Quantitative determination of the antibody response to the capsular polysaccharide of Bacteroides fragilis in an animal model of intraabdominal abscess formation.

The humoral antibody response to the capsular polysaccharide of Bacteroides fragilis was quantitated in an animal model of intraabdominal abscess formation using a sensitive quantitative radioactive antigen-binding assay. Antibody detected by this technique correlated highly with antibody measured by quantitative precipitin analysis (r = 0.943). Animals infected with encapsulated B. fragilis develop high levels of circulating serum antibody to the capsular polysaccharide. This antibody can be induced by implantation of live organisms, heat-killed organisms, heterologous strains of B. fragilis, and various outer membrane components that contain the capsular antigen. The immunogenicity of the capsular polysaccharide could be enhanced when administered as part of the outer membrane or when not separated from outer membrane proteins. Evidence of an antibody response to this capsular polysaccharide offers support for the demonstrated pathogenic potential of encapsulated B. fragilis.


Antimicrobial resistance and incidence of R factor among Salmonella isolated from patients with enteric fever and other clinical conditions in Madras, India (1975-1976)

The incidence of transmissible drug resistance among Salmonella isolated from patients with enteric fever and other clinical conditions is reported. All of the Salmonella isolated were studied for antimicrobial resistance. Of the 336 strains, five were multiply resistant to drugs including chloramphenicol, and four of these strains transmitted resistance to Escherichia coli F-Lac+. Multiply drug resistant E. coli were isolated from 12 patients receiving chloramphenicol, and in seven cases the E. coli transmitted drug resistance to sensitive Salmonella isolated from the same patients. The occurrence of multiple drug resistance among Salmonella was not found to be restricted to a single serogroup, and multiple drug resistance in Salmonella paratyphi A in India is reported for the first time. Although the incidence of Salmonella carring R factor is negligible, the unpredictability of its occurrence poses a potential threat in a country where typhoid is endemic.


Typhus fever: report of an epidemic in New York City in 1847.

An epidemic of thyphus fever in New York City in 1847 that was associated with massive immigrations from Ireland is described by review of the records of 138 cases admitted to The New York Hospital during a seven-week period. Medical understanding of epidemic diseases, of typhus, and of therapeutics is examined. Most patients (80%) acquired the disease during passage, but 20% of the cases resulted from secondary spread in New York. The illness was characterized by high fever, headache, myalgias, and loss of appetite. Complications, most commonly central nervous system dysfunction and secondary bacterial infections, occurred in 29% of the cases. The mortality rate was 11%. Therapy was directed at cleansing the bowel and diaphoresis. Bleeding was not employed. In spite of mistaken concepts about epidemic diseases, measures were employed that controlled spread of the disease.


Detection of hepatitis B surface antigen in potentially contaminated human plasma and plasma fractions.

A new method is described for the quantitative detection of HBsAg in whole human plasma and in plasma fractions. The nonantigen proteins are digested with pepsin at low pH, and the antigen is precipitated with PEG. With use of only 20 ml of contaminated plasma, as few as 5.0 x 10(6) HBsAg particles/ml can be detected--a 40-fold increase in the apparent level of sensitivity of the Ausria II RIA (2.0 x 10(8) particles/ml). With 500 500 ml or more of plasma or plasma fractions, fewer than 5.0 x 10(5) particles/ml can be assayed--a 400-fold increase in RIA sensitivity and 1/10 the antigen concentration found in sera that proved infective when injected into chimpanzees. The pepsin-PEG method was used to quantitate the particles per milliliter in four equivocal RIA samples from the NIH Bureau of Biologics, three of which were definitely shown to contain antigen. The method has also been employed to detect fewer than 2.0 x 1010(8) particles/ml of HBsAg in deliberately contaminated high purity AHF concentrates and may be useful for monitoring plasma fractions prepared on a large scale or for detecting the antigen in equivocal samples from blood banks.


S-carboxymethylcysteine in the treatment of glue ear: a double blind trial.

A double blind trial was carried out comparing S-carboxymethylcysteine (S-CMC; Mucodyne, Berk Pharmaceuticals) with inert placebo in the treatment of glue ear in fifty-two children who had not previously undergone surgery for the condition. The results, analysed after three months of treatment failed to demonstrate a significant reduction in the number of children receiving S-CMC who eventually required surgery for the condition.


Glossopharyngeal neuralgia with syncope.

Thirty-two cases of glossopharyngeal neuralgia complicated by syncope, cardiac arrhythmias or convulsions, singly or together, have been reported in the world literature. A further case is described and the clinical features of these thirty-three are reviewed. It is recommended that treatment should be undertaken as a matter of urgency. In the first place, Carbamezapine, with often the addition of Atropine, may prove effective. However, surgical intervention appears to give a better chance of permanent relief. Four alternative methods of surgery are discussed and the cervical or the intracranial approach recommended. Surgery should not be delayed in patients who fail to respond to medical treatment or in whom recurrence of symptoms occurs.


'Malignant lymphoepithelial lesions' (undifferentiated ductal carcinomas of the parotid gland). Three case reports and review of the literature.

Three cases of the so-cassed malignant lymphoepithelial lesion occurring in women are described. The authors, however, prefer to label the lesion 'undifferentiated carcinoma of the parotid'. From an accurate review of the world literature it appears that 23 cases of such lesion have been reported, 22 arising in the parotid and 1 in the submandibular gland. The malignant lymphoepithelial lesion has been mainly encountered in Eskimos and the three cases of the present report are the first to have been evidenced in Europe. The malignant lymphoepithelial lesion is discussed from the taxonomic, nosologic, pathogenetic, diagnostic and therapeutic points of view. The lesion does not seem to be of an autoimmune nature, unlike the benign lymphoepithelial lesion which is generally regarded as an autoimmune disease.


A priming effect of luteinizing hormone releasing factor with respect to release of follicle-stimulating hormone in vitro and in vivo.

Pituitary incubation studies were carried out which showed that in the rat luteinizing hormone releasing factor (LH-RF) can exert a priming effect on FSH secretion in vitro. It was found that, as for LH, the effect depends on protein synthesis. The priming effect of LH-RF with respect to FSH could also be demonstrated in vivo; however, the effect was less dramatic than for LH.


Hemagglutination by purified type I Escherichia coli pili.

Many enterobacteria can cause agglutination of erythrocytes, but previous investigations have not proven which components of the bacteria are responsible. We used a strain of Escherichia coli K12 which causes mannose-sensitive hemagglutination (HA) of guinea pig cells. Common pili were purified from these bacteria by shearing them from the bacteria followed by selective precipitation in acid and ammonium sulfate. Isopycnic centrifugation in cesium chloride removed the remaining outer membrane protein contaminants. These pili are pure by electron microscopy and gel electrophoresis. By amino acid analysis, they have a mol wt of 17,099 and consist of 45% nonpolar residues. These purified pili agglutinate guinea pig erythrocytes, a reaction that is inhibited by anti-pili antibodies and by saccharides related in structure to D-mannose. Proteolytic treatment of erythrocytes does not diminish HA but rather increases the pili-induced HA of human cells. Neuraminidase enhances HA and mannosidase slightly diminishes it. It is concluded that purified pili alone cause HA of erythrocytes by binding to mannose-like molecules on the erythrocyte surface. Thus HA by bacterial pili serves as a useful model system for the mechanism of bacterial pili attachment ot cell membranes.


H-2 effects on cell-cell interactions in the response to single non-H-2 alloantigens. I. Donor H-2D region control of H-7.1-immunogenicity and lack of restriction in vivo.

Genes in the H-2 complex regulate the relative immunogenicity of the H-7.1 histocompatibility alloantigen, as measured by survival times of H-7.1-incompatible skin grafts in vivo. The gene controlling relative rejectability of H-7.1-incompatible grafts has been mapped to the H-2D region. H-7.1-incompatible skin grafts donated by H-2Db donors were rejected significantly more rapidly by H-2a/H-2b heterozygous recipients than similar H-7.1-incompatible grafts donated by H-2Dd donors. Further, there was absolutely no evidence of H-2 restriction in cytotoxic effector activity. In vivo cross-priming, as indicated by accelerated secondary graft rejection, was extensive. The efficiency of cross-priming was dependent upon the primary and secondary graft donor H-2 haplotypes.


Preparative purification of the rat mast cell chymase: characterization and interaction with granule components.

The rat mast cell granule chymotrypsinlike enzyme was purified to homogeneity from 1 M NaCl solubilized membrane and granule-rich fractions of concentrated rat peritoneal mast cells by a preparative technique utilizing chromatography on Dowex 1, filtration on Sephadex G-75, and affinity chromatography with D-tryptophan methyl ester. Acid disk gel electrophoresis of the purified chymase disclosed a single stained band with activity being eluted from a replicate sliced gel in the same region. SDS-polyacrylamide gel electrophoresis of purified protein gave a single stained band that did not change in position with reduction and alkylation. Mast cell chymase is thus a cationic protein of 25,000 mol wt composed of a single polypeptide chain. The apparent K(m) of the chymase for BTEE was 1.5 x 10(-3) M and the V(max) was 67.8 mumol/min per mg. The enzyme was inhibited by TPCK and not by TLCK. The chymase complexed with native macromolecular rat mast cell heparin in molar ratios of 12:1 and 16:1, and complete heparin uptake occurred at a 40:1 ratio of chymase to heparin. Chymase activity was partially masked by combination with heparin in the isolated granule or experimental chymase-heparin complex, and soluble purified chymase was inhibited by concentrations of 5-HT comparable to those present in mast cells. It is therefore possible that the active site of chymase in the mast cell granule is largely masked by the combined effects of macromolecular heparin and 5-HT.


Absolute frequencies of lipopolysaccharide-reactive B cells producing A5A idiotype in unprimed, streptococcal A carbohydrate-primed, anti-A5A idiotype-sensitized and anti-A5A idiotype-suppressed A/J mice.

