[Pseudomonas putida: identification, antibiotic sensitivity and pathogenicity (author's transl)].

This work studies 51 strains of Pseudomonas putida, isolated from clinical specimens (17) and hospital environment (34). Identification is performed by study of 41 physiologica and biochemical characters and 78 nutritional characters. According to the two biotypes A and B, described by Stanier, Palleroni and Doudoroff, these 51 strains can be grouped as follows: 48 have typical characters of biotype A, widely predominant, 3 can be distinguished from biotype A only by their auxanogram and included in biotype B. Antibiogram pattern of P. putida shows two salient features: resistant to carbenicillin and sensitivity to kanamycin. Among 17 human isolates, only 4 have likely pathogenic significance. By intraperitoneal challenge in mice, one half of strains is avirulent, other strains have a very low virulence (LD50: from 2,2 to 5 X 10(8) viable cells). There is no relationship between experimental virulence and bacterial sources.


HLA markers in parents of triploid conceptuses.

Twenty-eight HLA-A and B markers have been tested in 49 couples who had one or more triploid abortions. The antigen frequencies were compared to those of 209 couples and 591 normal individuals as controls. No significant deviations were observed. However, a non significant excess of antigens shared in common by both parents was shown in comparison with the normal couples. This could be related to a possible dispermy mechanism. On the other hand, a slight excess of A 28 may be in relation to a possible anomaly of gametogenesis.


[Respiratory physiology during water immersion (author's transl)].

In this review, the author recalls the essential modifications induced by water immersion up to the neck. The ventilatory mechanics show an important decrease of end expiratory level being able to bring a ventilation in closing volume. We notice an increase of cardiac output, of pulmonary artery pressure and central blood volume. After the age of 25, we notice an hypoxia likely due to ventilation at closing volume level.


Complement activation and group B streptococcal infection in the newborn: similarities to endotoxin shock.

Serial measurements of CH50, C3, C4, and factor B were performed on three newborn infants with group B streptococcal sepsis. Two of the septic infants had a colonized but noninfected identical twin. All three infants with group B streptococcal sepsis had hypotension, prolonged coagulation times, neutropenia, and respiratory failure. During the course of the sepsis, factor B was depressed 30% to 35%, C3 was depressed 40% to 60%, and CH50 was depressed by 100% when compared to their cord blood levels. Two of the infants also had a 50% to 70% depression of C4. In contrast, no significant decrease in complement levels occurred in the siblings of the twins or in two additional control infants. These data are characteristic of older patients with Gram-negative sepsis and strongly suggest that the group B Streptococcus has endotoxin-like properties.


Responsiveness to an introductory meditation method.

Ratings from 84 students of selected attitudes before a brief introduction to a method of meditation and responses afterward correlated moderately, suggesting those favoring personal growth will favor meditation.


[Serratia marcescens in bovine mastitis. Bibliography and a case study (author's transl)].

The literature concerning Serratia marcescens in bovine mastitis is reviewed, and a case of acute mastitis at the Department of Obstetrics, The Veterinary College of Norway, in which Serratia marcescens was isolated in pure culture, is described. Serratia marcescens usually causes only moderately severe symptoms of mastitis, but relapses are common and cases tend to become chronic in nature. The bacterium produces an endotoxin, and this toxin has caused acute mastitis on experimental inoculation into pathogen free udders.


Studies of the pathogenesis of enteric E. coli infections in weaned pigs. The significance of the milk of the dam in preventing the disease.

Milk from sows whose progeny developed post weaning E. coli diarrhoea (PWD milk) and from sows which were immunized by intramuscular vaccination using a homologous strain of E. coli (immune milk) were tested in ligated segments of pig intestine. The results showed that PWD milk neutralized the enterotoxigenic, fluid accumulating capacity of the lysate of the disease-causing E. coli pathogen. A similar effect was seen by using immune milk (Table I). Neither PWD milk nor immune milk contained sufficient antibacterial activity to neutralize the fluid accumulating capacity of live cultures of E. coli O149:K91, while such activity was contained in immune serum. It is concluded that milk from sows whose progeny developed PWD contains antibodies capable of neutralizing the enterotoxigenic effects of the homologous E. coli organisms. It is suggested that the presence in milk from these sows of antibody-mediated activity against enteropathogenic E. coli organisms may be instrumental in preventing the disease in the progeny during the suckling period and consequently, when this protective milk supply stops at weaning, the disease may develop in susceptible animals, mainly because their own production of specific E. coli antibodies is insufficient to prevent PWD.


[The beneficial role of blood transfusion and preganancy in the survival of renal allografts].

This analysis involves 93 cases of transplants of non-related cadaver kidneys. The result was better (p = 0.02 at 1 year) in recipients transfused before the graft (73 cases) than in those who had not been trasfused (20 cases). However, this latter group had a shorter average period of haemodialysis (p = 0.05 than the first. The benefits of pre-immunisation appear from 1 to 2 transfusions or 1 pregnancy onwards (p = 0.02 at 1 year). Subjects transfused during the 6 months prior to the transplant had a graft which was functional more often than those who had been more than 6 months before the operation (p = 0.01 at 6 months). These results would be in favour of routine small quantity transfusions, approximately every six months in patients undergoing haemodialysis and on a waiting list for transplantation.


[Surgical treatment of mitral diseases with left atrial ectasia. New technic].

The authors describe a new technique of "H" plication of the left atrium which reduces the size of the chamber in patients with mitral insufficiency and ectasia of the left atrium. The development of massive artrial thrombosis during the immediate postoperative period results in a mortality of more than 50 percent. It was for this reason that plication of the left atrium was used in association with valve replacement using a pig heterograft in 3 patients with good immediate and mid-term results. Follow-up cineangiography was performed 6 months after surgery in 2 patients.


Detection of nucleoside Q precursor in methyl-deficient E.coli tRNA.

32P-Labeled tRNAAsn was isolated from methyl-deficient E. coli tRNA. Nucleotide sequence analysis showed that tRNAAsn contains three derivatives of the Q nucleoside, possibly Q precursors, in addition to guanosine in the first position of the anticodon. One of the Q precursors was isolated on a large scale. Its UV spectra were identical with those of normal Q, indicating that 7-deazaguanosine structure having a side chain at position C-7 is complete in the Q precursor. No radioactivity was incorporated into Q or Q precursors from either [methyl-14C]methionine, [1-14C]methionine or [U-14C]methionine, showing that methionine was not directly involved in the formation of Q.


Polynucleotides. L. Synthesis and properties of poly (2'-chloro-2'-deoxyadenylic acid) and poly (2'-bromo-2'-deoxyadenylic acid).

Poly (2'-chloro-2'-deoxyadenylic acid) and poly (2'-bromo-2'-deoxyadenylic acid) were synthesized from the corresponding diphosphates with the aid of polynucleotide phosphorylase from E. coli. UV, CD, acid titration and mixing with poly (U) were investigated. Comparing these properties with those of poly (A) and poly (2'-azido-2'-deoxyadenylic acid), it was found that 2''substituents exert significant effects on the thermal stability of these polynucleotides, though the overall conformational structure was not greatly changed.


Genetically determined differences in concentrations of isoaccepting tRNAs in Escherichia coli.

Two examples of genetically determined altered concentrations of isoaccepting tRNAs are presented. The concentrations of isoaccepting tRNAsThr are selectively changed by a mutation causing a fourfold overproduction of the cognate aminoacyl-tRNA-synthetase, the threonyl-tRNA synthetase, whereas the distribution of isoaccepting tRNAs of four control tRNA-species in these E. coli mutants was not affected by that mutation. Secondly evidence is presented for a correlation between mutations in structural genes of aminoacid biosynthetic enzymes and alterations in concentrations of cognate isoaccepting tRNAs in two different E. coli strains, auxotrophic for threonine, isoleucine/valine and leucine, and arginine respectively.


[Studies on enzyme preparation from microorganisms in the USSR].

The paper describes the most important investigations aimed at the preparation and examination of enzymes from microorganisms which have been recently carried out in the USSR. It discusses selected theoretical studies of the regulation of the enzyme synthesis by microorganisms. The paper presents data on the properties of certain enzymes which are of practical importance for different branches of people's economy and public health.


[Relationship between the content of some fractions of high molecular weight polyphosphates and total nucleic acids upon dehydration of the yeast Saccharomyces cerevisiae].

Essential redistribution of various polyphosphate fractions was shown during dehydration and subsequent reactivation of Saccharomyces cerevisiae 14. Dehydration no matter what method was used, was followed by an increase in the content of acid soluble polyphosphates (fraction Poly P1) and a decrease of that of salt soluble polyphosphates (fraction Poly P2). Reactivation of dehydrated yeast was, on the contrary, accompanied by a decrease in the PP 1 and an increase in the Poly P2 content. A direct correlation between the Poly P2 fraction and total nucleic acids was demonstrated under various conditions of dehydration and subsequent reactivation. An inverse correlation between the content of the Poly P2, fraction and nucleic acids, on the one hand, and that of the Poly P1 fraction, on the other, was observed. Study of activities of polyphosphatases, tripolyphosphatase, pyrophosphatase and ATPase in dehydrated yeast showed values similar to those in original cells.


[Immunoenzymatic method of determining protein hormones in the blood and biological fluids].

The author describes a method of determination of protein hormones in the blood and biological fluids, including peroxidase labeling the hormone, obtaining its specific antibodies and carrying out the reaction between the inadequate amount of antibodies and the hormone determined in the presence of labeled hormone. Sensitivity of the method constitutes 0.5 ng in the test, determination of a standard hormone added to the blood serum--94%.


The importance of HLA matching in primary cadaveric kidney transplantation in Gothenburg.

The importance of HLA matching was studied for 319 primary cadaveric kidney transplantations during the period 1969-1976. During 1969-1972 the HLA match was the basis for recipient selection and most cases belonged to match grade 0 or 1. Graft survival was significantly better for match grade 0. Within match grade 1 cases with one foreign HLA B antigen had lower graft survival than cases with one foreign HLA A antigen, indicating the importance of the HLA B series. During 1973-1976 the HLA match was hardly considered in recipient selection. HLA matching during this period seemed to be of less importance, except for match grade 0 and the totally mismatched cases. When matching was performed for the HLA B series, it was found that graft survival was significantly improved when no or only one foreign HLA B antigen was present. The prognosis for cases with foreign HLA B antigen was significantly better during the later period.


Long-term haemodialysis-an enhancing factor for cadaveric graft survival.

