[Effect of antibiotics on Francisella tularensis].

The minimum inhibitory concentrations of rifampicin, doxycycline, sisomicin, ciprofloxacin and phosmidomycin for various strains of Francisella tularensis were 0.5 to 2.0, 0.5 to 2.0, 0.125 to 0.4, 0.625 to 0.125 and 2.0 to 12.5 micrograms/ml, respectively. Ciprofloxacin and sisomicin had a marked bactericidal effect. The bactericidal effect of rifampicin was insignificant. Doxycycline and phomidomycin had practically no such effect. All the antibiotics had a post effect. The level of the post-antibiotic effect was different and depended on the antibiotic concentration.


[Dynamics of drug resistance of Vibrio cholerae isolated from surface water reservoirs in Siberia and the Soviet Far East in 1976-1990].

In the study on antibiotic resistance 1383 strains of El Tor Vibrio cholerae isolated from surface water reservoirs in 12 administrative territories of the Siberia and Far East within a period of 15 years were tested. The following antibiotics were used: ampicillin, streptomycin, monomycin, polymyxin, tetracycline, chloramphenicol, rifampicin and nalidixic acid. The resistance was unstable and its pattern was wave-like according to annual changes in the biological cycle. It was especially evident in regard to ampicillin, streptomycin, monomycin and polymyxin. The highest numbers of the strains were resistant to polymyxin, ampicillin and streptomycin (up to 100 per cent in some years). The lowest numbers of the strains were resistant to chloramphenicol (0.4 per cent) and tetracycline (1.9 per cent). No strains resistant to rifampicin and nalidixic acid were isolated. In some cases the antibiotic resistance level depended on the geographical zone where the strain was isolated. A direct quantitative dependence of the resistance level on the MIC was observed: the lower the MIC of the drug was, the lower the number of the strains resistant to it was. Within the 15-year period there was no general tendency to increase the resistance in V. cholerae to the antibiotics used.


[Effect of subinhibitory concentrations of antibiotics on catalase activity of plague microbes].

It was shown that the presence of subinhibitory concentrations of ampicillin, cefotaxime or gentamicin in the cultivation medium had a marked inhibitory effect on the catalase activity of plague microbe. The effect depended on the characteristic features of plague microbe strains and the incubation temperature. When the cells of a virulent strain of the plague microbe Y. pestis 1300 were cultivated at a temperature of 37 degrees C on a medium containing the subinhibitory concentrations of ampicillin or cefotaxime, the pathogen virulence for albino mice significantly decreased.


[Antibiotic sensitivity of plague microbe strains from foreign countries].

The method of serial dilutions on the Hottinger agar was applied to comparative assay of antibiotic sensitivity in 50 strains of the plague microbe isolated abroad and in 5 strains isolated in the plague focus in the Central Caucasus. The antibiotics used in the assay were the following: streptomycin, gentamicin, doxycycline, monomycin, kanamycin, tetracycline, erythromycin, ristomycin, lincomycin and polymyxin M. Irrespective of the origin, all the isolates were resistant to erythromycin, lincomycin and polymyxin M. The levels of the sensitivity to the other antibiotics were different. The data serve as a ground for the statement that there is no tendency to development of antibiotic resistance in the plague microbe in patients treated with high doses of the antibiotics and mainly streptomycin. Along with streptomycin, such antibiotics as gentamicin, tetracycline, doxycycline and kanamycin are useful in the therapy of plague and require further investigation.


[Effectiveness of cefotaxime in experimental plague infection].

Cefotaxime was shown highly efficient in prophylaxis and treatment of experimental plague infection in albino mice. The in vitro activity of cefotaxime against natural strains of the plague microbe was 32 to 64 times higher than that of cefazolin, cephalothin and cefmetazole. The combined use of cefotaxime with amikacin significantly increased the percentage of the survived albino mice with plague infection as compared to the use of the antibiotics alone.


[Doxycycline in the prevention of experimental plague induced by plague microbe variants].

A comparative study was performed on the efficacy of doxycycline in experimental plague infection induced in albino mice by strain 231 of the plague microbe and its variant 231 Fra- deprived of the ability to produce the fraction I antigen. It was shown that the LD50 for strain 231 during animal treatment with doxycycline was significantly higher than that for variant 231 Fra-. Prophylaxis of the plague infection caused by the Fra- forms of the plague microbe required significantly higher doses of doxycycline (ED50) than that of the infection caused by the Fra+ forms. The use of the daily maximum permissible doses of doxycycline (50 to 100 mg/kg a day) for 10 days in treatment of albino mice infected with the strain Fra- did not provide animal survival at the level higher than 60 to 70 per cent while the survival rate in the animals infected with the strain Fra+ of the plague microbe and treated according to the same scheme amounted to 90-100 per cent. The lower therapeutic efficacy of doxycycline in the treatment of the infection caused by the fractionless variant of the plague microbe should be considered in development of rational schemes for prophylaxis and treatment of plague.


[Effectiveness of phosphomycin and its combinations with amikacin and cefotaxime in experimental plague infection].

When administered intramuscularly in doses of 8 and 16 mg/mouse, phosphomycin was highly active in the treatment of albino mice with experimental plague infection (80-100-percent protection of the animals from death). Combinations of phosphomycin with cefotaxime in inefficient or not sufficiently efficient doses had a synergistic effect. When the albino mice were treated with combinations of phosphomycin and amikacin, the percentage of the survived animals significantly increased in comparison to that after the use of the antibiotics alone.


