible presence of two classes of membrane-bound polyribosomes in mitochondria.


[Laboratory controls in long-term treatment with anticonvulsive drugs (author's transl)]. In the treatment of epilepsy often several substances with anticonvulsive effect are combined. Possible drug interactions in these cases can change the desired effect of treatment. Simultaneous administration of clonazepam or dipropylacetate (the latter in a short term combination) with diphenylhydantoin can cause a significant increase of diphenylhydantoin serum concentrations and intoxications. The combination of carbamazepin with diphenylhydantoin can cause a decrease of diphenylhydantoin serum concentrations. The simultaneous administration of diphenylhydantoin and phenobarbital can produce a significant increase of phenobarbital levels in the statistical average and in the case of a combination of primidon and diphenylhydantoin an intoxication by the primidon metabolite phenobarbital. These possible interactions which are not obvious at the beginning of therapy are supplemented by other factors as intercurrent diseases or erratic drug intake. With routine measurements of serum concentrations of anticonvulsive drugs some of these interfering factors can be eliminated by realizing them in time. Treatment becomes more effective and side effects are reduced. The development of a new check list for the treatment of epileptic patients should also improve the control and give better informations about the course of the disease.


[Alport syndrom (author's transl)].

[Alport syndrom (author's transl)]. A deaf-and-dumb patient died at the age of ten of failure of the kidneys. An uncle of the boy died at the age of 42, an aunt at the age of 16 years, both of atrophic kidneys. The mother of the proband is suffering from hard hearing on one side and recurrent episodes of pyuria. Repeated examinations in two aunts revealed slight pyuria resp. erythruria. Contrary to most reports affected members of the family showed pyuria rather than haematuria. A special inheritance could not be proved.


[Mould infection causing obstructive bronchitis. Diagnostik and therapeutic approaches (author's transl)]. The authors compared the results of mycologic examinations of asthmatic and control patient's throat. Fungi other than Candida were cultivated from the throat in 15% of asthmatic children and 3% of controls. In secrets from the lower respiratory tract gained by bronchoscopy, laryngoscopy, or through tracheostomy there were moulds in 34% among the asthmatics and in 15% of the other cases. Allergic respiratory tract diseases facilitate the harbouring of moulds in the respiratory tract but do not influence the presence of Candida albicans. Moulds could often be cultivated even in patient not allergic to them. However there are chronic cases caused by immun reaction to the moulds in the patients' respiratory tract. Microscopic detection of budding and branching, myceliform fungi in the secret produced by coughing supports the diagnosis of mould causing chronic asthmoid bronchitis. New peroral broad spectrum antimycotics facilitate the treatment of such cases. The authors succesfully treated some patients with Clotrimazol (Canesten, Bayer) and all cases responded well to 5-Fluorocytosan (Ancotyl, Roche).


[Mophometric study of the mouth mucosa in leukoplakia simplex]. Examination of the leukoplakia simplex of the oral cavity localized on the buccal surface and in the bottom of the oral cavity was carried out in 11 cases using the method of stereological morphometry. It was established that: 1. Quantitative changes of the constituents of the cytoplasma coming into being during the process of the keratinization appear to be similar in both forms of the lokalization investigated; 2. these changes seem to be opposite to the process observed during the differentiation of the normal epithelium; 3. by comparing stereological, histopathological and clinical data a new form of leukoplakia simplex can be distinguished i.e. the indirect form of the metaplasia of the squamous epithelium. 4 Method of the stereological morphometry seesm to be suitable for the description of characteristic features of the keratinization.


Mutagenicities of quinoline and its derivatives. Quinoline, recently reported to be carcinogenic in rats [12], was mutagenic to Salmonella typhimurium tester strains TA100 and TA98 in the presence of the metabolic activation system S-9 mix. 2-Chloroquinoline, a non-carcinogen [12], was non-mutagenic with or without S-9 mix. 8-Hydroxyquinoline, which is t known to be carcinogenic, was mutagenic with S-9 mix to both bacterial strains. The mutagenicities of 17 other quinoline derivatives that are not known to be carcinogenic were tested, and 12 of these compounds were mutagenic.


