The distribution of 99mTc-EHDP in the tissues of the dog and its application in the assessment of fracture healing. Technetium-labelled ethane hydroxydiphosphonate (99mTc-EHDP) is a commonly used bone-scanning agent. After injection it leaves the circulation to enter bone and to be cleared by the kidney. The transcapillary exchange of 99mTc-EHDP in bone was examined and found to be low. The capillary movement was compared with that of sucrose, a freely diffusible substance, and it was found that the permeability ratio of 99mTc-EHDP to 14C-sucrose was similar to the diffusion coefficient ratio, suggesting that 99mTc-EHDP passes through the capillaries by the process of passive diffusion. The renal clearance of 99mTc-EHDP was 24 ml/min and was unaffected by the action of parathyroid hormone. After a fracture the bone blood flow increases, although the transcapillary extraction of 99mTc-EHDP does not change. This is because there is an increase, from recruitment and dilatation of capillaries, in the surface area available for exchange. Therefore the increased isotopic activity seen on a bone scan after a fracture is primarily related to an increase in bone blood supply from capillary enhancement within the cortex.


Micro-organisms in the bile. A preventable cause of sepsis after biliary surgery. The bile is infected in 31% of patients undergoing an operation for biliary disease and these patients have a significantly greater risk of developing wound sepsis and septicaemia than patients with sterile bile. Prophylactic antibiotics which achieve satisfactory serum rather than high bile levels have been shown to reduce the morbidity of biliary operation. However, only patients with infected bile benefit from prophylactic chemotherapy. Patients with infected bile can be satisfactorily identified by preoperative duodenal aspiration, operative Gram staining of bile, or clinical presentation. The high-risk patients requiring preoperative antibiotic cover include anyone over 70 years of age, jaundiced patients, those requiring emergency operation, patients with recent rigors, anyone having had previous biliary operations, and patients known to have choledocholithiasis.


Localized thrombus complicating saphenous vein grafts. Recurrence of symptoms after a long saphenous vein graft may be due to a variety of causes. When the graft pulse can still be felt the presence of a localized thrombus partially occluding the lumen must be considered. After arteriographic confirmation such a thrombus can be easily removed.


[Hormonal and nervous controls of the gastro-intestinal motility in the hen (author's transl)]. Nervous and hormonal controls of the gut system were studied in 42 hens using electromyography with transparietal electrodes. The results were analysed in relation with various biochemical parameters. The hormonal changes which occurred during sexual maturation and the ovulatory cycle induced directly the circadian organization of the motility of the gizzard and indirectly the motility of the intestinal tract. This resulted from variable metabolic requirements, the calcium being the most important element. An antagonism between gizzard and intestine motility was demonstrated. The pharmacological study confirmed the excitatory effect of the cholinergic system. For the adrenergic system, alpha receptors were predominant on the gizzard and beta receptors on the intestinal tract, especially in the distal part.


[In vitro predatory activity of a strain of Arthrobotrys oligospora Fres. Against a zooparasitic nematode]. The in vitro predatory activity of Arthrobotrys oligospora Fres. against larvae of Haemoncus contortus (Rudolphi) Cobb. was investigated on sheepdung agar. The technique employed is described and discussed. The data and observations presented indicate that temperature and number of larvae added to the fungus appear as important factors regulating the capturing efficiency. High trapping percentages were observed at 15 degrees C and 22 degrees C after a 24 hours' contact period, whereas at 10 degrees C a highly significative predatory effectiveness is not observed until 72 hours. In all experiments, where the plates contained more than 3 or 4 nematodes per square centimetre, the trapping percentage exceeds 50 p. cent  after a 7 days' contact period. The response of the fungus to an increase in the number of larvae is not univocal : at 10 degrees C and 22 degrees C the nematode-trapping efficiency does not seem to depend upon the larval dnesity of the inoculum; at 15 degrees C, on the contrary, the nematodes are all the more trapped as their concentration is high. At this temperature with 35 larvae p. square centimetre, a trapping percentage of 90 p. 100 can be observed.


[Evidence of an excretion of uric acid by a caecal pouch in the rabbit (author's transl)]. Uric acid was estimated in the blood plasma, the caecal content, and in the lumen of a caecal pouch in operated rabbits. It was also histochemically detected in the caecal wall. A non negligible excretion of uric acid through the perfused caecal pouch was demonstrated. There was also an accumulation of amorphous uric acid in the enterocytes, probably due to the absence of intestinal transit, and of microorganism's uricase.


[Short term toxicity of ochratoxin A: some biochemical lesions in the rat (author's transl)]. The blood serum level of total proteins, urea, total lipids, cholesterol and glucose, and the excretion of nitrogen in the urine were estimated in control or treated rats. Male adult rats were given the toxin per os (0, 0.5, 1 or 2 mg/kg) during 10 days. An increase in the urinary volume was observed, with a decrease in the total nitrogen concentration. Blood total proteins and urea levels were higher than in control animals but total lipids and cholesterol levels dropped. Blood glucose concentration remained unaffected. These effects were evident even for the lowest dose and their intensity increased with the amount of toxin given to the animals. Statistical analysis showed significant differences between the results obtained in control animals and those obtained in animals treated with either 2 mg/kg or--except for blood urea--1 mg/kg.


Pathological changes in spontaneous rupture of chordae tendineae. Eight patients with spontaneous rupture of mitral chordae tendineae have been studied. In no case was there a predisposing cause. Seven showed pathological fibrosis of the papillary muscle relevant to the ruptured chordae. It is postulated that papillary msucle dysfunction secondary to fibrosis may cause stretching of chordae and subsequent rupture. Five patients had mucoid degeneration of their mitral valves. Mucoid change appeared to develop only when the clinical history indicated a lengthy period of valvular dysfunction.


Gastric secretion and haematological findings in relation to mucosal atrophy after partial gastrectomy. Twenty-one patients (4 females and 17 males) were re-examined 20 years after partial gastrectomy for benign peptic ulcer. Different stages of morphological change in the gastric stump mucosa were compared with haematological parameters as well as with gastric acid and IF secretions. Biopsy specimens were taken by the direct vision technique. Haematological values including also serum vitamin B12, folate and Schilling test were determined. Gastric acid and IF secretions were lower in all patients with "selective parietal cell atrophy" in the gastric mucosa compared with those of other patients. Serum B12 and Schilling test values showed the same tendency. The present study indicates that it is possible to determine the gastric function dependent on parietal cells according to morphological criteria.


Immediate surgical treatment of major renal trauma. Of the 77 cases of renal trauma treated at Oulu University Central Hospital during the years 1965--1975, 60 injuries were minor and 17 severe. 73 of these injuries were closed and 4 penetrating. The rate of operative treatment in severe renal injuries was 88% minor renal injuries being treated conservatively. Primary exploration was done in 18 of the 77 cases and in all patients with penetrating injuries. Only 7 of the 73 patients with blunt trauma and one of the 4 patients with penetrating injury required nephrectomy, including one patient with renal carcinoma. 6 of the 77 patients died, most as a result of severe associated injuries, giving a mortality of 8%. None of the surviving patients treated for renal trauma suffered from major complications. In 13 of the 18 patients operated upon, renal injury was the main indication for operation. Operation was performed in 5 of the 18 patients after immediate radiological evaluation. The advantages of immediate surgical management in severe renal injuries are early and final treatment, short hospital stay, and low incidence of complications. Qualifications for emergency surgery are access to renal angiography and familiarity with reparative renal procedures.


Subcutaneous rupture of the urinary bladder. Fourteen patients operated upon for subcutaneous bladder perforation are reported. The majority of the patients (11/14) had intraperitoneal rupture of the bladder and multiple associated injuries (10/14), most often pelvic fractures (9/14). In 12 patients the injury was caused by a road traffic accident. 2 patients with extraperitoneal rupture presented with a typical history of a blow or kick in the lower abdomen following a drinking session. In doubtful cases cystography was the diagnostic method of choice. The principles of treatment we recommend are well known: urinary drainage with a catheter in all cases, and in intraperitoneal ruptures, prompt surgery.


Traumatic splenic rupture.

Traumatic splenic rupture. 71 patients with traumatic splenic rupture are reported. Most had severe associated injuries. In 44 patients the mechanism of trauma was blunt, in 10 penetrating, and in 17 iatrogenic, occurring most commonly (11/17) during operations for peptic ulcer. Splenectomy gave use to thrombocytosis which reached its peak about 2 weeks and returned to normal within one month after operation. Postoperative complications occurred in 24 of the 60 surviving patients (40%) of which most, 17 patients (30%) were infectious in origin. One patient developed deep venous thrombosis. Mortality was 16%. Associated injuries were the main cause of death in most patients (9/11), the ruptured spleen being responsible for only 2 deaths. None of the 17 patients with injury to the spleen alone died, whether associated with fractures of the left lower ribs or not. Primary unconsciousness, shock on admission, and multiple injuries, especially renal and hepatic, increased the mortality rate markedly. The necessity of drainage, the possibility of increased susceptibility of splenectomized patients to infection and thromboembolic complications and their prevention are briefly discussed.


Management of injuries of the large intestine. Blunt trauma accounted for 1/3 of the 32 patients operated upon for injuries of the large intestine and penetrating wounds for 2/3. Most of the blunt injuries (9/10) were caused by traffic accidents, and more than half of the penetrating ones (12/22) were stab wounds. The transverse colon was most commonly affected, followed by the ascending, descending and sigmoid colon, rectum and mesentery. Perforation of the small intestine was the most frequent associated intra-abdominal injury, occurring in 11 patients (34%). Most patients (22/32) underwent simple suture, 6 patients suture with proximal colostomy, 3 primary resection and one exteriorization, combined in all cases with broad-spectrum antibiotic coverage and drainage of the abdominal cavity. Injuries to the right and transverse colon were managed mainly with simple suture, and those to the left colon and rectum with suture and proximal colostomy. 50% of the patients had complications, most frequently wound infection and intra-abdominal abscess. The patients with simple suture had fewer complications than the others. In the absence of complicating factors injuries to the colon are best managed with simple suture, whereas in the presence of complicating factors and in injuries of the rectum, suture or resection with proximal colostomy, especially in cases of severe tissue destruction, remains the treatment of choice.