[Effect of protoplasting on antibiotic activity and resistance in the strain Streptomyces hygroscopicus 155].

The influence of protoplasting and protoplast regeneration in the presence of polyethylene glycol on antibiotic activity, components of antibiotic complexes and antibiotic resistance in Streptomyces hygroscopicus 155 was studied. It was shown that the protoplasting and protoplast regeneration influenced the antibiotic activity. The protoplast fusion resulted in increased isolation of variants with higher antibiotic activity. The processes also affected the components of the antibiotic complexes but had no effect on the strain resistance to some antibiotics.


[Detoxifying effect of antibiotics and their effectiveness in experimental plague at the stage of explicit intoxication].

The effect of antibiotics such as amikacin, rifampicin, doxycycline, polymyxin B and cefotaxime on the toxins of the plague microbe (lipopolysaccharide + fraction II according to Beiker) was studied in vitro and in vivo. The study on the antibiotic neutralization of plague toxins revealed that only polymyxin had toxin neutralizing capacity which depended on the dose. Investigation of the polymyxin effect at various stages of plague infection showed that when polymyxin in a dose of 1250 units and a mixture of plague toxins in lethal doses were administered simultaneously to albino mice, the positive effect amounted to 100 per cent. When the antibiotic was administered 30 or 60 minutes later, the antibiotic efficacy proved to be lower by 90 or 76.6 per cent, respectively. The intoxication in later periods (in 90-120 minutes) resulted in a decrease in animal survival up to 40-15 per cent. It was demonstrated on the model of the plague infection in albino mice that the use of amikacin, cefotaxime, rifampicin or doxycycline during polymyxin therapy at the stage of marked generalization of the infection provided a significant increase in the animal survival (60 to 80 per cent) as compared to that after the use of the same drugs alone (0 to 20 per cent).


[Experimental rationale for the feasibility of using sulacillin for the prevention of infectious complications of combined radiation and thermal injuries].

Concurrent radiation and thermal injury (IRTI) was simulated in Wistar rats. For prevention of the autoinfectious complications sulacillin, a combination of ampicillin and sulbactam, was used. The use of sulacillin was started on the onset of IRTI and continued for 7 days. The drug was administered intramuscularly twice a day. It was observed that the 8-day survival of the animals increased by more than 40 per cent and the statistical levels of bacteremia and bacterial endotoxemia significantly decreased. The experiments showed that sulacillin had no side immunodepressive effect and did not aggravate the affection of the blood system. The drug was recommended for further studies to provide evidence for rational schemes of antibacterial therapy in IRTI.


[Etiology of inflammatory maxillofacial diseases and estimation of the effectiveness of antibacterial drugs in vitro].

The results of identification of 710 clinical strains of anaerobic microorganisms isolated from the pathological foci of patients with maxillofacial diseases are presented. The species composition of the microflora associations in the cases with abscesses, phlegmon, lymphadenitis, osteomyelitis and parodontitis is described. Along with a high frequency of nonsporulating anaerobes, staphylococci, microaerophilic streptococci and in the cases with parodontitis actinomycetes, Bacillus licheniformis and Bacillus coagulans strains (1.6-15% of the isolated strains) were first detected in cases with various forms of the disease. Two groups of the drugs effective against the anaerobes were identified by the data on the antibiotic sensitivity. The lowest MICs along with the activity broad spectrum were defined for gramicidin, levomycetin and nitazol.


[Antibiotic therapy in children with pertussis].

The data accumulated within the last years required revision of the indications to the use of antibiotics in treatment of pertussis. One of the aims of antibiotic therapy in pertussis was to prevent colonization of B. pertussis in the respiratory tracts. With that end in view the choice of antibiotics should be limited by those, to which the pathogen is the most sensitive i.e. erythromycin, ampicillin and augmentin. Comparative efficacy of erythromycin and ampicillin during the first 2 weeks of the disease was studied in 79 infants at the age not older than 1 year with pertussis and it was shown that erythromycin was advantageous by its therapeutic activity and less side effects. Expedience of the antibiotic therapy during the spastic period for providing a preventive effect on development of bronchopulmonary complications was studied in 201 patients with pertussis. No preventive effect of the antibiotics on development of the bronchopulmonary complications defined by the secondary bacterial flora was recorded. In the group of the patients treated with the antibiotics prophylactically (group 1) the complications were 2.6 times more frequent than in the patients treated with pathogenetic agents alone (group 2). Intrahospital pneumonia developed in 8.9 per cent of the patients in group 1 and in 1.5 per cent of the patients in group 2. Therefore, antibiotics should not be used at the late periods of pertussis for prophylaxis of secondary bacterial complications.


[Methods of local antimicrobial therapy and prevention of postpartum endometritis].

To increase the effect of the treatment of puerperal endometritis, long-term washing of the uterus cavity with cool solutions of furacillin was used in 57 puerpera. The most favourable results were observed in 27 patients who at the final stage of the washings were treated with antibiotic solutions administered to the uterus cavity. The recovery terms, as well as the terms of the hospitalization lowered. For confirming the diagnosis of endometritis and control of the therapy efficacy cytograms of the metroaspirates were used. High efficacy of the prophylactic administration of antibiotics to the myometrium tissues during the cesarean section with high risk of infectious complications was also shown. Both the methods were recommended for their wide use in obstetric hospitals.


[Influence of peroxidation products of liposomal lipids on antibacterial activity of liposomes].