The absolute frequencies of B cells-producing A5A idiotype have been determined in vitro by limiting dilution analysis in a culture system in which every LPS-reactive B cell grows into a clone of IgM-secreting cells. Spleen cells from normal A/J mice contain 1 A5A-idiotype-producing B-cell precursor in 2.5 X 10(3) LPS-reactive B cells. Approximately a 10-20-fold increase in frequencies of precursor cells from antigen priming with Strep A-CHO (1 in 2.8 X 10(2)) or from sensitization with IgG1 anti-A5A idiotype (1 in 1.3 X 10(2)). Injection of IgG2 anti-A5A idiotype which has been shown to suppress A5A idiotype in vivo results in only a marginal and maybe insignificant decrease in precursor frequencies (1 in 6.7 X 10(3)). On the other hand, priming does not result in a detectable qualitative difference in the specific precursor cells, since each clone of B cells secretes 30 ng of A5A-bearing Ig within 8 days of culture, regardless of being unprimed or primed. Nearly half of all A5A idiotype-producing clones, both from unprimed as well as from primed mice, show antigen specificity in binding A-CHO. Priming by antigen, therefore, also results in a 10-fold increase in the frequency of idiotype positive B cells without antigen specificity. This result is a prediction of the network hypothesis.


Arthritis in rats after systemic injection of streptococcal cells or cell walls.

Further investigation of the biological properties of streptococcal cells and their components has produced a model of erosive synovitis in rats. A single intraperitoneal injection of an aqueous suspension of whole cell sonicate of group A streptococci into Sprague-Dawley rats induced an acute arthritis which evolved into a prolonged inflammatory process characterized by several complete or partial remissions, joint deformity, and ankylosis. The toxic moiety is a peptidoglycan-polysaccharide fragment of the cell wall which persists in tissue. Histologic features of the arthritis include an acute exudative phase followed by an erosive synovitis that leads to destruction of cartilage and subchondral bone and fibrous ankylosis of the joints. The arthropathic properties of whole cell sonicates of several species of streptococci are compared along with studies of the ability of heat-killed, whole cells of groups A, B, and C streptococci to induce arthritis in rats. Whole cells induce arthritis after a latent period of 57-120 days when group A cells are injected and 7-10 days when group B cells are tested.


T-cell regulation of human peripheral blood B-cells responsiveness.

We have investigated the influence of human T cells on the synthesis and secretion of immunoglobulin by peripheral blood B cells. The plaque-forming assay used, which identified the number of B cells secreting Ig, is a short-term assay which requires no exogenous stimulation. We have shown that the B-cell population alone contains fewer secreting cells than the total lymphocyte population, and that T cells are required to achieve maximal plaque-forming cell levels. Cycloheximide treatment of cells at concentrations known to inhibit protein synthesis does not affect the cooperative potential of these cells. Additionally, this cooperation effect is markedly better among autologous mixtures of Ig- and Ig+ cells, than among mixtures obtained from randomly selected individuals.


Sterol metabolism during germination of conidia of Aspergillus fumigatus.

The sterol content of germinating conidia of the opportunistic pathogenic fungus Aspergillus fumigatus has been correlated with germination phase and sensitivity to polyene antibiotics. The sterol and sterol ester contents of walls did not change during germination. The sterol ester content of membranes and cell sap remained constant during germination, whereas the sterol content increased during the outgrowth of germ tubes. On the basis of differential extraction studies it was concluded that the loss of resistance to polyenes that occurred in the early stages of swelling of conidia during germination was not due to a movement of sterol or sterol ester out of the wall. Radioactive-labelling experiments demonstrated that, although the amounts of conidial wall sterol and sterol ester did not change during germination, they were metabolically active. Changes in the turnover rate of wall and membrane sterol and sterol ester during germination were investigated and their relationship to a possible mechanism for the change from resistance to sensitivity to polyene antibiotics is discussed.


Determination of the mass of Mycobacterium leprae by electron microscopy.

The mass of Mycobacterium leprae, obtained as a pure suspension from tissues of infected armadillos, was measured electron microscopically using a technique that avoids the need for standards of mass. The mean mass of an individual bacterium was 3-9+/-1-0 (S.D.) X 10(-14) g. Comparative measurements were also made on a small sample of M. lepraemurium (whose mass is known). Calculation of the mass of an individual bacterium allows numbers of bacteria in samples to be estimated by direct weighing rather than by counting.


A Salmonella typhimurium endonuclease that converts native DNA to fragments of about 8 X 10(5) daltons.

Crude extracts of Salmonella typhimurium were found to contain an endonuclease that degraded double-stranded linear DNA from bacteria and phages to fragments with a molecular weight of about 8 X 10(5). The nuclease did not have an absolute requirement for Mg2+. One discrete intermediate product had a molecular weight of 6-6 X 10(6). Extracts from two different mutants were tested: one completely lacked the endonuclease activity (strain DB5575), and the other showed an absolute requirement for Mg2+ (strain 4543). No biological role has yet been found for this endonuclease of S. typhimurium.


Effect of a polyene antibiotic on growth and phosphate uptake by Candida albicans.

The polyene antibiotic, amphotericin, inhibited phosphate uptake in Candida albicans more strongly than it inhibited growth. Cultures grown from an inoculum of young (2 h) cells were more affected than those inoculated with old (24 h) cells. Thus, the polyene displays a double effect on C. albicans (and presumably on other eukaryotic cells): it interferes with membrane sterols and also inhibits synthesis of a factor (or factors) during growth. Whether this factor(s) interferes with the uptake of the polyene antibiotic or neutralizes its effect by reacting with it remains unsolved.


Bacteriophage-resistant mutants of Escherichia coli K12. Location of receptors within the lipopolysaccharide.

A series of mutants of Escherichia coli K12 resistant to lipopolysaccharide (LPS)-specific bacteriophages were isolated, and examined with regard to their general properties, phage typing, chemical analysis of their LPS, and genetic analysis. Fourteen classes of mutants were distinguished on the basis of phage typing and sensitivity to bile salts. Three of the mutant classes are sensitive to phages to which the parent is resistant. Mutants which are sensitive to bile salts generally lack heptose in their LPS, but two mutant classes are exceptions to this rule. Analyses of the sugars in the purified LPS of all mutant classes indicated that mutants were obtained which are blocked at most stages in core polysaccharide synthesis. On the basis of the chemical analysis, in conjunction with phage typing data and other known properties of the mutants, it is deduced which residue(s) is involved as a receptor for each of the phages used and which residues hinder these receptors. Some of the mutant classes do not seem to be changed in their LPS structure. Many of the mutations map in or near the rfa locus, but some are far removed from this region.


Bacteriophage-resistant mutants of Escherichia coli K12 with altered lipopolysaccharide. Studies with concanavalin A.

Three classes of mutants of Escherichia coli K12, isolated by selection for resistance to lipopolysaccharide-specific bacteriophages, were agglutinated by Concanavalin A which is presumed to interact with the lipopolysaccharide component of the outer membrane. Wheat germ and soy bean agglutinins did not agglutinate the parent or mutant strains. The adsorption of certain bacteriophages was also inhibited by Concanavalin A. The pattern of inhibition of adsorption of bacteriophages suggests that non-specific masking of receptors may occur, as well as specific masking of terminal glucose residues. Although bacteria were agglutinated by Concanavalin A, the permeability of the outer membrane seemed unaffected.


Characterization of pili determined by drug resistance plasmids R711b and R778b.

The bacterial drug resistance plasmids R711b and R778b, at present classified in the X incompatibility group, determine pili (designated 711) that resemble F pili morphologically. Like F pili, 711 pili adsorb F-specific filamentous bacteriophages to their tips, though more often in pairs, than singly. However, F-specific RNA-containing bacteriophages are not adsorbed to their sides, and strains carrying the plasmids are resistant to these phages. Pili determined by the only IncFV plasmid Folac are similar to 711 pili in their phage adsorption properties, but they are serologically different, as are F pili. It is concluded that F, Folac and 711 pili have basic differences in spite of a morphological resemblance.


Toxic encephalopathy due to ingestion of bismuth salts: clinical and EEG studies of 45 patients.

Forty-five patients taking bismuth subnitrate orally for therapeutic reasons were admitted to hospital with a myoclonic encephalopathy of acute onset. The clinical features were similar, mostly with mental confusion, disorder of walking and standing, dysarthria, and myoclonic jerks. In 31 cases the EEG showed a characteristic pattern, not previously recognised, which assisted differential diagnosis.


Stereotaxic thrombosis of inaccessible intracranial aneurysms.

Some intracranial aneurysms that might be considered inoperable by open craniotomy are readily treatable by stereotaxic thrombosis. This is possible because the stereotaxic technique requires only that some point on the fundus of the aneurysm can be punctured with a needle. Illustrative cases are given describing the successful treatment of aneurysms arising at the origin of the ophthalmic artery, within the cavernous sinus, within the sella turcica, and from the vertebrobasilar and the posterior inferior cerebellar arteries ventral to the brain stem. The aneurysms within the sella or cavernous sinus can be approached through the sphenoid sinus, and the aneurysms ventral to the brain stem can be approached through the clivus without opening the dura.


Investigation of variable factors in drilling bone.

Experiments were conducted to investigate the pressures that are exerted on drills during the preparation of bone. Twenty operators used six different types of drills at high and low speeds to prepare standardized holes and slots in animal bone. The peak vertical forces exerted varied between 5.98 and 24.32 newtons (x = 12.45 newtons). The mean vertical forces varied between 4.22 and 18.93 newtons (x = 9.16 newtons). Spear point and twist drills were associated with significantly lower operating pressures and shorter operating times than round and fissure burs. These differences, however, were much less than the interoperator variations.


Alterations of lymphocytes and of antibody content of human milk after processing.

The effects of pasteurization, lyophilization, and freezing on immunoglobulin and lymphocytes in human milk was studied. We found a significant decrease in total lymphocyte count after all three processing methods. Pasteurization and lyophilization caused a significant decrease in immunoglobulin concentration and in specific antibody titer to Escherichi coli. Freezing specimens up to four weeks resulted in no significant alteration of IgA content or in E. coli antibody titer. Since a major advantage of human milk is the transference of passive local immunity, these quantitative changes may have clinical importance.


Corneal ulcers associated with Goldenhar syndrome.

Two patients with Goldenhar syndrome developed corneal ulcers. Previous acid burn of the cornea and prolonged topical corticosteroid administration occurred in Patient 1. Predisposing ocular anomalies in patients with Goldenhar syndrome include corneal hypesthesia; keratoconjunctivitis sicca, and exposure secondary to eyelid colobomas, lacrimal gland and duct anomalies, dermoids and lipodermoids, and neurologic deficits. Serious ocular morbidity may be prevented by searching for and adequately treating these predisposing factors. It is possible that embryonic events contribute to ocular complications in Goldenhar syndrome, in part, by causing hypoplasia or abnormal function of the trigeminal and facial nerves.