Recovery and rehabilitation of elderly subjects with femoral neck fractures. The effects of operative methods and postoperative care were studied in a series of 87 patients with femoral neck fractures. Thirty nine patients were treated with the Thompson endoprosthesis and 48 with internal fixation. Half of the patients in both groups were given the routine postoperative physical therapy of the department and the other half intensive physical therapy. The patients' mean age was 73 years, and 75% of the patients were women. The patients fitted with a prosthesis were mobilised better than patients following internal fixation. The clinical results in the cases who had received intensive physical therapy and those given routine physical therapy did not differ during the postoperative follow-up period of 9 weeks. The patients' age did not influence recovery. Mortality during the 3 months of follow-up was 11.5%. The mean age of the patients who died was higher than that of the other patients. Wound infections occurred in 7%. The morbidity and mortality rates were the same for both groups. Postoperative mobilisation of elderly patients with femoral neck fractures causes a great deal of work to the nursing staff. Intensified physical therapy did not hasten the patients' recovery in this study.


The distribution of isoelectric points of human soluble proteins and in particular of the enzyme products of 88 human gene loci. The isoelectric points of the 'primary' isozymes coded for by 88 human gene loci have been determined. The distribution was found to be bimodal with an antimode at the 'physiological pH'. Soluble human proteins have the same distribution and this appears to be characteristic of soluble mammalian proteins in general. There may be some correlation with function, mitochondrial enzymes being more basic and hydrolytic enzymes being more acidic than other classes of enzymes. The bimodal distribution can be explained in terms of the buffering effects of the charged amino acids. Most proteins would thus appear to be charged at neutral pH values.


The frequency in Japanese of genetic variants of 22 proteins. I. Albumin, ceruloplasmin, haptoglobin, and transferrin. This paper presents the results of an electrophoretic survey of approximately 4000 individuals from the cities of Hiroshima and Nagasaki, Japan, for four serum proteins: albumin, ceruloplasmin, haptoglobin and transferrin. The haptoglobin gene frequencies obtained for the HP1-HP2 polymorphism are in agreement with earlier reports. Rare electrophoretic variants of albumin, ceruloplasmin and haptoglobin occur with frequencies of 2-48, 0-50 and 0-58 per 1000 determinations, respectively. The noteworthy finding of 8 distinct transferrin variants in these populations, with a combined frequency of 20-90 per 1000 determinations, is also presented. Four of these variants (Dchi, B1, B3, and DHIR2 which corresponds electrophoretically to D4) have been reported in other populations in Japan, but the other five have not previously been differentiated.


Visual classification of banded human chromosomes ii. classification and karyotyping of integrated density profiles. Visual classification and karyotyping of 897 integrated density profiles generated from straight and non-overlapping chromosomes from 22 trypsin-banded metaphases of average quality was carried out and evaluated. The results were compared with visual classification of photographic prints of the same 897 chromosomes. The experiments were carried out by one observer. About 5% errors were made in classification of isolated profiles; 0-5% errors were made in karyotyping profiles and about 3% errors were made in classification of isolated chromosome prints. The reason for the small error rate obtained by karyotyping profiles as compared to the error rate when classifying isolated profiles was assumed to be the use of a priori knowledge of the composition of (normal) metaphases and the possibility of making appropriate comparisons between the individual profiles within the metaphase. Comparison between classification of isolated prints and of profiles showed different error patterns on the basis of which it was assumed that prints constitute a better basis for visual classification than profiles. The results seemed to indicate two ways of improving computer classification of banded chromosomes: (1) information of value in the chromosomes (band pattern, shape etc.) should be extracted from the digitized chromosome image in a manner superior to the simple integration by which profiles are produced; (2) computer karyotyping should simulate the human method, thus taking advantage of a priori knowledge of the composition of the metaphases and being able to make appropriate comparisons between individual chromosomes.


Counting methods (EM algorithm) in human pedigree analysis: linkage and segregation analysis. The likelihood of human pedigree data can be written in such a form as to allow the computation of derivatives. This is done for various parameters in linkage and segregation analysis. The equations for the maximum likelihood estimates are represented in a particularly appealing form which allows iterative solutions. This process is an extension to pedigress of Smith's (1957) counting methods. All these procedures belong to a general class of MLE methods for incomplete data called EM algorithms (Dempster et al. 1976).


A new model for measuring breeding genetic distance. A model is proposed for measuring the genetic 'distance' between two populations having gene frequencies p and p. The measure of distance is based on a hypothetical selection process as follows: From population P a subpopulation P can be selected having gene frequency p. Let Po be the largest subpopulation yielding gene frequency p, then the relative size of Po to p--denoted by thetao (p,p)--is a measure of the 'closeness' of populations having gene frequencies p and p, and 1-thetao (p,p) whould be a reasonable measure of genetic distance. We show that the calculation of thetao (p,p) is a special case of the linear programming problem and derive algebraic expressions for thetao (p,p) in the two-allele case. We discuse some of the implications of the use of this measure of distance and compare it to others which have been proposed. We use linear programming methods to calculate genetic distance for three alleles.


A note on genetic distance.

A note on genetic distance. Various definitions of 'genetic distance' and 'frequency distance' are considered, together with the purposes for which they are used. There are at least seven simple definitions of 'genetic distance' which agree closely with each other and with a Mahalonobis-type D2 for qualitative characters, whereas other proposed definitions are mostly based on quite different approaches. The Mahalanobis-type definitions are also related to random drift.


Inbreeding in Norway.

Inbreeding in Norway. In Norway specified information of marriages between second cousins and closer relations has been recorded in the marriage certificates since January 1889. In addition, information was collected in the 1891 census and in the Medical Registration of Births (established in 1967). A ratio of second- to first-cousin marriages equal to or greater than 2 has been taken as some evidence indicating reliability of the source of data. Using this criterion, the information in the Medical Registration of Births seems most reliable, and that in the 1891 census possibly of similar accuracy. On the other hand, from 1890 the marriage certificates are unreliable with regard to the proportion of second-cousin marriages (ratio less than 1), and with regard to the proportion of first-cousin marriages from 1919. The present inbreeding in Norway is low (alpha4 = 0-000242), approximately one-eighth of the estimated level according to the 1891 census. The greatest reduction in inbreeding probably occurred after 1920.


[Effect of the pH of the medium on the growth of a carminomycin producer and on the biosynthesis of the carminomycin complex]. The effect of the nutrient medium acidity on the growth of the carminomycin-producing organism and formation of the carminomycin complex with its aid was studied. Satisfactory development of the organism was observed when pH of the nutrient medium on the culture inoculation was 4.9 to 8.5. A shift in the alkaline and acid values of pH to 6.3--6.4 was registered during the first 24 hours of the culture growth. The biosynthesis of carminomycin depended on the culture growth time and pH value of the nutrient medium and culture fluid during the fermentation process. Maximum production of the carminomycin complex and its active components was observed on the 7th--8th day of the culture growth. The medium reaction close to the neutral one was optimal for biosynthesis of the carminomycin complex and its active components. Under acid, as well as alkaline conditions the antibiotic production was markedly lower.


[Spontaneous variability of Actinomyces werraensis]. The study of spontaneous variation of Act. werraensis not subjected to the treatment with mutagens and stabilizing selection revealed 6 variants within the homologous series of hereditary variation of apigmental actinomyces. The example of revealing the proactinomycete-like variants in Act. werraensis confirmed the prognosticating principle of the homologous series law in the hereditary variation of actinomycetes. Correlation between the cultural and morphological features of the spontaneous variants and the antibiotic-production level was shown. It was found that the variants of Act. werraensis had a high variation coefficient characteristic of the wild type actinomycetes. A possibility of increasing the biosynthetic activity of Act. werraensis by selection of spontaneous variants with artificial mutagenesis was shown.


[Comparative study of the action of streptomycin on the variability of levorin and amphotericin B producers]. The study of the effect of streptomycin on viability of Act. levoris, strain LIA=0868 producing levorin and Act. nodosus, strain LIA-0861 producing amphotericin B showed that streptomycin had a lethal effect which increased with increasing of its concentration from I to 6 gamma/ml. While the lethal effect of streptomycin on the above cultures was comparatively the same, it had a selective effect on the levorin-producing organism and a marked inhibitory effect on the amphotericin B-producing organism. The selective effect of streptomycin was evident from inhibition of some types of the morphological mutants and variants characterized by a high level of levorin production and from selection of streptomycin-resistant variants. The inhibitory effect of streptomycin was evident from a marked increase in the number of the morphologically changed colonies and variants characterized by a low level of the antibiotic production.


[Lipid makeup of the initial and selected strains of Actinomyces levoris and Streptoverticillium mycoheptinicum in the process of antibiotic synthesis]. The study of the lipid composition showed that the rate of the changes in the fatty acid composition of neutral lipids and phospholipids in the selected strains was higher than that in the initial strains. The medium composition had the decisive effect on the fractional and fatty acid spectrum of the mycelium lipids. When the antibiotic-producing organisms were grown on the synthetic medium the phospholipids were the predominating fractions (70--90 per cent of the total lipids), while with the use of organic medium they amounted only to 30--40 per cent. The data were evident of complex correlation between the synthesis of fatty acids and polyenic antibiotics, i.e. levorin and mycoheptin.


[Acid-base equilibrium of D-(--)-alpha-aminophenylacetic acid]. Potentiometric titration was performed and the ioniziation macroconstants of D-(--)-alpha-aminophenylacetic acid and its methyl ether were determined. The constants were used for estimation of 4 microconstants of D-(--)-alpha-aminophenylacetic acid and the constants of the tautomeric equilibrium of the zwitter-ionic and neutral forms of the amino acid. Minimum solubility of D-(--)-alpha-aminophenylacetic acid was determined and pH-dependence of its solubility was estimated.


[Stability of the amidine analogs of penicillin and deacetoxycephalosporin to the penicillinase of Bacillus licheniformis 749/c]. Fermentative hydrolysis of 3 derivatives of 6-beta-amidinopenicillanic acid and I derivative of 7-beta-amidinodeacetoxycephalosporanic acid by penicillinase produced by Bacillus licheniformis 749/c was studied. It was found that 6-beta-[(hexahydro-IH-azepin-I-yl) methyleneamino] penicillanic acid, 6-beta-(N1 N-dimethylformamidino-N1) penicillanic acid and 6-beta [(morpholin-I-yl) methylenemino] penicillanic acid were hydrolyzed by the enzyme 50, 70, and 160 times respectively slower than benzylpenicillin. 7-beta-[(Hexahydro-IH-azepin-I-yl)' methylenemino] deacetoxycephalosporanic acid proved to be at least 10 times more stable to the effect of penicillinase than methicillin. In addition unlike the amidine analogues of penicillin the above compound had an inhibitory effect on penicillinase produced by Bacillus licheniformis 749/c.