The dynamics of accumulation of lipid peroxidation products (LPPs) in suspensions of phosphatidyl choline-cholesterol liposomes at various acidity levels was studied. It was shown that intensity of the accumulation of LPPs was inversely proportional to the suspension pH. When the liposomes were incubated together with the cells of Pseudomonas aeruginosa, there was a decrease in the level of LPPs in comparison to that in the suspension which did not contain bacterial cells. The accumulation of LPPs in the incubation medium correlated with the bacteria death rate in the suspension. There was a direct relationship of the antibacterial activity of the liposomal suspension on its content of LPPs.


Neurochemical and psychomotor interactions of new selective COMT inhibitors with clorgyline and nomifensine in levodopa-treated rats and mice.

The effects of three new catechol O-methyltransferase (COMT) inhibitors (nitecapone, entacapone and Ro 41-0960) were assessed on brain neurochemistry and psychomotor tests in levodopa/carbidopa-treated rats and mice. In neurochemical studies in rats, neither nitecapone (3 mg/kg) nor Ro 41-0960 (3 mg/kg) enhanced the levodopa/carbidopa (15/30 mg/kg)-induced dopamine levels in the hypothalamus and striatum, whereas 3-O-methyldopa (3-OMD) levels were suppressed. Adding clorgyline (8 mg/kg) elevated dopamine in the hypothalamus and striatum. 3,4-Dihydroxyphenylacetic acid and homovanillic acid levels were suppressed in the striatum and, to a lesser extent, also in the hypothalamus. Adding nomifensine (10 mg/kg) reversed the action of Ro 41-0960 on the 3-OMD levels and raised the homovanillic acid levels in the striatum. All COMT inhibitors (30 mg/kg) slightly enhanced levodopa/carbidopa (15/30 mg/kg)-induced hypoactivity in rats. Ro 41-0960 also augmented the effects of clorgyline and nomifensine on the locomotor activity. Levodopa/carbidopa (10/10, 25/25, 50/50, 100/100 mg/kg) dose-dependently decreased rectal temperature, rotarod time and spontaneous motility in mice. Additional COMT inhibition (30 mg/kg) had only minor effects on behavior. Ro 41-0960 (30 mg/kg) potentiated several behavioral effects of clorgyline (4 mg/kg) in the levodopa/carbidopa (10/10 mg/kg)-treated mice.


Influence of the endothelium on the responses to endogenous agonists in human internal mammary and gastroepiploic arteries.

The higher patency rate of internal mammary artery grafts compared to venous grafts has been ascribed to its endothelial function, namely a greater capacity to release endothelium-derived relaxing factor and to inhibit serotonin-induced contractions. Gastroepiploic and mammary arteries were obtained intraoperatively from 27 patients and suspended in organ chambers to record isometric tension. The relaxations to acetylcholine were similar in both vessels. The contractions to serotonin, normalized as a per cent of KCl (90 mM)-induced contractions, were 46 +/- 15% for the internal mammary artery and 18 +/- 5% for the gastroepiploic artery. Endothelium removal equally potentiated the responses to serotonin: the maximal responses (% of KCl) increased to 63 +/- 18% and 41 +/- 6%, respectively. The contractions to endothelin were also higher in the internal mammary artery: 166 +/- 19% vs 102 +/- 6% of KCl (p < 0.05), but were not affected by endothelium removal. However, the capacity to contract, expressed in tension developed, was higher in the gastroepiploic artery: the KCl (90 mM)-induced contraction was 2.6 +/- 0.3 g in the internal mammary vs 7.9 +/- 0.9 g in the gastroepiploic artery (p < 0.001). Histologically, similar wall thickness and paucity of atherosclerotic lesions were observed, but the medium was mainly elastic in the internal mammary and muscular in the gastroepiploic artery. Thus, despite a similar endothelial function and greater responsiveness of the mammary artery to endogenous vasoconstrictors when compared to a receptor-independent vasoconstrictor, the higher contractile capacity of the gastroepiploic artery might be a disadvantage in terms of graft function and patency.


Simultaneous measurement of renal blood flow of the outer and inner cortex by laser-Doppler flowmetry in anesthetized dogs: effect of enalapril diacid.

Renal hemodynamic effects of the angiotensin-converting enzyme inhibitor enalapril diacid (30 micrograms/kg, i.v.; n = 8) were examined using laser-Doppler flowmetry in anesthetized dogs. Two laser-Doppler flowmetry probes were applied simultaneously to measure the renal blood flow of the outer and inner cortex. Changes in cortical renal blood flow, obtained by the laser-Doppler flowmetry method, were intimately related to those in total renal blood flow measured with the electromagnetic flow probe during occlusion of the abdominal aorta or after administration of angiotensin II, norepinephrine, acetylcholine or dopamine. Enalapril diacid produced a significant increase in total renal blood flow, despite moderate hypotension. The blood flow of the inner cortex significantly increased by 21% following enalapril diacid, while that of the outer cortex did not. These data indicate that there may be a regional difference in the intrarenal vasodilating effect of enalapril diacid. These results also demonstrate that the laser-Doppler flowmetry method is suitable for the continuous measurement of directional changes in both outer and inner cortical blood flows.


Mitochondrial changes in phospholipid molecular species during the increased oxidative phosphorylation after hepatectomy.