Hydroxylation of three benzodiazepines in vitro.

Three structurally related benzodiazepines were studied as substrates for hydroxylation by liver microsomal enzymes of rats and mice. The Vmax was comparable for dechlorodesmethyldiazepam, desmethyldiazepam, and 2'-chlorodesmethyldiazepam in the two animal species. The apparent Km decreased from dechlorodesmethyldiazepam to 2'-chlorodesmethyldiazepam for liver microsomal enzymes from both animal species. The hydroxylation of desmethyldiazepam and 2'-chlorodesmethyldiazepam yielded two pharmacologically active metabolites, oxazepam and lorazepam, respectively.


GLC determination for ftorafur in biological fluids.

A GLC analysis for free ftorafur was developed to follow in drug disposition in body fluids of patients. The free drug was extracted from aqueous biological samples with chloroform, derivatized by methylation, and chromatographed on 1% HI-EFF 8BP using flame-ionization detection. The analysis is sensitive (0.25 microgram/ml of plasma) and specific for the intact molecule, and it does not interfere with subsequent fluorouracil analysis of the same sample.


Effect of auranofin on DNA and protein synthesis in human lymphocytes.

The effect of auranofin-a new oral gold compound for the treatment of rheumatoid arthritis-and gold sodium thiosulphate on DNA and protein synthesis, as well as their effect on membrane transport in stimulated lymphocytes was studied. It was found that only auranofin in the given concentrations inhibits the incorporation of 3H thymidine and 14C amino acids. The studies on membrane transport present evidence that the pharmacological action of auranofin might be mediated through its action at the cellular membrane level.


Arthritis and osteomyelitis due to Candida albicans: a case report.

A case of Candida albicans arthritis involving a knee and cuneiform bone is presented. As with other forms of candidiasis, multiple antibiotic treatment and hyperalimentation predisposed to the infection. Fourteen previously published cases are reviewed. The knee is the most common site of infection and there is a high frequency of associated osteomyelitis. Treatment with both amphotericin and 5-fluorocytosine seems to be effective. The case presented was treated successfully with a small dose of amphotericin followed by five and one-half months of 5-fluorocytosine.


Inhibitors of folate biosynthesis. 1. Inhibition of dihydroneopterin aldolase by pteridine derivatives.

2-Amino-6-carboxamido-7,8-dihydropteridin-4-one and 2-amino-6-hydroxymethyl-7,7-dimethyl-7,8-dihydropteridin-4-one have been shown to be good inhibitors of Escherichia coli dihydroneopterin aldolase, an early enzyme of de novo folate biosynthesis.


Attitudes to death: some historical notes.

Men have been talking of death from time immemorial - sometimes sublimely in prose and poetry, in painting and sculpture and in music - till silence seemed to fall in the recent past. Now men are again talking about death - interminably but colloquially. They talk on television, on the radio, in books and in pamphlets. Dr Kenneth Boyd therefore finds it entirely timely to offer this historical sketch of attitudes to death. The earlier part of his paper covers fairly familiar ground but his final and longest section on the work of a social historian, Philippe Ariès, may be new to many. Ariès is reinterpreting the long history of attitudes to death in a form which may well interest those who today are concerned with helping modern man to accept his own death - death which still, for most people, is the death of another, not of oneself.


Trisomy 22 with 'cat eye' anomaly.

The case of a 10-month-old girl with an extra G-like chromosome is presented. Quinacrine, trypsin-Giemsa, and reverse banding identified the extra chromosome as no. 22. The phenotype of the patient is unique in that unilateral iris coloboma was observed, unlike the 18 cases of full trisomy 22 already published. This represents the first reported case of full trisomy 22 with this coloboma, or 'cat eye' anomaly, which is usually associated with partial trisomy 22. It is suggested that the use of the term 'cat eye syndrome' be revised. The terms 'partial trisomy 22 syndrome' and 'trisomy 22 syndrome' should be used instead.


Effects of 2.6-4.0 GHz microwave radiation on E-coli B.

The effects of 2.6-4.0 GHz microwave radiation on living E. coli B bacteria were studied using measurement of the colony forming ability (CFA) of the cells and alterations in the molecular structure determined by comparing the infrared spectrum of irradiated and unirradiated cell cultures. At absorbed power levels of 20 mW in 1 ml of cellular suspensions (i.e., a specific absorption rate of 20 W/kg) for 10-12 hour exposures, no effects were observed on either the molecular structure or the CFA for this particular strain of E. coli.


Features of the normal menstrual cycle.

The information currently available concerning the endocrine aspects of the human menstrual cycle from puberty to menopause is briefly summarized. Features of abnormal menstrual cycles are defined and the endocrine features of the menopausal state summarized. Cautions are expressed regarding the physiologic nature of current and contemplated replacement therapy.


Contraceptive steroids and liver lesions.

Concern has been expressed about the possible untoward effect of oral contraceptives on the liver. During the past 10 yr an increasing number of cases of hepatic adenomas and related lesions has been reported in women using oral contraceptives. Such lesions occur only rarely, but it is the rarity itself that makes it difficult to evaluate the role of the contraceptive steroids. The enormity of the denominator in contraceptive steroid usage is so unwieldy that mechanisms to measure accurately the difference in an extremely small numerator are still plaguing the epidemiologist, who at best can supply only estimates. The data to date support an exceedingly low incidence of disease. This is much below the greater risks faced in accepted activities of daily living, particularly as affected by pregnancy itself. A plea is made to develop programs for better prospective evaluations of newer medications along with better animal experimental models.


The radiologic diagnosis of malignant tumors of the salivary glands.

Radiologic investigation of possible salivary gland malignancy may answer in part questions concerning the lesion under study. Is it an invasive tumor, as evidenced by tissue destruction? Is the tumor intrinsic or extrinsic in origin to the salivary gland? Does the tumor extend into the deep portion of the salivary gland or beyond it into surrounding soft tissues? Sialography plays the major diagnostic role in consideration of the radiologic diagnosis of malignant tumors of the salivary glands. However, certain advanced radiologic modalities such as salivary gland scanning with sodium pertechnetate or 67Gallium citrate, as well as cervical ultrasound and computed tomography, may prove useful. This paper attempts to provide some answers to these questions.


Reconstruction of the floor of the mouth following surgery for cancer.

The authors, members of a very active service of Head and Neck Surgery, tell of their experience with the reconstruction of the floor of the mouth following surgery for cancer. They feel that the simplest methods of reconstruction are the best.


Malignant lymphoma of the testis: a clinicopathologic study of 37 cases.

The clinicopathologic findings in 37 cases of malignant lymphoma with primary clinical manifestation in the testis were analyzed. Of these cases 34 were classified as histiocytic lymphoma and 3 as lymphocytic lymphoma. Patients usually presented with a painless small testicular mass of short duration. The peak incidence occurred in the fifth through eighth decades. Metachronous testicular involvement was noted in 35 per cent of the cases and simultaneous bilateral involvement in 3 per cent. In 25 per cent of the cases the first manifestation of lymphoma after orchiectomy was in the opposite testis. Regional and distant nodes were equally common sites of lymphoma after orchiectomy. The long-term survival of a few patients after orchiectomy may suggest that some malignant lymphomas are truly primary in the testis. However, the short interval free of disease and the rapid death of most patients imply that most testicular lymphomas are a manifestation of multicentric origin of systemic malignant lymphoma. The over-all 2 and 5-year survival rates were 30 and 20 per cent, respectively. Prospective studies are needed to define the optimal modality of treatment.


The ureter in pediatric renal allotransplantation.

The ureteral complications of 26 renal allografts in 20 transplant pediatric recipients are presented. The catastrophic events following extravasation are documented. The need for early diagnosis as an aggressive treatment is emphasized.


Renal lithiasis: a practical approach.

Management of most patients with calculous disease has been less than ideal in the past. Too often therapeutic efforts were limited to symptomatic calculi. Stones were allowed to pass or were removed, metabolic studies were incomplete, victims were dismissed and forgotten, and prophylactic measures were negligible and usually confined to milk restriction and use of distilled water. More patients were crippled with and died of recurrent calculous disease, urinary infection and progressive renal insufficiency than from any other upper urinary tract abnormality. During the last decade the development of a renal stone clinic at this institution has allowed a nephrourologic approach to the management of urolithiasis. This account of classification, diagnosis and management of the various syndromes associated with urolithiasis is based on the experiences gained during the last decade with this common but ill-understood urologic problem.


Emphysematous pyelonephritis.

We herein describe 2 cases of emphysematous pyelonephritis, which can be added to the 42 cases previously reported. Both female patients were diabetic and had Escherichia coli infections. Both had ureteral obstruction and underwent nephrectomy to survive septic and/or azotemic crises. Timely surgical intervention after unsuccessful antibiotics and conventional medical measurements is life-saving.


Fertility problems in the renal transplant patient.

Renal function, and pituitary and testicular hormone levels were correlated with spermatogenesis in 7 male patients who had undergone successful kidney transplantations. Functions of the pituitary-Leydig cell axis were not impaired. However, abnormal renal function had a direct adverse affect on spermatogenesis. Mechanisms causing infertility in post-transplant patients are reviewed.


Nicolo Paganini. Musical magician and Marfan mutant?

The thesis is advanced that Nicolo Paganini of Genoa (1782 to 1840), the greatest violin virtuoso of all time, owed his incomparable violin virtuosity to a fortuitous and fortunate coincidence of three factors: a soaring musical genius, a flair for the dramatic and ostentatious, and manual dexterity conferred by being born with the long fingers and hyperextensible joints of Marfan's syndrome. Ordinarily, an inborn connective tissue disorder is a calamity for the patient and a burden for society. In this particular instance, however, Marfan's syndrome bequeathed to posterity a legacy that will ennoble the human spirit for innumerable generations yet to come.


Clinical assessment of analgesics using ultrasonic stimulation. A new method.

