Obesity in schoolchildren and their parents. The height, weight and left triceps skinfold thickness of 2190 schoolchildren were measured and the heights and weights of their parents obtained from a postal questionnaire. Power-type obesity indices were used to correct weight for height in parents and children. Preliminary analysis of the distribution of obesity using arbitrarily chosen cut-off points to define the obese, normal and lean parent indicated the presence of a group of 'super-obese' families. The spline technique was used to analyse these data as continuous variables, and showed that the 'super-obese' group of families was too small to be of any practical importance. The relationship between obesity in parents and their children has also been investigated using the spline regression technique. The results show that the relationship is linear but that only 6% of the total variation of observed obesity in children is attributable to variation in the parents' reported obesity. However, a structural analysis indicates a direct relationship between obesity of parents and children. This is obscured in the regression analysis by the large within-subject variability of observed obesity in both parents and children.


Cerebral infarcts with arterial occlusion in neonates. Among 592 infants examined at autopsy during a four-year period, 32 (5.4%) had cerebral infarcts. Excluded were cases of traumatic hemorrhages and softening, periventricular leukomalacia, venous lesions, and any mass, including encephaloceles, with arterial distortion and infarction. Histological abnormalities were similar to those of infarcts in adults. Relatively advanced histopathological changes in some infants living only a few hours indicated that some infarctions may have occured in utero. The most common cause of arterial occlusion was embolization, with sepsis and disseminated intravascular coagulation playing a major role. The brains of term neonates were more frequently involved than those of premature infants. Multiple small infarcts occurred more often in premature infants. In most cases autonomic dysfunction with prolonged apnea, episodic seizures, and metabolic acidosis were the major associated clinical features, rather than focal neurological deficits. Similar cerebral infarcts in infants who survive with less severe systemic complications may lead to porencephaly, hemiplegia, mental and motor retardation, and recurrent seizures.


Weight at menarche in deaf girls.

Weight at menarche in deaf girls. Weight at menarche of a mixed longitudinal sample of deaf American girls was analysed with regard to its variability and association with their earlier than normal age at menarche. The 'critical weight' hypothesis of Frisch and Revelle (1970, 1971) specifies the attainment of a certain body weight necessary for the onset of menstruation with a concomitant reduction in its variability. The findings herein suggest this hypothesis is not applicable to deaf girls.


Clinical correlations of CT scan-detected calcifications of the basal ganglia. A review of CT scans of 7,081 patients demonstrated calcifications of the basal ganglia in 53. The calcifications were evident in the skull roentgenograms of only 4 patients out of 40 in whom both CT scans and plain roentgenograms were available, demonstrating the superior resolution of this new method. Seventy-five percent of the patients were older than 50 years of age. Of the younger patients, 5 had had prior cranial irradiation; 1 had received cranial irradiation and intrathecal methotrexate therapy for meningeal leukemia; and 2 others had deep-seated arteriovenous malformations. Serum concentrations of calcium and phosphorus were normal in all 46 patients in whom they were measured. We conclude that the detection of small calcifications of the basal ganglia in persons above 50 years of age is infrequently associated with either clinical signs of basal ganglia dysfunction or calcium and phosphorus abnormalities. Calcium deposition in these patients may be related to vascular changes associated with aging. In younger patients a specific pathogenetic factor or underlying process is infrequently found.


Central nervous system maturation in the stressed premature. The developmental sequence of sleep cycles has been found to be a useful index of central nervous system maturation in premature infants. To determine the effects of severe reversible stress on the maturation of sleep cycles, 6- to 8-hour sleep studies were done on 10 premature infants with severe hyaline membrane disease (HMD) and 10 healthy premature babies. The studies were done in the neonatal intensive care unit and included patients from 30 weeks' gestation to term and in all stages of the disease. Prior studies were confirmed showing that percentage of quiet sleep increases, transitional sleep changes little, and active sleep decreases from 30 weeks' gestation to term. In infants with severe HMD, the percentage of quiet sleep was less and active sleep higher than in unstressed infants of similar age who acted as controls. Once the infants recovered from HMD, sleep patterns became similar to those found in the control group. These data suggest that when respiratory distress occurs in the premature infant, there is a transient delay in central nervous system maturation as measured by sleep cycle analysis.


Maternal age, dizygotic twinning rates and age at menopause. The dizygotic (DZ) twinning rate declines after about maternal age 38 in Caucasian populations. Bulmer (1970) offered the explanation that waning ovarian function causes a decline in rates of double ovulation in originally twin-prone women. The present note suggests that some small part of the decline is caused by the earlier cessation of ovulation altogether in these women (presumably also as a result of waning ovarian function).


Subarachnoid spread of ependymoma: diagnosis and evaluation of therapy by computerized tomography. The potential of ependymomas to spread throughout the intracranial subarachnoid space is well documented, though the incidence is disputed. This relates in part to the time required for such metastases to produce symptoms. The diagnosis of such spread, however, is important for therapeutic management. This report demonstrates the effectiveness of computerized tomography in diagnosing spread of ependymoma throughout the basal cisterns and cerebral fissures.


A method for detecting errors in data of growth studies. The paper describes a new method used for data cleaning in growth and development studies. The method is essentially based on the assumption that an extreme value of a certain variable might be suspicious if other highly correlated variables show low compatibility with it and that, on the other hand, an extreme but possible value tends not to be erroneous if it is reinforced by another extreme but possible value of a highly correlated variable. Each variable was therefore included in at least two ratios with the highest correlated variables. A program was designed to detect extreme values of individual variables and extreme ratio values. This procedure with ratios was used to help to detect possible errors and discriminate them from true extreme values. Seen in the light of corrected data files against existing data files, the number of corrections was approximately 4.4%. If the real number of corrected errors is compared to the total number of subjects, this percentage reached 5.5%. If, when correcting, the real value was not detected with certainty, the erroneous value was then simply deleted. From our results, there is reason to believe that with this method few detectable errors will escape from the cleaning procedure. Conclusions for future correction procedures and for future growth studies in general, are also given in the paper.


Ventilatory capacity among highland Bods: a possible adaptive mechanism at high altitude. Ventilatory capacity (forced vital capacity, forced expiratory volume and maximal voluntary ventilation) among Highland Bods (3514 m altitude) was higher than in an ethnically similar population residing at a lower altitude in Kulu Valley (1500--2200 m). Increased ventilatory capacity appears to have developed among native highlanders as a consequence of a biological response to high altitude. Numerous factors such as low oxygen pressure, increased work-load and minimal air pollution may explain these findings.


Rifampin plus trimethoprim: bactericidal activity and suppression of resistance in human urine in vitro. The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine. Drug concentrations used were similar to those attainable in human urine. The combination was more effective than the individual drugs and than a combination of Tmp plus sulfamethoxazole (Smx). Tmp was bactericidal in urine and blocked the emergence of Ramp-resistant bacteria. Ramp was responsible for most of the bactericidal action of the combination but also potentiated the bactericidal activity of Tmp. Ramp suppressed the selection of thy- (Tmp-resistant) bacteria. Under the experimental conditions, Smx+Tmp was not more bactericidal than Tmp alone for most of the test organisms, despite strong synergy between the two at subinhibitory concentrations.


Gentamicin antibacterial activity in the presence of human polymorphonuclear leukocytes. Complete protection of Staphylococcus aureus Wood 46 from gentamicin bactericidal activity was documented for microorganisms located within polymorphonuclear leukocytes. The highest, still ineffective gentamicin concentration tested in the phagocytic assay was 80 times higher than the minimal concentration required to kill uningested organisms. Extracellular gentamicin activity was unaffected by the phagocytic process as demonstrated by microbiological and enzymatic assays, and liberation of intracellular S. aureus by lysis of neutrophils showed the bacteria to be fully susceptible to the antibiotic. These results were corroborated by studies performed with [14C]gentamicin; binding of the labeled antibiotic by resting neutrophils, or by neutrophils ingesting live, killed S. aureus or endotoxin-coated paraffin particles, showed no statistical differences and never exceeded 20% of the extracellular concentration. These results show that intraleukocytic S. aureus are protected from the bactericidal action of gentamicin and suggest that this protection can be explained by poor intracellular penetration of the antibiotic.


Bactericidal effect of combinations of antimicrobial drugs and antineoplastic antibiotics against gram-negative bacilli. Six antineoplastic antibiotics showed little antibacterial activity against 28 strains of four species of gram-negative enteric bacteria. By using the cellophane transfer technique, combinations of these agents with 16 antibacterial drugs usually showed indifference. However, combinations of mitomycin C, especially with the aminoglycosides, were synergistic on strains of Escherichia coli, Proteus, and Klebsiella pneumoniae. Bleomycin, on the other hand, often showed antagonism on strains of E. coli and K. pneumoniae with the beta-lactams, aminoglycosides, and other antibacterial agents. Checkerboard titrations and kinetic killing curves confirmed these findings.


Bronchial secretion levels of amikacin.

Bronchial secretion levels of amikacin. Amikacin was given to 14 noninfected men as three consecutive intramuscular injections (7.5 mg/kg) at 12-h intervals. Serum and bronchial secretion specimens were obtained at various times during flexible fiberoptic bronchoscopy after the final dose. Serum and bronchial secretion concentrations obtained between 1.5 and 2.0 h after the final dose ranged from 17 to 40 mug/ml and 2.3 to 8.4 mug/ml with a mean of 23.7 +/- 2.9 and 5.23 +/- 1.5 mug/ml, +/-1 standard error of the mean, respectively. The highest bronchial secretion concentration in each subject correlated with the highest serum concentration (r = 0.83, P < 0.001), and all concurrent serum and bronchial secretion concentrations demonstrated a significant correlation (r = 0.82, P < 0.001). Clearance occurred at the same rate (half-life serum = 2.84 h; half-life of bronchial secretion = 2.60 h, P > 0.5). The mean bronchial secretion concentration of the 15 specimens obtained more than 7 h after the final dose was less than 1.0 mug/ml, with a range from 0.3 to 1.6 mug/ml. It is concluded that amikacin may achieve minimal inhibitory concentrations for many gram-negative bacteria in the bronchial secretions of noninfected patients 1 to 2 h after the final dose. However, levels fall below the reported minimal inhibitory concentrations against negative bacteria 6 to 7 h after the final dose. Furthermore, bronchial secretion levels may never reach the minimal inhibitory concentration against Pseudomonas aeruginosa.