In 220 consecutive cadaveric kidney transplants, graft survival in patients dialysed for a period of two years or longer was significantly greater than in those dialysed for less than two years. More blood transfusions were received and the formation of HLA antibodies was greater in the group dialysed for more than two years. A positive cross match was the basis for excluding 21% of the HLA positive patients from transplantation during a one year period of observation. When these same HLA positive patients had more than two subsequent opportunities for donor-recipient selection the exclusion rate dropped to 2%. The longer period of dialysis with more blood transfusions had a favourable influence on cadaveric graft survival whereas the formation of HLA antibodies had a negative influence. Even in HLA positive patients graft survival was better in the long-term dialysis group when compared with the group dialysed for a shorter period. These results suggest that longer dialysis with more blood transfusions represents an enhancing factor for cadaveric kidney grafts.


Graft survival and blood transfusion.

The outcome of primary kidney transplantation in 244 patients was studied with reference to pre-transplant blood transfusions. Fifty-eight patients received kidneys from living related donors with one shared HLA-haplotype, 186 patients received kidneys from cadaveric donors. Graft survival was found to be significantly poorer in non-transfused patients, especially in patients receiving kidneys from living related donors. The degree of uraemic intoxication did not seem to influence the outcome.


A study of the fate of pairs of cadaver kidneys.

Follow-up data collected by the EDTA Registration Committee have been linked to donor and transplant information recorded by UK Transplant by forming a 'data interface' between the two Registries. The joint data have been used to study the fate of 243 pairs of kidneys used for first cadaver grafts in 1975 and 1976. The results of this preliminary study suggest that the transportation of kidneys and the cause of donor death do not affect graft survival. With a very small amount of data, analysis of the cause of failure suggests that this is not influenced by donor origins. The clinical condition at the time of grafting does not appear to have a major influence on the outcome of the graft. There seems little evidence to support the hypothesis that kidneys from the same donor share the same post-grafting fate.


Preservation of cadaveric renal allografts-comparison of flushing and pumping techniques.

A prospective clinical trial comparing flushing and ice storage using a new hypertonic citrate solution, with machine preservation by continuous perfusion showed early graft function was similar with each method, and preservation times were comparable. Good early function occurred in half the grafts with preservation times up to 24 hours. Graft survival at three and 12 months was similar with each method of preservation. Graft survival at 12 months was worsened by poor early graft function, whereas patient survival at 12 months was unaffected by early function or by the method of preservation.


Immunological diagnosis of rejection in human renal allotransplanted patients--a prospective study.

The object of this study has been to evaluate the recipient's immunological reactivity towards donor lymphocytes in relation to rejection episodes. All recipients (20) of local necrokidneys during 1976 were immunologically monitored immediately before transplantation and subsequently twice weekly for donor-specific complement dependent lymphocytotoxic (CDC) antibodies, antibody dependent cell-mediated cytotoxicity (ADCC) and cell-mediated lympholysis (CML). Experiments were performed until graft removal or dismissal (approx. 1100 patient days). Clinical diagnosis of rejection was made independently of immunological results. All clinically suspected rejection episodes, except one, were checked by microscopy. A positive CML-test accompanied 9 out of 11 rejection episodes; the test was negative on all other occasions. Positive CDC and ADCC tests exhibited no obvious correlation with rejection episodes: positive ADCC may be more frequent in clinically uncomplicated phases. Positive CML did not generally precede clinical graft rejection. Positive CML before transplantation was observed in two cases and was followed by irreversible, accelerated acute rejections. The CML-test may prove a reliable tool in rejection diagnosis and may yield results comparable with graft biopsy without inflicting any risk on the patient.


Assessment of whole blood for antibody-dependent cell-mediated cytotoxicity in kidney patients.

A test using whole blood for antibody-dependent cell-mediated cytotoxicity has been assessed in kidney patients. The antibody-coated target system comprised lymphocytes isolated from a normal donor sensitised with rabbit anti-human lymphocyte serum. Comparison of results obtained with whole blood and isolated lymphocytes from the same patients shows that the whole blood test amplifies the differences between normal subjects, dialysis and transplant patients. It probably combines the effects of depressed lymphocyte function and lymphopenia and thus represent a more physiological in vitro correlate for in vivo immune function.


Intensive plasma exchange, complement dependent microcytotoxicity and renal transplant rejection.

Intensive plasma exchange (IPE) was used to treat 13 rejection episodes in eight renal transplant recipients with biopsy evidence of humoral rejection. Prior to IPE, each patients had several rejection episodes treated with high dose steroids. The IPE-treated rejections had not responded to conventional anti-rejection therapy and all patients appeared likely to lose their grafts. IPE reversed 7 of the 13 rejections (5 of 8 patients responded). Two of the 8 grafts continue to have adequate function 6 and 8 months after IPE. IPE temporarily reverses rejection but not increase long term graft survival.


Monitoring and modulation of recipient immune responsiveness to prevent kidney graft rejection in the early post-transplant period.

In 41 consecutive living and cadaver donor renal transplant recipients, immunological monitoring was performed 2--3 times a week for the first two post-transplant months. Monitoring consisted of: 1) Circulating T and B cell levels (E-EAC Rosette assay) 2) T cell reactivity (PHA-Con A) 3) LMC and ADCC reactivity Rejection was diagnosed by standard techniques including radioisotope renal scans and biopsy in some cases. Immunosuppression consisted of prednisone, imuran, cyclophosphamide and horse ALG. In 32 rejection episodes in the first two months, 22 (68%) were associated with a rise in T cell levels. Rejection activity also correlated with an augmented PHA mitogenesis count of 20 +/- 5%. There was no positive correlation between Con A mitogenesis and rejection. There was also no correlation between rejection and circulating B cell levels. There was no significant correlation between a positive ADCC and graft rejection. Futhermore a positive ADCC in association with a negative LMC resulted in excellent long-term graft function. In conclusion, an excellent correlation of levels of circulating T cells and T cell reactivity with early in vivo rejection was shown.


Minimum steriod requirements in renal transplant patients monitored by urinary fibrin degradation products and complement.

The purpose of this study was to define the minimum steroid requirement in patients with a well established renal transplant, monitoring rejection by urinary fibrin degradation products (FDP) and complement (C3) measurements. Urinary FDP and C3 were measured daily over two years in ten patients who had a renal cadaveric transplant. Steroid therapy was reduced step-wise over an average period of fifty weeks to minimum values (range 5--10 mg, mean 7.0 mg prednisone). Three patients developed rejection when taking 7.5 mg prednisone for 10, 21 and 50 weeks respectively. In these three patients urinary FDP excretion rose markedly 12, 10 and 8 weeks respectively prior to the diagnosis of rejection and had fallen to pre-rejection values by the time any significant changes were observed in renal function. C3 appeared in the urine of two of the three patients who had graft rejection, heralding the diagnosis by 14 and 11 days respectively. The minimal steroid dosage varied from 0.06 to 0.24 mg prednisone/kg body weight (mean 0.11) and the three patients who rejected did so on doses of 0.10, 0.13 and 0.16 mg/kg. Doses of prednisone less than 10 mg per day risk the induction of rejection, depending upon the individual response of the patient.


Surgical complications in 500 kidney transplantations.

The surgical complications in a series of 500 transplantations done by a single transplantation unit with over ten years' experience in the field are reported. The complications are divided into vascular, urological and gastrointestinal. In addition, renal rupture, primary wound infections and operative deaths are reported. Most of the losses of transplants caused by surgical complications are due to renal rupture and vascular complications, accounting for 3.6 and 2 percent of losses respectively out of the 500 kidney transplants. The urological complications caused a loss of the remaining 1.2% of a total of 6.8%. tthe overall mortality was highest in gastrointestinal complications with 6% of the total of 10% deaths following surgical complications. The mortality rate in the group of patients with gastrointestinal bleeding and perforations and with acute pancreatitis was extremely high. More accurate screening for potential candidates for gastroduodenal ulceration and better prophylactic treatment is needed. More active treatment of acute pancreatitis is suggested.


Kidney graft rejection crisis: time-evolution, prognostic significance and role in infection.

For 255 kidney grafts performed during the past twelve years, 622 rejection crises (RC) were analysed. Irreversible RC occurred more frequently in second than in first grafts during the first post-operative trimester. A clear relationship between long term graft tolerance and RC occurring during the first post-operative month was observed. Infection was related to RC in 61% of cases. Infections following corticosteroid therapy after short intervals were usually characterised by a poor prognosis. These clinical features have practical implications for immunosuppressive treatment.


Kidney transplant artery stenosis. Interrelationship between blood pressure, kidney function, renin-aldosterone system and body sodium content.

Among 9 hypertensive recipients with kidney transplant artery stenosis (KTAS) evidence of increased activity of the renin system was present in 3. Surgical repair of KTAS in 4 recipients resulted in an increase in renal plasma flow and glomerular filtration rate associated with a decrease in exchangeable sodium and blood pressure. Peripheral plasma renin and aldosterone values were normal before and after operation in all. It is suggested that sodium retention may counterbalance increased activity of the renin system in KTAS. Preoperative determinations of plasma renin do not predict the effect of surgical repair of KTAS on hypertension.


Treatment of peptic ulcer in renal failure.

The occurrence and pathophysiology of peptic ulcer was studied in 117 uraemic patients. Ulcer disease was unusually frequent, and the highest incidence was found in patients on regular dialysis (48%). Factors implicated were hyperacidity, hypergastrinaemia, and the effect of dialysis itself. We found that the occurrence of gastrointestinal bleeding was lower post-transplant (7%), than pre-transplant (15%), and that bleeding in renal transplant patients was due more commonly to erosive gastritis than peptic ulcer. Cimetidene was given to 9 regular dialysis patients with peptic ulcer. Symptomatic relief and significant reduction of acid secretion was demonstrated, and no major side effects occured. There is a logical basis for conservative treatment of uncomplicated peptic ulcer in the dialysis patient, and further evaluation of cimetidene is indicated.


Successful haemodialysis and renal transplantation in a patient with haemophilia A.