A quantitative method for measuring pain threshold by the use of ultrasonic stimulation in man was designed and the possibility of clinical application in assessing analgesics was investigated. Ultrasonic stimulus was given to Japanese subjects on the palmer distal part of the 2nd, 3rd and 4th fingers of both hands. The latent time between start of the stimulation and withdrawal of the hand when perceiving pain was considered the pain threshold. The ultrasonic evoked pain was a sharp pin-prick type, without sensations such as thermal and mechanical. The pain threshold lowered with increasing either stimulus intensity or water bath temperature when the hand of the subject was immersed during measurement. Normal threshold to ultrasonic stimulation measured in both 50 men and 50 women gave nearly normal distribution curves; women being more sensitive to ultrasonics than men. Analgesia with codeine phosphate (20 mg p.o.), aspirin (1.5, 1.0, 0.5 g p.o.), aminopyrine (100 mg p.o.) and mefenamic acid (500 mg p.o.) in volunteers of both sexes was demonstrated significantly using this method under double blind circumstances. Pentobarbital, diazepam, butylscopolamine, bromelain and placebo each in the usual dose used clinically failed to alter the pain threshold. Humans were at least 25 fold more sensitive than mice to the analgesics used herein.


Change of macrophage migration inhibitory factor: possible indicator for postoperative prognosis.

Sixty three cancer cases who received minimum of the removal of the main tumor constitute the subjects of the present study. Macrophage migration inhibitory factor (MIF) of peripheral blood lymphocytes was studied using extirpated autochthonous tumor tissues as antigen and guinea-pig peritoneal exudative cells as indicator cells immediately before the operation and the fourth postoperative week. The results indicated that in those cases of relatively early stage, i.e. Stages I and II, whose tumor was believed to have been removed completely, MIF turned negative in 7/9 (77.8 per cent) after the operation, while in others with advanced cancer of Stage IV in which the tumor bearing tissue was probably not completely removed, MIF turned positive in most cases (13/17: 75.6 per cent) postoperatively, even though it was negative before the operation. In the cases of Stage III with cancer progressed to an intermediate degree, in about half of the cases (7/11: 63.6 per cent) MIF turned negative after the operation and in the other half (7/10: 70 per cent) MIF became positive postoperatively, suggesting that for MIF to persist the presence of certain amount of tumor tissue is necessary.


Studies on the effects of heterologous antisera against subcellular thymocyte fraction.

Subcellular fractions of mice thymocytes were used for sensitization of rabbits. The antisera were examined for their immunosuppressive potency in vivo by allogeneic murine tumor metastases system and on skingraft survival and in vitro by leukocyte agglutination tests. The results indicated that the most potent immunosuppressive antisera was that against the second fraction (Fr. 2) of the detergent soluble endoplasmic reticulum fraction from thymocytes.


Prehospital cardiac arrest after arrival of the Paramedic Unit.

Rapid response time by paramedic units made it possible to study 26 cases of "primary" cardiac arrests occurring after arrival of the unit. Ventricular fibrillation developed in 14 cases with prodromal ectopy in only two (14%) and rapidly increasing tachycardia in seven (50%). Countershock was successful in 12 (86%) and six (43%) survived. Bradycardia and asystole following countershock forecasted a fatal outcome. Brady-asystolic arrests (BAA) developed rapidly without much warning in 12 cases and were due to sinus arrest or severe sinus bradycardia in 92% and to atrioventricular block in 8%. BAA was 100% fatal. Coronary artery disease was diagnosed as the cause of BAA in seven (58%). All of the three cases, proven to be due to coronary artery disease at autopsy, had an occlusion of the proximal right coronary artery. In the remaining five (42%) cases, BAA was secondary to ruptured aneurysm (2), acute pancreatitis (1), chronic lung disease (1), and mitral stenosis (1). These observations emphasize a need for a more aggressive approach to prehospital management of brady-asystolic cardiac arrests.


[Experimental autotransplantation of the heart].

The paper analyses the results of 15 heart autotransplantations undertaken in puppies under deep hypothermia. The employed method of autotransplantation without division of the atrial septum is described. The characteristics of a adaptation of the cardiac autotransplant in the recipient body are presented along with the principles of correction of the changes observed in the early postoperative period.


[Automatic data processing in the studies of the electric activity of the heart].

A generalized analysis of the work going on at the Kaunas Medical Institute in automation of instrumental investigations is reported. The aim, destination and the field of application for the systems of automated analysis of electrocardiograms and rhythmograms, whose construction is based on the use of LIBM-22 and BECM-6 computers, are described. Fundamental prinicples laid at the root of the systems (data file, algorhythms employed, structure of response), mathematical and technical provisions, analysis of basic errors and possibilities of their elimination are presented.


[Basic trends in the use of mathematics and computer technics in cardiology].

Five cardinal, according to the author, trends in the utilization of mathematics and computing technique in cardiology are discussed, viz. in the diagnosis, including mass-examinations of the population; in prognosing, with screening at the time of mass-examination of the population groups of persons presenting risks as to the development of atherosclerosis, myocardial infarction, hypertensive disease, etc.; in the treatment; in the organization of information-search systems; in modelling. The significance of the cited trends for theoretical and practical cardiology is shown on examples from experience of the work carried out by research bodies headed by the author.


[Possibilities of the automatic data processing in differential diagnosis of arteriosclerotic cardiosclerosis and rheumatic heart disease complicated by auricular fibrillation].

The possibility of applying some mathematical methods for automating the process of differential diagnosis between atherosclerotic cardiosclerosis and rheumatic heart diseases complicated by auricular fibrillation, based on employing computing technique in processing the cardiointervalographic findings, is discussed. The processing of cardiointervalograms taken in 2 groups of patients with diseases in question (totaling 49 persons) aged over 45 evidenced that in the differential diagnosis mathematical expectation and dispersion of the R-R intervals duration are most informative signs. It is shown that for the purpose of automatic diagnosis of atherosclerotic cardiosclerosis and rheumatic heart diseases complicated by auricular fibrillation with the method under discussion the sufficient length of cardiointervalograms equals 130--150 R--R-intervals.


[Ergometric tests in cardiology (problems of standardization and automation)].

A method of ergometric tests furnishing a quantitative evaluation of the coronary and contractile function reserves and also ensuring safe examination has been devised. The veloergometric tests proceed under a continuous ECG and integral rheographic control with automatic throwing-off the load in case of ischemic changes of the ECG or reduction of the circulation volume. The amount of work done by the moment of throwing off the load was taken as a quantitative measure of the corresponding functional reserve. This principle served as a basis for constructing an electronic system automating the conduct and assessment of the veloergometric test. Examinations covered 890 healthy persons and patients. Future prospects for the use of biologically controlled ergometric tests are outlined.


[Use of mathematical analysis of the cardiac rhythm in evaluation of the functional state of a patient in surgical interventions].

In 112 patients mathematical analysis of the cardiac rhythm indices and a biochemical investigation were effected during operative interventions with diverse types of endotracheal anesthesia. The correlation analysis of the cardiac rhythm parameters showed that at the most traumatic moment of the operation the synchronization of the functional links aimed at maintaining homeostasis was going up. Pharmacological block of adrenergic receptors results in weakening correlational interlinks. By analyzing the degree of synchronization marking functional links of the cardiac rhythm parameters that characterize the vegetative homeostasis it becomes possible to obtain information as to the level of the level of the adaptive-regulatory mechanisms tension and the correspondence of the depth of anesthesia to the seriousness of the operation trauma at different stages of surgery.


[Effect of arteriovenous shunt and anastomosis on the central hemodynamics of patients kept on programmed hemodialysis].

Investigations of central hemodynamic indices made by the method of dye dilution in 30 patients kept on a programmed hemodialysis evidenced that the discharge of the blood through an arterio-venous shunt and fistula was one of the causes accounting for the development of the hyperkinetic circulatory syndrome, the fistula exercising a greater influence on the circulation than did the shunt.


[Retrospective evaluation of various methods of examination for prognosis of cardiac insufficiency in the subacute period of myocardial infarct].

A retrospective analysis of the informativeness of certain methods of examination for ascertaining the possibility of cardiac failure developing in the subacute period of penetrating, predominantly primary transmural myocardial infarction with no clinical signs of cardiac failure in the first three days after the onset of the disease. In 60 patients circulation time in the "arm--ear" area and in 25 of them the stroke and minute volumes by the dye dilution method were studied. The state of the fluid spaces was investigated in 18 patients and daily natriuresis in 23. In 36 patients the condition of the pulmonary circulation was judged  by means of roentgenogram. The high value of the information gained from study of circulation time and natriuresis and X-ray examination in the prognostication of the development of cardiac failure is shown.


[Computer programming for radiocardiography and radiocyclography].

Digital radiocardiography with linear programming, on the ALGOL language, by means of an ODRA-1204 computer is described. Determination of cardiac dynamical parameters of patients in rest and under load was carried out. Radioisotopic methods were combined with conventional cardiologic examinations, particularly the microcatheterization.


[Keratoplasty in performed ulcus corneae (author's transl)].

The best therapy in cases of perforated ulcus corneae is the immediately performed perforating keratoplasty with fresh material as the following up of 7 patients shows. Also in cases of perforated metaherpetic ulcus a satisfying improvement of the vision over a long period of time is possible. The surgical technique is described.


[Cataract extraction after a fistulizing operation (author's transl)].

A report is given on a method for cataract extraction after fistulizing operation. The incision is made in a straight line on the cornea underneath the fistula, so that the two ends of the incision are in the limbal region. This corneo-limbla incision does not injure the fistula. The closure is performed under the microscope with a continuous suture. The results obtained support the security of this method.


[Combined trephining with scleral flap (Elliot-Fronimopoulos) and intracapsular cataract extraction (author's transl)].

68 eyes of 51 non-selected patients on which a combined cataract extraction and Elliot's trephining with scleral flap (Fronimopoulos) had been performed between 1972 and september 1976, were re-examined between 6 and 48 months following operation. Postoperative complications were rare: there was one persistent shallow anterior chamber following excessive filtration, one increase of tension floowing a block of the trephine canal by vitreous, and one increase of tension following too tight suturing of the scleral flap which necessitated re-operation. Tension was compensated without therapy in 42 eyes (61,7%) and with local therapy in 24 eyes (35,3%). Only in 2 eyes (3%) normal intra-ocular pressure was not achieved. Altogether 97% of the eyes were compensated, some with additional local therapy. The combined cataract extraction and Elliot's trephining with scleral flap (Fronimopoulos) is an effective and low risk technique that is recommended in cases of cataract with raised intraocular pressure not controlled by medical treatment.


[The correction of the paralytic ectropion by simple belpharoplastic methods (author's transl)].

In cases of paralytic ectropion the slackened skin must not be resected but has to be used for the lifting of the lower eyelid. This aim can be reached by an antidromic skin shifting with an ypsiliform incision or in less difficult cases by a hook-shaped skin flap, who becomes effective as a curb of the lower eyelid by the exchange of the flaps.