[Effect of gentamicin on the state of cellular resistance]. The effect of gentamicin on the functional state of the cells of the reticuloendothelial system (RES) of the abdominal cavity of mouse macrophages and the cell culture of the rabbit embryon kidneys was studied. Gentamicin administered intramuscularly in multiple doses of I and 10 mg/kg for 6--14 days did not induce significant changes in the absorptive activity of the RES. In doses of 20 and 40 mg/kg gentamicin induced some inhibition of the absorptive activity of the abdominal cavity macrophages, which was accompanied by a decrease in the content of the total protein and an increase in the activity of the acid phosphatase in the cell cytoplasm. The changes were reversible and persisted for not more than 48 hours after the last administration of the antibiotic. Gentamicin inhibited the cell growth in the culture of the rabbit embryon kidneys in concentrations higher than 1000 mg/kg, LD50 of gentamicin for mice weighing 20--22 gm being 244 mg/kg. Preliminary administration of amigluracyl provided a decrease in the toxic effect of gentamicin in both the cell culture and the host, which was possibly associated with the anabolyzing effect of amigluracyl.


[Viability of a Bac. licheniformis 749/c culture and its formation of penicillinase during storage in the lyophilized state]. The amount of the enzyme produced and the colony morphology of Bac. licheniformis 749/C, the penicillinase-producing organism were studied after storage for 3 years in ampoules at a temperature of 4--10 degrees C, in lyophilized form in sodium glutamate, polyvinylpirrolidone, their mixture and horse serum. The highest rate of the culture growth was observed after storage in lyophlized form in sodium glutamate, though the culture was vialable in all other protective media. Two culture types approximately in an equal ratio were observed in the population platings of the culture lyophilized in various protective media.


[Antibiotic sensitivity of bacteria isolated in association with fungi]. Sensitivity of bacteria isolated from the bronchial contents of 414 patients with chronic non-specific lung diseases was studied with respect to 8 antibiotics. A significant decrease in the antibiotic sensitivity of cocci, i. e. staphylococci and streptococci isolated in association with fungi, i. e. Candida, Aspergillus and Penicillium was shown. The results of the study were confirmed experimentally in mixed incubation of the staphylococci with Candida albicans in vitro.


[Experimental study of the mutagenic activity of gentamicin sulfate in relation to the causative agent of plague]. Gentamicin sulfate was studied with an aim of obtaining mutants of the plague microbe with a changed character of requirements in the growth factors. The antibiotic provided a high yield of auxotrophic mutants and induced streptomycin resistance in some cells. Mutants with single dependence on arginine, leucine, histidine and uracyl were most often. Comparison of the data obtained with gentamicin and those obtained with other chemical mutagens showed that gentamicin by its mutagenic activity was only slightly inferior than the preparations of the group of supermutagens.


[Study of the pharmacokinetics of dicloxacillin used parenterally in an experiment]. Dicloxacillin was superior to oxacillin in the maximum levels and retention time in the blood of dogs and rats. Dicloxacillin was intensively excreted by the kidneys for 3 hours. For 24 hours 62 per cent of the drug was excreted with the urine. In intravenous administration to animals the peaks of the antibiotics levels in the blood and internal organs were achieved at earlier periods, while the circulation time was shorter than in intramuscular administration. The intramuscular use of the drugs had no advantages in the kinetics against the oral use.


[Basis for the administration of streptomycin and isoniazid in ultrasonic aerosols in the treatment of intrathoracic tuberculosis]. A total of 257 patients with intrathoracic tuberculosis were observed. The levels of streptomycin and isoniazide in the blood and lung tissue (132 resections) were studied comparatively after their administration by different routes (ultrasonic inhalation, per os and intramuscularly) in the doses of 1.0 and 0.6 gm of streptomycin and isoniazide respectively. On the basis of the data of the study it was conlcuded that concentrations of the tuberculostatic agents in the healthy ares of the lung tissue and the walls of the tuberculosis focus were much higher after the drug administration by the routine methods and remained at the minimum bacteriostatic level for 48 hours. Therefore, there is basis for considering administration of streptomycin and isoniazide in the form of ultrasonic aerosols quite justified in treatment of patients with intrathoracic tuberculosis since this administration route provided high levels of the drugs in the disease foci which meets the requirement of local therapy.


Permeability barrier to rifampin in mycobacteria. A strain of Mycobacterium intracellulare that exhibited natural resistance to rifampin was isolated. The ribonucleic acid polymerase was found to be susceptible to rifampin. Studies with Tween 80 suggested that a permeability barrier against rifampin was present in the intact organism. A type strain of Mycobacterium smegmatis, ATCC 607, considered resistant to rifampin also demonstrated a permeability barrier. The possibility that rifampin resistance in naturally occurring strains of mycobacteria and variable levels of resistance in strains of certain species of this organism are due to permeability barriers is discussed.


In vitro activity of netilmicin compared with gentamicin, tobramycin, amikacin, and kanamycin. The in vitro activity of netilmicin was compared with that of gentamicin, tobramycin, amikacin, and kanamycin against 636 strains of bacteria recently isolated from clinical sources. Gentamicin was the most active antibiotic, but netilmicin and tobramycin closely paralleled it. Netilmicin was generally four-to eightfold less active than gentamicin against Serratia and group A streptococci, and was twofold less active against Pseudomonas aeruginosa. When effects of inoculum size and concentration of divalent cations in the media were evaluated, netilmicin was shown to be similar to gentamicin in vitro. Minimum inhibitory concentrations for P. aeruginosa were increased as much as 18-fold when the Mg(2+) and Ca(2+) concentrations were increased to physiological levels in Mueller-Hinton broth.


Amphotericin B and filipin effects on L and HeLa cells: dose response. Amphotericin B (AmB) and filipin effects on L and HeLa cells were compared by monitoring drug-induced potassium leakage from cells, changes in radioactive uridine incorporation into cellular ribonucleic acid, protein leakage from cells, and cell viability. L cells were much more susceptible to both AmB and filipin than were HeLa cells, but the overall dose response was similar. For AmB, the various effects were easily separable. Potassium leakage occurred at the lowest concentrations of AmB and was reversible. Inhibition of uridine incorporation and loss of viability occurred at intermediate levels, and protein loss occurred at higher levels. In contrast, filipin was much more potent; its effects on potassium leakage were only minimally reversible, and the separation of the permeabilizing effects from complete cell lysis was possible only over a limited concentration range and for a short time.


Effect of probenecid on the blood levels and urinary excretion of cefamandole. Two oral 0.5-g doses of probenecid given 7 and 1 h before a single 1-g intramuscular dose of cefamandole resulted in higher serum levels of cefamandole than when cefamandole was given alone: 37 versus 20 mug per ml of serum, respectively. Cefamandole was not measurable (<0.3 mug/ml) at 8 h when it was given alone, whereas an average 8-h value of 2.9 mug/ml was obtained after pretreatment with probenecid. By prolonging the duration of these high cefamandole levels, probenecid should permit the treatment of more serious clinical infections, including those due to relatively resistant organisms, or permit a reduction in either the dosage of cefamandole or the frequency of administration.


Synergistic action of erythromycin and cefamandole against Bacteroides fragilis subsp. fragilis. Erythromycin and cefamandole have exhibited synergistic activity against eight strains of Bacteroides fragilis subsp. fragilis. In concentrations of only 0.25 to 0.5 mug of erythromycin per ml (easily obtainable with oral therapy), less than 0.4 mug (0.015 to 1.0) of cefamandole per ml inhibited the B. fragilis strains. In the presence of the erythromycin, the potency of cefamandole was increased more than 100-fold. On the basis of the mechanism of action of these two antibiotics, the synergism may be related to inhibition of beta-lactamase formation by the erythromycin, removal of the bacterial cell wall by the cefamandole permitting erythromycin penetration to the ribosomal level, and decreasing inoculum effect.


Renal pharmacology of netilmicin.

Renal pharmacology of netilmicin. Netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was studied for its effects on kidney function and mechanisms by which it is handled by the kidneys. Measurements of glomerular filtration rate (GFR) and urinalysis in chronic rat studies indicated that the nephrotoxicity of netilmicin was remarkably less than that of gentamicin. Gentamicin caused a dose-related reduction in GFR in association with glucosuria and elevated fractional excretion of K(+). By contrast, high doses of netilmicin produced only slight reduction in GFR with increased fractional excretion of K(+) but without glucosuria. In separate experiments, rats were shown to excrete 71 to 90% of netilmicin or gentamicin in 24 h after daily intramuscular administration of doses of 20 or 40 mg/kg for 4 days. In acute experiments on anesthetized dogs, GFR and renal plasma flow were unaffected at serum levels of 11.0 +/- 0.6 mug/ml maintained by constant infusion of netilmicin for 5 h. The renal clearance of netilmicin was significantly correlated with GFR. The urinary output of netilmicin was 80.0 +/- 4.2% of the infusion rate and was independent of urine flow over the range of 0.04 to 0.33 ml/kg per min. Preferential accumulation of netilmicin occurred in the renal cortex; the cortex-serum and medulla-serum ratios were 9.9 +/- 1.2 and 4.2 +/- 0.6, respectively. In addition, the extraction ratio of netilmicin, which was lower than that of inulin, suggested that netilmicin reabsorption occurs in the proximal tubule and results in cortical accumulation. It is concluded that netilmicin, like gentamicin, is excreted by the dog kidney by glomerular filtration plus limited reabsorption. However, the new drug is characterized by low intrinsic nephrotoxicity in rats.


Clavulanic acid: a beta-lactamase-inhiting beta-lactam from Streptomyces clavuligerus. A novel beta-lactamase inhibitor has been isolated from Streptomyces clavuligerus ATCC 27064 and given the name clavulanic acid. Conditions for the cultivation of the organism and detection and isolation of clavulanic acid are described. This compound resembles the nucleus of a penicillin but differs in having no acylamino side chain, having oxygen instead of sulfur, and containing a beta-hydroxyethylidine substituent in the oxazolidine ring. Clavulanic acid is a potent inhibitor of many beta-lactamases, including those found in Escherichia coli (plasmid mediated), Klebsiella aerogenes, Proteus mirabilis, and Staphylococcus aureus, the inhibition being of a progressive type. The cephalosporinase type of beta-lactamase found in Pseudomonas aeruginosa and Enterobacter cloacae P99 and the chromosomally mediated beta-lactamase of E. coli are less well inhibited. The minimum inhibitory concentrations of ampicillin and cephaloridine against beta-lactamase-producing, penicillin-resistant strains of S. aureus, K. aerogenes, P. mirabilis, and E. coli have been shown to be considerably reduced by the addition of low concentrations of clavulanic acid.