A 19-year old male with severe haemophilia A (factor VIII activity less than 1%) developed terminal renal insufficiency and was subsequently dialysed via an external arteriovenous shunt for one year. To prevent bleeding he received cryoprecipitate (2000-2500 units of factor VIII) three times a week during dialysis. After one year of uneventful dialysis he received a kidney graft from a cadaver donor that was matched for the B locus antigens. During the first two weeks after transplantation his factor VIII level was kept at approximately 70% by daily cryoprecipitate infusions. Thereafter he was free from bleeding at a level of 20% with prophylactic cryoprecipitate treatment (1000 units 3 times a week). He was discharged from the hospital five weeks after transplantation with excellent renal function (ECC 75 ml/min). No rejection crisis occurred. His factor VIII requirements remained unchanged after transplantation, indicating that the human kidney does not substantially contribute to the production of clotpromoting factor VIII.


Is renal osteodystrophy reversible?

In order to investigate the possible reversibility of renal osteodystrophy, eleven necrograft recipients were investigated six years after transplantation, when treatment with prednisone had been withdrawn for 1.5 years. Serum ionised calcium, phosphorus, alkaline phosphatases, PTH, skeletal radiography, Technetium polyphosphate (Tc-PP) bone scintigraphy and radial bone mineral content (BMC) were studied. Normal blood biochemistry, radiography and Tc-PP scintigraphy were found in nine (82%) of the patients, in contrast to the considerably higher frequency of abnormalities ordinarily found in haemodialysis patients. However, the radial BMC was significantly reduced (mean 13.5%) and identical with the BMC value in haemodialysis patients. We conclude that some regression of renal osteodystrophy may take place after a successful kidney transplantation, but that decreased mineralisation of the appendicular skeleton persists. Whether this latter finding is due to long-term steroid treatment or is an indicator of an irreversible component in renal osteodystrophy cannot be stated.


Ribonuclease activity in renal failure: evidence for toxicity.

The normal level of serum or plasma poly C-avid ribonuclease activity is 1047 +/- 247 U/mL. Serum levels increase proportionately with elevations in serum creatinine, reaching levels of 9,500-35,000 in patients undergoing dialysis. The levels can be normalised by successful renal transplantation but not by dialysis. Purified human urinary ribonuclease, a glycoprotein enzyme similar to the serum ribonuclease, was capable of: 1) inhibiting the incorporation of 3H-thymidine into mitogen-stimulated lymphocytes; 2) inhibiting the proliferation and growth of bone marrow red cell colonies; and 3) adversely affecting the growth and viability of precursor fat cells.


Antibodies in Escherichia coli urinary tract infection.

In 105 adults with E.Coli urinary tract infections, IgG coated bacteriuria was found in 8/9 with acute pyelonephritis (PN), 17/20 with chronic PN, and in only 2/76 with lower UTI. IgA was present in 66% of PN, but IgA secretory piece in less than 10%. These urinary IgG antibodies were, at least in part, synthesised in the kidney because serum IgG antibodies were detected by indirect immunofluorescence in only half the patients. 06, 018, 022 E.Coli serotypes were the three most frequently found O groups, but their prevalence in PN is not significant. The immunology of urinary tract infection (UTI) is still a subject of little interest in adult nephrology; but antibody production is a well-characterised event in pyelonephritis (PN), the study of which seems to be the best indirect procedure for localising the site of UTI. We have analysed the production of urinary and humoral antibodies, and their correlation with E.Coli serotypes in patients with E.Coli UTI.


Studies on the mechanism of renal tubular protein reabsorption.

Amino acids and derivatives were injected intravenously in normal man and the effect on the urinary excretion of albumin, free light chains and beta-2-microglobulin determined. From the results we hypothesise that the initial event in normal protein reabsorption is binding between a free positive amino- or guanidino-group of the protein molecule and a negative site on the tubular cell surface. This initial event in the reabsorption process is impeded by molecules containing similar charged groups (arginine, ornithine, lysine, EACA and Cyclocaprone). Using high doses of lysine, complete or near-complete inhibition of tubular protein reabsorption is obtained. The glomerular filtration rate in preliminary experiments is found to be of the order of 300 microgram/min for albumin.


Production of a functional eukaryotic enzyme in Escherichia coli: cloning and expression of the yeast structural gene for imidazole-glycerolphosphate dehydratase (his3).

A cloned segment of yeast DNA containing the structural gene for imidazoleglycerolphosphate dehydratase (D-erythro-imidazoleglycerolphosphate hydro-lase, EC 4.2.1.19) is transcribed and translated in Escherichia coli with sufficient fidelity to produce functional enzyme. This segment of yeast DNA was isolated as a viable molecular hybrid of bacteriophage lambda (lambdagt-Sc2601) which complements a nonrevertible hisB auxotroph of E. coli lacking dehydratase activity. The equivalent segments of DNA cloned from two independent his3 mutants of yeast lacking IGP dehydratase activity do not complement the hisB auxotroph. The two nonfunctional his3 alleles cloned in bacteriophage lambda can be recombined in E. coli to generate a hybrid phage which complements the hisB auxotroph. The dehydratase activity produced in E. coli by the cloned segment of yeast DNA strongly resembles the activity found in yeast.


Protein X is the product of the recA gene of Escherichia coli.

The inducible protein X of Escherichia coli has been compared to the recA+ protein made by specialized recA transducing phages. The molecular weights and isoelectric points of these proteins are identical. Two mutations located in the recA gene that alter the electrophoretic mobility or the isoelectric point of protein X have been studied. A recA12 mutant strain, deficient in homologous recombination and repair, produces a smaller-than-normal protein X. A transducing phage carrying the recA12 allele directs the synthesis of a smaller recA protein after infection of irradiated cells. A transducing phage carrying the recA region of a tif-1 mutant strain codes for a recA protein with an isoelectric point more basic than that of the lambdaprecA+ product. The protein X of a tif-1 mutant strain shows an identical shift in its isoelectric properties. Examination of several tsl- recA- strains indicates that protein X can be induced in several missense recA mutants but is not detected in tsl- strains carrying amber or deletion mutations of the recA gene. These results demonstrate that protein X is the product of the recA gene and that the tif-1 mutation alters the properties of the recA protein. A model is suggested for autoregulation of the recA protein in the induction of functions expressed in response to DNA damage (SOS functions).


Identification of the recA (tif) gene product of Escherichia coli.

Treatments that inhibit DNA synthesis in recA(+)lexA(+)Escherichia coli stimulate synthesis of a 40,000 molecular weight protein species (protein X). The protein X molecules produced by wild-type and mutant E. coli strains have been compared by two-dimensional gel electrophoresis. One recA mutant (DM1415 spr recA1) produced a protein X with a more acidic isoelectric point than protein X from the wild type, demonstrating that protein X is probably the product of the recA gene. Additional mutants carrying the recA-linked tif-1 mutation yielded a protein X that was more basic than the wild-type protein, indicating that the tif-1 mutation also alters the recA protein. Protein X molecules from the above mutants and wild-type E. coli have been shown to yield similar partial products upon limited proteolysis in sodium dodecyl sulfate, indicating they are the same protein species. These and additional studies suggest that (i) the tif-1 mutation alters a site on the recA protein that is sensitive to DNA synthesis inhibition, (ii) synthesis of recA protein is self-regulated, and (iii) synthesis of recA protein is also regulated by the lexA product with lexA-suppressor mutations such as spr resulting in constitutive synthesis of recA protein.


Biosynthesis of the covalently linked diglyceride in murein lipoprotein of Escherichia coli.

Biosynthesis of the diglyceride moiety of murein lipoprotein in Escherichia coli was studied by pulse-labeling with [2-3H]glycerol and subsequent chase. The evidence strongly suggests that the precursor of the glycerol moiety in lipoprotein is one of the major phospholipid species in E. coli. Studies of biosynthesis of lipoprotein in cerulenin-treated cells indicated that the nonacylated glycerol moiety of phosphatidylglycerol is the donor for the formation of a thioether linkage in the glycerylcysteine residue of the lipoprotein. This is supported by the observation that carbon 1 rather than carbon 3 of sn-glycerol is involved in this thioether linkage. We propose that the biosynthesis of lipoprotein proceeds as follows: apolipoprotein + phosphatidylglycerol or acyl phosphatidylglycerol leads to lipoprotein + phosphatidic acid.


Cloning of the silk fibroin gene and its flanking sequences.

Thirteen Escherichia coli clones containing the whole or a part of the fibroin gene (16 kilobases long) have been isolated. The starting material was DNA extracted from the posterior silk glands of Bombyx mori. Most clones were obtained from sheared DNA fragments linked by poly(dA)-poly(dT) joints to the plasmid pMB9. One of them includes the 5' end of the fibroin gene with a flanking sequence of 12 kilobases, and another includes the 3' end of the gene with a flanking sequence of about 1 kilobase. One clone was obtained by ligation, to pMB9, of a fragment generated by endodeoxy-ribonuclease EcoRI. This clone has a 21-kilobase insertion that probably includes the entire fibroin gene with flanking sequences at both ends. The cleavage sites for endodeoxyribonucleases EcoRI, HindIII, and BamHI have been established for the cloned sequences.


mRNA-dependent in vitro synthesis of ribosomal proteins L12 and L10 and elongation factor Tu.

RNA extracted from growing Escherichia coli can direct the in vitro synthesis of ribosomal proteins L12 and L10 and elongation factor Tu when an E. coli system is used. The synthesized L12 can be bound to L12-depleted ribosomes and the synthesized elongation factor Tu can form complexes with both elongation factor Ts and GDP. Guanosine 5'-diphosphate 3'-diphosphate has no effect on the synthesis of these proteins from an RNA template but inhibits their synthesis when a DNA template is used.


Regulation of synthesis and activity of a mutant RNA polymerase in Escherichia coli.

The expression of the genes specifying the beta and beta' subunits of RNA polymerase (nucleosidetriphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) was examined in an Escherichia coli strain bearing a temperature-sensitive mutation in the beta' subunit gene. A shift to 42 degrees results in a restriction of RNA chain initiation and a cessation of RNA synthesis. A shift to 39 degrees results in only partial restriction, allowing RNA and protein synthesis to continue. The partial restriction produces a 5- to 6-fold increase in the relative transcription rate of the beta and beta' genes and a concomitant increase in the relative synthesis rate of the beta and beta' proteins. The transcription rate of ribosomal protein genes was also increased somewhat. These results indicate that the genes specifying the beta and beta' subunits of RNA polymerase are regulated at the level of transcription and that this regulation is related to the transcription of ribosomal protein genes. Furthermore, the results indicate that this regulation of the beta and beta' RNA polymerase subunit genes is somehow triggered by a reduction in the ability of RNA polymerase to initiate transcription on the bacterial chromosome.


Nucleotide sequence of a mutant eukaryotic gene: the yeast tyrosine-inserting ochre suppressor SUP4-o.