The changes in liver mitochondrial and microsomal phospholipid molecular species were analyzed during the period of remarkably increased oxidative phosphorylation following partial hepatectomy in rabbits. At 24 hours after hepatectomy, phosphorylative activity increased significantly from 69.7 +/- 5.5 to 118.5 +/- 5.7 nmol of ATP synthesized/min/mg protein, compared to the sham operated group. The ratio of phosphatidylethanolamine to phosphatidylcholine (PE/PC) in mitochondria increased significantly in the hepatectomy group compared with the sham operated group. Remarkable changes in molecular species were observed in mitochondrial phosphatidylethanolamine. 1-Stearoyl-2-arachidonoyl species decreased in the hepatectomy group. On the other hand, microsomal phospholipids hardly changed compared with mitochondrial ones. The change in content of 1-stearoyl-2-arachidonyl phosphatidylethanolamine in mitochondria tended to return to normal levels concomitant with the normalization of phosphorylative activity. The changes in content of mitochondrial phospholipids, especially phosphatidylethanolamine, might also be related to enhancement of phosphorylative activity.


Topical antibiotics in cholecystectomy for gallstone diseases.

Efficacy of topical antibiotics in cholecystectomy for gallstone disease was evaluated. Forty-four patients who accepted topical single administration of 1 or 2 g each of latamoxef, cefmenoxime, cefotiam or cefamandole during operation were compared with 36 patients with systemic administration of cefem antibiotics by intravenous drip at a dose of 1 or 2 g, twice daily for postoperative 4 to 7 consecutive days. In topical administration group, concentration of each antibiotic in the gallbladder and common duct bile, gallbladder tissue, parietal peritonea and intra- and postoperative peripheral blood exceeded mostly MIC80 against bacteria usually existing in bile by biliary tract infection or bacteria by wound infection. There was no difference between the two groups in postoperative clinical course. Thus, an adequate prophylactic effect can be expected by topical use of antibiotic during cholecystectomy.


Epithelial modulation of antigen-induced tracheal smooth muscle contractions in actively sensitized guinea-pigs.

Coaxial bioassay system (guinea-pig trachea and rat anococcygeus muscle as donor and bioassay organs, respectively) and tracheal open ring preparations from ovalbumin-sensitized guinea-pigs were used to investigate the role of the epithelium in response to the antigen challenge. Ovalbumin induced concentration-dependent relaxations in the phenylephrine precontracted rat anococcygeus muscle suspended in the lumen of sensitized guinea-pig tracheal tube preparations in the presence of either indomethacin or mepacrine. Removal of the epithelium abolished ovalbumin-induced relaxation responses. In tracheal open ring preparations, epithelium removal shifted the ovalbumin concentration-response curve to the left in both the control and mepacrine-treated experiments. Indomethacin significantly potentiated the ovalbumin-induced contractions in epithelium-intact preparations, while in epithelium-denuded ones no significant change was observed. In the presence of indomethacin, the maximum contractile responses were significantly higher in epithelium-intact preparations than in epithelium-denuded ones. These results provide direct evidence for the release of epithelium-derived relaxant factor(s), which is (are) neither a cyclooxygenase nor a lipoxygenase product, in response to the antigen challenge. In addition, the observation of the increased maximum contraction to antigen in epithelium-intact preparations in the presence of indomethacin, suggests the involvement of contractile influences derived from the epithelium in antigen-induced responses of airways.


[The effects of centrifugal pump on liver support system with porcine liver perfusion].

The effects of vaneless centrifugal pump (Bio-pump P-80) on energy metabolism were studied, as compared with the roller pump, in an isolated porcine liver perfused with human blood for 6 hours. According to preliminary examination, flow rates were decided to 0.4, 0.8 ml/min/g in roller pump group, in Bio-pump pump group, respectively, not to increase more than 15 mmHg in initial portal pressure. During the perfusion, actual portal pressure was measured and circulatory resistance (portal pressure/flow rate) was calculated before perfusion and hourly after perfusion. Acetoacetate, beta-hydroxybutyrate, lactate and pyruvate, were measured at same times, from which values the ketone body ratio (acetoacetate/beta-hydroxybutyrate, KBR), reflecting the redox state of liver mitochondria, was calculated. In the Bio-pump group, in spite of its high flow, circulatory resistance was low at every hour during the perfusion. KBR was increased rapidly from 0.40 to 1.39, 2.59, 2.75, 2.38, 2.41, and 1.82 and lactate was decreased rapidly from 7.96 to 3.90, 1.77, 1.29, 1.33, 1.34, and 1.25 mmol/L at the respective hours after perfusion. There were significant differences at 2 and 4 hours after perfusion in KBR and after 2 hours of perfusion in lactate as compared with the roller pump group (p < 0.05). These results suggested that the Bio-pump is available for constant and high flow to the liver and helpful to elevate the mitochondrial NAD/NADH ratio (oxidized and reduced forms of free nicotinamide-adenine dinucleotides), leading to and enhancement of metabolic capacity of the perfused liver.


Glucagon enhances bile flow, bilirubin uridine diphosphate-glucuronyltransferase activity and biliary bilirubin monoconjugate excretion in the rat.