[On the treatment of acute arterial circulatory disturbances of the retina and optic nerve (author's transl)].

After discussing basic therapeutic principles for the treatment of acute arterial occlusions of the retina and N. opticus (fibrinolysis, anticoagulation, corticoids, vasoactive drugs) the problems in employment of vasodilating drugs and the necessity of concomitant administration of strophanthine or digitalisglycosides are outlined. Results obtained after the administration of 3,7-Dimethyl-1-(5-oxo-hexyl)-xanthine (Pentoxifylline, Trental) in the treatment of 49 cases suffering from occlusion of the retinal vessels and 23 cases with vascular occlusion in the N. opticus are reported and commented with a view to the bad prognosis of these serious disorders, 55% of the patients showing definite improvement of visual acuity. Therapeutic guidelines resulting from these experiences are presented.


[Graphical methods in data analysis (author's transl)].

Data analysis is concerned with attentive description and communication of the information contents of a body of data. Background information, conceptual insight and especially graphical methods play a key role in data analysis for developing a feeling for the data both by formal procedures to be applied in the light of specified models and even more by informal inference or methods that are suggestive and conctructive. This paper reviews graphical methods useful for description, screening, analysis, cross-examining, selection, reduction, presentation and summary of data: for uncovering distributional peculiarities and understanding the structure underlying experimental and survey data. Moreover scatter plots, probability plots and residual plots provide insight into the possible inappropriateness of certain assumptions of the statistical model. Some techniques are illustrated by examples: four-dimensional data may be reprented as scatter plot on ordinary graph paper by using a combination of 2 different sets of symbols for at most 7 different levels of the third variable (formula: see text) and of the fourth variable (formula: see text). Comments on the use of tables and graphical methods, a small overview of the latter and of the scope of applications endeavour to pave the way such that structures may be better understandable and unanticipated characteristics may be spotted.


The advantage of heterotopic cardiac transplantation over orthotopic cardiac transplantation in the management of severe acute rejection.

The major problems with organ transplantation are rejection of the allograft and the side effects of antirejection therapy. This report describes the successful treatment of a patient in whom rejection of the donor heart developed 10 months after implantation. The recipient's own heart had been left intact and was able to support the circulation during the period of rejection. Indications are that the "rest" period of 10 months was beneficial to the myopathic left ventricle of the recipient's heart.


Surgical treatment of echinococcal cyst of the heart. Report of two cases and review of the world literature.

The case histories of two children with echinococcal cysts of the left ventricular myocardium are reported. Both patients underwent successful enucleation of the cysts, after initial local treatment with 0.5 percent silver nitrate solution. A previous review of the world literature on the surgical treatment of echinococcal cyst of the heart, published in 1971, is brought up to date by the addition of 60 new cases to the 118 cases then described. Instillation of 0.5 percent silver nitrate solution into the cyst cavity is now a routine procedure in our institution to sterilize the cyst and to kill the scolices. This substance is preferable to formalin and hypertonic sodium chloride solution, because it acts rapidly and is nontoxic and nonabsorbable. The two children in this report are the first in whom silver nitrate solution was used to sterilize the myocardial cysts.


Antimicrobial agents--Part II. The aminoglycosides: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, neomycin.

Aminoglycoside antibiotics are poorly absorbed from the gastrointestinal tract, do not penetrate well into the cerebrospinal fluid, are minimally bound to plasma proteins, and are rapidly excreted by the normal kidney. Neomycin is limited by its toxicity to irrigating and topical preparations or to oral medication for surgical bowel preparations or hepatic coma. Streptomycin has only a few specific indications, because newer agents are available that have broader spectrums of activity. Kanamycin is indicated in serious gram-negative infections in which Pseudomonas aeruginosa is not a likely causative agent. Gentamicin, tobramycin, and amikacin are effective against a broad spectrum of gram-negative organisms including P. aeruginosa. In general, both gentamicin and tobramycin are more active in vitro than amikacin on a weight basis; however, higher serum levels are achievable with amikacin than with the two others. Amikacin is probably the aminoglycoside of first choice when gentamicin resistance is strongly suspected.


Evaluating the quality of ambulatory health care: a review of emerging methods.

While hospital quality evaluation activities have progressed dramatically in recent years, there has not been a comparable development and implementation of methods for the review and evaluation of ambulatory health care. Various technical problems regarding ambulatory records and the nature of ambulatory care itself have combined to retard the evolution of review methods. These problems are discussed, as are current efforts to overcome them. We have reviewed the relevant issues and literature and have attempted to provide a conceptual framework for better understanding the measurement of ambulatory health care quality. A selective bibliography of literature relating specifically to ambulatory care quality evaluation is presented as a guide to further study.


Respiratory failure.

Patients with respiratory failure should be approached in a systematic way, with emphasis both in diagnosis and treatment on arterial blood gases. The intelligent assessment of oxygenation, ventilation and acid-base balance, based on physiologic principles, can make the management of these patients very rewarding. The physiologic principles outlined here should be well understood by anyone entrusted with the care of these patients. They provide the cornerstone of diagnosis and management, and will remain valid long after current clinical dogma has been revised.


Mastoidectomy update.

The long-term results of 375 primary mastoidectomy operations for chronic otitis media and chronic mastoiditis are described and discussed. Two-thirds of these cases were open cavity mastoidectomies and 1/3 closed cavity mastoidectomies. Primary pathology was cholesteatoma in 1/3 and granulation tissue in 2/3 of the cases. The method of reducing the size of the mastoid cavity by sculpturing mastoid cavity by sculpturing mastoid cortical bone is most important in avoiding large postoperative cavity problems. Principles and methods are described. Healing (dry ear) is a more important management objective than hearing and, indeed, enhances the prospects of obtaining a long-term hearing result. Three important phases of controlling mastoid disease (preoperative, operative, and postoperative) are equally stressed. Intact wall tympanomastoidectomy is not recommended in sclerotic mastoids (the majority of our cases) as being unsafe and unnecessary. Revisions, mostly minor, were done in 31% of the cases for a total of 521 procedures. We recomment a one-stage tympanomastoidectomy. Multiple planned procedures are, in the main, unnecessary and should be avoided to reduce unnecessary hospitalization and expense.


Quantitative microscopy of enzyme reactions in tissue sections.

Microdensitometry makes it possible to measure reaction products in discrete regions of tissue sections. Single cells, or groups of cells, can be selected for measurement. In this way, it is possible to obtain quantitative data from enzyme reactions, and to relate activities to histology. Some examples are given to illustrate the application of this technique.


A method of morphological identification of individual neurons in the brain in vivo and after fixation.

Pyramidal neurons from layers III and V of the cat brain cortex being stained with methylene blue are revealed in vivo in specially prepared cortex specimen by means of contact micro-objectives in the reflected light. Small pieces of the brain tissue with identified neurons are excised after their fixation in situ under visual control and are placed in special grid-baskets in definite positions. Orientated and fixed by the basket's edges a bit of tissue is subjected to further histological treatment. This method permits the investigation of the same neurons after fixation by means of histological techniques suited for light or electron microscopy.


Intracellular development of membrane protein of influenza virus.

The intracellular development of membrane protein (MP) of influenza A virus was investigated by immunofluorescent staining. Monospecific antiserum was prepared by immunizing rabbits with MP eluted from SDS-polyacrylamide gels of SDS-disrupted NWS virions. In the productive infection in clone 1-5C-4 cells, MP antigen was first detected over the whole cell at 4 hr after infection, concomitantly with the appearance of hemagglutinin (HA) antigen in the cytoplasm, and bright nuclear fluorescence was then observed. Nucleoprotein (NP) antigen was detected in the nucleus prior to the appearance of fluorescence of MP antigen and thereafter the cytoplasmic fluorescence developed. Late in infection, all of these three antigens were observed predominantly in the cytoplasm with stronger fluorescence at the cell surface. Essentially similar findings were obtained in the abortive infections in L cells and BHK cells. The above results suggest that the membrane protein of influenza A virus is present in the nucleus as well as in the cytoplasm of infected cells.


[Biochemical typing of Klebsiella strains isolated from clinical cases].

228 Klebsiella strains were isolated from 300 Klebsiella suspected materials obtained from Hacettepe Children's Hospital using biochemical methods. 122 strains out of 228 Klebsiella isolations were identified as K. aerogenes, 39 as K. ozaenae, 39 as K. edwardsii, 17 as K. pneumoniae, 9 as K. atlanta and 2 strains as K. rhinoscleromatis. We believe that these biochemical typing methods may be used routinely with certainty.


[Postoperative focal salmonella infections of hydatid cysts].

S. typhi and S. typhimurium were isolated from postoperative cavities of hydatid cysts of two patients. Both focal salmonella infections were cured by using appropriate antibiotics.


[Fungal infections following renal transplantation].

Following the immunosuppressive treatment, applied after renal transplantations, infectious diseases are seen more frequently. Inspite of more frequency of bacterial infections, they can usually be controlled because of their easier diagnosis and treatment. However the mycotic diseases are usually fatal because of their easier diagnosis and treatment. However the mycotic diseases are usually fatal because of the difficulty in their diagnosis and treatment. The immunosuppressive treatment agents are cytotoxic medicines, codticosteroids, antilymphocytic sera (or antithymocytic sera) and radiation. The mycotic infections, more often encountered are candidiasis, aspergillosis, nocardiosis, cryptococcosis and phycomycosis. There are certain medicines used today in the treatment of deep mycotic infections. These are amphotericine B, 5 fluorocytosine and imidazol derivatives.


Leprosy in Sydney: a brief account.

Individuals with leprosy and those incubating the disease continue to enter New South Wales from endemic areas. With early diagnosis and treatment, the prognosis is good. The diagnosis should be considered in any patient who has lived or worked in a leprosy endemic country and who presents with an unusual or persistent skin erpution (especially if there is associated hypoaesthesia) and/or mononeuritis or mononeuritis multiplex. Occasionally the disease presents inother guises; biopsy of the appropriate tissue and staining for acid-fact bacilli, as well as haematoxylin and eosin, will usually indicate the correct diagnosis.


Preservation of cadaver of renal allografts: comparison of ice storage and machine perfusion.

Preservation of cadaveric renal allografts by ice storage and by machine perfusion after a preliminary flush with a hypertonic citrate solution has been compared in a prospective clinical trial between matched pairs of kidneys from the same cadaver donor. Over a two-year period, ice storage after flushing with the new solution gave results comparable with machine perfusion. Times of warm ischaemia and total times of storage were similar in ice-stored and machine-perfused kidneys and averaged about 16 hours. In each group of recipients, more than half of the kidneys had good early function and one-year survival times were also similar.