One of the eight endonuclease EcoRI fragments of yeast DNA that hybridize to yeast tRNATyr has been identified with the genetically defined nonsense-suppressor locus SUP4. This identification was achieved by analyzing the meiotic linkage between the genetic determinant for the SUP4 phenotype and that for an electrophoretic variant of the EcoRI fragment. The SUP4 gene was then cloned from an ochre-suppressing yeast strain and analyzed by DNA sequencing. A wild-type SUP4 gene and two other genetically unidentified tRNATyr genes were also sequenced. The sequence of the ochre suppressor differs from that of the wild-type genes by virtue of a G.C leads to T.A transversion in the base pair that codes for the wobble position base of the tRNATyr anticodon. All four genes contain, immediately to the 3' side of the anticodon triplet, a 14 base pair tract that is not present in mature tRNATyr. Although the four genes, which represent three unlinked chromosomal loci, all encode the same mature tRNA sequence, there is virtually no observable sequence homology between the three loci in the region preceding the 5' end of the mature tRNATyr sequences.


Cloning and mapping of the replication origin of Escherichia coli.

The replication origin of Escherichia coli has been cloned on a nonreplicating DNA fragment coding for ampicillin resistance. This recombinant DNA, named pSY211, replicates depending on the presence of the replication origin and can be recovered as a closed circular plasmid DNA of 10.7 megadaltons (Mdal). A restriction map has been constructed. EcoRI cleaves pSY211 into two fragments: one is the ampicillin fragment of 4.5 Mdal and the other is a chromosomal fragment of 6 Mdal and contains the origin. The 6 Mdal EcoRI fragment has four BamHI sites, three HindIII sites, and one Xho I site. A mutant of pSY211 has been isolated which is lacking two BamHI fragments of the chromosomal fragment. In recA hosts, pSY211 is lost at a high frequency. In recA+ hosts, pSY211 is integrated into the chromosome due to nucleotide sequence homology between pSY211 and the replication origin of the E. coli chromosome. The integration site has been mapped. We conclude that the replication origin is located at a site between uncA and rbsK, at about 83 min on the genetic map of E. coli.


Thermosensitive mutation in Escherichia coli simultaneously causing defects in penicillin-binding protein-1Bs and in enzyme activity for peptidoglycan synthesis in vitro.

A thermosensitive mutant of Escherichia coli K-12 was isolated in which the membrane fractions were deficient both in penicillin-binding protein-1Bs, the major components of protein 1 [Spratt, B.G. & Pardee, A.B. (1975) Nature 254, 516-517] and in activity for in vitro peptidoglycan synthesis. The mutant was also supersensitive to many kinds of beta-lactam antibiotics. All these phenotypic changes were found to be caused by a single mutation (mrc). Genetic mapping studies show that the mrc mutation was located at about 3.3 min on the E. coli chromosome linkage map [Bachmann, B.J., Low, K.B. & Taylor, A.L. (1976) Bacteriol. Rev. 40, 116-167]. Penicillin-binding protein-1Bs seemed to be identical to one of the essential enzymes involved in crosslinking of peptidoglycan and the target of cell-lytic action of penicillins. Possible functions of some other penicillin-binding proteins in compensating for lack of protein-1Bs were also proposed.


Codon specificity of UGA suppressor tRNATrp from Escherichia coli.

A synthetic polyribonucleotide, poly(U5,G), was used to study the codon specificity of wild-type and UGA suppressor tRNATrp from Escherichia coli. Phe (UUU) incorporation directed by this synthetic messenger is reduced somewhat by omission from the incubation mixtures of Val (GUU), Leu (UUG), or Cys (UGU). In contrast, omission of Cys stimulates Trp incorporation, and this effect is much more pronounced with the UGA suppressor tRNATrp than with wild-type tRNA. The apparent replacement of Cys by Trp is specific, because the omission of Val or Leu slightly inhibits Trp incorporation. These data suggest that the UGA suppressor tRNATrp can translate codons of the form UGN (N is any ribonucleotide). In other words, the suppressor tRNATrp translates codons that properly match two out of the three anticodon nucleotides.


Initiation of polypeptide synthesis with various NH2-blocked aminoacyl-tRNAs under the direction of alfalfa mosaic virus RNA 4.

Initiation of polypeptide synthesis in a cell-free system of Escherichia coli directed by alfalfa mosaic virus RNA 4 was studied by using either fMet-tRNA or Ac-Phe-tRNA as initiator tRNA. Initiation with fMet-tRNA yielded a product that was identical to the authentic viral coat protein except that the NH2-terminal serine was preceded by fMet instead of being acetylated. When Ac-Phe-tRNA was used as initiator, the biosynthetic product was 10-12 amino acid residues longer, the extra amino acids being located at the NH2-terminus. fMet-tRNA and Ac-Phe-tRNA did not compete for ribosomes during initiation of protein synthesis, as became evident from incorporation studies using both initiator tRNAs simultaneously. It is concluded that E. coli ribosomes recognize two sites on the 5' end of alfalfa mosaic virus RNA 4 that are separated by a region of about 30 nucleotides. The results are in complete agreement with the 5'-terminal nucleotide sequence of this RNA [Koper-Zwarthoff, E. C., Lockhard, R. E., RajBhandary, U. L., Alzner-deWeerd, B. & Bol, J. F. (1977) Proc. Natl. Acad. Sci. USA 74, 5504-5508].


Contrast variation study of specifically deuterated Escherichia coli ribosomal subunits.

A neutron small-angle scattering analysis has been done on partially deuterated 30S and 50S subunits of Escherichia coli ribosomes by the contrast variation method. The results indicate that the central regions of both particles are RNA-rich whereas their exteriors are protein-rich. The segregation of RNA and protein is much greater in the 50S subunit than in the 30S; the 30S subunit approaches a homogeneous mixture of RNA and protein. In both structures the most probable separation between the centers of mass of their protein and RNA distributions is small, although substantial variation of this parameter is possible within experimental error.


Phalloidin-induced actin polymerization in the cytoplasm of cultured cells interferes with cell locomotion and growth.

Phalloidin, the toxic drug from the mushroom Amanita phalloides, was injected into the cytoplasm of tissue culture cells and the changes in intracellular actin distribution were followed by immunofluorescence microscopy with actin antibody. At low concentrations, phalloidin recruits the non- or less highly polymerized forms of cytoplasmic actin into stable "islands" of aggregated actin polymers and does not interfere with the preexisting thick bundles of microfilaments (stress fibers). Differential focusing shows that these islands of phalloidin-induced actin polymers occur at a level in the cytoplasm that is above the submembranous bundles of microfilaments present on the adhesive side of the cells. The pattern of cytoplasmic microtubules remains unaffected by the injection of phalloidin; however, filamin, a protein usually associated with actin in the cytoplasm, is also recruited into the islands. At higher phalloidin concentrations, contraction of the cell is observed. These results are discussed in the light of previous biochemical studies by Wieland and Faulstich and their coworkers [for a review see Wieland, T. (1977) Naturwissenschaften 64, 303-309] on the in vitro interaction of phalloidin with muscle actin, which have documented that phalloidin reacts stoichiometrically with actin, promotes actin polymerization, and stabilizes actin polymers. In addition, we show that microinjection of phalloidin interferes in a concentration-dependent manner with cell locomotion and cell growth. These results indicate that a well-balanced controlled reversible equilibrium between different polymerization states of actin may be a necessary requirement for cell locomotion and may also influence other cellular functions such as growth.


Isolation and characterization of a lambdapolA transducing phage.

A plaque-forming lambdapolA phage was isolated from a population of transducing phage made in vitro from Escherichia coli DNA and a phage vector digested with restriction endonuclease HindIII. Amber mutations, in genes whose products are necessary for late protein synthesis (Q) and cell lysis (S), were crossed into the lambdapolA phage. Infection of either polA+ or polA- bacteria with this phage, under conditions permitting DNA replication but preventing phage production and lysis, elevated the levels of DNA polymerase I to between 75- and 100-fold that detected in a wild-type strain. The kinetics of enzyme production suggest that the polA gene is transcribed from its own promoter rather than from any of the well-characterized phage promoters. The fragment of E. coli DNA within the lambdapolA phage comprises approximately 5000 base pairs, sufficient to accommodate the polA gene and one, or two, coding sequences for smaller proteins.


Neurophysiological and behavioral evidence for selective reinnervation in skin-grafted Rana pipiens.

Rana pipiens with skin dorosoventrally reversed can respond to stimulation of the back with forelimb wipes to the belly and to stimulation of the belly with hindlimb wipes to the back. These "misdirected wiping responses" have been explained in terms of two alternative hypotheses of nerve regeneration: nerve respecification or selective reinnervation. Experimental behavioral and neurophysiological experiments reported here support the selective reinnervation hypothesis. Severing ventral nerves, which normally innervate the belly, greatly reduced the percentage of misdirected responses on stimulation of belly skin grafted to the back, while severing dorsal nerves, which normally innervate the back, increased the percentage of misdirected responses elicited under the same circumstances. Moreover, neurophysiological recordings of grafted animals showed three effects of skin grafting on nerve distributions: (i) termination of dorsal and ventral nerve receptive field at graft edges; (ii) overlap of nonadjacent ventral nerve receptive fields; and (iii) dorsal coursing of ventral nerves to reinnervate target belly skin displaced to the back. These neurophysiological observations, and particularly the third effect, also support selective reinnervation as the mechanism of nerve regeneration in skin-grafted Rana pipiens.


The no-reflow phenomenon in experimental free flaps.

The no-reflow phenomenon was studied following reconstitution of blood flow by microvascular anastomosis in an ischemic and denervated free epigastric flap in the rabbit. Microscopic, histological, angiographic, and hematological studies demonstrated the progressive nature of this obstruction to the peripheral blood flow after increasing periods of ischemia. This obstruction reached a point of irreversibility after 12 hours of ischemia, leading to ultimate death of these flaps. These results are consistent with the hypothesis that an ischemia-induced no-reflow phenomenon is caused by cellular swelling, intravascular aggregation, and the leakage of intravascular fluid into the interstitial space. Similarities between these experimental findings and human observations are made. The clinical importance of early diagnosis and treatment of ischemic tissues is emphasized.


Chimney sweeper's disease revisited: first case reported in a black. Case report.

We present a case of occupation-related carcinoma of the scrotum (chimney sweeper's disease) in a black man. The history of this disease is outlined.