Intravenous infusion of glucagon (100 micrograms/hr/100 g body weight) in rats produces a 20 to 35% increase in bile flow and enhances the activity of hepatic bilirubin uridine diphosphate-glucuronyltransferase to 132% after a 90 min infusion. When a bilirubin load is given to produce a constant and apparently maximal biliary bilirubin excretion rate (or transport maximum) the administration of glucagon increased the bilirubin transport maximum. The excretion rate of bilirubin monoglucuronides was more enhanced than that of diglucuronide. The enhanced rate of glucuronidation, assayed in vitro, correlated with the augmented biliary output and inversely with the plasma unconjugated bilirubin levels. It is concluded that glucagon, at the dosage used, leads to a higher formation rate of bilirubin monoconjugates and that the choleresis, also induced by the hormone, enhances the biliary secretion of the monoconjugates formed. The enhanced conjugation results in a decreased plasma concentration of unconjugated bile pigment and the associated choleresis leads to a decreased di- to monoconjugate ratio, opposite to what has been observed during bilirubinostasis and cholestasis. The secretory efficacy, as assessed from the bile-to-plasma concentration ratio, is enhanced for all bilirubin pigments after glucagon administration.


[A case of retroperitoneal ganglioneuroma].

A 50-year-old woman was admitted under a diagnosis of abdominal tumor. Ultrasonography and CT scanning were performed, and a right retroperitoneal tumor was detected. Absolute curative resection was performed. The resected tumor was 13.5 x 11.5 x 9.0 cm, and histologically diagnosed as ganglioneuroma. To our knowledge, 99 cases have been reported in Japan. During a twelve-month follow-up period, the postoperative course was uneventful and no recurrence had been noted.


[Treatment of first restenosis by recurrent angioplasty. Immediate results and angiographic follow-up after 6 months].

This report summarises the authors' experience of 421 patients treated for a first restenosis by repeat conventional balloon angioplasty with a high 6 months angiographic follow-up (84%). The immediate results were significantly less than those obtained during the same period with initial angioplasty procedures (94.5% success and 0.9% complications without any deaths during the hospital period). The 39.9% recurrent restenosis rate, on the other hand, is the same as observed after a first procedure. The risk factors of a second restenosis seem to be different from those of a first restenosis. A shorter interval between the first and second angioplasty (< 3 months) was associated with a 55% risk of restenosis compared with only 36% when the interval was > 3 months. Two operative factors were associated with a high risk of recurrent restenosis: a maximum inflation pressure > 7 atm and > or = 3 balloon inflations. These results seem to be important and should be taken into consideration when deciding on the management of patients presenting with a first restenosis.


[Can patients with severe left ventricular dysfunction be treated by coronary artery bypass surgery?].

Forty three men and 3 women, with an average age of 59 years (13 to 78 years) underwent aorto-coronary bypass surgery despite severe left ventricular dysfunction (ejection fraction < 35%); 96% of the patients had previous infarction; 60% (N = 28) had unstable angina, 52% (N = 24) had had pulmonary oedema or an episode of congestive cardiac failure. The average ejection fraction was 29 +/- 4%, range 17 to 35%. Thirteen patients had ventricular aneurysms, 4 had grade 3 or 4 mitral regurgitation. The coronary lesions were usually multivessel left main coronary (6), triple vessel disease (27), double vessel disease (12), single vessel disease (1). The average number of bypass grafts per patient was 2.3. The average aorting clamping time was 63 minutes (range 26 to 133 minutes). There were 4 mitral valve replacements, 4 resections of ventricular aneurysms and 1 double procedure (aneurysmectomy and valve replacement). The operative mortality was 2.1% (1 death). During an average follow-up period of 27 months (range 3 to 90 months), there were: 2 recurrent infarctions, 13 episodes of cardiac failure and 8 cardiac deaths (cardiac failure: 5, sudden death: 2, recurrent infarction: 1). Two patients underwent cardiac transplantation. The regression of angina (90% of operated patients were asymptomatic) and the low operative risk, justify aortocoronary bypass surgery despite left ventricular dysfunction in patients with severe symptoms (unstable angina, chronic, invalidating angina). The medium-term results indicate a high risk of cardiac failure which is partially responsible for the secondary mortality rate of 17% at 2 years.


[VVI mode cardiac pacing: cause or risk factor of cerebral embolism?].

Epidemiological studies suggest that VVI pacing is associated with a higher risk of embolic complications than atrial or dual chamber pacing. However, no studies have been performed on pacemaker patients admitted to a neurological department with a cerebral embolism. The authors report the cases of 8 patients (6 men and 2 women) with an average age of 74 years and having the following characteristics: 1) a cerebral embolism, 2) a permanent cardiac pacemaker (7 VVI and 1 DDD mode). The average delay between implantation of the pacemaker and the neurological complication was 31 months. Cardiological investigations at the time of admission showed: a clinically evident cause of cardiac embolism in 3 cases (2 with VVI and 1 with DDD pacing); paroxysmal or permanent atrial fibrillation in 4 cases with VVI pacing at the time of the embolic event (in only one case at the time of implantation); various echocardiographic abnormalities in 6 of the 7 patients who underwent this examination, mainly left atrial dilatation (6/7), septal wall motion abnormalities in all related to ventricular pacing and unexplained left ventricular dilatation in 2 patients with VVI pacemakers. These results suggest that although the etiology of cerebral embolism was probably multifactorial in some patients, VVI packing probably a predisposing role, though not the only cause, and could be considered to be an embolic risk factor as suggested by previous epidemiological studies. These preliminary retrospective data should be interpreted cautiously taking into account the small population size. Prospective studies on pacemaker patients with cerebral embolism are required.


[Heart surgery in normothermia and aerobiosis: apropos of 530 patients].