Effects of interferon and adenine arabinoside treatment of hepatitis B virus infection on cellular immune responses. Fifteen patients with chronic hepatitis B were treated with adenine arabinoside (Ara-A) or human leukocyte interferon (HLI). Cellular immune response to hepatitis B virus surface antigen and antigens prepared from herpes simplex virus, varicella zoster virus, and cytomegalovirus was measured by a lymphocyte blast transformation assay and an assay for interferon production. Measurements were made before, during, and after antiviral treatment. Unlike patients convalescing from acute hepatitis B, only 2 of 15 patients with chronic hepatitis B had significant blast transformation to hepatitis B surface antigen. One such response occurred during the pretreatment period of HLI therapy, and the other was in a patient undergoing low-dose (<10(5) U/kg per day) HLI therapy. Mononuclear cell cultures were tested for interferon production in the presence of hepatitis B surface antigen. Cells from only 1 of 15 patients produced detectable levels of interferon. In contrast, all of these patients had normal cellular immune responses to herpesvirus antigens. Transformation responses to herpes antigens decreased three- to fivefold after patients were treated with >10(5) U of HLI per kg per day. Antiviral therapy with <10(5) U of HLI per kg per day or Ara-A did not produce a detectable depression of transformation response. Ara-A produced marked lymphocytopenia and a marked lymphocyte fragility after 5 or more days of therapy. In vitro Ara-A was toxic to lymphocytes at concentrations as low as 0.5 mug/ml. These changes in lymphocyte parameters may affect the outcome of antiviral therapy.


Pharmacokinetics of intravenous piperacillin in patients undergoing chronic hemodialysis. The pharmacokinetic properties of piperacillin, a piperazine derivative of ampicillin, were determined in seven patients with creatinine clearances less than 7 ml/min who were undergoing chronic, intermittent hemodialysis. A two-compartment linear model was used to analyze the data. Mean elimination half-life was 1.26 +/- 0.1 h; the mean elimination constant was 0.95 +/- 0.08 h-1; the mean volume of distribution was 0.16 +/- 0.02 liters/kg of body weight; the mean volume of the central compartment was 0.10 +/- 0.01 liters/kg of body weight; and the mean clearance was 0.09 +/- 0.01 liters/h per kg of body weight. Mean elimination half-life while off dialysis of 2.1 h.


Antibacterial activities, nephrotoxicity, and ototoxicity of a new aminoglycoside, Win 42122-2. Win 42122-2 is a new aminoglycoside antibiotic obtained from a mutant strain of Micromonospora purpurea. In vitro and in vivo comparisons of Win 42122-2 with gentamicin and amikacin revealed that Win 42122-2 generally was less active than gentamicin against Pseudomonas and many Enterobacteriacae, especially Klebsiella and indole-negative Proteus. Against most gentamicin-susceptible isolates, Win 42122-2 was more active than amikacin. Gentamicin-resistant clinical isolates were usually resistant to Win 42122-2, although it was active against certain gentamicin-resistant organisms, depending upon the aminoglycoside-modifying enzymes harbored by the organism. However, Win 42122-2 was markedly less toxic than gentamicin in subacute nephrotoxicity studies in rats, ototoxicity experiments in guinea pigs, and ataxia determinations in cats. This series of antibacterial determinations and toxicity evaluations indicated that the reduced toxicity of the antibiotic may be sufficient to provide an improved therapeutic ratio over gentamicin and other aminoglycosides, even though Win 42122-2 is less potent than gentamicin against some bacteria.


Fortimicin A: collaborative in vitro susceptibility. Comparison with amikacin and gentamicin against 11,840 clinical bacterial isolates. The susceptibility of 11,840 clinical bacterial isolates to fortimicin A was determined by agar dilution or broth microdilution methods and compared with their susceptibility to amikacin and gentamicin. In general, the in vitro activity of fortimicin A was essentially the same as that of amikacin. Significant exceptions were the increased effectiveness of fortimicin A against Serratia marcescens and the greater activity of amikacin against Pseudomonas and other nonfermentative gram-negative bacilli. On a weight-for-weight basis, gentamicin showed greater activity than the other two antimicrobial drugs against most species; S. Marcescens was the major exception. However, at concentrations equivalent to achievable nontoxic serum levels, the proportion of isolates inhibited by the three drugs was quite comparable. There were several strains with unusually high resistance to one or more of the tested antibiotics. These usually occurred in one of the six participating institutions and could be traced to specific enzyme-producing or permeability mutants endemic to that particular institution.


Amikacin pharmacokinetics in pediatric patients with malignancy. The pharmacokinetics of amikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and normal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 min produced concentrations in serum of 29.3 +/- 5.7 micrograms/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 +/- 1.7 micrograms/ml and at 6 h of 1.2 +/- 0.3 microgram/ml. The serum half-life was 1.24 +/- 0.09 h, volume of distribution was 0.26 +/- 0.02 liter/kg, and total body clearance rate was 131 +/- 10 ml/min per 1.73 m2. No accumulation of amikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.


Susceptibility of Pseudomonas maltophilia to antimicrobial agents, singly and in combination. Pseudomonas maltophilia is resistant to most of the commonly used antimicrobial agents including those active against Pseudomonas aeruginosa. The susceptibility of 14 clinical isolates of P. Maltophilia to 18 antimicrobial agents was determined by broth dilution testing. All organisms were susceptible to trimethoprim-sulfamethoxazole (TMP-SMZ), minocycline, and LY127935. A total of 87 and 79% of the organisms were susceptible in vitro to colistin and chloramphenicol, respectively. With the exception of sisomicin, the organisms were resistant to the aminoglycosides. Of 21 combinations of antimicrobials examined for synergy, only the combination of TMP-SMZ with carbenicillin was consistently (86%) synergistic in vitro. Supplementation of the testing media with calcium and magnesium increased the minimal inhibitory concentrations for the aminoglycosides, the penicillins, and TMP-SMZ against P. maltophilia.


Chlorhexidine as an effective agent against Chlamydia trachomatis in vitro and in vivo. In a small field trial, chlorhexidine (50 micrograms/ml) was as effective against clinical trachoma as topical tetracyclines or oral co-trimoxazole; in vitro, 2.5 micrograms/ml was chlamydicidal.


Evaluation of gentamicin and penicillin as a synergistic combination in experimental murine listeriosis. The administration of a combination of penicillin and gentamicin to mice given an intraperitoneal challenge of a highly pathogenic strain of Listeria monocytogenes resulted in increased survival as compared with groups receiving penicillin alone or gentamicin alone or a control group that received no antibiotic. The median survival of animals that eventually died was no longer than in groups receiving single antibiotics and suggests that additional studies should be carried out to further investigate the possibility of synergism in animal models.


In vitro activity of LY127935, a new 1-oxa cephalosporin, against aerobic gram-negative bacilli. A total of 434 clinical aerobic gram-negative bacillary isolates were tested against LY127935, a new 1-oxa cephalosporin, and compared with other cephalosporins, penicillins, and aminoglycosides by a broth microdilution technique. Cefotaxime (HR756), a new semisynthetic cephalosporin, and LY127935 were more active, and showed lower minimum inhibitory concentrations (ranges, less than or equal to 0.12 to 2.0 micrograms/ml), than cefamandole, cefoxitin, and cefazolin against Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus mirabilis, indole-positive Proteus spp., Serratia marcescens, Providencia spp., and Citrobacter spp. Against P. aeruginosa, pepercillin, azlocillin, and mezlocillin were the most active beta-lactam agents; 64 micrograms/ml inhibited 99, 93, and 87% of the isolates, respectively. LY127935 and cefotaxime at 16 micrograms/ml inhibited 71% of Pseudomonas isolates, whereas the aminoglycosides gentamicin, tobramycin, and amikacin at a concentration of 4 micrograms/ml inhibited 84, 88, and 93%, respectively. Minimum bactericidal concentrations were determined for all isolates and were generally the same as the minimum inhibitory concentrations.


Effect of cefamandole nafate on blood coagulation and platelet function. Platelet function and coagulation were tested after brief in vivo exposure to cefamandole nafate and in the presence of various concentrations of the drug in vitro. Alterations in hemostatic function were observed only with exposure to drug concentrations severalfold higher than those expected to prevail clinically.


Stimulation of L-asparate beta-decarboxylase formation by L-glutamate in Pseudomonas dacunhae and Improved production of L-alanine. The formation of L-asparate beta-decarboxylase by Pseudomonas dacunhae was compared on media containing a variety of organic acids and amino acids as a carbon source. Although the enzyme was formed constitutively when the organism was grown on basal medium or on that containing tricarboxylic acid cycle intermediates, it was induced twofold by L-glutamate and repressed one-tenth by L-serine. L-Glutamine, L-proline, L-leucine, glycine, and L-threonine also showed induction effects lower than that of L-glutamate. L-Glutamate derepressed the serine effect. This glutamate effect was observed effect was observed with other microoganisms, e.g., Achromobacter pestifer and Achromobacter liquidum. Since the intermediates from L-glutamate metabolism had no effect, this induction effect was specific to L-glutamate. The formation of some glutamate-related enzymes was measured and is discussed in relation to the formation of L-asparate beta-decarboxylase. L-Asparate beta-decarboxylase was purified to an electrophoretically homogenous state from L-glutamate-grown cells of P. dacunhae, and some properties were compared with those of the enzyme from fumarate-grown cells. The two enzymes were identical in disc electrophoresis, molecular weight, and some enzymatic properties. The industrial production of L-alanine from L-aspartic acid acid was improved by using the culture broth with highly induced L-asparate beta-decarboxylase (9.4 U/ml of broth).


Specificity of bacteriolytic enzyme II from a soil amoeba, Hartmannella glebae. Two bacteriolytic enzymes were produced when Hartmanella glebae was grown in the presence of both Enterobacter aerogenes and Alcaligenes faecalis. The identification of enzyme I as N-acetylmuramidase was reported earlier. Enzyme II was purified by gel filtration on a Bio-Gel A column. A recovery of 68.76% with 72.3-fold purification was obtained. It was found that 5 and 10 mM MgCl2 significantly increased the bacteriolytic activity. It is a basic protein. The cell walls of Micrococcus lysodeikticus were lysed by the enzyme, and the products of digestion were purified by Amberlite CG-120 and Sephadex G-15 chromatography to facilitate the detection of amino sugars. After reduction of the oligosaccharides with sodium borohydride and acid hydrolysis, the amino sugars were identified by paper chromatography. It was found that enzyme II cleaved the glycosidic bond between N-acetylmuramic and and N-acetylglucosamine of the peptidoglycan moiety of the cell walls. Thus, the enzyme was identified as endo-beta-N-acetylmuramidase.