Catheter versus slow-flow carotid angiography in a highly vascularized process of the brain.

The benefits of the direct-puncture carotid angiography with the proximal-compression technique are not fully evaluated if not compared with a more simple diagnostic procedure, i.e. the femoral-catheter technique. In order to discuss this, a case history of a patient who underwent simultaneously both types of examination is presented.


Survey of reviewed patients with renal transplantation.

In 110 patients 119 renal transplantations were performed from 1968 until May 1, 1975. In this survey data are given on the recipients and the transplanted kidneys. For the following papers on different complications with renal transplantation the X-ray pictures taken until May 1, 1976 were reviewed and correlated with clinical findings.


Urological complications after kidney transplantation.

The uroradiological changes and complications with 110 patients who did undergo a total of 119 renal transplantations are discussed under the following 4 topographical headings: perirenal and intrarenal, ureter including the anastomosis, bladder, urethra. In our material we found a lymphocele in 1 patient, papillary necrosis in 3, ureteral obstruction in 6, urinary leakage in 23, reflux in a total of 23, renal calculi in 1 and bladder concrements in 1.


Angiographic aspects in kidney transplantation.

In 61 of the 110 patients with renal transplantation an angiography was performed. Besides the indication for angiography different pathological changes are illustrated: arterial stenosis, arteriovenous fistula, dissection of the arterial wall. Before angiography it is necessary to be informed about the operation technique. Sometimes different projections must be applied to get sufficient information about the arterial system of the transplant.


Gastrointestinal complications after renal transplantation.

In our series of 110 patients, 22 developed a total of 32 gastrointestinal complications after renal transplantation, leading to a fatal issue in 9 (41%). Upper gastrointestinal bleeding is to be regarded as the principal complication which, particularly in combination with liver failure due to Australia antigen positive hepatitis, led to death. Other complications were pancreatitis, diffuse oesophagitis, ileus, fistulae with abscesses, and malignancy. The radiological findings, pathogenesis and therapeutic results are discussed.


Pulmonary complications after renal transplantation.

This study presents an analysis of the nature and incidence of pulmonary complications in the first 110 patients to undergo renal transplantation in Nijmegen. The complications are divided into primary and secondary complications. An unmistakable relation to immunosuppressive medication was established in both groups. The radiological manifestations of the pulmonary lesions were atypical due to the use of large doses of immunosuppressive drugs. Pulmonary complications account for 45.1% of the total mortality after renal transplantation. Differential diagnosis from pulmonary oedema associated with rejection is exceedingly difficult, but of paramount importance.


Skeletal changes after renal transplantation.

The skeletal changes which can occur as a result of immunosuppression, and in particular as a result of hypercorticism, are discussed with reference to the findings obtained in 110 patients who received one or more kidney allografts. The hyperparathyroidism which often persists even after renal transplantation, is briefly discussed. In 21 patients, a total of 55 localizations of epiphyseal aseptic necrosis were found. In 3 patients, moreover, four medullary infarcts developed. Three osseous inflammatory processes were observed in addition. The various radiological features and the possible aetiology are discussed.


Clinical aspects of renal transplantation.

Progress in kidney transplantation is not so much hampered by the difficulties of the surgical procedure as by the problems of immunologic rejection and the complications of the immunosuppressive treatment. The radiologic investigation is an indispensable tool for the diagnosis of these, often life-threatening, complications and transplantation programmes cannot function adequately without the help of experienced radiologists. Further improvement in kidney graft survival awaits a breakthrough in the knowledge of the immunological phenomena that govern the rejection reaction.


The effect of fasting on gallbladder opacification during oral cholecystography: a controlled study in normal volunteers.

The effect of fasting on gallbladder opacification during oral cholecystography was studied in 10 normal volunteers using 2 oral cholecystographic agents, iopanoic acid and sodium tryopanoate. Radiographs made 15 hours after ingestion of the contrast agents revealed good opacification of the gallbladder in all subjects when iopanoic acid was administered with a meal and when sodium tyropanoate was administered in the fasting state; in only 2 subjects when iopanoic acid was given in the fasting state; in 3 when given in the fasting state with ox bile; and in 3 when sodium tyropanoate was given with a meal.


The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbits.

Experimental atherosclerosis in rabbits was associated with a suppression of prostacyclin generation from exogenous arachidonic acid by the coronary vascular bed. The spontaneous formation of prostacyclin by incubated rings of mesenteric artery was also diminished. These results suggest that in atherosclerosis an impaired activity of the endothelial prostacyclin synthexizing system contributes to the intra-arterial formation of thrombi.


Experimental atherosclerosis in rabbits: platelet aggregation, thromboxane A2 generation and anti-aggregatory potency of prostacyclin.

Experimental atherosclerosis in rabbits was associated with increased aggregation of their platelets to arachidonic acid, and with increased generation of thromboxane A2 by their platelet-rich plasma. A heightened susceptibility of platelets to the anti-aggregatory action of prostacyclin against the ADP-induced aggregation was also observed. It is concluded that in advance atherosclerosis the platelet system is hypersensitive to biologically active metabolites of arachidonic acid.


Prostaglandins and renin release: I. Stimulation of renin release from rabbit renal cortical slices by PGI2.

Prostaglandins have been shown to be involved in the mechanism of renin secretion in a variety of situations. Both arachidonic acid and prostaglandin endoperoxide have been shown to release renin from cortical slices and to be converted to PGI2 by cortical microsomes. In the present studies PGI2 was found to cause a time dependent increase in renin release from rabbit renal cortical slices, a system isolated from any indirect effects that result from the administration of prostaglandins in vivo. The stimulation was linear up to 30 minutes and effective over a range of concentrations from 10(7 M to 10(-5) M. At similar concentrations 6-keto-prostaglandin F1alpha was not active on these slices. Thus, it is proposed that PGI2 exerts a direct effect on the release of renin from cortical cells and may be the mediator of arachidonate or prostaglandin endoperoxide stimulated renin secretion.


Prostacyclin-like activity in rat vascular tissues. Fast, long-lasting inhibition by treatment with lysine acetylsalicylate.

Both arterial and venous tissues obtained from normal rats released prostacyclin (PGI2)-like activity, as marked by its potent inhibitory effect on platelet aggregation. Intraperitoneal or intravenous administration of a single dose of a soluble lysine salt of acetylsalicyclic acid (L-ASA, 1-400 mg/kg) resulted in abolition or substantial reduction of prostacyclin-like activity released from rat vasculature. The inhibitory effect of L-ASA was evident one minute after its i.v. administration to the animals, persisted for at least 24 hours and was still detectable (in venous tissues only) 168 hours later. Venous tissues were inhibited by doses of L-ASA as low as 1 mg/kg, whereas arterial tissues were not inhibited by doses of LA-ASA lower than 10 mg/kg. This difference may possibly be related to the lower prostacyclin-like activity shown by rat venous tissues compared to arterial ones. It is suggested that L-ASA or part of its molecule may bind to and inhibit cyclo-oxygenase in the blood vessel wall in a manner similar to the acetylation of platelt cyclo-oxygenase.


Effects of 13, 14-dehydroprostacyclin methyl ester on the feline intestinal vascular bed.

The effects of a stable PGI2 analog, 13, 14-dehydro-PGI2 methyl ester and several vasoactive hormones were compared in the feline intestinal vascular bed under conditions of controlled blood flow so that changes in perfusion pressure directly reflect changes in vascular resistance. The PGI2 analog decreased perfusion pressure in a dose-dependent fashion when injected in the range of dose of 0.03-3 microgram and was quite similar to PGE2 whereas isoproterenol was somewhat more potent as a vasodilagor in the feline intestinal vascular bed. The present data show that 13, 14-dehydro-PGI2 methyl ester has potent vasodilator activity in the intestinal vascular bed.


Double isotope derivative dilution method for the determination of prostaglandin F and E type metabolites in urine.

This method was developed for the quantitative determination of the main ureinary metabolite (MUM) of prostaglandin (PG) F and E type in man or experimental animal. This method was based on the extraction of PG-MUM after addition of 3H-PG-MUM, the esterification with 14C-acetic anhydride and the separation and purification by column chromatography. Excretion values of adult men were PGF-MUM 1.46--15.01 microgram/8 hr (n=11), PGE-MUM 0.8*--15.42 microgram/8 hr; and with women, PGF-MUM 0.41--7.75 microgram/8 hr (n=11), PGE-MUM 0.60--11.39 microgram/8 hr.


A review of the health effects of ingested asbestos.

Occupational studies indicate that a human health hazard may exist for ingested asbestos since the death rates due to digestive system cancers are elevated in asbestos workers. This finding may be related to the swallowing of asbestos that was inhaled and cleared from the respiratory system via the respiratory clearance mechanism. Published animal ingestion experiments have serious shortcomings in their design and execution which make their interpretation very difficult. Animal ingestion and human autopsy studies suggest that asbestos fibers may penetrate the digestive tract and migrate to other locations in the body.


Human ecology in understanding environmental health problems.

The role of human ecology in understanding of environmental health problems is discussed, and the importance of study on "regional" ecosystems is emphasized in consideration of recent arguments on theoretical frame work of human ecology. After brief conceptual discussion on "regional" ecosystems, the environmental health on hunter-gatherer populations, and then, the influence of agricultural development is discussed in relation to the "closedness" of regional ecosystems. Finally, by an example, e.g. islanders on small islands of southern Japan, the differentiation of economic activities by island is shown as the most important regulating factor for the accumulation of mercury in islanders.


The health implications of open leaf burning.

Because leaf burning emissions contain polycyclic aromatic hydrocarbon compounds which have varying potential for causing cancer in animals; because carcinogenesis in one or more animal species creates a strong index of suspicion that the same chemical will be carcinogenic for humans; because safe levels for human exposure to chemical carcinogens cannot be predicted on the basis of animal or epidemiological data; and finally, because it is impossible to quantify the human risk of developing cancer to which leaf burning might contribute, it is both unwise and dangerous to permit the further contamination of the environment by chemical carcinogens from leaf burning emissions.


Treatment of malignant gliomas and brain metastases in adults using a combination of adriamycine, VM 26, and CCNU. Results of a type II trial.