Between February and October 1991, 530 consecutive patients underwent myocardial revascularization or valvular surgery with warm continuous antegrade and retrograde cardioplegia (37 degrees C). Three hundred and thirty three patients had isolated myocardial revascularization, 159 valvular surgery alone and 25 had combined valvular and coronary bypass. The global mortality was 5.1%, 3.7% for coronary bypass, 7.5% for valvular surgery and 8% for combined valvular and coronary surgery. A multivariate analysis identified the "reperfusion time" as the only predictive factor of hospital mortality (p < 0.001). Intraortic balloon counterpulsation was required postoperatively in 3.2% of cases, 5.2% of coronary bypass and 0.8% of the valvular patients. Inotropic drugs were used to come off cardiopulmonary bypass in 16.5% of coronary and 37.5% of valvular patients. There were 0.9% perioperative infarctions: 1.2% in the coronary bypass cases and 0.6% in the valvular cases. Spontaneous return to sinus rythm was observed in 87.9% of cases. The average "reperfusion time" was 20.48 +/- 0.7 mn. Analysis of the influence of aortic cross clamp time on cardiac morbidity in two groups of coronary patients (Group I: short cross clamp time less than 60 mn; Group II: long cross clamp time, 60 to 33 mn) showed that the hospital mortality, the prevalence of the use of inotropic drugs and balloon counterpulsation the postoperative cardiac index, the rate of spontaneous de fibrillation and the reperfusion time did not depend on the aortic cross clamp time. Cardiac morbidity.


[Value and limits of balloon laser-assisted angioplasty in the treatment of acute obstruction during percutaneous transluminal coronary angioplasty].

One of the problems of percutaneous transluminal coronary angioplasty is acute occlusion during the procedure, the main cause of serious complications and emergency coronary bypass surgery. Acute occlusion is generally related to severe intimal dissection and/or thrombosis. In animal experiments, it is possible to treat intimal dissection and dessicate thrombi by balloon laser angioplasty. Using this method, a programmed laser energy may be delivered to the arterial wall via a fiber optic system linked to a Nd:Yag laser during classical balloon inflation. This has been proposed for the treatment of acute coronary occlusion. Between September 1989 and August 1990, 923 patients underwent coronary angioplasty at the Centre Cardiologique du Nord. Peroperative acute occlusions occurred 52 times (3.9%) in 52 patients. Sixteen patients who were "candidates" for emergency coronary bypass surgery (residual stenosis > or = 75%; delayed flow; myocardial ischaemia) were treated by laser balloon angioplasty, 14 with success (87%). Two patients had to be operated as an emergency. There were no hospital deaths. The average follow-up was 4.7 months for the 14 non-operated patients. Systematic control coronary angiography was refused by 2 asymptomatic patients. In the other 12 patients investigated 1 to 17 months after the procedure, there were 10 restenoses (76%), 6 of which were treated by repeat angioplasty and 3 by coronary bypass surgery. These results show that balloon laser angioplasty is very effective in the treatment of peroperative acute occlusions, enabling emergency coronary bypass surgery to be avoided in 87% of cases, but it is associated with a very high restenosis rate which is difficult to accept.


[Calcium channel inhibitors and ventricular filling].

Abnormalities of ventricular relaxation and compliance often precede changes in systolic function in ischemic and hypertrophic or hypertensive heart disease. Several studies using non-invasive methods have confirmed the beneficial effects of calcium channel blockers on left ventricular diastolic function in ischemic and primary hypertrophic cardiomyopathies. Their usefulness remains controversial in secondary cardiac hypertrophy such as in hypertensive heart disease. Improved left ventricular isovolumic relaxation and filling results more from the coronary and peripheral vasodilatory effects of calcium channel blockers than from a direct action on the cardiac muscle.


[Effects of angiotensin II on intrinsic contractibility of the myocardium in the guinea pig].

Analysis of the contraction-relaxation coupling of guinea pig left ventricular papillary muscle was performed with and without angiotensin II (Ang II 10-6 M). The inotropic and lusitropic properties of Ang II were evaluated at 20 degrees C, 30 beats/min, CaCl2 6H20 2 mM and pH 7.4, under low load (isotonic conditions) and high load (isometric conditions). The maximum velocity of contraction (max Vc) and relaxation (max Vr) were calculated from isotonic contraction having as its only load that corresponding to the imposed preload at Lmax. The maximum positive (+dF/dtmax) and negative values (-dF/dtmax) of the derivative of the force were calculated during isometric contraction. The coefficients, R1 = max Vc/max Vr and R2 = (+dF/dtmax)/(-dF/dtmax), were calculated. These two coefficients allow the contraction-relaxing coupling to be assessed at low and high loads respectively. In the presence of Ang II, the increase in the isotonic velocity of relaxation (1.93 +/- 0.26 vs 3.15 +/- 0.35 Lmax/sec; p < 0.001) was greater than that of the isotonic velocity of contraction (0.74 +/- 0.05 vs 1.02 +/- 0.07 Lmax/sec; p < 0.001). This results in a decrease in the ratio of the velocities of isotonic contraction and relaxation (R1) (0.44 +/- 0.06 vs 0.35 +/- 0.05; p < 0.01). Under isometric conditions, Ang II induced a proportional increase in the parameters of contraction and relaxation. Consequently, there was no significant change in the R2 coefficient (1.22 +/- 0.06 vs 1.12 +/- 0.08). Moreover, Ang II did not induce any change in the sensitivity of the relaxation with respect to load.(ABSTRACT TRUNCATED AT 250 WORDS)


[Study of new thrombolytic agents in myocardial infarction: a multicenter randomized trial (APSAC versus rt-PA)].