Gallbladder disease as a side effect of drugs influencing lipid metabolism. Experience in the Coronary Drug Project. We analyzed data obtained during the Coronary Drug Project to discover the influence of the drugs used on the frequency of gallbladder disease. Of 2680 placebo-treated men who had had myocardial infarction, gallbladder disease developed in 69. Corresponding figures for those given 2.5 mg of estrogen, 5.0 mg of estrogen and 1.8 g of clofibrate per day were 46 of 1061, 47 of 1081 and 42 of 1051, respectively. Each treatment group differed from placebo by over twice the standard error of the difference, life-table analysis yielding P less than 0.05 for each drug-placebo comparison. Forty-five variables, including age, body weight, blood pressure, serum lipids and blood sugar, were evaluated as risk factors. Age significantly correlated with prevalence of known gallbladder disease at entry (r = 0.066, P less than 0.001). No variable yielded a strong and consistent correlation with the incidence of subsequent new gallbladder disease. Gallstone formation is a risk whenever clofibrate or estrogen is prescribed.


A semiquantitative culture method for identifying intravenous-catheter-related infection. We evaluated a semiquantitative culture technic for identifying infection due to intravenous catheters: rolling the catheter segment across blood agar. This method was compared to broth culture. Of 250 catheters studied, 225 (90%) had low-density colonization on semiquantitative culture (less than 15 colonies on the plate) although 49 (19.6%) of these grew some organisms in broth or on the plate. None of these catheters led to septicemia. Twenty-five catheters (10%) grew greater than or equal to 15 colonies by the semiquantitative technic; most gave confluent growth. Septicemia originated from four of these catheters (P = 0.008). Of 37 catheters exposed to bacteremias from distant foci of infection, four yielded matching growth in broth, whereas none were concordant with the blood isolate on semiquantitative culture. Local inflammation was associated with high-density colonization semiquantitative culture (P less than 0.001). The semiquantitative technic distinguishes infection (greater than or equal to 15 colonies) from contamination and is more specific in diagnosis of catheter-related septicemia than culture of the catheter in broth.


Penicillopepsin from Penicillium janthinellum crystal structure at 2.8 A and sequence homology with porcine pepsin. The polypeptide chain of the acid protease penicillo pepsin folds via an 18-stranded mixed beta-sheet into two distinct lobes separated by a 30-A long groove which is the extended substrate binding site. The catalytic residues Asp-32 and Asp-215 are located in this groove and their carboxyl groups are in intimate contact. Alignment of the amino acid sequence with that of pepsin shows regions of high homology.


Radio-fibrinogen catabolism and fibrin products for the assessment of renal disease. The methods for dynamic assessment of intrarenal coagulation in the renal glomerular diseases are reviewed. Particular emphasis is placed on the radio-fibrinogen catabolism study and its potential for monitoring the activity of nephritis and renal transplant rejection.


[Post-amputation dehiscence. A problem resolved]. 70 peripheral amputations of the lower extremities in arteriosclerotic and diabetic vasculopathics have been examined. In a number of cases, the postoperative period was complicated by dehiscence of the suture on the stump, with lengthening of hospitalization time, risk of infection in the underlying bone and thus further amputation. To solve this problem, dehiscence was treated with dermo-epidermal autografts to cover the missing tissue area. The dehiscence was cleaned with compresses of 2% amuchina associated with topical instillations of Lincomycin hydrochloride. The cure percentage after grafting was about 80%.


[Use of cortisone in the symptomatic treatment of malignant bronchopulmonary tumors]. 86% of 1703 subjects with primary malignant bronchopulmonary tumours treated over a period of 5 years responded solely to symptomatic management. Attention is drawn to the poor results offered by polychemotherapy and to satisfactory treatment of 82 patients with 6-methylprednisolone acetate. This drug was chosen on account of its ease of administration and fewer side-effects by comparison with cortisones given per os.


[Long-term treatment of arthrosis using Arumalon]. Cartilage and bone marrow extracts have been used to enhance cartilage mucopolysaccharide levels. The value of this form of treatment was appraised in 250 groups of 250 patients with well established arthrosis. Comparison was made between standard management with anti-inflammatory drugs, analgesics, anti-rheumatic compounds, physiotherapy and heat treatment, and management with the addition of cartilage and bone marrow extracts (Arumalon) over a period of 5 yr. Patients who received Arumalon had a lower frequency of painful exacerbations, a lower and more delayed frequency of functional incapacity, and a slower and less striking radiological progression. These results corroborate experimental and clinical data in the literature. They were particularly marked in 50 cases of gonarthrosis.


[Clinical diagnosis of Creutzfeldt-Jakob disease based on a case report]. The authors report a case of Jakob-Creutzfeldt disease diagnosed at autopsy. In the discussion attention is called to characteristic clinical manifestations and possibilities of intravital diagnosis of the disease.