Catabolism of 5-chlorosalicylate by a Bacillus isolated from the Mississippi River. A strain of Bacillus brevis isolated from a polluted section of the Mississippi River was shown to utilize 5-chloro-2-hydroxybenzoate (5-chlorosalicylate) as a sale source of carbon and energy. Enzymic analyses of cell-free extracts prepared from 5-chlorosalicylate-grown cells demonstrated that the initial step in the pathway involved cleavage of the aromatic ring between C1 and C2 by a specific 5-chlorosalicylate 1,2-dioxygenase. Loss of chloride from the growth substrate occurred after ring fission and was probably enzyme mediated. An intermediate chlorolactone apparently lost chloride by enzymatic hydrolysis with formation of maleylpyruvate. Maleylpyruvate was further degraded by both glutathione-dependent and glutathione-independent mechanisms, with these reactions being identical to the terminal reactions of the gentisate pathway. It was suggested that this novel 5-chlorosalicylate pathway may have evolved by recruitment of enzymes from an ancestral gentisate pathway.


Catalase activity during the recovery of heat-stressed Staphylococcus aureus MF-31. Sublethal heating of Staphylococcus aureus produced little loss of catalase activity, but incubation of the injured cells in tryptic soy broth, with or without 10% NaCl added, produced an 85% decrease in catalase activity. Cells recovered in tryptic soy broth demonstrated increases in catalase levels after approximately 5 h, whereas in tryptic soy broth with 10% NaCl the levels remained low for at least 12 h. Thus, the loss of catalase activity during the recovery period was greater than during the heat treatment.


Enterobacteriaceae isolated from iguanid lizards of west-central Texas. The prevalence of members of the family Enterobacteriaceae in the intestines of seven species of iguanid lizards native to west-central Texas was determined. Of the 67 lizard specimens examined, 48.7% were infected with Salmonella and 9% were infected with Salmonella arizonae. Two lizard species (Sceloporus olivaceus and Crotaphytus collaris) were shown to have a 100% prevalence of Salmonella.


Characteristic gamma-lactone odor production of the genus Pityrosporum. Mass spectrometric-gas chromatographic analysis of culture headspaces revealed that members of the genous Pityrosporum produce volatile gamma-lactones during growth on lipid-containing media. Representative members of other yeast genera found on humans failed to produce these compounds. Addition of lecithin, oleic acids, triolein, or human sebum to the culture media stimulated gamma-lactone production by Pityrosporum species. All yeasts tested produced isopentanol and phenylethanol. Production of gamma-lactones may serve as a valuable characteristic in the identification of organisms of the genus Pityrosporum.


Role of plasmids in mercury transformation by bacteria isolated from the aquatic environment. Eight mercury-resistant bacterial strains isolated from the Chesapeake Bay and one strain isolated from the Cayman Trench were examined for ability to volatilize mercury. Mercury volatilization was found to be variable in the strains tested. In addition, plasmids were detected in all strains. After curing, two of the bacterial strains lost mercury resistance, indicating that volatilization is plasmid mediated in these strains. Only two cultures demonstrated ability to methylate mercuric chloride under either aerobic or anaerobic conditions. Methylation of mercury, compared with volatilization, appears to be mediated by a separate genetic system in these bacteria. It is concluded that mercury volatilization in the estuarine environment can be mediated by genes carried on plasmids.


Production of arsine and methylarsines in soil and in culture. Arsenate, arsenite, monomethylarsonate, and dimethylarsinate were added to different soils, and evolution of gaseous arsenical products was determined over 3 weeks. Arsine was produced in all three soils from all substrates, whereas methylarsine and dimethylarsine were produced only from methylarsonate and dimethylarsinate, respectively. At least three times more arsine than dimethylarsine was produced in soil incubated with dimethylarsinate. Resting cell suspensions of Pseudomonas and Alcaligenes produced arsine as the sole product when incubated anaerobically in the presence of arsenate or arsenite. In all instances, no trimethylarsine was observed, nor could any evidence be shown for the methylation of any arsenical substrate in soil or in culture. It was concluded that reduction to arsine, not methylation to trimethylarsine, was the primary mechanism for gaseous loss of arsenicals from soil.


Indole-3-lactic acid as a tryptophan metabolite produced by Bifidobacterium spp. Fifty-one strains of the genus Bifidobacterium have been found to accumulate indole-3-lactic acid in culture broth. The isolated metabolite was identified through mass and nuclear magnetic resonance spectroscopy. All the microorganisms tested, as resting cells, have been shown to be able to convert L-tryptophan into L-indole-3-lactic acid.


Biodegradation of polystyrene, poly(metnyl methacrylate), and phenol formaldehyde. The biodegradation of three synthetic 14C-labeled polymers, poly(methyl methacrylate), phenol formaldehyde, and polystyrene, was studied with 17 species of fungi in axenic cultures, five groups of soil invertebrates, and a variety of mixed microbial communities including sludges, soils, manures, garbages, and decaying plastics. Extremely low decomposition rates were found. The addition of cellulose and mineral failed to increase decomposition rates significantly.


[Hormonal stimulation and in vitro cellular differentiation in the integument of the desert locust Schistocerca gregaria (author's transl)]. Spontaneous cellular differentiation (glandular units appearance with a well-defined duct) is observed in larval integument of Schistocerca cultured in an hormone free medium. Hormonal stimulations modify the expression of this phenomenon, particularly the frequency of new elaborated duct cells belonging to secretory units. The most effective factor is supplied by the prothoracic glands. Complete secretory units can be observed but the glandular cells are in an undifferentiated and unfunctional state. They appear active if the corpora allata act after the prothoracic glands. Corpora allata alone or synthetic juvenile hormones have an inhibitory effect. The addition of alpha-ecdysone permits only cellular divisions, a preliminary and indispensable condition for ulterior differentiation. Between cuticles deposited with beta-ecdysone, new formed ducts take place in the theorical imaginal exuvia. These observations prove that the elaboration and the activity of imaginal glandular units are conditioned by the larval hormonal context: by contrast, sex dimorphism is only a genetic dependant process.


A method for the in vivo experimental study of meiotic prophase in the golden hamster (Mesocricetus auratus). Gonads of 15 day-old hamster fetuses were grafted under the kidney capsule of adult ovariectomized females. In 81.8% of the grafts, the germ cells developed and completed meiotic prophase; they reached the diplotene stage and gave rise to primordial follicles. These grafts could survive well in the host for at least 20 days. Meiotic prophase was not initiated within 24 h of grafting in contrast to the in vivo condition where it is observed 24 h after birth. In grafted ovaries, 69% of the germ cells were at the leptotene stage on day 3. By day 5, most of them were either at the zygotene (15%) or pachytene stages (60%). Oocytes at the diplotene stage were found from day 5 onwards and on day 7, 30% of the germ cells had already reached this stage. The highest numbers of atretic germ cells could be found on days 1, 9 and 10 post graft. It is noteworthy that the number of germinal cells remaining in the ovary 10 and 20 days after grafting were 11.4% and 12.9% of the total number of germinal cells present in normal animals of the same ages post-partum. This point is discussed in detail.


[Some observations on the formation of the primary tunica albuginea in the ovary of the chick embryo (author's transl)]. The ovarian cortex of chicken embryos of 10 to 14 days of incubation was observed in order to study the formation of the primary tunica albuginea and to discern in its cells an ultrastructural confirmation of an eventual steroidogenic capacity which has been proposed by some authors. From observations at the electron microscope, it is probable that the mesenchyme-like cells which constitute the primary tunica albuginea may originate from the somatic cells of the cortex, either from those of the germinal epithelium, or from those which, because of their position, may be termed prefollicular. There is not apparent ultrastructural confirmation of an active steroidogenic capacity in the albugineal cells. A possible physiological difference between clear cells and dark cells due to a different electron density, is furthermore discussed.


Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. We have characterized the clinical and laboratory features of 27 patients who had in common a recurring, superficial, nonscarring type of cutaneous lupus erythematosus (LE) that occurred in a characteristic distribution (subacute cutaneous lupus erythematosus [SCLE]). This clinically distinct form of cutaneous LE has not previously been analyzed as a separate entity and thus, its clinical importance has not been fully appreciated. We found that these patients frequently had a mild systemic illness marked by musculoskeletal complaints and serologic abnormalities. Forty-eight percent had systemic LE by American Rheumatism Association criteria; however, none had serious CNS or renal disease. Thus, those with SCLE are a subset of patients with LE who generally have an illness intermediate in severity between discoid LE and severe systemic LE.


Melanoma resembling spindle and epithelioid cell nevus. Three cases of malignant melanoma resembling spindle and epithelioid cell nevus histologically are presented. Lesions having histologic features of spindle and epithelioid cell nevus (Spitz nevus or juvenile melanoma) at or after puberty should be regarded with caution, particularly when they are heavily melanized. Such lesions are in a histologic "gray zone" and may be malignant.


Ultraviolet irradiation-induced inflammation: effects of steroid and nonsteroid anti-inflammatory agents. The effect of combined topical applications of a steroid and nonsteroid anti-inflammatory agent on erythema induced by ultraviolet-B irradiation (UV-B) was evaluated. In human volunteers, the combination more effectively suppressed UV-B--induced erythema than either agent alone. When applied singly, the nonsteroid agent was far more effective than the steroid. The combination, or either agent alone, was most effective when applied immediately after irradiation. This study demonstrates that for the treatment of UV-B--induced erythema, the anti-inflammation effects of these two classes of anti-inflammatory agents are greater when used in combination than when either agent is used alone. However, the effect of the combination in this study is not sufficiently long-lasting to be therapeutically useful.