Tolerant response of Streptococcus sanguis to beta-lactams and other cell wall inhibitors. In contrast to group A streptococci or Streptococcus pneumoniae, cells of Streptococcus sanguis (group H) do not exhibit the irreversible effects of penicillin treatment, such as loss of viability or lysis. On the other hand, the same bacteria show typical effects of penicillin, such as morphological alterations, reduction in the rate of cell wall synthesis, and secretion of murein and lipoteichoic acid polymers into the medium. A novel effect of cell wall inhibitors was also noted: treatment with beta-lactams or with fosfomycin, d-cycloserine, or beta-halogeno-d-alanine caused the release of substantial amounts of glycerol lipids into the growth medium. The antibiotic "tolerance" of S. sanguis is interpreted in terms of the hypothesis that the activity of bacterial murein hydrolases is essential for the irreversible effects of cell wall inhibitors.


Unusual susceptibility of Erwinia amylovora to antibacterial agents in relation to the barrier function of its cell envelope. Wild-type strains of the bacterial phytopathogen Erwinia amylovora (the cause of fire blight disease of apples and pears) are markedly susceptible to novobiocin, deoxycholate, and sodium dodecyl (= lauryl) sulfate. The inhibitory concentration, expressed as the concentration causing a 99% inhibition of growth, of these three antibacterial agents were 15 to 100, 40 to 800, and 50 to 800 mug/ml, respectively, depending on the E. amylovora strain. Growth of strains of other Erwinia spp. and Salmonella typhimurium is not affected at all, or is only slightly affected, at these concentrations. Introduction of the F'lac(+), RP1, and R100drd-56 (but not E-lac(+)) plasmids into an E. amylovora strain results in enhanced susceptibility to novobiocin and sodium dodecyl sulfate but not to deoxycholate. E. amylovora wild-type strains spontaneously release a periplasmic enzyme, cyclic phosphodiesterase, but not a cytoplasmic enzyme, glucose-6-phosphate dehydrogenase, into the growth medium. Addition of MgCl(2) (20 mM) and NaCl (84 mM) to tryptone broth stimulates the growth of wild-type E. amylovora strains and reduces or eliminates leakage of the periplasmic enzyme. Mutant strains of E. amylovora, selected for resistance to each separate antibacterial agent (or to all three of them), showed a direct correlation (in all but the novobiocin-resistant mutant) between drug resistance and reduced periplasmic leakiness. The relatively low maximum growth temperature (<37 degrees C) of E. amylovora seems unrelated to periplasmic leakage, as judged from the inability of added MgCl(2) to raise the maximum growth temperature, although the generation time at 30 degrees C is reduced from 108 to 54 min upon the addition of 20 mM MgCl(2). The extensive leakage of periplasmic enzyme and unusual drug susceptibility of E. amylovora strains might stem from some defect(s) in some cell envelope component(s) other than the lipopolysaccharide of these bacteria (which contain the usual liposaccharide constituents).


Extreme sensitivity of staphylococcal enterotoxin B and C production to inhibition by cerulenin. Production of staphylococcal enterotoxins B and C was completely inhibited by concentrations of cerulenin (4 mug/ml and 2 mug/ml, respectively) that did not affect either growth rate or final growth density. Type A toxin formation was not similarly inhibited.


Cephradine penetration into cerebrospinal fluid and effects of its administration into the cerebral ventricles of cats. In cats that had high, sustained serum concentrations of cephradine, penetration of the drug into the cerebrospinal fluid (CSF) was poor. Serum cephradine levels were, on the average, 100-fold higher than the CSF levels. On the other hand, the direct injection of cephradine into the lateral cerebral ventricles of cats yielded high CSF cephradine concentrations without evidence of central nervous system toxicity.


Susceptibility of anaerobic bacteria to cofoxitin and related compounds. Cephalothin, cefazolin, cephradine, and cefoxitin inhibited more than 75% of 326 anaerobic bacteria in vitro, but cefoxitin was the most effective against anaerobes in general and Bacteroides fragilis in particular.


Gas chromatographic determination of 5-fluorocytosine: a modified extraction method. A modified procedure for the gas-chromatographic determination of 5-fluorocytosine in serum is described. A more volatile solvent mixture for extraction is used to reduce sample preparation time before chromatography. Comparison of values from assay of 12 serum samples by our method and the reference method gave a correlation coefficient of 0.99.


Absorption of orally administered nafcillin in normal healthy volunteers. The absorption of orally administered nafcillin sodium monohydrate buffered with calcium carbonate was studied in 10 healthy human volunteers. Dosages of 500 mg and 1 g were studied in fasting and nonfasting states. There was considerable individual variation in the absorption of nafcillin, although measurable serum concentrations were obtained in all subjects. With few exceptions, peak serum concentrations were reached faster and were more predictable in the fasting state than in the nonfasting state. In the majority of subjects, food interfered with nafcillin absorption. Measurable serum concentrations persisted for 4 h in almost all subjects, but there were no or negligible serum concentrations at 6 h. The mean serum concentrations obtained in the present study were higher than those reported in an earlier study.


In vitro studies on netilmicin, a new aminoglycoside antibiotic. Netilmicin, a semisynthetic derivative of sisomicin, was tested in vitro against 600 clinical bacterial isolates. At a concentration of 1.56 mug/ml, over 90% of gram-negative bacilli were inhibited. Netilmicin was substantially more active against isolates of Serratia marcescens and Enterobacter spp. than gentamicin, sisomicin, tobramycin, or amikacin. Isolates of Staphylococcus aureus (both penicillin G susceptible and resistant) were quite susceptible to netilmicin. Most isolates of Klebsiella spp. and Serratia spp. and some of the isolates of Pseudomonas aeruginosa that were resistant to gentamicin proved to be susceptible to netilmicin.


Effects of gestational age, birth weight, and hypoxemia on pharmacokinetics of amikacin in serum of infants. The serum pharmacokinetics of amikacin were studied in 36 infants treated for suspected bacterial infection. A prolonged serum half-life was associated with the related variables of birth at an early gestational age, low birth weight, and hypoxemia. A postnatal age effect was not apparent when hypoxemic infants were excluded.


Penetration of cefazolin into pleural fluid. Single doses of cefazolin, 500 mg intramuscularly and 1 g intravenously, were administered to 16 patients having lung pathology who were scheduled for thoracic fluid aspiration. Pleural fluid and serum samples were taken at intervals of 30 to 240 min for determination of cefazolin levels. The levels obtained were variable; however, the levels of cefazolin in pleural fluid generally exceeded the reported minimal inhibitory concentration values for Staphylococcus pneumoniae and Staphylococcus, and group A beta-hemolytic streptococcus. In addition, the pleural fluid levels exceeded the minimal inhibitory concentration for cefazolin against most of the Klebsiella and Haemophilus influenzae strains. These data show that cefazolin, despite its comparative high protein binding, produces levels in the pleural fluid capable of inhibiting the organisms commonly found in respiratory tract infections.


In vitro synergism between carbenicillin and aminoglycosidic aminocyclitols against Acinetobacter calcoaceticus var. anitratus. Acinetobacter caleoaceticus var. anitratus is a nonfermentative, gram-negative bacillus that has been demonstrated to cause severe infections, usually in hospitalized patients. Since mild to moderate resistance of A. calcoaceticus to one or more aminoglycosidic aminocyclitols has been noted to occur, a study was undertaken to evaluate the activity of combinations of carbenicillin with either kanamycin, tobramycin, or gentamicin against 28 isolates of A. calcoaceticus obtained from clinical sources. Synergism (defined as at least 100-fold-increased killing at 24 h by the combination as compared with the most efficacious of the individual antibiotics) was demonstrated against 26 of 28 strains of A. calcoaceticus with carbenicillin plus kanamycin and carbenicillin plus tobramycin and against 25 of 28 strains with carbenicillin plus gentamicin. The median increased killing for the 28 strains was 4.2 log(10) with carbenicillin plus kanamycin and with carbenicillin plus tobramycin and 3.1 log(10) with carbenicillin plus gentamicin. The most important determinant of synergistic potential of each combination was the level of resistance of each strain of A. calcoaceticus to the aminoglycoside component of the combination.


Exudate levels and bactericidal activity of cefazolin in a new local infection system using rat granuloma pouches. An experimental local infection system has been developed in which exudates are induced with croton oil in granuloma pouches of rats. This system provided a suitable model for the evaluation of the therapeutic effect of two antibiotics, cefazolin and cephalothin. Exudate levels of cefazolin were found to be higher than those of cephalothin, and these levels correlated with the higher serum level of cefazolin. The therapeutic effect of cefazolin, after intramuscular injection of 20 mg of each antibiotic per kg, was superior to that of cephalothin in eradicating both Staphylococcus aureus and Escherichia coli.


Uniform susceptibility of various strains of Coccidioides immitis to amphotericin B. The susceptibility of 12 strains of Coccidioides immitis to amphotericin B (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 mug/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 mug/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 mug/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of C. immitis strains to amB.


Response of influenza virus-infected mice to selected doses of ribavirin administered intraperitoneally or by aerosol. The effects of graded doses of ribavirin administered either by aerosol or intraperitoneally were compared in influenza virus-infected mice. The median effective dose values (based upon percent survival) were 3.3 and 15.8 mg/kg per day for the aerosol and intraperitoneal routes, respectively. Lung lesion scores and titer of virus were lower after aerosol than intraperitoneal therapy.


In vitro antibiotic susceptibility of salmonellae. In vitro antibiotic susceptibilities were determined for 101 strains of salmonellae. Resistance to chloramphenicol and ampicillin was low. Cefamandole was active against the majority of strains and deserves further evaluation.


Effect of anaerobiosis on antimicrobial susceptibility of staphylococci. The minimum inhibitory concentration (MIC) of 12 antibiotics was determined for four strains of staphylococci (representing the three major species) under aerobic and anaerobic conditions by using the broth dilution method. Nine of the antibiotics showed no significant difference between aerobic and anaerobic MIC for any of the four cultures. Gentamicin and kanamycin showed a small, but significant, increase in MIC for at least two strains under anaerobic conditions. Trimethoprim was less effective against all strains under anaerobic conditions.