Forty-three patients with inoperable and/or recurring malignant gliomas and 30 patients with multiple recurring brain metastases were treated with a combination of adriamycine (45 mg/m 2 and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m 2 for 2 days) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitroso-urea (CCNU) (60 mg/m 2 for 2 days). These cycles of treatment were repeated as soon as the hematologic restoration was complete. The treatment was well-tolerated and the clinical condition of 31 out of 43 glioblastoma patients improved during the 2 months after the beginning of the treatment. Six out of eight patients with breast cancer metastases, one out of 13 with bronchial cancer metastases, and three out of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results reveals the following characteristics:  1. A low degree of efficiency of this combination in the treatment of brain metastases, except for breast cancer metastases. 2. Absence of complete correlation between the clinical results observed and the cinegammagraphic developments 3. Similarity of the results independent of the initial localization 4. Establishment of a 6-month median survival period, with ten patients at present in a state of apparently complete remission, 180-506 days after beginning of the treatment.


Clinical investigations of muscle contractility.

The use of tests of muscle contractility based on electrically stimulated contractions means that information obtained from the more traditional tests of voluntary muscular performance and strength may be complemented by indices which are independent of volition and independent of muscle mass. Such tests are no longer limited to peripheral muscles but may now be applied to a large proximal muscle--the quadriceps femoris. This report describes the in vivo testing of a drug's pharmacological activity on the quadriceps muscle by a study of the relative forces produced by different frequencies of stimulation. It also illustrates that hypothyroidism is not the only endocrine disorder whose treatment may be monitored by measuring the speed of muscle relaxation. Finally, it describes a patient whose quadriceps weakness was explained by the demonstration of the failure of the muscle to maintain tension during prolonged stimulation.


Prevention and treatment of septal deformity in infancy and childhood.

There are two basic types of septal deformity, namely anterior nasal deformity and combined septal deformity, which may occur independently or both together. They are considered to be acquired from different types of pressures on the foetus during pregnancy or parturition. The incidence of anterior nasal deformity was found to be 4% in cases of spontaneous vaginal delivery, but 13% in cases of increased pressure as persistent occipitoposterior. The combined septal deformity is part of a facial deformity, and is best tested by using simple nasal testing struts. The incidence of straight septa varied with the degree of pressure with an average of 42%. In adult surveys a little over 20% are straight. Methods of manipulation are described using special infant forceps. Indications for manipulation are: Stuffy nose, feeding problems and sticky eyes. The procedure and results of rapid maxillary expansion are presented.


[Direct pernodal lymphography (an alternative technique) (author's transl)].

A lymphographic technique via direct injection into superficial inguinal lymphnodes is described which has proved useful in infants.


[Treatment of rheumatic polyarthritis with levamisole in 26 patients].

Twenty-six patients with rheumatic polyarthritis (serologically positive) were treated with levamisole at a daily dosage of 150 mg. Treatment was continuous for 3 months and 2 days weekly afterwards. Although improvement may appear from the 1st month onwards, it is more frequent between the 1st and 3rd month (13 good or very good results among the 16 patients still treated) and may even improve afterwards (11 good or very good results among the 11 patients still treated in the 6th month). However, the value of levamisole, which appears to be an active drug against rheumatic polyarthritis, is limited by the frequency of side-effects. In 17 cases the trial had to be discontinued for this reason. The most serious side-effects were of haematological nature (2 leukopenias, 1 thrombocytopenia), but in these patients agranulocytosis was not found.


Does sarcoma occur in man after intramuscular iron?

Several factors influence the induction of sarcomas at the site of iron carbohydrate complex injection in high dosage, in animals. 1. Species specificity: tumours have been induced in rats, mice and hamsters but not in guinea pigs or dogs; 2. dose-response: a threshold dose may be defined and the yield of tumours increases with the dose; 3. the amount of residual iron at the injection site: the effect is a local oncogenesis; 4. the latent period relative to life span in the species: the probable latent period in man has been estimated to be 15-20 years. Since iron-dextran was introduced 22 years ago, nine malignancies in man allegedly related to iron-complex injection have been described in five reports during the period 1960-1977. A critical review of the information available on these cases suggests that in one case only is the data sufficiencyl strong to support the probability of iron-dextran induced sarcoma in man. Soft tissue tumours of the buttock are not rare: on the basis of this single case a causal relationship in man cannot yet be made.


Ferastral treatment of three healthy phlebotomized males.

Iron deficiency anaemia was produced by repeated phlebotomies in three healthy males. The storage iron was estimated as 666, 522 and 750 mg. After treatment with 1 000 mg of Ferastral the blood haemoglobin concentration rose at an average daily rate of 0.1 g/100 ml/day. Ninety per cent of the injected iron could be accounted for, and the utilization was estimated to about 70-80%. Side effects comprised pain and discolouration at the injection site.


A clinical investigation of an iron-poly (sorbitol-gluconic acid) complex, Ferastral, for the treatment of iron deficiency anaemia.

A clinical investigation of an iron-poly (sorbitol-gluconic acid) complex, Ferastral, for the treatment of iron deficiency anaemia has been performed. The study was designed to determine the dose schedule, efficacy and tolerance of the drug. Two dose intervals were used, 500 mg of iron once a week or every third day. The study comprised 26 adult patients. After single doses of 500 mg of Ferastral given every third day levels of iron and unsaturated iron binding capacity (UIBC) in serum were estimated. Maximum values of iron in serum after the first injection were reached after 24 hours in two patients. After the second injection there was a further increase in the iron concentration with maximum values after 24 to 48 hours. A decrease in UIBC was seen in all patients. Urinary excretion of iron was about 15%. Most of the excretion took place during the first 72 hours following the injection. The haemoglobin increase was more rapid in the group receiving 500 mg of iron every third day. The difference was statistically significant two to four weeks after commencing treatment. After five weeks the difference in haemoglobin increase was no longer statistically significant. After eight weeks the mean haemoglobin had reached 13.1 g/100 ml in the group treated once a week and 13.4 g/100 ml in the group treated every third day. The preparation was well tolerated by all patients treated. No local or general side effects were observed.


Haemoglobin synthesis following injection of iron-poly (sorbitol-gluconic acid) complex, Ferastral.

Ferastral, a new iron-poly (sorbitol-gluconic acid) complex for parenteral use has been given to 22 patients with iron deficiency anaemia. The patients were divided in two groups. Group I received a suboptimal dose of Ferastral iron corresponding to 90% of the iron calculated to normalize the haemoglobin value. Increases in total haemoglobin and also blood losses were measured. The availability of the injected iron for haemoglobin synthesis ranged from 63% to 111%. Group II received an amount of Ferastral-iron calculated to be necessary for normalization of the haemoglobin plus an additional 500 mg of Ferastral-iron. In this group the haemoglobin increase was rapid. In 7 weeks 10 out of 14 patients had reached a normal haemoglobin level.


Iron-poly (sorbitol-gluconic acid) complex and iron-dextran in the treatment of severe iron deficiency anaemia.

An investigation has been carried out to study the efficacy of iron-poly (sorbitol-gluconic acid) complex (Ferastral) in the treatment of iron deficiency anaemia. Ferastral was given by the intramuscular route every second or third day in a dose of 500 mg, divided in two injections. These were compared with the results of a group treated with iron-dextran given by Total Dose Infusion (TDI). A total of 38 patients were treated with either Ferastral or iron-dextran by TDI, respectively, given according to random allocation. The total dose of iron given in both groups was 1 500 mg of elemental iron. The parameters investigated were haematocrit and haemoglobin. Side-effects were also recorded. The results in the group treated with Ferastral where the mean initial haemoglobin value was 9.5 g/100 ml showed a mean haemoglobin increase to 13.2 g/100 ml after eight weeks. Initial haemoglobin values and haemoglobin increase for iron-dextran by TDI were quite similar. Three patients in the Ferastral group had transient discolouration at the site of injection and one patient in the iron-dextran TDI-group had a serious allergic reaction.


Clinical trial of a new intramuscular iron preparation in iron deficiency anaemia.

A new intramuscular iron preparation (Ferastral) permitting high doses of iron (500 mg) to be given in two simultaneous of 250 mg, was tested in 20 courses given to 11 patients with iron deficiency anaemia. The total iron doses given ranged from 1 000-2 500 mg. The amount injected was calculated from the degree of haemoglobin deficiency. Additional 500-1 000 mg iron were given to fill the depots. Haemoglobin regeneration was satisfactory. Bone marrow aspiration to assess storage iron 2-14 weeks after treatment was carried out in most patients and showed restoration of stainable iron in bone marrow in those cases given Ferastral in doses of 500-1 000 mg greater than calculated to normalize haemoglobin concentrations. In two patients with persistent continued blood loss the bone marrow remained negative for stainable iron. Side-effects were negligible.


Ferastral in the treatment of patients with inflammatory anaemia.

An investigation has been performed with a new parenteral iron preparation, iron-poly-(sorbitol-gluconic acid) complex (Ferastral) in the treatment with iron deficiency anaemia associated with inflammatory diseases, mainly rheumatoid arthritis. Fifteen moderately anaemic patients entered into the trial. These patients constituted a special group in whom the MCHCs were subnormal. Observations were made concerning the occurrence of side-effects. Particular attention was paid to those-side-effects which are known to be associated with the use of parenteral iron preparations in the treatment of rheumatoid subjects. Ferastral was administered by intramuscular by intramuscular injection. The single doses given on any one occasion varied from a minimum of 100 mg to a maximum of 500 mg, divided into two separate injections. The results of therapy, measured at eight weeks, showed significant increases in haemoglobin concentrations. Increases in erythrocyte count, MCHC and serum-iron concentration were also found. There were no signs of acute toxic effects with Ferastral and in no patient was there exacerbation of arthritis as has been previously reported with iron-dextran.


Clinical trial of Ferastral in iron-deficient, non-pregnant patients in Ibadan, Nigeria.

Fifteen patients with proven iron-deficiency anaemia treated with intramuscular injections of Ferastral, iron-poly (sorbitol-gluconic acid) complex, have been studied. Fourteen showed a satisfactory rise in haematocrit. No local or systemic complications were observed. One patient with iron-deficiency anaemia due to a bleeding malignant lesion did not achieve a satisfactory haematocrit level although the bone marrow showed iron repletion following the injection. It is concluded that Ferastral is an effective drug in the treatment of iron-deficiency anaemia.


The use of Ferastral in iron-deficient, non-pregnant Gambian adults.