Lymphocyte response to phytohemagglutinin in atopic dermatitis. Studies of patients with atopic dermatitis (AD) have demonstrated several clinical and laboratory indications of immunity defects, but with frequently contradictory results. We have recently shown that many patients with negative cutaneous delayed type hypersensitivity to candidin and streptokinase-streptodornase may have normal in vitro lymphocyte transformation to the same antigens. We hypothesized that this represents recovery of immunocompetent cells when they are isolated in vitro. This report describes phytohemagglutinin-induced transformation of lymphocytes immediately after isolation and after four days in culture (precultured). Responses of lymphocytes from patients with AD were initially subnormal, but increased to normal levels after the preculture period. Our results suggest that defective immune function in AD is not due to a permanent intrinsic lymphocyte defect, but is more likely due to factors associated with disease activity and severity.


Herpetiform blisters in systemic lupus erythematosus. Four patients with systemic lupus erythematosus (SLE) had a vesicobullous eruption that histologically resembled dermatitis herpetiformis. Immunofluorescence microscopy patterns in the skin studied in three patients, however, were characteristic of SLE. Treatment of the underlying collagen-vascular disease improved the eruption, while recurrence coincided with exacerbation of the systemic disease. This distinctive lesion is an important parameter of SLE activity.


Necrolytic migratory erythema without glucagonoma. Two patients with clinical and histologic findings consistent with necrolytic migratory erythema are presented. Unlike previously described patients with this disorder, neither patient had substantially elevated glucagon levels nor an associated pancreatic islet cell tumor. The cause of the skin disease in these patients remains unknown but may be related to the underlying small-bowel disorder present in both.


Possible Kawasaki disease in a 20-year-old woman. We describe a 20-year-old woman in whom an illness developed that was consistent with Kawasaki disease. Kawasaki disease may not be confined exclusively to the pediatric age group.


Intracranial calcifications and dyskeratosis congenita. We describe two brothers with dyskeratosis congenita and intracranial calcifications. The calcifications were massive, approximately symmetric, and showed a predilection for the basal ganglia and dentate nuclei. No underlying causes for this finding were identified. Idiopathic familial intracranial calcification of this type has been described, but an association with dyskeratosis congenita has not previously been observed.


Assessment of individual renal function in children using 99mTc-DTPA. Differential renal function assessment using 99mTc-DTPA was carried out in 12 children aged between 3 weeks and 11 years who had undergone surgical procedures which allowed separate access to the urine output from each kidney. The results correlated well with those obtained by measuring individual kidney creatinine clearances. The best result was obtained using the technique of deconvolution analysis (r = 0.98; P less than 0.001). We conclude that the method is accurate and recommend its use in the management and follow-up of patients with asymmetric renal disease.


Persistent pulmonary hypertension and abnormal prostaglandin E levels in preterm infants after maternal treatment with naproxen. Twins and a singleton were born at 30 weeks' gestation although naproxen (d-2 (6'methoxy-2-naphthyl) propionic acid) had been given to the mothers in an attempt to delay parturition. Inhibition of prostaglandin synthesis was shown by very low plasma concentrations of prostaglandin E and the ductus arteriosus remained closed despite signs of pulmonary hypertension with severe hypoxaemia. Abnormalities in blood clotting, renal function, and bilirubin metabolism were also found and one infant died. Further studies of the benefits and risks of the inhibition of prostaglandin synthesis are required before this treatment of preterm labour is accepted.


Maturation of caffeine elimination in infancy. The developmental changes in caffeine elimination were studied in 7 infants aged between 2 1/2 weeks and 6 months. Adult plasma clearance rate of caffeine was achieved at 3 to 4 1/2 months of age. Plasma half-life and elimination rate reached adult levels after 3 to 4 1/2 months and seemed to exceed adult capacity thereafter. No significant changes in apparent volume of distribution were noted. Our data provide some indication of the age in infancy when the low rates of caffeine elimination in the neonate increase to the adult rate.


Effect of puberty on rates of bone growth and mineralisation: with observations in male delayed puberty. The bone mineral content (BMC) and body height were measured in 301 normal children and adolescents aged 7--20 years, and in 8 boys with constitutional delayed puberty aged 14--17 years. Serum testosterone was measured in the last group as well as in a subpopulation of the normal children and adolescents. The growth spurt, which coincided with a steep increase of serum testosterone in boys, indicated a great change in skeletal growth and mineralisation in both sexes. After the growth spurt, linear growth slowed down considerably while bone mineralisation rose steeply. When low levels of serum testosterone were maintained, as in delayed puberty, these combined changes of skeletal growth and mineralisation did not occur. It is suggested that gonadal hormones are the true initiators of the short-lived growth spurt as well as of prolonged acceleration of bone mineralisation.


Concentration of zinc in the hair of schoolchildren. The concentration of zinc in the hair of 219 schoolchildren aged between 10 and 11 years was measured and related to height, weight, estimates of consumption of zinc-rich foods, number of children living at home, and rank in family. None of the correlation coefficients between hair zinc and the other variables was significant. Mean concentration of zinc was higher (P less than 0.001) in the girls (146 microgram/g; 2.23 mumol/g) than in the boys (118 microgram/g; 1.81 mumol/g). Eight children (3.7% of the total) had less than 75 microgram/g (less than 1.15 mumol/g) zinc in their hair but only one of them was below the 10th centile for height or weight--a girl with coeliac disease.


Cerebrospinal fluid immunoglobulins in children. Cerebrospinal fluid (CSF) immunoglobulins were measured in 62 normal children, in 9 children with purulent meningitis, and in 10 children with presumptive viral meningitis. The mean values in normal children were IgA 0, IgM 0, and IgG 0.84 +/- 1.4 mg/100 ml (+/- SD). The mean levels of all CSF immunoglobulins were raised in acute bacterial meningitis and were significantly greater than the levels found in viral meningitis. CSF IgM was 0.16 +/- 0.5 mg/100 ml in viral meningitis compared with 2.64 +/- 2.06 mg/100 ml in bacterial meningitis (P less than 0.01). However, these values overlapped to a considerable extent and, generally, measurement of CSF immunoglobulins did not enhance diagnostic accuracy in this group of children.


Treatment of a neonate with propionic acidaemia and severe hyperammonaemia by peritoneal dialysis. A moribund newborn infant with propionic acidaemia and severe hyperammonaemia was successfully treated by peritoneal dialysis. The removal of ammonia and possibly additional toxic metabolites by peritoneal dialysis may be life-saving in newborn infants with propionic acidaemia or other hyperammonaemic syndromes.


Transient infantile hyperthyrotropinaemia. Report of a case. A case of transient hyperthyrotropinaemia was found by mass screening for neonatal hypothyroidism using the paired TSH assay method. The patient was a baby boy born at term after a normal pregnancy who grew without any abnormal signs or symptoms. For the first 7 months after birth, his serum TSH was abnormally high while his total serum T4, T3, and free T4, T3 were within normal limits, exept for slightly low free T4 level at 7 months. The raised serum TSH decreased spontaneously to within normal limits after he was 9 months old.


Metabolism of toxaphene components in rats. Metabolic fates of 14C-toxaphene and two of the toxic components of toxaphene were studied in vitro by using rat liver enzyme preparations. The enzyme systems involving toxaphene metabolism were characterized, using known cofactors and inhibitors to activate or inhibit individual enzyme reactions. The nature of toxaphene metabolites was studied through derivatization of metabolic products via chemical and enzymatic treatments. The results of the in vitro studies were compared to the metabolic patterns observed in vivo to ascertain the relative importance of each enzyme system in the total process of toxaphene degradation and excretion.


Light and electron microscopic observations of the acute sublethal hepatotoxic effects of Mirex in the rat. The fire-ant poison, Mirex, was administered via stomach tube (dosage 200 mg/kg) to 50 adult Mai-Wistar male rats and the resultant histopathologic lesions produced in their livers after six days post-intubation are described. Light (LM) and electron microscopic (EM) technques revealed cellular and subcellular alterations in response to this sublethal dosage. Pathologic lipid accumulations occurred in Mirex-exposed rats and this fat appeared in a distinctive periportal zonation pattern. Additional lesions were detected in centrolobular zones with the EM and included severe glycogen depletion, altered regularity in the architecture of rough or granular endoplasmic reticulum (GER), dilated GER cisternae, free ribosomes, and proliferation of smooth endoplasmic reticulum. Periportal hepatocytes exhibited apparent reduction in numbers of cytoplasmic organelles and development of many, large lipid-containing vacuoles. Myelin figures were sometimes associated with developing lipid (liposomes), suggesting a contribution of myelin membranes to the developing lipid droplets or vice versa. Biochemical studies revealed that glycogen levels dropped markedly, lipid content greatly increased, and protein/DNA and RNA/DNA values decreased.


Contamination of human milk with chlorinated pesticides in Guatemala and in El Salvador. In Central America huge amounts of persistent organochlorine pesticides are being used. This paper presents data on organochlorine residues in human milk. The samples studied were collected from areas with different spraying patterns. The results show very high contamination rates with organochlorine pesticides, especially with DDT. The highest levels were found in cotton-growing areas. Compared with residue levels in areas where cotton is not grown the difference was found to be statistically significant. Many of the quoted values are among the highest reported for the Western World. However, very high residue levels were also found even in Guatemala City, suggesting that other than agricultural uses of pesticides are important contamination sources. It is believed that these high levels of pesticide residues in human milk reflect a high contamination among the population in general.


Fate and comparative toxicity of metallothioneins with differing Cd/Zn ratios in rat kidney. Metallothioneins with differing Cd/Zn ratios were prepared in vitro from rat liver zinc-thionein by replacing zinc with cadmium and were injected intraperitoneally to female rats. The distribution of cadmium, zinc, and copper in the kidney supernatant fraction was determined using a Sephadex G-75 column. The distribution pattern of cadmium and zinc changed dramatically within 24 hr after the injection. The changes were explained by the degradation and re-synthesis of metallothionein in the kidneys. The necrotic changes of renal tubular lining cells were correlated to the amount of cadmium in the metallothionein but not to the amount of metallothionein (protein).