A hundred and eighty three patients with a primary myocardial infarction less than 4 hours old were included in a double blind trial versus placebo comparing an isolated plasminogen streptokinase activator complex (APSAC: 30 mu in 5 mn) and tissue type plasminogen activator (rt PA: 10 mg bolus followed by 90 mg in 130 mn). Clinical evolution, side effects, patency of the artery responsible for infarction, left ventricular contractile function (contrast angiography on the 7th day and angioscintigraphy on the 21st day) and infarct size were studied. The two groups were comparable in age (54 +/- 11 years), delay in randomisation (170 +/- 50 mn), infarct site and severity of cardiac failure. There was no significant difference in hospital mortality (7 in the rt PA group and 5 in the APSAC group) or in adverse effects (haemorrhage: rt PA: 9 patients, APSAC: 11 patients). The patency was 72% in the APSAC and 76% in the rt PA group. Left ventricular function and infarct size were comparable in the two groups: angiographic EF (0.50 +/- 0.1 in the APSAC and 0.52 +/- 0.1 in the rt PA group: NS); asynergic score (11.3 +/- 1.7 in the APSAC and 10.5 +/- 1.8 in the rt PA group: NS); infarct size (10.9 +/- 8.0 in the APSAC and 9.4 +/- 7.2 in the rt PA group: NS). This trial shows that these two thrombolytic agents have the same efficacy. The authors recommend adaptation of the dosage of rt PA to body weight.


[Macrocreatine kinase, a cause of MB isoenzyme levels falsely elevated].

The authors describe two cases of falsely elevated CPK-MB levels due to the presence of a Macro-CPK. The quantification of the mass of CPK-MB gave values lower than the cut-off level. Electrophoresis of CPK isoenzymes showed a type 1 Macro-CPK in one case and a type 2 Macro-CPK in the other. The authors recommend electrophoresis of CPK isoenzymes or quantification of mass if the clinical evolution or ECG changes do not correlate with the CPK-MB levels or if there is a low global CPK with high CPK-MB levels.


[Ventricular tachycardia in a patient with rate-responsive cardiac pacemaker].

The authors report a case of syncopal ventricular tachycardia in a patient with a respiratory-dependent rate responsive pacemaker, followed-up for valvular heart disease with severe left ventricular dysfunction and sustained atrial and ventricular arrhythmias. The introduction of low dose betablocker therapy with reinforcement of the treatment of cardiac failure controlled the ventricular arrhythmia, after suppression of the data responsive function had been shown to be ineffective. The authors discuss the role of the rate responsive function in the triggering of the ventricular tachycardias.


[Fungal thrombus of the right atrium on a central venous catheter. Apropos of a case].

The authors report the case of a 9 year old child in an intensive care unit after multiple trauma, presenting with a candida septicaemia and a central venous catheter. Echocardiography, performed because of the inefficacy of medical treatment, showed a right atrial thrombus. Surgical ablation was decided because of its extreme mobility and persisting infection, and resulted in cure of the patient.


[Mycotic aneurysm of the carotid artery secondary to acute bacterial endocarditis].

Mycotic aneurysms of the extracranial carotid arteries are rare. A new case of mycotic aneurysm of the bifurcation of the carotid artery secondary to acute bacterial endocarditis affecting the aortic valve is reported. Simultaneous treatment of the two lesions was instituted. The twenty six cases of mycotic aneurysm of the extracranial carotid arteries previously described in the literature are reviewed by the authors.


[Intellectual development after relaxing the diet at the age of 5 years in typical phenylketonuria].

No satisfactory controlled trial has yet been completed on typical phenylketonuria (PKU) patients whose treatment was relaxed at the age of 5 years. 27 children having typical PKU were treated before the age of 3 months. The intake of phenylalanine and protein was carefully regulated during the first 5 years of life, after which the treatment was relaxed. All children were evaluated after at least 6 years on the relaxed diet. Their IQ scores and school performance were related to the degree of dietary control and plasma phenylalanine values. The IQ scores at 5 years of age were 100 +/- 10.8. Continued evaluation showed that IQ scores remained unchanged. Poor school performance was twice as frequent as in general population; the deficit in the IQ score of this group was 8 points below that of normal sibs. There was no correlation between plasma phenylalanine and the IQ score after the age of 5 years. The positive control decreased with aged. Children with typical PKU have an IQ deficit relative to their normal sibs just before relaxing treatment. Good dietary control until 5 years of age, maternal intelligence and continuing evaluation during relaxing diet are the best conditions for optimal intellectual progress. There is no evidence that continued treatment during adolescence is beneficial.


[Pica and iron deficiency in adolescence].

Pica is a habit disorder involving the compulsive, irrational ingestion of nutrient or non-nutrient substances which usually, in young infants, include clay and earth. Pica is rare in adolescents but is more likely to occur in subjects with severe iron deficiency. 17 (16 girls, 1 boy) cases of pica were recognized over a period of 4 years in an adolescent unit. 15 of the cases presented with anemia and/or iron deficiency. Hematological and biochemical investigations included measurements of hemoglobin content, MCV, serum iron and ferritin, transferrin saturation and serum iron-binding capacity. Blood loss was considered as a possible cause in all patients. 13 of the patients ingested large amounts of raw rice and 11 ingested ice cubes; 10 patients ingested both substances. Their mean serum ferritin was 7.17 ng/ml and the mean hemoglobin was 8.7 g/dl. One out of 7 patients showed intestinal blood loss. Excessive menstrual bleeding occurred in 8 girls. All patients were treated with adequate amounts of iron. Pica disappeared within a few weeks, although biochemical evidence of iron deficiency persisted in some patients. In one case, pica persisted despite correction of the iron deficiency. Pica is more prevalent in lower socio-economic classes and in some areas, such as the island of Reunion. It may be masked, and must be looked for in adolescents presenting with signs of iron deficiency. Treatment of the iron deficiency is usually followed by its disappearance.