A new parenteral iron preparation, iron-poly (sorbitol-gluconic acid) complex, (Ferastral) has been evaluated in the treatment of iron-deficient, non-pregnant Gambian adults. A total of twenty patients of both sexes were included in the study. The cause of anaemia in the majority of cases was hookworm infection but also other diagnostic categories were present. Sixteen patients completed their treatment without difficulty. All patients showed a good initial haematological response. Over the first three weeks the mean daily increments followed a linear trend. There was a significant inverse correlation between initial haemoglobin concentration and the increment in concentration after three weeks treatment. Side-effects were noted in four patients; in two patients it was ascribed to treatment, in two there was concurrent infection. Parenteral iron therapy is considered to have definite advantages over oral iron in the tropics because of certainty of administration, replenishment of iron stores, and effectiveness when small bowel disease or dietary factors reduce absorption.


The treatment of iron-deficiency anaemia with a new intramuscular iron preparation (Ferastral).

The treatment of iron-deficiency anaemia in pregnancy with a new intramuscular iron preparation, iron-poly (sorbitol-gluconic acid) complex (Ferastral), has been assessed and compared with oral iron therapy. Sixty-one of the eighty-four patients studied, many of whom had mild to moderate degree of anaemia were treated with Ferastral. The results were satisfactory, the mean increase of haematocrit at the sixth post treatment week was 28.7% for the whole series. Complete correction of anaemia was achieved in most patients between the 4th and 6th week of treatment. The mean haematocrit of the group treated with oral iron was initially significantly higher than for the group treated with Ferastral. At the first follow-up, two weeks after beginning treatment, the mean values for both groups were similar; at four weeks, those receiving Ferastral had a significantly higher mean PCV than those on oral iron, and remained so through the period of observation. No side-effects were detected using 10 ml of Ferastral intramuscularly on alternate days. The mean hospitalization time of patients with severe to moderate anaemia was reduced when given parenteral therapy, and the frequency of blood transfusion in these patients was also decreased.


Ferastral, an iron-poly (sorbitol-gluconic acid) complex, in the treatment of severe iron-deficiency anaemia in pregnancy.

Thirteen pregnant women with iron-deficiency anaemia have been treated with Ferastral. In a further seven women, Ferastral was given 24 hours before delivery, when induction of labour was indicated, to investigation of iron concentration in maternal serum, cord blood and amniotic fluid simultaneously. The efficacy of Ferastral was demonstrated by a significant increase in haemoglobin and haematocrit. No serious reactions occurred and no evidence was found of disturbance of liver or renal function. It was shown that Ferastral does not pass the placental barrier and that no direct transport takes place through the uterine wall or amnion. No effects on the newborn were demonstrated.


Studies on the effect of parenteral iron, Ferastral, an iron-poly(sorbitol-gluconic acid) complex, on blood coagulation in man.

The possible influence of Ferastral, an iron-poly(sorbitol-gluconic acid) complex, on blood coagulation in man was investigated. Ferastral added to plasma produced no changes in blood coagulation until a final concentration of 2 000 microgram/ml (35.8 mmol/1) was used, when minimal changes in blood coagulation factors were observed. Five patients were given an intramuscular injection of 250 mg Ferastral. No changes in blood coagulation and thrombocyte function were observed up to 5 hours after the initial iron injection.


An evaluation of two immunological methods in the diagnosis of bacterial meningitis: the effect of ultrasonic treatment of the cerebrospinal fluid.

Counterimmunoelectrophoresis (CIE) and fluorescent antibody (FA) technique were evaluated in the diagnosis of bacterial meningitis caused by Neisseria meningitidis (groups A, B, C), Streptococcus pneumoniae and Haemophilus influenzae type b. FA was positive in 80% and CIE in 70% of the 59 cases of bacterial meningitis investigated. Ultrasonic treatment of the cerebrospinal fluid (CSF) increased the efficacy of CIE from 50% to 70%. By FA it was possible to demonstrate bacterial antigen in CSF up to 3 days after the beginning of antibacterial therapy. Bacterial antigens could be demonstrated by the two immunological methods from 2 to 24 days when stored at 20 degrees C. At storage at 4 degrees C the antigens were demonstrable for 2 to 13 weeks by FA and for 2 to 10 weeks by CIE.


Occurrence and transfer of ampicillin resistance associated with ampicillin-resistant Haemophilus influenzae isolated from a case at a day-care centre.

A 1-year-old boy with recurrent otitis media had been repeatedly treated with antibiotics. A few days after withdrawal of administered ampicillin he again contracted otitis media and ampicillin-resistant Haemophilus influenzae was isolated. The strain was serologically untypable. No ampicillin-resistant H. influenzae was found in his family or at the day-care centre that he attended. The ability to produce the beta-lactamase elaborated from this strain could be transferred to ampicillin-sensitive strains of H. influenzae and Escherichia coli in frequencies of 0.7 X 10(-7) and 4.1 X 10(-4) respectively. The transcipients obtained were ampicillin-resistant and beta-lactamase producing. In the transcipients of E. coli, however, the marker for ampicillin resistance was quite unstable.


Cerebral cryptococcosis. Report of an unusual case.

A case of cerebral cryptococcosis associated with pulmonary and bone lesions is described. While discussing some general data of the literature, the authors outline the rarity of granulomatous CNS Cryptococcosis. From a clinical standpoint the similarity with tuberculous processes is emphasized. The methods of histopathologic diagnosis both intraoperatively and in permanent sections are discussed.


A comparison between an equimolar inhaled dose of ibuterol and terbutaline in asthmatics.

The effect of equimolar doses of ibuterol, 0.75 mg, and terbutaline, 0.50 mg, was compared in 16 asthmatics. Both drugs were given double-blind in a single dose by inhalation. The drugs did not significantly differ from each other in any of the parameters used in the trial. Both had rapid onset of action on the bronchospasm as measured with a Wright's peak flow meter. The effect was still statistically significant 300 min after the inhalation compared with the pre-treatment values. Neither drug had any effect of clinical importance on heart rate or blood pressure. No side effects were observed during the trial.


[Clinical importance of disorders of vitamin D metabolism].

Some aspects of disordered vitamin D metabolism are reviewed. The causes and consequences of diminished blood levels of 25-OH-D3 are discussed. The role of 1,25(OH)2D3 in calcium and phosphorus homeostasis is presented and the diseases associated with alterations of this hormone are described.


[Pancreatitis following kidney transplantation].

Follow-up of 249 recipients of cadaver renal allografts revealed 14 cases of pancreatitis. The minimum follow-up time was 2 1/2 years and the maximum 12 1/2 years. In 9 patients acute pancreatitis occurred within 4 months, 5 died from hemorrhagic-necrotizing disease. Later, 2 lethal cases of abscess-forming pancreatitis, 1 benign acute and 2 chronic forms were observed. The mortality in post-transplant pancreatitis is 7 out of 14, which corresponds to 7% of all fatalities after transplantation. Many different factors contribute to the development of pancreatitis, the most important being steroid medication.


[Pleural empyema and Tauroflex. Study of a new bactericidal agent].

A pilot study of 8 cases of lung empyema treated with taurolin, a new bactericidal agent, is reported. Rapid sterilization of exudates and favorable clinical course are discussed. Thanks to the absence of toxicity and its bacteriological efficacy, taurolin is a useful therapeutic agent in pleural empyema. Its use in the prophylaxis of complications in thoracic surgery is suggested.


[Are allogeneic spongiosa grafts ready for general practice?].

9 subjects with 23 infrabony pockets were filled with 2 differently stored allogenic implants. After 6 months the average pocket reduction was 2.7 mm and bone apposition was 1.0 mm. Surgical corrections were often necessary because of postsurgical flap shrinkage. The relatively demanding procedure makes allogenic bone implants with questionable success not yet an acceptable operative technique for the nonspecialist.


[The effect of fluoride application following enamel etching on the adaptation and adhesiveness of adhesive fillings].

The application of fluoride to etched enamel and the subsequent influence upon the marginal adaptation and retention of adhesive restorations was examined in vitro. Results showed that amine fluoride (F- = 1.15%, I.E. 0.01%) and 8% SnF2 (F- = 1.94%) did not affect wetting of the conditioned enamel by sealer and composite material. However, a reduction in retentive potential evidenced by a partial loss of the restoration feather margin during circulation bathing was observed. Consequently, during adhesive restorative procedures, a fluoride treatment of etched enamel prior to sealer application and composite insertion is contraindicated. Upon completion of adhesive restorations a fluoride application, for example Elmex Fluid, to the entire operation field is, however, recommended.


[Physiology of the gingivo-dental sulcus].

The gingival sulcus is formed by the space between the sulcular epithelium, the junctional epithelium, and the wall of the tooth. The functioning of its different parts is important in the early changes taking place when marginal plaque is accumulating. The cellular turnover of the junctional epithelium is very high, which could explain its high healing potential. The intercellular spaces are wider in the junctional epithelium, when compared to those of the sulcular or oral epithelia. Polymorphonuclear leucocytes can migrate through these spaces, attracted toward the sulcus by chemotactic substances. Numerous substances have been shown to permeate the junctional epithelium, both toward the sulcus and from the sulcus within the connective tissue. The sulcus is normally sterile and will tend to eliminate any foreign particle. Leucocytes and desquamated epithelial cells will also tend to leave the gingival sulcus and will be found in saliva. Various instruments, such as paper or celluloid strips of platinum loops, can be used to collect the content of the gingival sulcus. Quantitative investigations can be performed by analyzing crevicular fluid or the products of washings of the marginal gingiva.


[The centric relation. IV. Variations in condylar positions according to the methods of measuring centric relation and to the patient's clinical type].

When recording and transferring centric relation onto an articulator errors can be minimized by proper use of dental materials. Remaining errors may be due to either the patient or the clinician. 3 recording techniques (Lucia, Dawson, Ramfjord) are being tested by 2 operators on 12 patients. In order to get a proper centric relation one must not rely upon a technique of taking it but rather on an adequate clinical evaluation of the TMJ at that moment. The role of inadequate intermaxillary relationship upon painful TMJ syndroms cannot be underestimate.


Erythromycin and anaerobes: in vitro aspects.

Anaerobic organisms are being increasingly recognised as important causes of serious infection in man. Sampling procedures, transport of specimens and laboratory techniques need to be constantly monitored and improved if the causative organisms are to be consistently recovered from clinical specimens. Once the organisms have been isolated, their susceptibility to antibiotics should be determined so that the clinician can base his antibiotic therapy on reliable laboratory results. There are many variables in the sensitivity testing of anaerobes--these may account for the difficulty reported by some workers in obtaining consistently reliable results with some antibiotics, including erythromycin. These problems can be largely overcome if a standardised procedure is adopted. It is clear from the published data that erythromycin has considerable in vitro activity against many strains of anaerobic bacteria, both sporing and non-sporing. There is a broad spectrum of activity with some strains being very sensitive and a few strains being resistant. M.I.C. values range from 0.04 microgram./ml. to 20 microgram./ml. or more. Further studies are now needed to assess the role of erythromycin in the treatment of anaerobic infections in vivo.