Sorption-desorption characteristics of methyl parathion by clays. Methyl parathion (O,O-dimethyl O-(4-nitrophenyl) phosphorothioate) adsorption was studied on montmorillonite, kaolinite, halloysite, natural zeolite, ion exchange resins and calcium carbonate. Methyl parathion was highly adsorbed by montmorillonite, followed by zeolite, and very little adsorption was obtained on kaolinite and halloysite. Calcium carbonate did not exhibit any adsorption. The values of the partial molar free energy "delta G" were calculated for all systems. For the montmorillonite-methyl parathion system, the calculated partial molar heat of adsorption "delta H", and the conformity of the data to Freundlich equation indicated a possible physical mechanism of adsorption. Increasing acetone concentration decreases methyl parathion adsorption and dehydration increased adsorption in the nonaqueous system. Moreover, the increased adsorption on the swollen clay indicated that methyl parathion was adsorbed on the interlamellar surfaces of the clay. This was also in agreement with the results of the desorption studies, since the insecticide was not desorbed using the same aqueous acetone solution. This indicated that methyl parathion was adsorbed as a water-insoluble organic compound.


Accelerated parathion degradation in soil inoculated with acclimated bacteria under field conditions. The feasibility of decontaminating soil at parathion spillage or disposal sites by inoculation with a highly acclimated culture of parathion-degrading bacteria was demonstrated under in situ field conditions. The acclimated culture (AC), capable of utilizing parathion as a sole carbon and energy source, was inoculated into Yolo silt loam soil in which parathion was applied at rates up to 5000 kg/ha. The AC was shown to be capable of completely degrading parathion in soil containing up to 1250 kg/ha of parathion within 35 days. A slower rate of parathion degradation by the AC was observed when the pesticide was applied as the commercial 46.5% emulsifiable concentrate than when applied as the 98% technical grade. The ability of the AC to degrade parathion deteriorated at application rates greater than 1250 kg/ha. The AC may have been adversely affected by the accumulation of the parathion hydrolytic products, p-nitrophenol and ionic diethyl thiophosphate, which were tentatively identified in soil samples.


Cholinesterase surveillance of aerial applicators and allied workers in the Democratic Republic of the Sudan. During the seasonal aerial application of insecticides on cotton, a cholinesterase surveillance program was realized and the adherence of the safety measures in connection with insecticides was supervised. No cases of ill health or poisoning due to the handling of the insecticides are known to have occurred amongst the pilots, entomologists, and aircraft engineers. Only a small number of ground personnel and landing strip workmen showed temporarily depressed cholinesterase levels while engaged in this program.


Anatomy of the human seminal vesicles and ejaculatory ducts. Anatomical dissections of the seminal vesicles and ejaculatory ducts were carried out in 20 autopsy and 10 operative specimens. Seminal vesiculography and casting were made. Vesiculography was conducted on 50 cases of schistosomal seminal vesiculitis. The seminal vesicles were of variable size and three main anatomical types. In normal seminal vesicles the ampullary vesicular angle was acute and the average length of the ejaculatory duct was 2.2 mm with an antero-medial concavity.


A correlation between a spectrophotometric quantitation of rabbit spermatozoan motility and velocity. Rabbit sperm motility was measured spectrophotometrically and a sperm motility index (SMI) was obtained. A comparative analysis between the SMI values and the velocity of motile sperm (obtained by time lapse photography of sperm tracks) was performed. The SMI specifically was compared to the mean velocity of the first 300 sperm cells observed and to the mean velocity of just the first 300 progressively motile sperm cells. In both comparisons, the SMI was highly correlated to the sperm track length (sperm velocity). In addition, a modification of the spectrophotometric procedure is described which allows measurements of the SMI to be made on semen extended into egg-yolk glycerine cryopreservation agents.


Nongonococcal urethritis.

Nongonococcal urethritis. The nongonococcal urethritis (NGU) syndrome is a group of sexually transmitted infections that together exceed the frequency of gonorrhea in men in most urban areas of Europe and the United States, and probably in much of the remainder of the world. "Nongonococcal" is preferred to the term "non-specific" urethritis because the latter is less precise and carries the inaccurate implication that the causes are unknown and perhaps unknowable.


[Evaluation of the protein quality of Erythrina edulis (balú)]. The protein content (N x 6.25) of the seeds of Erythrina edulis (balú) varies between 18-21%; when the fraction corresponding to non-protein nitrogen is extracted with trichloroacetic acid (10%), this value decreases to 14-15%. Remarkable differences in the distribution of the protein fractions are observed when two schemes of extraction are assayed. The amino acid analysis shows that this legume has similar or higher amounts of most amino acids than those present in other leguminosae; the calculated chemical score and protein score show that methionine is the first limiting amino acid and tryptophan, the second. The protein efficiency ratio (PER) of thermically-treated flours has the highest value at 30 minutes of treatment (1.15).


[Characteristics of urban families with malnourished infants]. Some essential aspects of families with malnourished infants being treated in the Nutritional Rehabilitation Centers managed by the Corporation for Infant Nutrition (CONIN) of Santiago, Chile, were studied in depth. The purpose was to identify and quantify some variables of the family environment as a previous necessary step for the application of an adequate social treatment. The design used is of a descriptive nature. The sample is representative of two of the Centers. The data obtained revealed the following: 1) the families belonged, without exception, to a low socioeconomic level, 21% in extreme poverty; 2) 64.8% of the mothers exhibited a low affectivity index, and in 88.1% of the families a pattern of a most deficient parent-child communication prevailed; 3) 90.4% of the families lived almost totally isolated from the rest of the community; 4) 76.4% of them had an internal physical environment with extremely scarce color stimuli, brown being the predominant color. The findings also revealed that in these families both physical and emotional environments are highly negative and hinder the maintenance of a normal nutritional condition of the child once he returns home after discharge from the Center. This implies not only a late discharge of the child (at a high institutional cost), but it also entails a high risk of his relapsing into malnutrition unless affectivity, communication, physical environment and perhaps other intra-family conditions improve.


[A new method of preserving chicken eggs at environmental temperature]. A new method of preserving eggs at room temperature is discussed. The method consists in the "plastification" in situ of the shell, using a liquid synthetic polyvinyl chloride acetate plastic. The plastified eggs and controls were stored under laboratory conditions at 22 degrees C, and the following variables were studied in relation to time: pH of the thick and fluid white, and of the yolk, loss of weight, diameter, yolk index and Haugh units. The results indicated that this new method preserves edible eggs for periods longer than 135 days.


[Effect of diseases on the nutrient intake by suckling calves]. An energy and protein intake test was applied to 341 female nursed calves under production conditions. Their daily intakes of skim milk enriched with milk substitute, fodder concentrates, and hay were recorded and their daily energy and protein intakes calculated. Their feed consumption was characterised by cumulative nutrient intake curves, depending on the time of foremilk feeding (K-I-period). Energy and protein intake figures were related to the findings obtained from daily health control, with the view to defining the effects of pneumonia or diarrhoea on feed intake. Both diseases were found to cause significant reduction in nutrient intake, depending on the given type of disease and severity, with their negative impact having been most markedly shown in the context of dry feed intake. The delay caused to the development of dry feed consumption by diseases of the respiratory and digestive tracts was many times longer than the time of the clinical course. The above observations provided some cues for conclusions regarding the approach to be taken by the veterinarian to diagnosis, therapy, and rehabilitation of affected calves. Certain concepts were derived from the findings as to how to feed calves to forestall developmental disorders.


[Studies of cardiac pathomorphology in swine which died during transport]. The following findings were obtained from pathomorphological examination of the myocardium of 100 pigs which had died on transport: Degenerative or necrobiotic changes of certain myocardial fibres were recorded from 73 per cent of all cases, usually in the form of granular degeneration (60 per cent). They were "scattered" in 33 per cent of all cases, "multiple" in 22 per cent, and "frequent" in five per cent. In 26 per cent, the myocardial fibres had undergone coarse granular or hyalin plaque-type decomposition, among them with "scattered" manifestation in 15 per cent, "multiple" in four per cent, "frequent" in five per cent, and "massive" in two per cent. Moderate focal resorptive myositis was recorded from eight per cent, while earlier myocardial scars were exhibited by four per cent. The figure for reactive inflammatory processes was twelve per cent. Prestatic hyperaemia of different degrees had taken place in 75 per cent of all animals, and it had been accompanied by varied congestion. The following results were obtained from comparative checks of 100 hearts of clinically intact pigs after slaughter under normal conditions: Granular degeneration was recorded only from 18 per cent of all cases, with actual manifestations "scattered" in 16 per cent and "multiple" in two per cent. Their myocardial fibres had undergone coarse granular or hyalin plaque-type decomposition of moderate intensity in three per cent only, all of them having been "scattered". Reactive inflammatory changes were not recorded at all and signs of prestatic hyperaemia only in 46 per cent. The degenerative-necrobiotic alterations of myocardial fibres which had been observed in the context of death on transport are interpreted as a result of hypoxaemic or hypoxic conditions accompanying acute shock-type circulatory failure in pigs.


[Studies of bovine Mycoplasma mastitis. 3. Testing of biochemical properties of Mycoplasma strains isolated from 3 stocks]. Thirty-two isolates of altered milk samples taken from cows with mastitis on three industrialised dairy cattle units were biochemically tested following five passes through no-inhibitor media, assessment of filtratability through 450-nm-membrane filter, and clone assay. Something between five and ten clones of each of the strains involved were tested for their growth properties both at 22 degrees C and in no-serum media, sensitivity to digitonin and capability of aesculin hydrolysis. TTC reduction (triphenyltetrazolium-chloride), as well as for decomposition of glucose, arginine, and urea. The properties found were characteristic of M. bovis, A. laidlawii, and A. axanthum, and of the family of mycoplasmataceaea in the strains of one of the stocks.


[Studies of bovine Mycoplasma mastitis. 4. Serological classification of Mycoplasma strains isolated from 3 stocks]. Thirty-two isolates from altered milk samples taken from cows with mastitis of two herds were serologically tested by the WHT against rabbit hyperimmune sera of 16 reference and type strains. The strains tested were associated and grouped in the following way: 16 M. bovis, nine A. laidlawii, and seven A. axanthum. The classification of on M. bovis strain was confirmed by SHT. Five isolates from another stock, with biochemical properties related to the family of mycoplasmataceae, were not serologically identified.