Problems in clinical organ preservation.

Effective preservation of donor organs is essential for successful renal cadaver transplantation. Three problems of direct clinical relevance are discussed: (i) agonal damage to the donor kidney; (ii) extracorporeal preservation; (iii) effects of preservation on antigenicity. Current techniques for preserving donor kidneys by continuous perfusion and by ice storage are described.


[Identification of plasmodial antibodies in the immunodiagnosis of malaria (author's transl)].

Out of 880 sera which were examined for antibodies to plasmodia 69 (7.8%) reacted only with P. falciparum antigen, 371(42.2%) reacted only with P. fieldi antigen, and 440 (50%) responded to both antigens. These groups were differentiated further with antigens from P. vivax, P. ovale, and P. malariae. The results showed that the P. ovale antigen was distinguished by a marked activity with those sera that had reacted only with P. fieldi in the screening test. With sera that had responded to both antigens or only to P. falciparum antigen in the screening test there was no such clear differentiation of the antibodies. P. falciparum was a less sensitive antigen for the demonstration of plasmodial antibodies (590, i.e. 57.8%, of the sera were positive) than P. fieldi (811, i.e. 91.2% of the sera were positive). The explanations given in the literature for the group and species specific reactions are discussed.


[The idiopathic tetany syndrome in general practice (author's transl)].

The relevance, to general practice, of the various views on the idiopathic tetany syndrome is discussed. The effect of a drug (Frubiase Calcium forte), which largely metts the requirements stemming from the above, on all important symptome and diagnostic signs was found to be statistically superior to placebo on the basis of a randomised double blind trial in 80 patients.


[New stereotactic treatment of spasmodic torticollis with a brain stimulation system (author's transl)].

The author reports here on a new method for treating spasmodic torticollis with the permanent implantation of a brain stimulation system (Medtronic) in the extrapyramidal-motor thalamic nuclei (V.o.a./V.o.i.) and the subthalamic zona incerta including the pyramidal tracts H1 and H2 (according to Forel). Thanks to stimulation which lasts 30--40 minutes and is determined and undertaken by the seven patients themselves, control over the position and the morbility of the head is attained while simultaneously suppressing the symptoms of spasmodic torticollis. This new stereotactic and functional method of neurosurgical treatment for functional disturbances of the motor systems is not destructive and entails neither operative complications nor side-effects.


[The toxicity of massive dosis of VM26 (4-demethyl-epipodophyllotoxin-beta-D-thenylidene glucoside). A contribution to the therapy of advanced ovarian cancer (author's transl)].

19 patients with advanced ovarian cancer (FIGO-stages IIb-IV) were treated by ultra-high doses of VM26 partly according to positive oncobiograms during Multiple-drug-stoss-therapy. The toxic reactions and the cytostatic effect were investigated. The range of 57,9% remissions and the moderate toxicity suggest a specific application of VM26 in advanced ovarian cancer.


A study of antibiotic therapy in fever of unknown origin in neutropenic cancer patients.

Neutropenic cancer patients were given carbenicillin, cephalothin, and gentamicin (CCG) during 51 evaluable episodes of fever of unknown origin. Patients in whom fever persisted despite these antibiotics and in whom infection had not been documented were randomized after 3 days either to discontinue antibiotics or to add chloramphenicol or clindamycin to CCG. During 19 episodes (37%) an infection was documented during the first 3 days, and during an additional 12 episodes (24%) there was a response in 3 days without a focus of infection or an identifiable organism. Two patients died within 3 days, and one developed renal failure. Seventeen febrile episodes (33%) were unresponsive to CCG after 3 days and were randomized. Klebsiella was cultured in 4 of 6 patients randomized to stop antibiotics within a week of cessation, and 3 of these patients died. Of 11 episodes randomized to continue antibiotics, all patients were alive at 2 weeks after randomization and 9 after 4 weeks. This study, albeit small, demonstrates no advantage to withholding treatment in unremitting fever of unknown etiology and indeed strongly suggests that in this clinical setting, antibiotics once started should be continued until bone marrow recovery.


Replication of plasmid pSC101 in Escherichia coli K12: requirement for dnaA function.

Replication of pSC101 was analyzed by using DNA-DNA hybridization and alkaline sucrose gradient centrifugation. Mutants of the dnaA gene were tested for their capacity to replicate pSC101 DNA at a non-permissive temperature. Only a small amount of radioactive precursor was incorporated into pSC101 DNA in dnaA mutants at 42 degrees C whereas active incorporation into plasmid DNA took place in dnaA+ strain under the same conditions. The effect of the dnaA mutation was grater on plasmid DNA synthesis than on host chromosomal DNA synthesis. The numbers of copies of pSC101 per chromosome in wild type and dnaA strains, grown at 30 degrees C, were about 8 and 2, respectively. These results indicate that the dna A gene product is required for the replication of pSC101 DNA.


Fine structure physical mapping of 4S RNA genes on mitochondrial DNA of Saccharomyces cerevisiae.

We have localized the genes for mitochondrial 4S RNA on the physical map of the mtDNA of several Saccharomyces cerevisiae strains by hybridization of iodinated 4S RNA to the restriction fragments obtained with endonucleases HindII + III, EcoRI and HapII. The data indicate that 5-8 of the 4S RNA genes are dispersed over a large area of the genome whereas the rest (about 18 genes) is located within an area of about 9000 bp in length (about 18 genes) is located within an area of about 9000 bp in length (about 12% of the genome) between the markers for chloramphenicol and paromomycin resistance (RIB 1 and PAR 1 loci). Within this region a cluster is present of 5 genes on a DNA fragment of 460 bp.


RNA-linked nascent DNA pieces in T7 phage-infected Escherichia coli cells. I. Role of gene 6 exonuclease in removal of the linked RNA.

The presence of RNA-linked nascent DNA pieces in T7 phage-infected Escherichia coli cells has been shown by the selective degradation of the 5'-hydroxyl-terminated nascent DNA, produced by alkali or RNase treatment, with spleen exonuclease. At 43 degrees C, the proportion of RNA-linked DNA pieces in nascent short dna is 50 to 60% in T7 ts136 (ts mutant of gene 6) phage-infected E. coli, whereas that in T7 wild-type phage-infected cells is less than 6%. Joining of the nascent pieces is greatly retarded in T7 ts136-infected E. coli temperature sensitive polA mutants at 43 degrees C. These results suggest that gene 6 exonuclease plays a role in removal of the linked RNA during the discontinuous replication of T7 DNA.


Gene affecting longevity of messenger RNA: a mutant of Escherichia coli with altered mRNA stability.

We have screened 897 temperature sensitive growth mutants of E. coli for mutant strains showing longer mRNA half-life. The fate of pulse-labelled RNA was examined at 42 degrees C after cessation of RNA synthesis and with prior exposure to nonpermissive temperature (42 degrees C). Eight stains showed altered turnover of RNA (presumably mRNA), and further analysis on mutant strain JE15144 indicated that the stability of pulse-labeled RNA as well as of tryptophan (trp) mRNA increased four to seven fold over its parental strain at 42 degrees C. At 4 min or 10 min after addition of rifampicin, some 70 to 80% of polyribosome in the growing cells could still be conserved in JE15144 cultured at the nonpermissive temperature while little, if any, polyribosomes remained in its parental strain (PA3092) under the same condition. Two generation times were required for complete stoppage of growth of this mutant strain after shifting to 42 degrees C, and protein synthesis continued at a significant, but slightly reduced, rate at 42 degrees C. However, functional decay of mRNA in the mutant strain, with respect to the capacity for producing peptides, appeared to be similar to the parent strain, with half-lives of 3.5 min in PA3092 and 4.7 min in JE15144.


Prophage induction in Escherichia coli K12 cells deficient in DNA polymerase I.

The induction of prophage lambda by ultraviolet light has been measured in E. coli K12 lysogenic cells deficient in DNA polymerase I. The efficiency of the induction process was greater in polA1 polC(dnaE) double mutants incubated at the temperature that blocks DNA replication than in polA+ polC single mutants. Similarly, the polA1 mutation sensitized tif-promoted lysogenic induction in a polA1 tif strain at 42 degrees. In strains bearing the polA12 mutation, which growth normally at 30 degrees, induction of the prophage occurred after the shift to 42 degrees. It is concluded that dissapearance of the DNA polymerase I activity leads to changes in DNA replication that are able, per se, trigger the prophage induction process.


Insertion of the tetracycline resistance translocation unit Tn10 in the lac operon of Escherichia coli K12.

The majority of TN10 insertions in the lacZ gene of Escherichia coli occurred in a small region of the promoter distal part of the gene. The resulting mutations were polar on lacY and reverted to Lac+ at a frequency of 10(-8). None of the revertants were Tcr. Furthermore Lac+ Tcr revertants could not be selected directly. Relief of polarity revertants of the lacZ::Tn10 mutants were formed at a frequency of 10(-5) - 10(-4). Most resulted from a deletion event internal to the transposon which removed the Tcr genes and the putative transcription terminator. It is postulated that a fragment of Tn10 remains at the original insertion point to cause a revertible Lac- mutation.


Synthesis of ribosomal proteins in merodiploid strains and in minicells of Escherichia coli.

Merodiploid strains of Escherichia coli containing episomes which carry one or several of the ribosomal protein (r-protein) transcriptional units were analysed to see whether the increase in the number of gene copies leads to an increased synthesis of the respective r-proteins. It was found that the amount of ribosomal proteins was (with the only exception of ribosomal protein S20) independent of the number of gene copies present. The comparison of the in vivo stability of r-proteins in haploid and merodiploid strains did not, within the time resolution of the experiment, provide any evidence for an increased rate of degradation of those proteins coded by more than one gene copy. These results indicate a tight coupling between the amount of ribosomal proteins synthesized and the level required irrespective of the number of gene copies present. With the aid of minicells from a strain containing the episome F'101 which carries the thr-leu segment of the chromosome it was demonstrated that (i) in vivo synthesis of r-protein S20 could proceed in the absence of the synthesis of ribosomal RNA and of other r-proteins, and (ii) r-protein S20 was degraded under conditions where it was not assembled into ribosomes.


Antimutagens against mutT.