Incidence and elimination of R plasmids in Vibrio cholerae. Of 124 strains of Vibrio cholerae, 32 were multiply resistant to antibiotics. This resistance appeared to be determined by R plasmids on the basis of their effective elimination by sodium dodecyl sulfate, acridine orange, ethidium bromide, and ultraviolet radiation.


Distribution of amikacin in serum, muscle, and fat in children after a single intramuscular injection. Amikacin concentrations in serum, muscle, and fat were determined in 41 children after intramuscular administration of 7.5 mg/kg of body weight. At 1.5 h amikacin reached peak concentrations in serum (mean value, 14.9 mug/ml) as well as in muscle (2.2 mug/g) and fat (1.89 mug/g) tissue; from then on all concentrations declined. Amikacin concentrations exceeded 1 mug/g in muscle for at least 3 h and in fat for at least 4 h.


Production of an antibiotic by an organism from human feces. An antibiotic-producing, gram-positive, rod-shaped bacterium was isolated from an individual who often lacked coliforms and fungi in fecal samples. The cell-free antibiotic is 1,200 daltons and Pronase sensitive and was shown to have activity against some coliforms and yeast.


Drug resistance in group D streptococci of clinical and nonclinical origin: prevalence, transferability, and plasmid properties. Group D streptococci isolated from clinical specimens and from sewage were investigated with regard to resistance to tetracycline (Tc), erythromycin (Em), and chloramphenicol (Cm). The median values of the percentages of resistant strains from sewage were: for Tc, 14%; for Em, 2.8%; and for Cm, 0.1%. For the recent isolates of clinical origin, resistance percentages found were 58% for Tc, 12% for Em, and 14% for Cm, and, in comparison to clinical isolates from 1964, the incidence of drug resistance slightly increased. In strains of both sources, the drug resistance was often found to be transferable to another group D streptococcus, probably by conjugation. Two strains were able to transfer their Em resistance to a streptococcus strain of group B. No transfer of drug resistance to a group A streptococcus and Escherichia coli was observed. All beta-hemolytic streptococci were also bacteriocinogenic, and frequently these properties were found to be transferable. The function, size, and base composition of the plasmids of two drug-resistant Streptococcus faecalis strains were investigated; strain M439 harbors at least two conjugative plasmids: pRI401, molecular weight 30 x 10(6), coding for Tc resistance, and pRI402, molecular weight 41 x 10(6), coding for Em resistance. Strain M403 carries one single conjugative plasmid species, coding for Tc resistance. The molecular weight of this plasmid, pRI404, was 37 x 10(6). The guanine plus cytosine content of these plasmids was 35 to 36%.


Penetration of cefamandole into spinal fluid. Twelve patients, aged 6 months to 62 years, with proven bacterial meningitis, were given a single intravenous dose of cefamandole (33 mg/kg) 75 to 140 min before a routine lumbar puncture. Infecting organisms included Haemophilus influenzae (eight cases), Streptococcus pneumoniae (two cases), and Neisseria meningitidis and beta-hemolytic streptococcus (one each). Cerebrospinal fluid (CSF) was analyzed by microbiological assay for cefamandole. The median concentration was 0.60 mug/ml, ranging from undetectable to 7.4 mug/ml. CSF cefamandole concentrations correlated with CSF protein: in six patients with CSF protein less than 100 mug/dl, the range of drug concentration was 0 to 0.62 mug/ml; and in six patients with CSF protein above 100 mg/dl, the range was 0.57 to 7.4 mug/ml. No significant correlation was noted between severity of illness, type of organism involved, or patient age and concentration of drug achieved.


Inhibition of influenza virus ribonucleic acid polymerase by ribavirin triphosphate. Ribavirin 5'-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5'-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5'-triphosphate and guanosine 5'-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.


Nafcillin entry into human cerebrospinal fluid. The entry of nafcillin into the cerebrospinal fluid (CSF) of humans was studied in the absence of meningeal inflammation. Twenty studies were performed in 18 patients receiving 40 mg of sodium nafcillin per kg intravenously over 30 min. The CSF specimens were obtained at 1, 2, 3, and 4 h postinfusion, and sera were obtained at 5 min and 1, 2, 3, and 4 h. Nafcillin was uniformly detected in the lumbar CSF at 1 h, peaked at 2 h postinfusion, and was still detectable in the CSF of three of four patients studied at 4 h.


Distribution of gentamicin and amikacin in rabbit tissues. Rabbits were injected intramuscularly with gentamicin and amikacin (15 mg of base per kg), and the antibiotic levels in tissues were determined 20 h after either a single or multiple injections. Disk diffusion assays, with Bacillus subtilis ATCC 6633, were carried out both on homogenates and on supernatants deproteinized with trichloroacetic acid. Both assays indicated that the kidney is the major site of antibiotic deposition. Antibiotic levels increased after multiple doses. Gentamicin levels in other tissues were higher than those of amikacin. The assay of trichloroacetic acid-treated material was more sensitive than the assay of the total homogenate.


Comparation interferon- inducing and antiviral properties of 2-amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), tilorone hydrochloride, and polyinosinic-polycytidylic acid. 2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166), polyinosinic acid-polycytidylic acid [poly(I:C)], and tilorone HCl induced high levels of serum interferon in mice. Each consequently protected mice against infection with several viruses. After daily injection of inducer, mice developed a reduced interferon response (hyporeactivity) to each compound. However, hyporeactivity developed more slowly to U-25,166 and poly(I:C) than to tilorone HCl. After onset of hyporeactivity, 5 to 6 days without each inducer were required before normal serum interferon levels could be stimulated. Animals also developed a hyporeactive state as a consequence of Semliki Forest or encephalomyocarditis virus infections. By day 2 of either infection, mice had a suppressed interferon response to tilorone HCl, but remains responsive to poly(I:C) or U-25,166 until day 4. In vivo, poly(I:C) stimulated interferon production in a variety of cells and organs, whereas the tilorone HCl and U-25,166 responses involved a nonlymphoid component of the reticuloendothelial system. In vitro, poly(I:C) induced interferon in a variety of murine cells, U-25,166 was active in murine thymus and spleen organ cultures, and tilorone was inactive. These data indicate that U-25,166 is an interesting low-molecular-weight interferon inducer.


Evaluation of three newer methods for investigating protein interactions of penicillin G. THE INTERACTION OF PENICILLIN G WITH HUMAN SERUM PROTEINS WAS EVALUATED BY THREE DIFFERENT TECHNIQUES: rate of dialysis, cross-linked dextran exclusion, and ultracentrifugation. The rate-of-dialysis technique demonstrated that penicillin G binding to serum was immediate but incompletely reversible. Cross-linked dextran adsorbed or trapped significant amounts of penicillin G, necessitating correction factors of more than 10%. Ultracentrifugation was found to be the most reliable method for quantitative protein-binding determinations of penicillins.


Small pet aquarium frogs as a source of Salmonella. Salmonellae were isolated from 21% of the samples of freshwater aquarium frogs tested and from 25% of the samples of aquarium water containing these frogs. The salmonellae were Salmonella arizonae, S. bovis-morbificans, S. hadar, S. saint-paul, S. typhimurium, and S. worthington. These isolations were made over a period of 9 months and from three different cities. This association of salmonellae with frogs may contribute to cases of human salmonellosis since other aquarium species have already been shown to contribute to such cases.


Characterization of the predominant bacteria occurring in the rumen of goats (Capra hircus). A total of 44 strains of bacteria were isolated from rumen contents of the goat. Based on morphology, Gram stain, anaerobiosis, motility, and fermentation end products, they were grouped into 11 different types. For each type, all or representative strains were characterized in detail. The type, number of strains characterized over total number of strains, and identification were as follows: type 1, 6/21, atypical Butyrivibrio fibriosolvens; type 2, 6/9, atypical Butyrivibrio fibrisolvens; type 3, 3/3, genus uncertain; type 4, 2/2, genus uncertain; type 5, 3/3, Streptoccous bovis; type 6, 1/1, Butyrivibrio fibrisolvens; type 7, 1/1, Bacteroides ruminicola subsp. ruminicola; type 8, 1/1, Bacteroides ruminicola subsp. brevis; type 9, 1/1, family Peptococcaceae, genus uncertain; type 10, 1/1, genus Bacteroides; type 11, 1/1, genus Bacteroides. About 70% of the isolated strains were classified as Butyrivibrio, which is quite high compared with previous studies in cattle on similar rations. Of the 30 strains listed as type 1 and 2, the 12 studied further were characterized as atypical Butyrivibrio fibrisolvens, which differed from the species description primarily by their inability to hydrolyze starch and lack of gas production.


Bacterial metabolism of quaternary ammonium compounds. Of 10 quaternary ammonium compounds tested for biodegradation by the biological oxygen demand technique, only decyl- and hexadecyltrimethylammonium bromides were decomposed by organisms derived from sewage and soil. A mixture consisting of individual strains of Pseudomonas and Xanthomonas grew in solutions containing decyltrimethylammonium bromide as sole carbon source. The xanthomonad metabolized this quaternary ammonium compound in the presence of other organic molecules. The products of this activity included 9-carboxynomyl- and 7-carboxyheptyltrimethylammonium, suggesting that the terminal carbon of the decyl moiety is oxidized and the resulting carboxylic acid is subject to beta-oxidation.


Growth of heat-injured Vibrio parahaemolyticus in media supplemented with various cations. Mid- to late logarithmic growth phase cells of Vibrio parahaemolyticus grown in tryptic soy broth (TSB) containing 0.5, 3.0, and 7.5% NaCl were heated for 8 min at 45 degrees C in 0.1 M phosphate buffer (pH 7.2) containing 3% NaCl. Colony formation on thiosulfate-citrate-bile salts-sucrose agar (TCBS) containing 2% NaCl was greatest for unheated cells that had been grown in 7.5% NaCl-TSB; cells grown in 0.5% NaCl-TSB formed a greater number of colonies on 1.0% NaCl-TCBS. Thermal injury was evident in heated cells, regardless of the NaCl concentration in TSB growth medium. The effects of Mg2+, K+, and Li+ added as chlorides to 0.5% NaCl-TSB on the growth of nonheated and heated V. parahaemolyticus were studied. Lower levels of Mg2+ and slightly higher levels of K+ were required to replace Na+ in TSB inoculated with thermally injured cells that had been originally grown in 3.0 and 7.5% NaCl-TSB. LiCl had an inhibitory effect on both nonheated and heated cells when present in the recovery medium (0.5% NaCl-TSB) at concentrations as low as 0.5%. Increased numbers of colonies were formed by heated cells plated in MgCl2-supplemented TCBS, regardless of the NaCl concentration in the original growth medium. Potassium had little, if any, effect on colony formation by nonheated V. parahaemolyticus recovered on TCBS and may have had a detrimental effect on heat-injured cells.