[Results of blood transfusion in anemia of dairy cattle with references to serological tolerance]. Therapeutic use of blood transfusion as a life-saving step in cases of dairy cattle anaemia cannot be recommended unless serological tolerance is taken into due consideration. The results obtainable from cross-testing and biological testing are useless in avoiding transfusion problems caused by blood groups in situations of first transfusion. Suitable donors can be identified only by haemolysis and haemolysis inhibition tests. Preliminary selection of donors in advance is permissible for first transfusions. The most important antigens, which may correspond with normal agglutinins, must not be present in the blood patterns of selected donors. Blood transfusion without knowledge of serological tolerance and compatibility between donor and recipient may be justified in emergency situations, yet, together with desensitisation.


[Uterus development in swine from birth to 8 months of age]. Macroscopic examination was applied to the ovaries and histological tests to the uterus of 108 pigs aged between one and 240 days. The results have shown that the growth of the uterus in swine had not taken place with continuity. Extraordinarily strong thickness growth of the endometrium and myometrium was observed over the first three months of age. Thickness growth of both layers then continued at reduced rate. The uterine glands began to develop from superficial epithelium in the second week of age and reached the basal part of the endometrium in the fourth week. Both the number of uteroglandular sections per visual field and the glandular surface over the whole area of the endometrium, as recorded from cross-section specimens, increased strongly over the first three months of age, followed by less marked change. Continued development and maturation of the elements involved took place between the twelfth and 24th weeks of age, with the uterine glands acquiring capacity of secretion. Stagnation is uterus development and growth was observed at the age of over 180 days. The most favourable date for zootechnical stimulation of puberty was considered to lie in the period between 170 and 200 days of age, whereas biotechnical induction of puberty might give best results when applied at an age between 180 and 200 days.


[Control of swine parturition. 1. Results of clinical, histological and hematological studies of parturition induction in swine using prostaglandin F2 alpha]. Parturition was induced to 23 sows on the 112th day of pregnancy by intramuscular injection of 7.5 mg PGF2 alpha (Dinoprost-Upjohn Co.). Onset of parturition was achieved within 27 hours and 52 minutes +/- four hours and 54 minutes in 21 animals (91.3 per cent). Average litter size was 11.33 piglets, with parturition time per litter having been five hours and 45 minutes +/- two hours and 39 minutes. Stillbirths accounted for 6.3 per cent. The average birth weight, 1.245 g +/- 264 g did not differ with significance from that of the controls. The physiological process accompanying parturition is described in greater detail. Unobstructed re-intergration with further reproduction of animals which had received PGF2 alpha treatment is established with hard evidence on the basis of clinical examination of oestrus, ovulation, conception, and farrowing rates as well as by histological examination of the endometrium. Alterations in the blood state recorded from animals with PGF2 alpha treatment close to full term were identical with those recorded from untreated animals.


[Ophthalmologic evaluation at the age of 2 years of newborn infants hospitalized in the neonatology center at Rennes]. The eyes of 1 466 children (88.3% of the total) who were admitted to the Centre for premature babies and the neonatal intensive care unit at Rennes between 1973-1975 were re-examined at the age of 2 years. There were 839 premature and 226 term babies whose weight was appropriate for gestational age, and 74 premature and 327 term babies who were small for dates. 95 (6.5%) had eye disorders at the age of 2. Abnormalities were more common in infants with a Birth weight of less than 1 500 g and in those with a gestional age of less than 28-30 weeks. Boys were more commonly affected than girls. 38% of the children with eye disorders had other problems of which the commonest was mental retardation (75%). There was no relation between perinatal complication and the incidence of eye disorders. The most common abnormality was squint (94%) but other problems were major (blindness, cataracts, retrolental fibroplasia). 37% of the abnormalities had not been diagnosed until found in the survey at the age of 2 years.


[Extramembranous glomerulonephritis during congenital syphilis]. A 3 month old girl with congenital syphilis presented with the nephrotic syndrome due to extra membranous glomerulonephritis. The presence of the first component of the classical pathway of complement activation (C1q) in the glomerular deposits and the antitreponemal antibodies in circulating cryoglobulins (titre 1 : 320) support the hypothesis that immune complexes are responsbile for the glomerulonephritis in congenital syphilis.


[Severe allergic cutaneovisceral vasculitis in children. Apropos of 6 cases]. Six children aged between 10 months and 13 years with allergic vasculitis are described. The features they had in common were necrotic skin lesions, involvement of various viscera and signs of hypersensitivity reactions. Histological changes of allergic vasculitis were present in the small vessels of the skin. This condition has features in common with both polyarteritis nodosa and with anaphylactoid purpura. Severe cases that do not respond to corticosteroids may respond to immuno-suppression with cyclophosphamide.


[Calcified constrictive pericarditis manifested by isolated hepatomegaly]. Calcified constructive pericarditis was discoverd in a 14 year old boy who presented with isolated hepatomegaly. No cause could be found. He was cured by surgery.


[Congenital tracheal stenosis and supernumerary bronchi]. A child is described with a segmental congenital tracheal stenosis who also had a supernumerary bronchus with an accessory lobe arising from the trachea. Because of progressive tracheal obstruction, surgery to the trachea and bronchi was undertaken. The stenosis was relieved successfully.


[Plasma levels of phenobarbital in epileptic children. Effect of combination with other anticonvulsants]. The effect of age on the steady state levels of phenobarbitone, alone and when given with phenytoin, sodium valproate and ethosuccimide has been measured in 1 361 children whose ages ranged from one month to 12 years. The relationship between dose and plasma level differed in those under 2 years from those aged between 2 years and 12 years. The addition of the other drugs altered the pharmacokinetics of phenobarbitone.


Governmental toxicology regulations: an encumbrance to drug research? The science of toxicology has become infinitely more complex and sophisticated over the past 20 years, a trend which has been particularly marked within the research-based pharmaceutical industry. Governmental rules and regulations have had a strong impact on the types of toxicity test now performed on drugs both in the course of their development and after their introduction on the market, and have thus contributed to the increased cost--in terms of time and money--of drug development. However, it will never be possible to measure or predict the safety of drugs in man by the application of toxicological techniques alone. Close collaboration between toxicologists and the authorities responsible for drawing up toxicological regulations is called for in order to ensure that the rules applied during the important and fascinating process of discovering and developing new drugs do not become unnecessarily burdensome.


[Unexpected and unexplained infant death. Epidemiologic and comparative study of Belgian and immigrant populations]. The medical records of 299 Belgian and immigrant children who died between 15 days and one year in the years 1970-1977 have been analysed. Fifty two died of congenital malformations, 119 of major infections and 128 died suddently for no obvious reason; neither the clinical history nor the laboratory data would account for death. In both the Belgian and immigrant population the children who died suddenly and unexpectedly did not differ from the other groups of children who died in respect of social class, mother's age at delivery, her parity and medical history, the baby's gestational age, birth weight and Apgar score, the method of feeding, the physical growth or psychomotor development. Infection is not more frequent in the week before death and there is no seasonal variation. The majority of unexpected deaths occur between 2 and 4 months of age and the child is most often discovered between 6 and 12 a.m. These characteristics are also observed in children who die of sudden infant death syndrome.


The no-effect level, an old bone of contention in toxicology. This discussion of the NEL presents some thoughts how toxicologists could be encouraged to use more sophisticated modern techniques for the study of various environmental chemicals. It is proposed to use the concept of the NEL only for data obtained by conventional techniques in routine toxicity experiments. Information on the mechanisms of the biologic effects of chemicals should, whenever possible, be used preferentially for the assessment of human risk and should therefore also be considered for the establishment of the ADI.


Toxicological barriers to providing better drugs. The unmet needs of the sick demand that toxicologic requirements do not stifle the rational search for new and better remedies. A number of conceptual problems hamper the rational use of toxicological testing. These include: a misplaced confidence in the value of animal testing, a failure to make sophisticated risk-benefit analyses, the proliferation of new tests of uncertain validity, and improperly executed retrospective case control studies. Rugulatory barriers include the ever increasing bureaucratic demand for toxicological testing, the unseemly willingness of regulatory agencies to yield to hysterical or cynical consumer group pressures, the unreasonable demand for "superiority" of new products before the granting of registration, and the temptation to institute expensive but untested post-marketing surveillance schemes. Economic obstacles to new drug development have become formidable, and new demands for toxicologic studies in animals and humans are adding to these problems. Finally, some examples of unwise regulatory decisions involving saccharin, spray adhesives, Depo-Provera, and a new anti-metabolite are given.


United States governmental efforts to improve the regulation of toxic substances. The U.S.'s efforts to improve its regulation of toxic substances presently have their focus in the administration of the Toxic Substance Control Act (TSSC), the Cancer Policy of the regulatory agencies, and the Drug Regulation Reform Act. By improving interagency communication and cooperation as well as establishing a coherent federal approach to the control of toxic substances with public and industrial input, the U.S. government should significantly strengthen the functioning of its regulatory agencies while decreasing the financial burden for everyone involved.


The acute toxic effects of hexachloro-1 : 3-butadiene on the rat kidney. A single intraperitoneal injection of hexochloro-1 : 3-butadiene (HCBD) at 100 mg/kg or above produced renal tubular necrosis in the rat by 24 h. Histological examination of the kidneys indicated damage to the straight portion of the proximal tubules. Urinary analysis showed diuresis, increased proteinuria and an increase in the excretion of N-acetyl-beta-D-glucosaminidase, and alkaline phosphatase at doses above 100 mg/kg. At doses below 100 mg/kg only a mild increase in protein excretion was observed. Twenty-four hours after 200 mg/kg HCBD, i.p., there was a marked decrease in the glomerular filtration rate (inulin clearance) and in the clearance of the organic anion (p-aminohippuric acid, PAH) and the organic cation (tetraethylammonium bromide, TEA) by the kidney. HCBD did not affect the accumulation of PAH or TEA by renal cortical slices when added in vitro at a concentration up to 0.1 mM. However, a decrease in PAH, but not TEA accumulation, was seen in renal cortical slices from rats treated with HCBD 24 h previously. Mercuric chloride (HgCl2), a known nephrotoxin, was used as a positive control for these studies. HCBD appears to specifically damage the straight portion of the proximal renal tubule and thereby selectively damage the organic anion transport system.