In E. coli strain 91P containing the mutator gene mutT-, caffeine, spermine and quinacrine, but not guanosine, act as antimutagens, reducing the frequencies of mutation from ara- leads to Ara.


Stimulation of cell division by T4 infection in Escherichia coli dnaEts at nonpermissive temperature.

Filamentous cells resulting from growth of a dnaEts mutant of Escherichia coli at high temperature were stimulated to divide by infection with bacteriophage T4. The effect appears to be related to T4 DNA synthesis; no increase in cell number took place in chloramphenicol-treated. T4-infected cells nor in cells infected with DNA synthesis-less mutants of T4. The ability of cells to divide after T4 infection was dependent on the length of time that the cells had been grown at 42 degrees C, indicating that a potential for cell division accumulates during preincubation.


Analysis of mitochondrial ribosomal proteins of Saccharomyces cerevisiae by two dimensional polyacrylamide gel electrophoresis.

Proteins from mitochondrial ribosomes of Saccharomyces cerevisiae were analysed by a two dimensional gel electrophoresis method. Each ribosomal subunit revealed a reproducible characteristic pattern of protein components. The 37S small subunit contained 33 protein species with an average molecular weight of 27,300 daltons (ranging from 60,000 to 95000 daltons). The 50S large subunit showed 38 protein species with an average molecular weight of 23,000 (ranging from 41,000 to 10,000 daltons). Ribosomes from various sources were compared on the basis of protein composition.


On the formation of rho- petites in yeast. II. Effects of mutation tsm-8 on mitochondrial functions and rho-factor stability in Saccharomyces cerevisiae.

1. In non-fermentable substrates growth of mutant tsm-8 cells of Saccharomyces cerevisiae is restricted to about one generation after shift from 23 to 35 degrees C. Non-permissive conditions (35 degrees C, glycerol) cause a gradual decrease in respiration to about 20% of the activity at permissive temperature 23 degrees C). 2. Anaerobically grown and glucose-repressed mutant cells exhibit a decreased adaptation rate of mitochondrial functions to aerobic growth and non-fermentative growth, even at 23 degrees C, as revealed by determination of respiratory rates and mitochondrial protein synthesis. 3. At 35 degrees C, rho+ cells of mutant tsm-8 are converted to p- cells within 6-8 generations of growth, in all fermentable substrates tested. Drugs or antibiotics as nalidixic acid, acriflavin, chloramphenicol and erythromycin, bongkrecic acid, antimycin and FCCP, as well as anaerobiosis, have little or no influence on this kinetics. A heat shock does not yield rho- petites to a significant  extent. 4. Reversion of tsm-8 cells to wild type function, which occurs spontaneously with a frequency of 10(-8), is found to be due to a mitochondrial mutational event.


Regulation of the intracellular concentration of T4 induced tRNA.

We have studied the biosynthesis of T4 induced tRNA's upon infection of E. coli BE cells in low phosphate (l.p.) medium (10(-4) M PO---4). Under out experimental conditions the onset of phage DNA synthesis occurs about 15 min after infection, while the first intracellular phage appears one hour later. Amounts of newly synthesized DNA and phage burst size are equivalent to the values obtained in standard (M9) medium (10(-1) M PO---4). We present evidence that the synthesis of mature tRNA's and of at least one dimeric precursor drastically declines 20 min after infection. In addition we show that T4 induced tRNA molecules are stable and that the triphosphate nucleoside precursor pool does not change significantly during infection. Therefore we conclude that T4 induce tRNA molecules behave similarly to other early gene products.


Transcription of the argF and argI genes of the arginine biosynthetic regulon of Escherichia coli K12, performed in vitro.

The cell-free transcription of the argF and argI genes of the arginine biosynthetic regions is described using an S-30 system capable of coupled in vitro transcription-translation. Template DNA isolated from two independently isolated arginine transducing phages was used in this work. Steady state mRNA synthesis was observed which was attributed to RNAase degradation. Regulation of argF mRNA synthesis, directed by the argF gene carried on the specialized transducing phage phi80dargF is effected to the extent of at least 95% by the arginine holorepressor at the transcriptional stage and at least 80% of the regulation of the expression of the argI gene is mediated at the transcriptional stage. Evidence is presented which indicates that the arginine holorepressor prevents RNA polymerase from binding to the arginine promoter and suggests that the operator and promoter sites may overlap.


Genetic studies of hybrids between coliphage lambda and salmonella phage P22: genetic analysis of the P22-lambda hybrid class.

P22-lambda hybrids which retain the protein coat of P22 have been isolated and characterized into two types. Type 1 hybrids which have the c through O-P genes of lambda are unable to grow lytically on Salmonella typhimurium. On the other hand, type 2 hybrids which contain only the c region of lambda, plated on S. typhimurium. Both hybrid types retained the generalized transducing and antigenic conversion capabilities of P22.


Function of the tof gene product in modifying chemical stability of trp messenger RNA synthesized from the PL promoter of lambda trp phage.

The trp operon translocated into the early region of phage lambda can be transcribed under the control of two promoters, the authentic trp promoter (Ptrptrp mRNA) and the PL promoter of the N gene (PLtrp mRNA) (Imamoto and Tani, 1972; Ihara and Imamoto, 1976a). PLtrp mRNA is stabilized with time after infection: at early times after infection chemical degradation of PLtrp mRNA is two-fold slower than for Ptrptrp mRNA, while at later times the stabilization of PLtrp mRNA is almost total. The stabilization of PLtrp mRNA is markedly reduced when the activity of the tof gene product is low due to a missense mutation of the tof gene. In contrast there is no significant reduction in stabilization when N function is lost by an amber mutation. On the basis of these and other experiments with lambdatrp susN7 tof12 phage, it is inferred that stabilization of the PLtrp mRNA is brought about by a modification of the "decay trigger", at least in part by the protein product of the tof gene.


Directed integration of an F' plasmid by integrative suppression: isolation of plaque forming lambda transducing phage for the dnaC gene.

A new approach for isolation of a plaque forming lambda specialized transducing phage is described. It consists of directed transposition of an F' plasmid into the gal region of a dnaAts galE- Escherichia coli strain by integrative suppression and deletion of the chlD region in order to shorten the distance between the marker of interest on the F' and the prophage serving to prepare an LFT1 lysate. An F' danC+thr+ plasmid was used here and lambdadthr and lambdaddnaC phages were isolated. In addition, lambdapdnaC was obtained from a double lysogen for lambdaddnaC and lambda b2.


Relation between F, R1, R100 and R144 Escherichia coli K-12 donor strains in mating.

E. coli K-12 recipient mutants defective in conjugation with a F donor (ConF- mutants) were tested for recipient ability with donor strains carrying a R1drd19, R100-1 or R144drd3 plasmid. It appeared from these tests that F and R1 donor strains are closely related in mating in that they both, unlike the R100 and R144 donor, use the recipient outer membrane protein pOmpA for the initial steps of the mating process. The isolation of recipient mutants defective in conjugation with a R100 donor (ConR100- mutants) yielded some mutants that were defective in crosses with F, R1 and R100 donors. This result was taken as evidence that F, R1 and R100 donors share some property in their mating interaction with E. coli K-12 recipient strains. A R144 donor is completely different from F, R1 and R100 donors in initial mating interactions with a recipient.


Multiple effects of an RNA polymerase beta' mutation on in vitro transcription.

S. tyrphimurium strain BY324 is temperature sensitive due to a mutation (rpo C32) in the gene for the RNA polymerase beta' subunit. Transcription of T7 DNA by RNA polymerase purified from this strain is temperature sensitive in vitro. The enzyme is slightly defective in template binding and RNA chain initiation, but the major defect is in RNA chain elongation. The rate of RNA chain elongation is reduced 4-5 fold relative to wild-type. RNA chain termination does not appear to be affected by the beta' mutation. While the elongation defect is suppressed by glycerol or dimethylsulfoxide, the initiation defect is not. Possible roles for the beta' subunit in enzyme function are discussed in light of these results.


The frequency of P1 transduction of the genes of Escherichia coli as a function of chromosomal position: preferential transduction of the origin of replication.

The frequencies with which the generalized transducing phage P1 transduced 26 selected markers on the E. coli. chromosome were measured. The frequencies were found to vary relative to argH+ = 1 from a maximum of 6.8 near the origin of replication to a minimum of 0.23 for a marker not far from the terminus. The low frequencies obtained for some markers were shown not to result from poor expression under the selective conditions employed. When plotted as a function of marker position on the chromosome the frequencies were found to exhibit a series of peaks and troughs which correspond to those in gene density noted by Bachmann et al. (1976). The possible relationship of these results to the structure of the E. coli chromosome and to the mechanism of generalized transduction are discussed.


Transformation of Escherichia coli by a specific DNA restriction fragment.

Specific transformation of a rifampicin sensitive strain of Escherichia coli to rifampicin resistance has been performed by a single, defined DNA restriction fragment carrying the genetic information for the beta subunit of E. coli RNA polymerase. In this transformation the transforming genetic character has been substituted for the corresponding recipient gene locus by recombination. The value of the described transformation system for locating genetic markers on DNA restriction fragments is discussed in comparison to previously reported in vitro systems.


Regulation of the dnaA product in Escherichia coli.

When an E. coli mutant (CRT46, dnaA46), thermosensitive in the initiation of DNA replication, grows at intermediate temperatures its DNA/mass ratio is somewhat lower than normal, but the cells possess an excess of initiation capacity, which can be expressed in the absence of protein synthesis and lead to the accumulation of anomalously high amounts of DNA. A shift-up in temperature causes inhibition of initiation, and at the same time the production of initiation capacity is accelerated. After a shift-down in temperature initiation is released but the production of capacity is inhibited. The initiation capacity is thermolabile. The simplest explanation of these observations is that the dnaA product has a dual role: a positive function as an initiator of replication and a negative control function in its own synthesis.


Identification of the sid outer membrane receptor protein in Salmonella typhimurium SL1027.

A protein of molecular weight 78,000 daltons, missing in albomycin and phage ES18 resistant mutants, has been identified in the outer membrane of Salmonella typhimurium SL1027. Mutants with a tonB like resistance and over production of outer membrane proteins due to iron shortage were also isolated. The mutation which leads to the protein deficiency maps in the sid gene region, the mutation related to overproduction of proteins maps near trp. Although the S. typhimurium and the E. coli protein mediate translocation of the iron complex ferrichrome and the structurally analogous antibiotic albomycin through the outer membrane no cross-reactivity exists in binding the phages T5, T1 and ES18 or colicin M.