Toxic effect of water-soluble fractions of crude, refined, and weathered oils on the growth of a marine bacterium. The water-soluble fractions of three crude and two refined oils reduced the growth rate and maximum cell density of the marine bacterium Serratia marinorubra grown in batch culture. The weathering of a crude and a refined oil was simulated in the laboratory. The water-soluble fractions remaining from this process were more toxic to S. marinorubra than were the parent unweathered oils. Increases in the magnitude of toxic effect of 3 to 30 times were observed as a function of decreasing the concentration of yeast extract in the cultures from 0.1 to 0.05 and 0.01%. The toxicity did not correlate with the concentration of total water-soluble fraction or of aromatic hydrocarbons in the water-soluble fraction. Affected cultures did not exhibit a residual toxicity after being back-inoculated into control media.


Urease assay and urease-producing species of anaerobes in the bovine rumen and human feces. A growth medium and test were developed for rapid detection of urease in fermentative anaerobic bacteria. Using nonselective rumen fluid roll-tube agar medium and the new test, it was confirmed that Peptostreptococcus productus is often the most numerous urease-forming species in human feces. Also, some fecal strains of Ruminococcus albus, Clostridium innocuum, and Clostridium beijerinckii produced urease. Single strains of Fusobacterium prausnitzii, Coprococcus catus, and Streptococcus mitis that were strongly ureolytic on isolation later lost this ability. Urease activity was also detected in many strains of nonselectively isolated rumen species. They include Succinivibrio dextrinosolvens, Treponema sp., Ruminococcus bromii (not previously known to be present in the rumen), Butyrivibrio sp., Bifidobacterium sp., Bacteroides ruminicola, and P. productus. Most P. productus strains contain urease; however, the uniformity of this feature in the other species noted above is not known. The urease in many of these species was not detected if the growth medium contained 0.2% or more (each) yeast extract and Trypticase.


Catalase and enumeration of stressed Staphylococcus aureus cells. The effects of catalase on the enumeration of stressed (heated, reduced water activity, or freeze-dried) Staphylococcus aureus cells on several selective media were examined. The addition of catalase greatly increased the enumeration of stressed cells. The beneficial effects of catalase were most pronounced on those media least efficient in enumeration of stressed staphylococci, showing increases in enumeration of up to 1,100-fold. The effects of catalase appear to be due to the reduced ability of stressed cells to repair and form colonies in the absence of an exogenous decomposer of H2O2. Thermally stressed cells were more sensitive to H2O2 than unstressed cells. During recovery, stressed cells overcame the requirement for catalase. These findings implicate H2O2 as a factor in the failure of certain selective media to adequately enumerate stressed cells and demonstrate that the addition of catalase to these media markedly increases their productivity.


Laminarinase (beta-glucanase) activity in Bacteroides from the human colon. Laminarin, a beta(1 leads to 3)-glucan similar to those found in plant cell walls, is fermented by some species of anaerobic bacteria from the human colon. Laminarinase (EC 3.2.1.6) and beta-glucosidase (EC 3.2.1.21) activities were determined in strains representing Bacteroides thetaiotaomicron, Bacteroides distasonis, and an unnamed deoxyribonucleic acid homology group of Bacteroides fragilis. In all three species, laminarinase activity was inducible by laminarin and was predominantly cell bound. The products of laminarinase activity varied with each species. In the case of B. thetaiotaomicron, the major product of laminarin hydrolysis was glucose (70 to 90%), and there were small amounts of laminaribiose (G2) and oligomers of glucose as high as G4. In the case of group '0061-1,' glucose (40 to 50%) and oligomers of glucose as high as G6 were found. The laminarinase of B. distasonis differed from the laminarinases of the other two species in that it mainly produced oligomers of glucose (G2-G5). beta-Glucosidase activity was also found in all three species. beta-Glucosidase was induced by glucose-containing disaccharides as well as by laminarin. The beta-glucosidases of the three Bacteroides species differed with respect to level of activity, induction pattern, and sensitivity to inhibition by D-glucono-1,5-lactone.


Production of antibody against aflatoxin B1. Antibody against aflatoxin B1 was obtained after one multiple-site injection of bovine serum albumin-aflatoxin B1 conjugate into rabbits. The antibody has greatest binding efficiency for aflatoxin B1, less efficiency for B2, G1, and Q1, and least for aflatoxicol, G2, and M1. Sterigmatocystin, coumarin, and 4-hydroxycoumarin did not give a cross-reaction with the antibody. The sensitivity of the binding assay for detection of aflatoxin B1 is in the range of 0.2 to 2.0 ng per 0.5-ml sample. Detailed methods for the preparation of the conjugate, production of immune serum, and methods for antibody titer determination are described.


Minimal requirements in defined media for improved growth of some radio-resistant pink tetracocci. Defined media permitting extensive growth of representative pink radio-resistant tetracocci (Micrococcus radiodurans, Micrococcus roseus, and Micrococcus radiophilus) and two controls (an ultraviolet-sensitive mutant of M. radiodurans and Micrococcus luteus) are described. Availability of Fe (especially Fe3+) proved essential for good growth, as evidenced by (i) favorable effects of hydroxamic acids, e.g., salicylhydroxamic acid, and (ii) the growth promotion by hemin when joined with elevated concentrations of Fe. Cobalamin (B12) and methionine were interchangeable as an absolute requirement for methionine not affected by B12. M. luteus required neither. Pink radio-resistant micrococci may form a coherent group. Some divergences among them might be attributable to the method for isolating them, which for ordinary bacteria would be mutagenic to the point of total lethality. The ecology of these tetracocci vis-à-vis other pink-red radio-resistant organisms is discussed in relation to a question: can these bacteria be isolated without dependence on radiation as the cardinal selective factor?


Growth of desulfovibrio in lactate or ethanol media low in sulfate in association with H2-utilizing methanogenic bacteria. In the analysis of an ethanol-CO(2) enrichment of bacteria from an anaerobic sewage digestor, a strain tentatively identified as Desulfovibrio vulgaris and an H(2)-utilizing methanogen resembling Methanobacterium formicicum were isolated, and they were shown to represent a synergistic association of two bacterial species similar to that previously found between S organism and Methanobacterium strain MOH isolated from Methanobacillus omelianskii. In lowsulfate media, the desulfovibrio produced acetate and H(2) from ethanol and acetate, H(2), and, presumably, CO(2) from lactate; but growth was slight and little of the energy source was catabolized unless the organism was combined with an H(2)-utilizing methanogenic bacterium. The type strains of D. vulgaris and Desulfovibrio desulfuricans carried out the same type of synergistic growth with methanogens. In mixtures of desulfovibrio and strain MOH growing on ethanol, lactate, or pyruvate, diminution of methane produced was stoichiometric with the moles of sulfate added, and the desulfovibrios grew better with sulfate addition. The energetics of the synergistic associations and of the competition between the methanogenic system and sulfate-reducing system as sinks for electrons generated in the oxidation of organic materials such as ethanol, lactate, and acetate are discussed. It is suggested that lack of availability of H(2) for growth of methanogens is a major factor in suppression of methanogenesis by sulfate in natural ecosystems. The results with these known mixtures of bacteria suggest that hydrogenase-forming, sulfate-reducing bacteria could be active in some methanogenic ecosystems that are low in sulfate.


Lactobacilli isolated from the stomach of conventional mice. Twenty strains of lactobacilli isolated from the stomach of conventional mice were tested for their ability to ferment or hydrolyze substrates that may be present in the stomach habitat. The lactobacilli could be placed in four groups (A to D) depending on their ability to ferment N-acetylglucosamine, dextrin, cellobiose, gum arabic, and xylan. The majority of the isolates belonged to groups A and D. Group A strains did not resemble previously described Lactobacillus species, but group D strains were identified as L. leichmannii. A representative group A isolate colonized the surface of the nonsecretory epithelium of the stomach of gnotobiotic mice; a group D isolate did not.


Comparison of four selective agars for the isolation of pseudomonads. Significant differences were found between Dettol (chloroxylenol) agar, nalidixic acid-cetrimide agar, and two other cetrimide-containing agars used for the isolation of small numbers of pseudomonads.


Butyl rubber stoppers increase the shelf life of prereduced, anaerobically sterilized media. Butyl rubber stoppers as compared with neoprene or black rubber stoppers significantly increased the shelf life of prereduced, anaerobically sterilized media for growth of obligately anaerobic bacteria.


Medium for the selective isolation of members of the genus Pseudomonas from natural habitats. A new medium was developed that was superior to four others tested in selecting for members of the genus Pseudomonas.


Spoilage association of chicken leg muscle. The ability of pure cultures of bacteria isolated from spoiling chicken leg muscle to produce strong off-odors was tested by using sterile leg muscle sections. Changes in the flora during storage and the incidence and identity of organisms capable of producing strong off-odors were noted.


Response of microorganisms to an accidental gasoline spillage in an arctic freshwater ecosystem. The response of microorganisms to an accidental spillage of 55,000 gallons of leaded gasoline into an Arctic freshwater lake was studied. Shifts in microbial populations were detected after the spillage, reflecting the migration pattern of the gasoline, enrichment for hydrocarbon utilizers, and selection for leaded-gasoline-tolerant microorganisms. Ratios of gasoline-tolerant/utilizing heterotrophs to "total" heterotrophs were found to be a sensitive indicator of the degree of hydrocarbon contamination. Respiration rates were elevated in the highly contaminated area, but did not reflect differences between moderately and lightly contaminated areas. Hydrocarbon biodegradation potential experiments showed that indigenous microorganisms could extensively convert hydrocarbons to CO(2). In situ measurement of gasoline degradation showed that, if untreated, sediment samples retained significant amounts of gasoline hydrocarbons including "volatile components" at the time the lake froze for the winter. Nutrient addition and bacterial inoculation resulted in enhanced biodegradative losses, significantly reducing the amount of residual hydrocarbons. Enhanced biodegradation, however, resulted in the appearance of compounds not detected in the gasoline. Since the contaminated lake serves as a drinking water supply, treatment to enhance microbial removal of much of the remaining gasoline still may be advisable.