Endosulfan poisoning and chronic brain syndrome. The author describes a case of acute poisoning by endosulfan (a chlorinated hydrocarbon insecticide) in an industrial worker, with residual psychiatric syndrome. The acute phase was manifested by repeated convulsions and impaired consciousness. After recovery the patient became disoriented and agitated. The residual phase, 2 years after initial hospitalization, was manifested by cognitive and emotional deterioration, severe impairment of memory and inability to perform any but the simplest tasks. Psychological tests revealed gross impairment of visual-motor coordination. The differential diagnosis of chronic brain syndrome requires accurate history and milder cases of endosulfan poisoning may easily be overlooked or misdiagnosed.


[A fatal monointoxication by flurazepam (Dalmadorm). Problems of the toxicological interpretation (author's transl)]. A death case following a suicidal overdose of flurazepam (Dalmadorm) is reported. The body was found after 3 month near a highway. The course of the intoxication is in question as benzodiazepines are believed to be relatively save drugs. The death might have occured rapidly because of the acute toxic actions of the drug overdose as well as after a protracted course involving additional complications like inflammatory alteration of the myocard or hypothermia during a coma. Flurazepam and its major metabolites were analysed in blood and urine. The toxic levels of flurazepam (0.51 mg/l), N1-desalkylflurazepam (0.14 mg/1) and N1-hydroxyethylflurazepam (9.0 mg/1) in the blood amounted to 20--50 times higher than therapeutic levels, with flurazepam and metabolites being in only slight altered relation to each other. The overdose is considered to have been above 2.4 g (80 tablets). The resorption of the drug was complete. The analytical findings in blood and urine as well as in the GI-tract are in satisfactory agreement. The analytical data of flurazepam and its metabolites are discussed in detail, taking metabolic and pharmacokinetic parameters, autopsy findings and case circumstances into consideration. A final decision about the course of the intoxication is not possible. This case shows however the fatal consequences of a flurazepam overdose although alcohol or other drugs were not involved.


Constraints of drug regulation on the development of new drugs. A review is given of the various regulations for the preclinical and clinical evaluation of new drugs, their effects on the clearance of new medicines for general use by practising physicians, and their repercussion on industrial drug research. Undoubtedly, extensive and continuously increasing regulatory procedures, which in addition have to be satisfied repeatedly in individual countries, claim an unproportionally high percentage of the industrial capacity for research and development of new drugs, leaving too little for basic research, which is a prerequisite for the discovery of new medicines that are more than just "me too" products. Despite the fact that regulatory language differs from scientific attitude and arguments, the wall of regulations should be neither too thick nor too high to impede research and to hinder the prompt application of important new drugs. Even the most sophisticated and extensive drug regulations cannot prevent the use of drugs which is not indicated, because it is impossible to regulate ignorance. To regulate drugs is necessary, but the governments and their drug agencies should also encourage drug research and should support industry in the development of new drugs. On the other hand, the drug companies must adhere to the accepted standards and create an atmosphere of confidence by presenting reliable and complete data.


Lanthanon-induced hepatotoxicity and its prevention by pretreatment with the same lanthanon. Intravenous injection of the light lanthanon praseodymium nitrate (10 mg/kg) into rats causes a marked liver toxicity which becomes manifest in hypoglycemia, inhibition of RNA and protein synthesis and accumulation of fat in liver tissue. All these effects can be nearly abolished by pretreating rats with a small dose (5 mg/kg) of the same lanthanon. This is neither due to a decreased uptake into the liver nor to an increased excretion rate of the lanthanon. It is assumed that the pretreatment may increase unspecific binding sites or reversibly block them, thus protecting the organism from the irreversible lethal effect.


Genetic control of responsiveness of rat liver supernatant aldehyde dehydrogenase to phenobarbital and 3-methylcholanthrene. The responsiveness of the hepatic supernatant NAD+-dependent aldehyde dehydrogenase with a high Km value (high Km-AldDH) to phenobarbital (PB) and 3-methylcholanthrene (3-MC) treatment was studied in male rats of three strains; Wistar, Long-Evans, and Sprague-Dawley. A remarkable strain difference in the response of the enzyme to PB or 3-MC was observed. In rats of the Wistar strain the enzyme activity remained unchanged ("non-responsive") in all rats after treatment with PB while it increased ("responsive") 5- to 19-fo-d in all rats after treatment with 3-MC. The enzyme activity increased 8- to 20-fold and 2- to 8-fold respectively after treatment with PB and 3-MC in all rats of the Long-Evans strain. In rats of the Sprague-Dawley strain the enzyme activity remained unchanged in half of all the rats treated with PB or 3-MC and increased 2- to 7-fold over the basal level in half of the treated rats. The non-responsive rats to PB were all responsive to 3-MC treatment while the responsive rats to PB were responsive in 65% and non-responsive in 35% to 3-MC treatment.


Activity of N-acetyl-beta-glucosaminidase in lymphocytes of rats exposed to mixture of nitrogen oxides and chlorine. Activity of N-acetyl-beta-glucosaminidase (GS) has been cytochemically studied in peripheral blood lymphocytes of rats exposed to the mixture of nitrogen oxides (1.22 mg/m3) and chlorine (1.02 mg/m3) during a period of 12 weeks. The decrease of the total lymphocyte count and in increase of the count of GS-positive lymphocytes with cytoplasmatic but not exclusively lysosomal localization have been noted after exposure. The increase of the count of lymphocytes containing the enzyme within both lysosomal granules and cytoplasm has been correlated with the exposure time and accompanied by diminishing the count of lymphocytes containing the enzyme within the lysosomal granules exclusively. The authors believe the changes noted above may result from toxic damage of lysosomes or the immune response of lymphocytes against antigens released from the damaged tissues.


Whole body autoradiography of 3H-phencyclidine in mice. The present whole-body autoradiographic study demonstrates that the circulatory system is practically free of radioactivity, already 5 min after intravenous administration of 3H-Phencyclidine to mice. At this time, however, high radioactive levels appear in the lachrymal gland, nasal mucosa, bone marrow and spleen, as well as in the urinary, digestive, respiratory and reproductive systems. High accumulation is maintained up to 20 min after administration and, thereafter, radioactivity declines continuously with increasing time. After 6 h, radioactivity disappears in most organs, but remains notable in the kidney, lung and liver, as well as in the salivary and lachrymal glands. After 24 h, detectable amounts still persist in the liver, lung and in the salivary and lachrymal glands. The brain shows very low amounts of radioactivity during the whole period of observation. In pregnant mice, the drug accumulates in the placenta and partly crosses the placental barrier into the foetal tissues.


Metabolism of toluene in man: gas-chromatographic determination of o-, m- and p-cresol in urine. Complete separation of phenol, o-, m- and p-cresol was achieved by capillary gas-chromatography. Urinary concentrations of cresols were determined quantitatively in samples from 10 male workers exposed to toluene. Besides p-cresol, o- and m-cresol were found to be urinary compounds in the case of the exposed group in contrast to normal persons. This finding was proved by gas-chromatography/mass spectrometry. The difference between both groups is significant. It is concluded that beside hippuric acid o-, m- and p-cresol are metabolites of toluene.


Absorption of paraquat by rat gut in vitro. Regional differences. The absorption of radioactively labeled paraquat was measured in rat ileum, jejunum and colon by a micro everted sac technique (Semenza and Muhlhaupt, 1969). The absorption rate increased linearly over the range of concentrations measured (10(-5) to 10(-2) M) and was enhanced by nearly 50% in the absence of sodium ions. The absorption rate decreased in the order: ileum, jejunum, colon whereby in the colon still 65% of the values of the small intestine were observed.


Intracranial compliance during the post-operative period after surgery for intracranial aneurysms. Generalised post-operative cerebral vasospasm is a major factor in delineating poor operative results following direct ruptured intracranial aneurysms. Continuous monitoring of intracranial pressure seems to be particularly helpful on such occasions, and intracranial compliance determination as well. High intracranial compliance values suggest that even small intracranial volume increases may induce rapid intracranial pressure and situations likely to produce neurological deterioration.


[Introduction to neuropsycholinguistics]. The authors summed up the evolution of the current neuropsicolinguistics and of its origins. They proposed a general definition of the aphasic disorders in relation to the psycholinguists capacities involved. The paper finish with a brief reference to the variety of types of the aphasics disorders according with its fluent or non-fluent caracter.


[Evaluation of intelligence with non-verbal tests in aphasic patients]. Eight patients with cerebral vascular disease and aphasia were studied just after the stroke. The clinical, neuropsychiatric, EEG and neuro-radiological aspects were evaluated. The patients were submitted to the psychological and phonoaudiological studies. The authors correlated the neurological lesions to the structural alteration of the intelligence, to the praxic and estheognostic alterations and also to the language disturbances. The criterions adopted by the World Health Organization and the genetics classification of Jean Piaget were used for the intellectual level classification. The results suggest that the intelligence evaluated through Leither's non-verbal test is better preserved in some asphasics.


[Atypical Sturge-Weber disease associated with metameric angiomatosis. Case report and review of the literature]. Possibly the first case of Sturge-Weber disease associated with metameric limbs and trunk cutaneous hemangioma is reported. Roentnographic findings including contrast studies and computerized axial tomography are presented and discussed. Comments are made upon the relations between neurocutaneous angiomatosis.


[Embolism of a carotid-cavernous fistula with preservation of arterial circulation. Case report]. A case of carotid cavernous fistula of high flow by rupture of intracavernous aneurysm with similar intracavernous aneurysm not ruptured is reported. Good results were obtained by muscle embolus technique controlled by a thread, with preservation of the circulaion of the carotid artery. The author emphasizes the simplicity of this technique and comments other techniques registered in the literature.


[Immunoglobulins of the normal cerebrospinal fluid. II. Relations and indices]. Relations and quocientes of cerebrospinal fluid (CSF) immunoglobulins G (IGG) and serum (S) IGG were studied in 50 patients with chronic headache, normal neurological examination and normal electroencephalogram. CSF was normal as to: pressure, cytology, total proteins, protein fractions and immunoglobulins (IGG, IGA and IGM) contents. In all cases the CSF sample studied was collected from cisterna magna. The relations and quocients studied were: CSF IGG/CSF TOTAL PROTEIN, CSF IGG/CSF ALBUMIN, CSF IGG/CSF PRE ALBUMIN+ALBUMIN, (CSF IGG/S IGG) / (CSF ALBUMIN/S ALBUMIN) and (CSF IGG/S IGG) / (CSF PRE ALBUMIN+ALBUMIN) / (S ALBUMIN). It was found that the best index to appraise the behavior of IGG is: (CSF IGG/S IGG) /(CSF PRE ALBUMIN+ALBUMIN/S ALBUMIN) that shows an average of 0.56 and a standard deviation of 0.32 in the material studied.