[Case of Jakob-Creutzfeldt disease with rarely observed location of lesions (the so-called Heidenhain syndrome)]. The authors describe a case of Jakob-Creutzfeldt disease in a 64-year-old women. The peculiarity of the case lay in the fact that besides atrophic lesions of frontal lobes, extensive spongiform degeneration was present in both occipital lobes--corresponding to the so-called Heidenhain syndrome of classical neuropathology. The clinical counterpart of this location of the lesions, apart from dementia, were quadrantic hemianopsia and changes in EEG records.


[Therapeutic effects of nicofibrate on diabetic hyperlipemia]. The plasma lipid picture before, during and after 4 months of administering p-chloro-phenoxy-alpha-isobutyrrate of 3-hydroxy-methylpyridine hydrochloride (Nicofibrate) in a group of diabetics was studied. Treatment led to a significant reduction in plasma cholesterol and triglycerides and brought the lipoprotein picture back within the norm. Nicofibrate did not lead to significant increases in uricaemia nor to any worsening in carbohydrate tolerance. At the doses used, a significant drop in plasma prothrombinic activity was encountered, while no noteworthy variations were observed in the other biohumoral parameters examined. In the light of these results, the various aetiopathogenetic aspects of the hyperlipaemia so frequently observed in diabetes mellitus are discussed.


[A chapter of historical pathology: scurvy in a 17th century document]. The translation form Latin of a XVIIth century medical document concerning scurvy is reported. Stress is laid on the importance of historical research of this type as an intellectual exercise and as a historical curiosity.


[Ventilation and continued positive-pressure respiration in resuscitation]. Expiratory positive pressured used as a routine procedure in patients with healthy lungs and those with serious pulmonary alterations since 1973 is described. It has been found that CPPV offers effective opposition to the gradual desaturation of arterial blood in O2 encountered with IPPV.


Estrogen and endometrial carcinoma.

Estrogen and endometrial carcinoma. 1. It has become evident that the estrogen secreting tumors of the ovary are associated with endometrial carcinoma, but this association is most easily observed in the postmenopausal patient where the incidence of carcinoma has been reported at 10.3% (1.  02) to 24% (83). 2. The most consistent association of endometrial carcinoma is with polycystic ovarian disease, where 19 (34), 21 (152), and 25% (150) of young women with endometrial carcinoma had Stein-Leventhal syndrome (67). 3. A very significant discovery became known in 1967 when the peripheral aromatization of delta4 androstenedione to estrone was reported by Kase (94) and MacDonald (111,112). Since that time we have learned that endometrial carcinoma patients have an increased peripheral conversion (139) (0.1% compared to 0.027%), which is similar to that found in obese and aging patients, by Hemsell, et al (77). This can be 2 to 4 times greater than the young adult or the patient without cancer. Estrone produced peripherally in normal postmenopausal women can amount to 40-60 microng/day and rise as high as 120-180 microng/day in the endometrial neoplasia group (39). Similarly patients with polycystic ovary disease, hyperthecosis and lipoid cell tumors of the ovary demonstrate androgen excess with extraglandular conversion to estrone (2). 4. It has become apparent that the principal estrogen in the postmenopausal patient is estrone and that the estrone-estradiol ratio in the serum is higher in postmenopausal women with corpus cancer than similar patients without cancer (135). Clearly, we must find the effect of this estrone excess at the nuclear "acceptor" level; and does this imbalance create a hormonal environment conducive to the development of endometrial carcinoma when age (an extremely important factor) and an oncogenic agent are added? 5. With the lack of ovarian estrogen there is a relative excess of adrenal testosterone, dihydrotestosterone and delta4 androstenedione, the available precursors of extraglandular estrone (1). 6. With the passage of time it appears that endometrial carcinoma is associated with hypothalamic "hyperactivity" (31) which exhibits immunologic-biologic dissociation of LH as previously observed in persistent trophoblastic disease when measuring hCG. The significance of this is still unknown. In a like fashion a significant number of the at risk polycystic ovary disease patients have an increased LH secretion. 7. Patient susceptibility is required as seen in animal experiments where prolonged administration of stilbestrol is used and still only rabbits and mice developed a malignant change. 8. Long term exogenous estrogen appears to have caused malignant changes in the endometrium, but it was universally given over  a prolonged period (4 or more years). The recent retrospective studies demonstrate an association of oral estrogen therapy with endometrial cancer, but prospective studies investigating dose and duration of all estrogen preparations need to be undertaken. 9...