Hydrogen utilization by clostridia in sewage sludge. A sporeformer morphologically different but physiologically similar to Clostridium aceticum Wieringa was isolated from sewage sludge. It used large amounts of H2 and CO2, converting them chiefly to acetic acid. Growth occurs anaerobically on yeast extract alone, but after the nutrients in yeast extract are used, growth continues at a reduced rate, supported by the conversion of the gases to acetate.


Analysis of ochratoxin B alone and in the presence of ochratoxin A, using carboxypeptidase A. A method is described for ochratoxin B analysis, which is adapted to the earlier described method of ochratoxin A analysis, using carboxypeptidase A (K. Hult and S. Gatenbeck, J. Assoc. Off. Anal. Chem. 59:128-129, 1976). The fluorescence spectra of ochratoxins A and B coincide too much to allow direct discrimination of the two compounds. A method using the differences in kinetic parameters of the enzymatic hydrolysis of the two compounds is suggested for the analysis of mixtures of the ochratoxins.


Cellulolytic cocci isolated from the cecum of guinea pigs (Cavia porcellus). Five strains of anaerobic, gram-variable cellulolytic cocci, belonging to the genus Ruminococcus, were isolated from the cecum of a guinea pig. They differed from most previously described strains of cellulolytic ruminococci as follows. (i) Lactate was the major fermentation product; lesser amounts of formate and ethanol and a trace of succinate were also produced, along with an uptake of acetate. (ii) No growth occurred at 30 degrees C; however, good growth was observed at 38 and 45 degrees C, (iii) Glucose, cellobiose, cellulose, xylose, arabinose, xylan, sucrose, and lactose were fermented by all strains. Rumen fluid was required for growth in a complete medium containing all nutrients previously found to be required by species in this genus. Limited growth occurred when rumen fluid was replaced by yeast extract, and maximum, but delayed, growth occurred when a water extract of alfalfa was added to the complete medium. No qualitative differences were found in the cell wall amino acids and sugar composition of these strains as compared to Ruminococcus flavefaciens and Ruminococcus albus; however, cell walls of the guinea pig strains appeared to contain a higher proportion of glucose.


Production and counting of spores of Clostridium chauvoei. The concentration and viability of spores produced by four different strains of Clostridium chauvoei (C. feseri) grown in a modified medium for 18 days are described. The medium yielded enough viable spores for experimental work.


National dermatology manpower requirements: the experience of prepaid group practices. Ten prepaid group health plans across the country were surveyed as part of an effort to estimate the need for dermatologists in the United States. Although generalizing the experiences of prepaid group practices to the general population is at best an imprecise approach, the dramatic shortage suggested by the data cannot be completely ascribed to the method used. Whereas the average ratio in the surveyed plans was 2.8 dermatologists per 100,00 subscribers, there are only about 1.9 dermatologists providing patient care per 100,000 persons in the general population. The difference between prepaid plan subscribers and the general population in annual visits to dermatologists is even more dramatic: 193 per 1,000 subscribers compared to 84 per 1,000 population.


Treatment of lip keratoses (actinic cheilitis) with topical fluorouracil. Topical (5-fluorouracil [5-FU]) as a 5% solution was used to treat isolated actinic keratoses of the lips as well as diffuse actinic damage of the lower lip. Although producing considerable temporary discomform final results proved excellent, with recurrences in only two of 12 patients treated. Preliminary biopsy of suspicious infiltrated areas is mandatory, as is careful follow-up to ensure complete healing. Topical fluorouracil is an alternative to surgical excision of the vermillion border of the lip in those patients with severe diffuse actinic damage of the lips.


Acute panniculitis: a clinical and histopathologic study of 34 cases. Thirty-four patients had histopathologic findings of acute panniculitis. 15 had clinical findings of erythema nodosum; 6 had infectious lesions; and 5 had Weber-Christian-like conditions with recurrent febrile suppurative or nonsuppurative nodular eruptions; 3 of the 5 had amylase and lipase enzyme abnormalities with or without pancreatic disease. Five additional patients had acute panniculitis that would be termed "deythema induratum" or "nodular vasculitis" by most clinicians, and the subsequent pathologic findings and courses were consistent with this view. Two patients had limited, traumatic panniculitis, forming a distinctive group, but trauma was a factor in lesion formation in all groups, and one patient had vasculitis. Whereas acute panniculitis, with or without fat necrosis, may be associated with many inflammatory syndromes of the skin and subcutaneous tissue and may rarely occur in all, the most common relationship is with erythema nodosum in its most acute forms.


Intrauterine herpes simplex infections.

Intrauterine herpes simplex infections. Most dermatologists are familiar with the manifestations of neonatal herpes simplex infections. Few, however, are acquainted with the concept of intrauterine herpes simplex infections. This article describes two additional cases of intrauterine herpes simplex infections with congenital malformations. Common features included intrauterine growth retardation, microcephaly, encephalitis, chorioretinitis, psychomotor retardation, and recurrent, grouped, cutaneous vesicles. Seven similar cases with congenital malformations are reviewed as well as cases of intrauterine herpes simplex infection without congenital malformations. We propose that intrauterine herpes simplex infections be termed "early" when there is evidence of disturbed embryogenesis or "late" when congenital malformations are less specific or inapparent. We further suggest that the spectrum of intrauterine infections is similar to that of neonatally acquired infections.


Tumor cell characterization of histiocytic medullary reticulosis. Tumor cells from a 10-year-old boy was suspected histiocytic medullary reticulosis were examined and were found to have receptor sites for complement, the ability to phagocytize latex beads, and the electron microscopical picture of immature histiocytes. These findings strongly support the diagnosis of histiocytic medullary reticulosis. This disorder and the method of examination of the tumor cells are discussed.


Mycophenolic acid in the treatment of psoriasis: long-term administration. Thirty five patients with psoriasis (plaque type 26, guttate 3, pustular 4, and erythrodermic 2) were treated with oral mycophenolic acid for a period ranging from 52 to 104 weeks. The average follow-up was 89 weeks, and the dose schedule ranged from 2,400 to 7,200 mg daily. Excellent response was noted in 20 patients, good in 13 patients, and poor in 2. The most common clinical side effects were in the gastrointestinal tract, namely, diarrhea, nausea, abdominal cramps, and soft stools. A high incidence of herpes simplex, herpes zoster, and a flu-like syndrome was noted. Laboratory abnormalities consisted of mild blood hemoglobin reduction, one case of leukopenia (3,9000 WBCs per cubic millimeter), two cases with thrombocytopenia and mild elevation of alkaline phosphatase. Mycophenolic acid appears as a promising drug for the treatment of severe psoriasis.


Primary cutaneous coccidioidomycosis: a review of the literature and a report of a new case. A 31-year-old woman working in the laboratory with the mycelial phase of Coccidioides immitis developed a firm, raised, erythematous lesion on the left index finger. A biopsy specimen of the lesion grew a white mold that proved to be C immitis. A sinus tract communicating with the lesion and extending into the proximal phalanx developed. The expressed pus was positive for the tissue form of C immitis by potassium hydroxide and periodic acid-Schiff stains and fluorescent-antibody techniques. The sinus tract was irrigated with an aqueous solution of amphotericin B (Fungizone). The tract closed and the lesion decreased in size. Healing was completed in ten weeks. Primary cutaneous disease must be distinguished from disseminated disease with cutaneous manifestations. In the majority of cases, primary disease heals spontaneously whereas disseminated disease usually requires systemic treatment with amphotericin B.


Tropical rat mite dermatitis.

Tropical rat mite dermatitis. We had a patient with dermatitis caused by the bite of Ornighonyssus bascoti (Hirst), commonly referred to as the tropical rat mite. The bite of this mite resulted in a severely pruritic papular dermatitis in our patient. Accurate identification of the mite indicated the presence of rat infestation.


Pigmented basal cell cancer masquerading as superficial spreading malignant melanoma. A 49-year-old woman of Spanish descent had a pigmented lesion on the thigh present for many years, which enlarged recently. The lesion showed notching and black, brown, and blue colors that led to the initial diagnosis of superficial spreading malignant melanoma. Results of skin biopsy disclosed the lesion was a basal cell epithelioma with large amounts of melanin in the dermis. This report illustrates the importance of considering pigmented basal cell epithelioma in the differential diagnosis of superficial spreading malignant melanoma.


Follicular atrophoderma and basal cell carcinomas: the Bazex syndrome. Seven members of one family had rare, inherited syndrome of follicular atrophoderma, basal cell carcinomas, and localized anhidrosis. Associated findings in some subjectes were generalized hypohidrosis and "eczema" involving the face shortly after birth. This syndrome shows dominant inheritance, possible x-linked. Follicular atrophoderma is an important skin manifestation, as it has been associated in all reported cases with other systemic or cutaneous abnormalities.


Intraventricular haemorrhage in the preterm infant without hyaline membrane disease. The clinicopathological associations of 33 singleton infants who died with intraventricular haemorrhage (IVH) without hyaline membrane disease (HMD) ('IVH only') were compared with those of 39 infants who died with IVH+HMD over the same gestation range in order to determine what factors other than those related to HMD may contribute to the pathogenesis of IVH. The incidence of 'IVH only' was inversely related to gestational age in the Hammersmith birth population, whereas the incidence of IVH+HMD rose to a peak at 28-29 weeks' gestation. Infants with 'IVH only' lived longer on average than those with IVH+HMD despite a lower birthweight and shorter gestation. Infants who died in the first 12 hours from 'IVH only' had suffered severe birth asphyxia but in those who died later the main symptom was recurrent apnoea. Fewer infants with asphyxia but in those who died later the main symptom was.recurrent apnoea. Fewer infants with 'IVH only' were given alkali therapy or were connected to the ventilator as compared to those with IVH+HMD, but there were no differences in alkali therapy in those who lived for 12 hours or more. In the 'IVH only' group there was a high incidence of haemorrhage from other sites and of bacterial infections. It is suggested that, in the absence of HMD, extreme immaturity is the main factor determining the occurrence of IVH. Birth asphyxia, apnoeic attacks, haemorrhage, and infections may play subsidiary roles, possibly through development of metabolic acidosis.


Neonatal records and the computer.