Paramecium fusion rosettes: possible function as Ca2+ gates.

The function of a specific intramembrane particle array, "the fusion rosette," an essential requirement for exocytosis of trichocysts in Paramecium, was probed with a temperature sensitive secretory mutant (nd9). The cells were grown at 27 degrees C, the nonpermissive, nonreleasing temperature at which fusion rosettes do not assemble. Exocytosis could be triggered, nonetheless, by addition of 40 micrometer ionophore A23187 and 15 mM Ca2+ but not Mg+. Rosette function is bypassed by this procedure, suggesting that during normal release, the rosette acts as a Ca2+ channel that allows development of a site-specific increase in Ca2+, which in turn induces fusion and release.


Dextroamphetamine: cognitive and behavioral effects in normal prepubertal boys.

The behavioral, cognitive, and electrophysiological effect of a single dose of dextroamphetamine (0.5 milligram per kilogram of body weight) or placebo was examined in 14 normal prepubertal boys (mean age, 10 years 11 months) in a double-blind study. When amphetamine was given, the group showed a marked decrease in motor activity and reaction time and improved performance on cognitive tests. The similarity of the response observed in normal children to that reported in children with "hyperactivity" or minimal brain dysfunction casts doubt on pathophysiological models of minimal brain dysfunction which assume that children with this syndrome have a clinically specific or "paradoxical" response to stimulants.


Right-left asymmetrics in the brain.

Structural asymmetries between the hemispheres are found in the human brain. Asymmetries in the auditory regions and in the Sylvian fissures are present even in the fetus. The Sylvian asymmetries may have existed in Neanderthal man and are found consistently in some apes. They may relate to right-left differences infunction. Thus, the striking auditory asymmetries could underlie language lateralization. The asymmetries in the frontal and occipital lobes and the lateral ventricles are correlated with hand preference. Anatomical asymmetries may help to explain the range of human talents, recovery from acquired disorders of language function, certain childhood learning disabilities, some dementing illnesses of middle life, and the evidence for behavioral lateralization in nonhuman primates.


Fetal and maternal indications for considering abortion.

Medical indications for abortion rest on estimating the risk of an abnormal outcome of pregnancy. Recent advances have greatly increased our ability to predict the outcome for both mother and child. Given the safety of amniocentesis and the many disorders now diagnosable prenatally, genetic counseling has evolved from a level of only making a statement of chance to that of knowing the karyotype and genotype of the fetus. Fetal indications for abortion include risk of abnormality from either genetic or environmental factors. Maternal indications include physical or mental disorders which may jeopardize the patient's health. The physician and the geneticist must recognize the pregnancy at risk and fully inform the couple early enough to permit investigation, diagnosis, and decision on termination.


Spontaneous passage of bullet during voiding.

The second instance of a bullet voided spontaneously via the urethra was reported and the related literature was briefly reviewed.


Meningomyelocele skin defects.

Meningomyelocele skin defects in ten newborn infants were closed with bilateral lumbar transposition flaps and split-thickness skin grafts. Eight repairs healed promptly without incident. The superficial layer of the flaps in one patient necrosed and were replaced by skin grafts. One patient died of pneumonia and overwhelming sepsis, though the flaps and grafts were healing without reaction. These flaps were useful, even when small, because their placement could be varied to completely cover the defect.


An evaluation of levamisole for treatment of ascariasis.

Levamisole (Decaris, Belgium) was tested in Iran, Brazil, and in Mississippi and Louisiana for its efficacy as a single-dose oral treatment for Ascaris infections. Subjects were children ages 2 to 15 years, and numbers treated with levamisole and comparative anthelmintics are as follows: 453 with levamisole; 461 with piperazine citrate; 17 with pyrantel pamoate; and 19 with a placebo. Cure rates and total reduction in mean egg counts observed were 92% and 98% respectively for levamisole and 66% and 90% for piperazine. Sixteen of 17 treated with pyrantel pamoate were cured. In none of the drugs were there notable side reactions, but in all four studies side effects were more frequent with piperazine than with levamisole. Levamisole was found to be a well-tolerated, highly effective single-dose ascaricide. It should prove to be particularly useful for mass chemotherapy in Ascaris control programs.


Seven-day clotrimazole therapy for vulvovaginal candidiasis.

There were 150 patients with mycologically proven vulvovaginal candidiasis in a randomized, non-cross-over study which compared seven-and 14-day treatment courses of clotrimazole vaginal tablets (Gyne-Lotrimin) with a 14-day treatment course of miconazole nitrate 2% vaginal cream (Monistat). Adequate data for analyses were obtained for 117 patients. When patients were reexamined four or more weeks after completion of therapy, success rates, based on clinical and mycologic criteria, were: 88% for patients treated with clotrimazole for seven days, 84% for clotrimazole 14-day treatment, and 78% for miconazole nitrate 14-day treatment. There were no drug-related adverse reactions. Thus a seven-day course of therapy with clotrimazole is effective as is a 14-day course of either clotrimazole or miconazole nitrate 2% for the treatment of Candida vaginitis. Statistical analysis revealed no significant differences among the clotrimazole seven-and 14-day treatment groups and the miconazole nitrate 14-day treatment group. The shorter period of administration required for this new antifungal agent should result in better patient compliance and an improved success rate in the rate in the treatment of this frequently encountered infection.


Hypertension and anesthesia: cause for concern.

Our clinical experience and the literature regarding anesthetic management of the hypertensive patient are reviewed. Preoperative evaluation and treatment of all hypertensive patients, regardless of their degree of lability, is recommended. For emergency surgery on an untreated hypertensive patient, control of blood pressure with nitroprusside should be attempted before an awake or rapid sequence intubation. The evaluation of hypertension, the physiology of idiopathic hypertension, and the effects of treatment are discussed.


Skin protothecosis in a patient with renal allograft.

The case history of a 30-year-old male kidney transplant patient who developed cutaneous protothecosis is presented. The lesions, initially located over the forearm and around the site of previous AV shunt, consisted of maculopapular areas which opened spontaneously and drained purulent sanguineous material. Culutre of drainage grew Prototheca wickerhamii. Other virulent organisms, ie. Klebsiella pneumoniae and Pseudomonas aeruginosa, were also grown. The patient died of Klebsiella septicemia and shock. Protothecosis is an uncommon algal infection in man. This is the first report of the disease among recipients of a renal transplant.


Treatment of duodenal ulcers with cimetidine.

A total of 55 patients were treated with the histamine H2-receptor antagonist cimetidine (Tagamet: SKF) in an endoscopically controlled double-blind trial. Cimetide (200 or 300 mg every 6 hours) was administered to 36 patients, and placebo to 19 patients. Only patients who had been confirmed by endoscopy as having uncomplicated duodenal ulcers were admitted to the trial. Drug or placebo was administered in a randomized double-blind fashion for 6 weeks. Patients underwent clinical examination at weekly intervals. Haematological assessment was made weekly for 7 weeks, and biochemical variables were measured once a week or once every 2 weeks for 6 weeks. Endoscopy was repeated at 6 weeks unless the patient had to be excluded from the trial because of incessant pain after 14 days. No antacid or other treatment was allowed. Seventy-eight per cent of the patients became free of symptoms when treated with cimetidine, and 47% when treated with placebo (chi2 = 5,2235; P less than 0,025 in favour of cimetidine). Endoscopic evidence of healing revealed an improvement of 69,5% in those treated with cimetidine and one of 42% in those treated with placebo (chi2 = 3,8731; P less than 0,05 in favour of cimetidine). No haematological or biochemical changes were noted. It is concluded that the histamine H2-receptor antagonists have a definite place in the treatment of duodenal ulceration.


Culture and microscopy of microorganisms in frozen sections.

A simple method is described in which frozen sections are prepared from tissue cell suspensions with added microorganisms and then cultured. The enhanced growth of the organisms makes their indentification easier. A number of applications is suggested.


Natural occurrence of Aspergillus fumigatus in cane sugar mills.

The environmental distribution of Aspergillus fumigatus in 2 cane-sugar mills and one paper factory in northern India is compared with 2 localities in Delhi. The preponderance of the species at the U.D. Sugar Mills, Shamli, was contrary to its low prevalence in the University of Delhi campus and at Subzimandi, the vegetable and fruit market of Delhi. Aspergillus fumigatus accounted for 42.5% of the total aerial fungal colony counts recorded in the Shamli Mills as against 2% in Delhi. The predominant aerial fungus at Subzimandi was A. niger whereas aspergilli were overshelmingly outnumbered by other fungi in the University of Delhi campus. Within the Shamli Mills, the bagasse-containing sites had a significantly higher aerial prevalence (50.3%) of A. fumigatus than the bagasse-free sites (13.5%). Furthermore, A. fumigatus was more prevalent in the operational (57.2%) than in the non-operational period (23.8%) of the mills. The high frequency of isolations of A. fumigatus from and its dense population in sugar-cane bagasse seemed to suggest a special association of the fungus with this substrate.


Isolation of UV-sensitive variants of CHO-K1 by nylon cloth replica plating.

Techinques are described which permit the identification and isolation of UV-sensitive variants from mutagenized populations of Chinese hamster ovary (CHO) cells. Identification is based on the observation that within two days after receiving a dose of approximately 240 ergs/mm2 of UV irradiation most of the cells in a colony of CHO detach from the surface of a plastic tissue culture dish. At a lower dose of UV, which does not kill or detach a significant number of parental cells, UV-sensitive colonies are killed and become detached. Thus a clear plaque is produced in a lawn of unirradiated parental cells, marking the site occupied by a sensitive colony. Live cells from such sensitive colonies have been recovered from a nylon cloth replica prepared prior to irradiation and characterized. One UV-sensitive variant (CHO-UV-1) is indistinguishable from parental cells in X-ray resistance, chromosome number, generation time, and duration of the phases of the cell cycle. For UV irradiation the hit number (-n), shoulder width (Dq), and mean lethal dose (Do) for the variant are 2.8, 21 ergs/mm2, and 21 ergs/mm2, respectively, as compared to 2.6, 36 ergs/mm2, and 45 ergs/mm2 for CHO-K1 cells. These values have not changed for a period of eight months in culture.