An immunofluorescent study of basement membranes in squamous cell carcinoma of the cervix, vagina, and vulva. Basement membranes of 33 samples of in situ or invasive squamous cell carcinomas of the cervix uteri, vagina, and vulva were studied by defined immunofluorescence technics. Pooled serum from patients with bullous pemphigoid, containing specific antibody to squamous epithelial basement membrane, was utilized. Essentially normal basement membranes were found in all cases of in situ carcinoma and in 18 cases of invasive carcinoma. Basement membranes appeared poorly formed in three specimens with invasion and were absent in the remaining three. These findings support the premise that penetration of the basement membrane is not a valid criterion for distinguishing in situ from invasive squamous cell carcinoma.


Apertognathia: its challenge and conquest. Report of a case. Apertognathia or open-bite deformity is the cause of poor speech, loss of masticatory function, and the resultant embarrassment of patients. The treatment of these malocclusions embodies the use of our own technical, scientific, and physiologic knowledge, coupled with the research of others. This article gives a solution to an unusual case and points out the present techniques and research are only building blocks for the future.


Radioisotope determination of apical seal integrity of silver point-filled endodontic teeth after ultrasonic vibration. Twenty-six human mandibular incisors with single root canals were instrumented and obturated with silver points and sealer. The efficacy of the initial seal was tested by immersion in radioiodine and counted for gamma radiation. Subsequently, the teeth were subjected to the vibration of an ultrasonic scaling device and reimmersed in the isotope so that the integrity of the apical seal could be re-evaluated as a function of increased radioiodine uptake and, thus increased gamma radiation. No significant difference was found after use of the Cavitron device.


[Effect of Prednimustine (Leo 1031) in chronic lymphatic leukemia]. 46 ambulatory patients with chronic lymphocytic leukemia were treated with Prednimustine either continuously (daily or each other day 20 mg) or intermittently (daily 20 mg for 14 days, followed by a pause of 4 weeks). A good response was seen in 28 patients lasting up to 17 + months (mean 4,5 + months) after terminating therapy. Patients without prior chemotherapy have improved earlier and to a smaller amount of the total dose applicated. Signes of bone marrow toxicity (anaemia, thrombocytopenia) were observed in 8 cases, gastrointestinal side effects in 7 cases, cutaneous exanthema in 3 cases, and one patient exhibited a severe stomatitis after treatment. Prednimustine constitutes an effective drug for chronic lymphatic leukemia.


The evaluation of peripheral auditory function in infants and children. The technique of electrocochleography described, although invasive, has proved to be innocuous in our experience. It provides precise information concerning peripheral auditory activity in response to sound stimulation at frequencies across the audible range. The most valuable application of the technique in clinical practice is in testing the hearing of infants and children who are too young to test by standard behavioral audiometric techniques, and in testing the hearing of children with behavioral problems or mental retardation;


Idiopathic respiratory distress syndrome (IRDS): intermittent positive pressure ventilation (IPPV) versus continuous positive pressure ventilation (CPPV), a comparative study. 59 patients with IRDS treated with CPPV in 1973-1974 are compared with 59 patients treated with IPPV in 1971-1972. With CPPV there was a reduction in mortality from 40.7% to 32.2%. CPPV as compared to IPPV reduced right to left shunting from the 6th hour of life onwards. Elevated oxygen supply was needed for shorter time and time of mechanical ventilation as well as duration of intubation could be reduced. The frequency of pneumothorax during ventilation was unchanged. The frequency of bronchopulmonary dysplasia could be reduced. One third of the surviving patients had neurological symptoms at the age of one year, the frequency was lower in the CPPV group. One patient in the IPPV group was severely damaged. The results obtained are in favour of CPPV as compared to IPPV for mechanical ventilation in patients with IRDS.


[To the Treatment of myelomeningocele (author's transl)]. Social importance of myelomeningocele specially in Great Britain is stressed and surgical treatment in 24 hours after birth is necessary. Severe complications as infections of the CNS and others in consequence of the neurogenic bladder are demonstrated. The manifold problems of these infants and their families need an individual plan for treatment and care. Interdisciplinary cooperation is the condition for the success of rehabilitation.


[Action of pharmacological effectors on hematocrit and lactate dehydrogenase activity changes in experimental ischemic shock]. The experimental ischemic shock induced by removing tourniquets in rats, were studied. Durin 164 hours, the variations of the values of hematocrit and of muscle and plasma dehydrogenase lactate activity were followed up; the modifications of these variations after pharmacological high doses of dexamethasone phosphate, hydrocortisone hemisuccinate and aprotinine administered intravenously, were evaluated. The best action was noted after dexamethasone phosphate treatment.