Neonatal records and the computer. To use a combined single document clinical case sheet/computer record which can form the basic document for a life medical record is a practical proposition. With adequate briefing doctors and nurses soon become familiar with the record and appreciate its value. Secretarial and clerical requirements are reduced to a minimum as transcription of medical data is eliminated, so greatly speeding up processing and feed back to the medical services. A few illustrations of trends in neonatal statistics and of computer linked maternal/neonatal data are presented.


Controlled trial of azathioprine in treatment of steroid-responsive nephrotic syndrome of childhood. A controlled trial of azathioprine treatment of steroid-responsive frequent-relapsing nephrotic syndrome of childhood failed to show a therapeutic effect on the stability of remission after withdrawal of corticosteroid treatment.


1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy. Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.


Renal osteodystrophy in nondialysed adolescents. Long-term treatment with 1alpha-hydroxycholecalciferol. The effects of small oral doses (1-2 microgram/day) of 1alpha-hydroxycholecalciferol, given for 1 to 2 years, have been examined in four nondialysed adolescents with chronic renal failure and bone disease. Treatment increased calcium retention and plasma calcium, and decreased plasma levels of alkaline phosphatase, hydroxyproline, and immunoreactive parathyroid hormone. X-ray abnormalities of bone regressed, and 2 patients underwent successful surgical correction of knock-knees; bone histology in these 2 was normal at the time of operation. 2 patients developed hypercalcaemia which promptly reversed when 1alpha-hydroxycholecalciferol was withdrawn. In one patient treatment was initially successful, but later there was biochemical, radiographic, and histological evidence of relapse. Long-term treatment of such patients with 1alpha-hydroxycholecalciferol may be effective and facilitate the surgical correction of deformities, but this is not invariable. Toxic effects are similar to those of vitamin D itself, but are more readily reversible.


Acute bacterial maningitis in childhood: aspects of prehospital care in 687 cases. Some basic features of the prehospital management of children with acute bacterial meningitis were ascertained by a retrospective review of case notes. A diagnosis of intracranial infection was considered in 63% of general practitioners' referral letters and was more often considered for older than younger children. 47% of children had received antibacterial chemotherapy before hospital admission. Such treatment did not appear to have jeopardized the outcome. The possibility of delay in the admission of children to hospital at weekends is discussed.


Neonatal vaccination with 'universal strength' BCG vaccine. 'Universal strength' BCG vaccine was given to 219 neonates and 2 months later 159 infants were Mantoux-tested with 5 Tu PPD-S and their BCG scars measured. The results showed a satisfactory conversion rate of over 90%. Though 30% of the lesions discharged, this only lasted for a few days and the vaccine was well tolerated and acceptable for use in neonates.


Primary hyperparathyroidism in a child. Use of jugular venous catheterization in diagnosis. A 10-year-old boy with a parathyroid ademona is reported. Parathyroid hormone estimations of samples obtained by selective jugular venous catheterization were useful in diagnosis and for localizing the tumour before operation.


Duodenal intubation with secretin stimulus for diagnosis of giardiasis. The use of secretin to facilitate the demonstration of Giardia lamblia in duodenal juice was studied in children under investigation for chronic diarrhoea. 30 children aged 3 months to 13 years, whose stools were negative for G. lamblia, were studied. G. lamblia was demonstrable in a sample of duodenal juice in 1 of the 30 children before an intravenous injection of secretin (1 or 2 mg/kg), but in 9 of the 30 children after secretin. It is concluded that examination of duodenal juice after secretin stimulus is an effective method of showing giardial infestation.


Bacterial colonization of infants raised in incubators and under radiant heaters. To assess the effect of open radiant heaters on bacterial colonization of neonates, 24 infants were raised under radiant heaters and 34 in standard incubators. Cultures of the nose, groin, and umbilicus were taken daily for the first 3 days of life. For infants raised in incubators, colonization rates with Staph. aureus ranged up to 47%. Among infants raised under radiant heaters (8 of whom had topical antibiotics applied to the umbilicus), only one was colonized with this organism. Even if the 8 treated infants were excluded, the prevalence of Staph. aureus was significantly greater at the umbilicus and groin in infants raised in incubators.


Cardiovascular effects of apnoea in preterm infants. Cardiovascular reflex responses have been studied in 9 newborn preterm infants with apnoeic episodes and in 2 preterm infants with periodic breathing. Respiration, blood pressure, heart rate, and peripheral blood flow were simultaneously recorded. Peripheral blood flow was measured in the leg by venous occlusion plethysmography. During apnoea, bradycardia and peripheral vasoconstriction occur. There is little change in blood pressure though pulse pressure increases. No cardiovascular changes were seen before the onset of apnoea. Periodic breathing had little effect on peripheral blood flow. Preterm infants with gestations as low as 27 weeks apparently have well developed chemoreceptor reflexes which would tend to preserve blood supply to the brain during conditions of hypoxia.


Deafness after bacterial meningitis.

Deafness after bacterial meningitis. Seventeen children with previous bacterial meningitis and 17 sib controls were examined clinically and otoscopically. They were also tested with air-conduction and bone-conduction audiometry and evaluated by tympanometry. There were no major neurological abnormalities and few otoscopical signs of ear disease. 21% of the ears showed abnormalities on air-conduction audiometry but all were normal on bone-conduction audiometry. 30% had abnormal middle-ear pressures (more negative than 100 mm water) on tympanometry and 7% had abnormal compliance of the drum. There were no significant differences on any test between the postmeningitis children and the sib controls. Population studies have confirmed that minor hearing loss due to middle-ear dysfunction is common in children, but is probably temporary in most of them. We have found no excess of middle-ear dysfunction and no sensorineural deafness in these postmeningitis children, but other workers have shown that nerve deafness may occur in association with clinical neurological damage. However, much of the deafness attributed to bacterial meningitis in other studies may well reflect population variability.


Autoantibodies to Tamm-Horsfall protein in detection of vesicoureteric reflux and kidney scarring. Measurement of IgG antibodies to Tamm-Horsfall protein (ATHA) in 92 bacteriuric schoolgirls aged 5-12 did not show a significant rise compared with the titres found in the sera of 24 healthy controls. ATHA titres showed no correlation with the presence of vesicoureteric reflux or kidney scarring and it is concluded that measurement of serum ATHA is of no value as a screening procedure for the detection of vesicoureteric reflux.


Porcine pancreatin as a source of salmonella infection in children with cystic fibrosis. Contamination of a powdered preparation of pancreatin with Salmonella schwarzengrund and S. eimsbuettel resulted in the infection of at least 31% of one group of paediatric patients with cystic fibrosis. The pancreatin contained very small numbers of Salmonellae, the infecting dose in at least one child being less than 44 organisms. More stringent bacteriological standards are needed for pharmaceuticals and foods used by paediatric patients.


Salt-losing syndrome in 2 infants with defective 18-dehydrogenation in aldosterone biosynthesis. Two infants presented with a salt-losing syndrome, the presenting features of which were subtle. One case appeared to be transient. Deficient production of aldosterone was shown by plasma renin activity and plasma aldosterone profile. Gas chromatography-mass spectrometry of urine indicated a defect in 18-dehydrogenation of 18-hydroxycorticosterone. Treatment with salt supplements and 9alpha-fludrocortisone reversed the salt-losing state and in one case treatment was later stopped. Although the disease may appear transient, the biochemical defect is persistent and for adequate growth a positive salt-balance is necessary.


Cause of death in tetanus neonatorum: study of 233 cases with 54 necropsies. Of 125 newborn infants with tetanus studied clinically, 75 died. Hypothermia and bronchopneumonia were the commonest events leading to death. A sudden drop in the amount of sedation required, loss of or diminished tetanal signs, and hypothermia usually indicated the onset of bronchopneumonia. A later series of 108 cases with 75 deaths (54 necropsies) formed the basis of a pathological study. Pulmonary pathology was found in 46 out of the 54 necropsies: mainly pulmonary haemorrhage, aspiration pneumonia, and bronchopneumonia, particularly of the right upper lobe. Adrenal haemorrhage and renal vein thrombosis also occurred.


Hypoglycaemia in congenital adrenal hyperplasia. Two young children with salt-losing congenital adrenal hyperplasia developed profound hypoglycaemia. In one child hypoglycaemia occurred after a prolonged fast and in the other it was precipitated by infection. This complication may be more common than the literature suggests, and emergency treatment with glucose or hydrocortisone, given by injection, should be given to any child with the disorder who suddenly or unexpectedly collapses.


The cartoon in doctor-patient communication. Further study of the Arthritis and Rheumatism Council handbook on gout. A sample of 50 consecutive patients with gout was tested by means of a multiple-choice knowledge-testing questionnaire based on the Arthritis and Rheumatism Council's Gout: A Handbook for Patients. Patients were divided into two groups: (a) those tested with an illustrated booklet containing 89 cartoons, and (b) those tested with an unillustrated booklet with text exactly the same as in the illustrated booklet. No significant difference was observed in either the overall test scores between the two groups or between individual question scores. It was concluded that increasing the number of illustrations in the Arthritis and Rheumatism Council's handbook on gout had not significantly increased the value of this material as a communication aid. Certain sources of error have been discussed including the possibility of an 'interest factor' due to the inevitable interest patients have in reading about their own disease, and also the possibility that technical factors to do with page layout and picture/text imbalance might be responsible for failing to show differences between the two groups.


Factors in resistance to and recovery from M. pulmonis-induced arthritis in mice. A previous infection of C3H mice with viable Mycoplasma pulmonis organisms protected them from arthritis induced by intravenous inoculation of these organisms, whether or not their initial arthritis had resolved at the time of challenge. Although spleen cells obtained from such animals conferred resistance to acute arthritis in syngeneic recipient mice, convalescent-phase serum was much more effective in this respect. In addition, the transfer of 'immune' spleen cells to M. pulmonis-infected mice treated with cyclophosphamide did not prevent them from dying, whereas the transfer of convalescent-phase serum to such animals reduced the incidence of mortality. Since M. pulmonis organisms are rapidly inactivated in mice treated with convalescent-phase serum it is suggested that the transferred serum may act by promoting phagocytosis of the mycoplasmas. Although the reason for some mice developing a prolonged arthritis is not clear, the results show that humoral immune mechanisms are more important than cell-mediated ones in preventing acute arthritis and that the humoral mechanisms are of greater importance than the cell-mediated in resistance to and recovery from a generalized mycoplasma infection.