Kinetics of induction of error-prone repair of bacteriophage lambda by temperature shift in an Escherichia coli dnaB mutant.

Preincubation at 42 degrees, before infection at permissive temperature by phage lambda, of an Escherichia coli dnaB mutant, provokes a significant increase in survival and mutagenesis of ultraviolet irradiated phage as well as mutagenesis of untreated phage. Similarly to UV irradiation and many chemical mutagens, the inhibition of DNA synthesis by temperature shift of this dnaB mutant induces SOS repair. This work shows that replication blockage in bacterial DNA is not only mutagenic for bacterial DNA itself (Witkin, 1975) but also for normally replicating lambda DNA, probably due to induction of diffusible products.


Regulation of hemoglobin synthesis during the development of the red cell (third of three parts).

In this article we have surveyed the current state of knowledge regarding the accumulation of globin mRNA and hemoglobin in red cells. We have attempted to examine the interplay of numerous processes that seem to be necessary to achieve this highly differentiated state. Finally, we have made an effort to formulate some of the mechanisms whereby individual red cells may come to contain varying proportions of specific hemoglobins. The past several years have been characterized by a veritable explosion of knowledge concerning the globin structure genes, and the structure, transcription, processing and function of globin mRNA in erythroid cells. It now seems possible to analyze the earlier stages of erythropoiesis by cultivation and examination of erythroid colonies in vitro. The primary differentiation events leading to the production of specific globins, especially for hemoglobin F production in man, are now experimentally accessible. There is good reason to hope that these advances will soon permit achievement of the long desired therapeutic goal of enhancing hemoglobin F synthesis in patients with  severe beta-chain hemoglobinopathies. Our aim has been to review the scientific information that might provide the rationable for amelioration of the clinical phenotypes in patients inheriting abnormal globin genes.


Effect of weight loss without salt restriction on the reduction of blood pressure in overweight hypertensive patients.

Overweight patients with uncomplicated essential hypertension were followed up biweekly for six months: 24 not receiving antihypertensive-drug therapy (Group I) and 83 on regular but inadequate (despite drug manipulation) antihypertensive-drug therapy (Group II). All patients in Group I and 57 randomly selected patients from group II (IIa) participated in a weight-reduction program. The remaining 26 from Group II (IIb) did not receive a dietary program. Salt intake was in the normal range in all three groups. All patients on the dietary program lost at least 3 kg (mean, 10.5 kg), and all but two showed a meaningful reduction in blood pressure; 75 per cent of Group I and 61 per cent of Group IIa returned to normal blood pressure. The weight and blood-pressure reductions were highly significant (P less than 0.001), were present in both sexes and all ages, and were directly associated. In Group IIb, no significant change in blood pressure or weight occurred (P greater than 0.30).


Serological studies on twelve species of Candida.

Two main types of immunological reactions are tested in twelve species of Candida. The agglutination reaction produces agglutination varying from +/-, or trace, to ++++ or .100 per cent agglutination. This is due to cross-reactions among the Candida and cannot be completely removed by adsorption. The precipitin reactions seem to give the most specific results, and most of the cross-reaction bands are adsorption-removable.


Generality of the functional structure of the neocortex.

The fundamental similarities between various neocortical areas are elaborated by pointing out the common principles of its afferent, intrinsic, and efferent organization, with special emphasis on the generality of thalamocortical circuits. Interareal differences in morphology and function can be considered as accidental, i.e., depending on the circuit in which a given cortical area is involved. The neocortex is a link in the chain of afferent-efferent signal processing, and can be understood as a cooperative network that acts as a nonlinear spatiotemporal filter with adaptive properties (memory) and that transforms afferent signal flow. It is assumed that these filter properties are identical for all neocortical areas. The functional role of a circumscribed cortical area depends exclusively on its position uithin a certain functional circuit and is defined by it.


[Biosynthesis and structure of the yeast fatty acid synthetase complex].

Genetic as well as biochemical data suggest that the yeast fatty-acid synthetase complex has an (AB)6 protein structure where A and B represent multifunctional polypeptide chains with molecular weights of 185000 and 180000 daltons, respectively. Subunit A contains at least 3 and subunit B4 of the 8 known biochemical functions of the multienzyme complex. It is concluded that this complex structure has evolved from the corresponding prokaryotic system of monofunctional enzymes due to a selective advantage regarding the biosynthesis and assembly of the complex components.


Effects of Escherichia coli lipopolysaccharide on renal glomerular and tubular adenylate cyclase.

The effects of Escherichia coli lipopolysaccharide (LPS) on adenylate cyclase have been tested using renal tubular membranes and renal glomeruli isolated from rats. E. Coli LPS did not stimulate glomerular and tubular basal adenylate cyclase activity whereas it was an activator in the presence of fluoride. The effect of E. Coli LPS was immediate but was greater after 20 min preincubation. Maximum stimulation of both glomerular and tubular fluoride sensitive adenylate cyclase occurred at 125 microgram/ml of E. Coli LPS with an apparent Km (dose corresponding to 50% of maximum stimulation) of 30 microgram/ml. Above 125 microgram/ml there was a decrease in adenylate cyclase activity. E. Coli LPS produced an increase in the maximum velocity of both enzymes but did not affect their affinity for adenosine triphosphate. E. Coli LPS did not potentiate the effect of parathyroid hormone on glomerular and tubular adenylate cyclase. The lipid A moiety which is common to all LPS whatever the original strain gave results similar to those obtained with the entire LPS. This effect was specific and did not depend on the phospholipidic structure in general since no activation was obtained in the presence of phosphatidylserine.


Psychotropic effects of carbamazepine in epilepsy: a double-blind comparison with phenytoin.

The "psychotropic" effects of carbamazepine were evaluated with phenytoin (Dilantin) as reference agent in a counterbalanced, crossover study. Forty adult epileptics were given a series of neuropsychologic tests and the MMPI after 4 months on each agent. Most abilities were much the same with either anticonvulsant, but there were fewer errors with carbamazepine on mental tasks requiring attention and problem solving, and some improvement in emotional status was suggested. The findings were consistent with patient reports of improvement in alertness and mental functioning. These results combine with the excellent anticonvulsant properties of carbamazepine to support its use as an anticonvulsant.


[Parietal cell vagotomy (PCV): the treatment of choice of duodenal ulcer].

Gastric resection or vagotomy plus drainage are not easy alternatives for the treatment of duodenal ulcer. More complications are met after resection, more relapses after vagotomy, whereas the postoperative sequelae are the same for both operations. Vagotomy of the parietal cells is designed to prevent all such sequelae by leaving the innervation of the antrum intact so that drainage can be omitted. Experience has so far shown that very few complications occur, whereas severe and slight dumping and diarrhoea are virtually eliminated. Gastric emptying times are slightly affected (a little longer for solids and a little quicker for fluids), but drainage in non-stenosing cases of duodenal ulcer is not necessary. The true average incidence of recurrences after this operation cannot yet be determined, since the results of the published series vary considerably. This may be due to the continuous progress being made in the development of the surgical technique. Random studies comparing this operation with other forms of duodenal management are urgently required. It is, of course, essential for surgeons practising the new operation must, as in the case of other delicate surgial procedures, to receive a proper training at specialised centres.


Nucleic acid metabolism of placenta and fetus.

The preceding résumé of placental nucleic acid metabolism indicates considerable changes in RNA and DNA during the course of pregnancy in both human and animal experiments. The presence of an active protein-synthesizing apparatus closely allied with DNA and RNA metabolism has been observed in placental preparations; future studies should reveal even more direct relationships. The specific regulatory role of nucleic acids in normal and abnormal placental function is still unknown. In truth, such specific regulatory or control mechanisms are generally unproved among the entire mammalian (eukaryotype) system. Progress in learning about placental function and control may require more detailed information regarding RNA metabolism from molecular biology. The regulatory control of fetal or intrauterine growth as it relates to nucleic acids remains even more obscure. One of the major drawbacks in this study has been our inability to label fetal tissues adequately during the major portion of the pregnancy. The problem is made even more complex by the many factors involved in intrauterine growth, such as blood volume, uterine blood supply, oxygen flow and transfer, hormonal effects, and nutritional status, in addition to nucleic acids.


Necrotizing fasciitis in postpartum patients. A report of four cases.

Necrotizing fascitis is a rare but rapidly progressive soft tissue infection not previously reported in an obstetric patient. Since cure is dependent on rapid recognition and early surgical intervention, 4 cases are reported herein, the bacteriology discussed, and the literature reviewed.


Ectopic pregnancy in kidney transplant patients. A diagnostic challenge.

Two cases are presented which illustrate the diagnostic dilemma encountered when ectopic pregnancy occurs in renal allograft recipients. A plan of management is outlined for this situation.


Hydrops fetales and congenital toxoplasmosis. Value of direct immunofluorescence test.

Congenital toxoplasmosis is sometimes difficult to diagnose clinically and histologically, since it can present in diversified forms. The present report deals with a rare type of toxoplasma infection that resulted in a stillborn with hydrops fetales and extensive fetal placental calcification. The direct toxoplasma immunofluorescence test was of great value in the diagnosis.


Histologic fate of tympanic membrane and ossicle homografts.

1. The biologic behavior and usefulness of homologous incus grafts preserved in Cialit compare favorably with that of ossicular autografts. 2. Reconstruction of the transplanted incus correlates with the period of its immersion in preservative: the briefer the period of exposure to fixative, the more rapidly resorption and substitution occur. The longer the preservation time, the slower the rate of incus transplant reconstruction. 3. The preserved heterograft bone chip is unsuitable, since it disintegrates completely irrespective of the duration of its preservation. 4. The configuration of all bone chips is extensively altered after implantation. Autograft and homograft bone chips are both poorly tolerated. Chemical fixation does not alter this reaction. Fragments are shortened, softened, and rounded off. Heterologous bone chips are completely resorbed.


Comparison of homograft preservation techniques.

Much practical experience with homograft materials has been gained in cardiac surgery, vascular surgery, orthopedics, plastic surgery, ophthalmology, and otology; and a fair amount is known about the morphological and histological consequences of the use of these materials. There are still arrears in chemical engineering in otology, but construction of better bioprostheses may become possible in the long run. Empirical data indicate that until that time the use of mercury salts and 70 per cent alcohol will remain the preservation techniques of choice in otology.