[Progressive extrinsic ophthalmoplegia; case report]. A case of progressive ophtalmoplegia and ptosis affecting a 12 year old boy is reported. A miopatic pattern was detected by the electromyography, the cerebrospinal fluid showed an increase of the protein content and retinal pigmentary degeneration was detected. This findings call the attention for a more widespread degenerative disorders affecting not only the muscular sistem but other organs as well.


[Subacute sclerosing panencephalitis with partial remission]. Subacute progressive panencephalitis is usually a progressive and fatal disease, being uncommon temporary or definitive remissions. A three years old boy, previously vaccinated against measles, developed trembling, progressive and severe mental deterioration, partial seizures and myoclonic jerks. The electroencephalogram showed periodic high amplitude waves concomitantly with myoclonic jerks and the cerebrospinal fluid revealed an increase of the gammaglobulin fraction (16,8), benjoin coloidal reaction shifted to the left and the antimeasles antibody titres were positive (complement fixation text 1:16; neutralization test 1:32). In spite of that, two months after the beginning of the illness the patient showed mental and motor improvement and similar modifications of the electroencephalographic aspects and now, eleven months later, is well, remaining only a slight motor and mental deficiency.


Modified rotatory instruments for transphenoidal surgery: technical note. A series of modified gyratory bayonets instruments is described. They have the advantage to allow any adjustable position within a 360 degree rotation angle, during the various surgical steps of transphenoidal surgery, thus keeping the surgeon's hand always at the same position.


Isolated ultrafiltration in the treatment of dialysis ascites. Three patients with dialysis ascites improved markedly after treatment with isolated ultrafiltrations. This simple, noninvasive technique should be applied first to patients with dialysis ascites before resorting to more drastic therapeutic measures.


Digoxin removal from a patient with renal failure by hemoperfusion with Amberlite XAD-4 resin. A digitoxic patient with severe renal failure underwent two hemoperfusion treatments with Amberlite XAD-4 resin. Digoxin clearances calculated from plasma flow rates and plasma digoxin concentrations, as well as from the amount of digoxin eluted from the used columns, were superior to those previously described for peritoneal dialysis, hemodialysis and charcoal hemoperfusion. There was a temporary improvement in the patient's life-threatening digitoxic cardiac rhythm with the first hemoperfusion, and a permanent improvement after the second hemoperfusion. It is submitted that hemoperfusion with this resin may significantly lessen manifestations of digoxin poisoning and may hasten digoxin elimination in digitoxic patients with renal failure.


Long-term clinical assessment of combined ACAC hemoperfusion-ultrafiltration in uremia. ACAC hemoperfusion was used in series with a small fluid removal system for a clinical trial in the treatment of uremia. A 22-month trial included a pretest control period, test period and a post-test control period. The most significant observations from this trial are: 1) the predialysis body weight of the patient could be maintained closer to the patient's dry weight; 2) there was a significant increase in hematocrit; and 3) there was insufficient removal of urea. With the development of an effective urea removal system, a more compact artificial kidney than any presently available will become feasible.


Removal of endogenous middle molecules by hemoperfusion. In four regular dialysis patients, the removal of uremic middle molecules was studied during a three-hour hemoperfusion using a column containing 300 gm of activated carbon encapsulated with cellulose. Middle molecules in plasma were determined by high-speed gel filtration followed by gradient elution chromatography. Different adsorption characteristics were shown for the four middle molecule fractions measured. The initial clearances for middle molecule fractions were about 120 ml/min; clearances were 20-50 ml/min after two hours, and less than 25 ml/min, with release of some middle molecule fractions from the column, after three hours. The findings suggest that saturation of the column occurs after two to three hours of perfusion. Thus, prolongation of the perfusion time beyond two hours appears to be of little benefit. The reduction of middle molecules in plasma by a three-hour hemoperfusion was in magnitude, similar to that obtained by three-hour dialysis with a large surface area dialyzer or high-flux membrane.


Evaluation of the impact of ultrafiltration on dialyzer clearance. The influence of ultrafiltration on dialyzer clearance is analyzed. As the starting point for the analysis, the known theoretical and experimental expressions for clearance are utilized. The results obtained theoretically are verified with experimental data.


A detoxification scheme for liver assist utilizing plasmapheresis, bioincompatible sorbents and dialysis. The rationale behind the design of a sorbent-based detoxification system for use as a liver assist is presented. A membrane-based plasmapheresis system giving high plasma flows (greater than 40 ml/min) with maximum transmission of albumin makes this concept feasible.


Performance of baffled bubble blood oxygenators. Bubble blood oxygenators equipped with baffles of various types in the oxygenating column were studied. The rate of hemolysis, the volumetric coefficient for oxygen absorption into blood, and the fractional gas holdup were found to be affected mainly by the superficial gas velocity. When compared with the conventional bubble blood oxygenator without baffles, the bubble oxygenators equipped with various types of baffles (i.e., horizontal perforated baffles, radial vertical baffles, and a concentric hollow cylinder with and without horizontal perforated baffles) showed less hemolysis, larger gas holdup and higher values of the coefficient for oxygen absorption. Values of the heat transfer coefficient on the surface of the cylindrical baffle, which is useful as a built-in heat exchanger, were several times greater than those for single-phase heat transfer in conventional blood heat exchangers.


Ultrastructural characteristics of dog and human platelets adherent to native and collagen-coupled cuprophan. Adhesion of human and dog platelets to native and collagen-coupled Cuprophan under defined flow conditions was studied by scanning and transmission electron microscopy. Dog platelets, singly adherent to and uniformly distributed on both native and collagen-coupled Cuprophan, extend slender pseudopods across the surface without evidence of degranulation. Human platelets, while not adhering to native Cuprophan, formed irregularly shaped, semi-confluent cytoplasmic sheets on the collagen-coupled surface. Extensive cytoplasmic reorganization and degranulation suggests a post-release state of the human platelets. Aspirin had no apparent effect on either human or dog platelet adhesion or upon the apparent release state of the human platelets.


The dura mater valve: in vitro characteristics and pathological changes after implantation in calves. Human dura mater valves of various sizes with rigid and flexible stents were tested in an in vitro pulsatile mock circulatory system. A 22-mm flexible stent valve incorporating a new fabrication technique showed almost the same pressure gradient as a 28-mm rigid stent valve. The backflow/stroke volume ratio was about 4% at a net flow of 10 L/min. One hundred and five rigid stent-mounted dura mater valves were used in 51 pump implantations for up to 316 days. Collagen fiber degeneration began three months after implantation. Microscopic and macroscopic calcification of the valve tissue was seen in eight out of 105 valves, giving an overall incidence of 7.6%. The calcified degeneration was dystrophic in nature, not accompanied by cellular reactions, and was seen in the areas of the valve under stress. The degenerative changes were more severe in the left side than in the right side of the total artificial heart. These findings suggest that mechanical damage to the tissue plays an important role in the pathogenesis of calcification.


Orally diluting hemofiltration.

Orally diluting hemofiltration. Orally diluting hemofiltration (ODHF), herein reported, is a new technique where the body fluid is purified by cooperative procedures of dilution-supplementation with oral electrolyte solution and filtration using the RP-6 dialyzer. One uremic patient was maintained for two months on a five-hour, three-times-per-week ODHF schedule, and another patient was maintained for four months on the same regimen with no supportive hemodialysis.


Regeneration of dialysate.

Regeneration of dialysate. Large amounts (250 liters) of dialysate fluid are needed for dialysis of patients with chronic kidney diseases. A reduction of these amounts is obtainable by regeneration. With the Redy system, in which urea is decomposed by the enzyme urease, only 5.5 liters of dialysate is used. Other systems depending solely on sorption of urea still need excessive amounts of sorbents and no alternative, in the form of stable chemical binding, is available. If, therefore, further reduction of dialysate volume is desired, the problem of urea removal must be solved.


Theoretical aspects of adsorption of polar substances from polar solvents. The efficiency of adsorbents for hemoperfusion and dialysate regeneration can be increased if suitable catalysts are fixed on their surface in an appropriate density. Suitable catalysts are oxides and salts of the transition metals. The appropriate surface density of the catalysts depends on the molecular data of both catalyst and toxin to be removed, as well as on the distribution of the adsorption sites on the adsorbent surface area. The distribution of the adsorption sites is determined by means of photoelectron spectroscopy and adsorption and desorption measurements.


Semibiological left heart assist: in vitro evaluation. A semibiological left heart assist device has been designed and built at the Cardiothoracic Institute and National Heart Hospital, London, England. This device is a Dacron/polyurethane conduit between the left ventricle and aorta in which part of the conduit assumes the function of a pumping chamber. This segment is enclosed by two biological valves and has side arm. A polyurethane balloon is inserted through this side arm, and is pumped in a synchronously counter-pulsating manner. Upon completion, the balloon can be removed without thoracotomy and with the conduit left in situ. Under simulated physiologic pressure and rate conditions, the pumping device gives reasonably good performance.


Initial experiences with continuous ambulatory peritoneal dialysis. Continuous ambulatory peritoneal dialysis (CAPD) has been initiated on 51 patients: 27 females (mean age -- 43.9 years) and 24 males (mean age -- 46.4 years). This group has been observed for a total of 1420 patient weeks of treatment (27.3 patient years). Thirty-six episodes of peritonitis have been noted among 19 patients. The overall incidence was one episode per 39.4 patient weeks. Recurrent episodes of peritonitis resulted in discontinuation of CAPD in five (9.8%) of the patients. Three (5.9%) of the patients were unable to continue with CAPD because of its inability to control extracellular fluid balance. In the patients who transferred from intermittent peritoneal dialysis to CAPD, there was a 4.5 mg/dl drop in serum creatinine and a 34 mg/dl drop in mean BUN values. There was a rise of approximately 2 gm in the hemoglobin levels of this group of patients. If the problem of peritonitis can be solved, CAPD will become the dialytic treatment of choice for the majority of patients with end-stage renal disease.