[Causes and modalities of pediatric ambulatory care in ten hospitals in the Ile-de-France region].

The increasing shortage of financial resources requires optimal use of hospital care by patients. However, the studies carried out to date in France have been limited to patients who are hospitalized, and have not included those seen as out-patients. All patients seen as out-patients in 10 hospitals in the Paris district (3 pediatric hospitals and 7 pediatric departments located in hospitals for adults and children), during the week of 19-26 April 1989, were given a questionnaire on the age, sex, nationality, socio-cultural and economic features of the family, history of earlier medical visits or admissions, the existence of pediatrician or practitioner, and the means and time taken to get to the hospital. Medical diagnosis was established for each patient following the WHO International Classification of Diseases (9th edition). 2,365 out of 2,675 questionnaires were usable. The main features were: 50% of patients were less than 3 years old, 55% were of French origin; 78% belonged to families with relatively low socio-economic status. Both parents had professional activities in 49% of families, 7% of mothers did not speak or write French. The ratio of patients aged less than 3 years admitted to the emergency ward was higher than the average. The most frequent diseases presented by these patients were respiratory (23%), infectious (14%), gastro-intestinal (10%) and neurological (7%); 14% of the patients were seen for symptoms that could not be assigned to a specific disease. 39% of patients were seen in out-patient clinics and 61% in emergency wards. 40% were sent by a health professional to out-patient clinics and only 25% to emergency wards. Despite the fact that this study is subject to particular conditions, i.e., relative frequency of infectious diseases due to seasonal causes, it suggests that the hospital is becoming the primary source of health care with an increasing percentage of patients seen in "emergency", even though this emergency is often more apparent than real. Health care networks should be established.


[Granulosa cell tumors of the ovary in children and adolescents. Multicenter retrospective study in 40 patients aged 7 months to 22 years].

Juvenile granulosa cell tumors (JGCT) of the ovary are rare in children. The over-all outcome after surgery is relatively good, but the indication and type of complementary treatment for severe forms are still unclear. A retrospective survey of the majority of patients with JGCT of the ovary admitted between 1965 and 1990 to 11 French oncologic pediatric centers was carried out. Medical records including surgical and histological data, were analyzed and each tumor was retrospectively classified by the same pathologist according to the Wollner classification. There were 40 patients aged 7 months to 22 years (mean: 6 years); 28 were less than 10 year old at diagnosis. Three had enchondromatosis (Ollier's disease). At diagnosis, all patients presented with an abdominal tumor, 23 had developed manifestations of precocious pseudopuberty, 2 had signs of virilization after a normal puberty and 2 had secondary amenorrhea. Surgery was always the primary treatment: unilateral ovariectomy in 35 cases, bilateral in 4 and biopsy alone in 1 case. There were 21 stage I, 1 stage II, 16 stage III and 2 stage IV cases. 13 patients received combined chemotherapy and 2 abdominal radiotherapy. 34 patients were alive and disease-free 10 months to 26 years after surgery and 6 died. All 23 patients with precocious pseudopuberty had a favorable outcome. This study confirms earlier reports. Unilateral ovariectomy is the first-choice therapy. There is no evidence that tumors complicated by rupture and hemoperitoneum require chemotherapy. Combined chemotherapy does not appear to improve the prognosis for the rare malignant forms. The factors of good prognosis are age less than 10 years and the presence of precocious pseudopuberty.


[Schwartz-Jampel syndrome (osteochondromuscular dystrophy)].

Schwartz-Jampel syndrome is a rare disorder inherited as an autosomal recessive trait and characterized by growth retardation, multiple skeletal abnormalities, myotonia-like muscle disorders and unusual facies. Case n. 1: A boy, aged 3 years 4 months, was admitted for acute respiratory disease. His main abnormalities included rigid facial expression, blepharophimosis, puckered lips, short neck, pectus carinatum, acetabular dysplasia with coxa vara, platyspondyly and marked growth retardation. There was a continuous muscle fiber activity at rest, with abnormal discharges originating in the muscle component of the neuromuscular junction. Blood investigations revealed low values of IgA. The child died at 4 years. Case n. 2: The sister of case n. 1 was examined at 14 months of age. She presented milder facies abnormalities, difficulties of gait because of stiff hips, muscular hypertrophy, coxa vara and growth retardation. X-rays showed skeletal abnormalities and the electromyogram was similar to those of her brother. She had dislocation of her optic lens. These 2 sibs have the characteristic manifestations of Schwartz-Jampel syndrome. Parental consanguinity was also present. The IgA deficiency observed in case n. 1 and the lens dislocation in case n. 2 have both been occasionally reported in this syndrome.


[Continuous arteriovenous hemofiltration. Management in case of neonatal leucinosis].

Neonates with classic maple syrup urine disease (MSUD) undergo rapid neurological deterioration by the end of the first week of life. Exchange transfusion and peritoneal dialysis are the usual emergency treatment. Continuous arteriovenous hemofiltration (CAVHF) appears to be safe and more rapidly effective. Martin was born at the 37th week from a normal pregnancy. Abnormal movements of legs and lethargy appeared on the 7th day of life. Progressive brain dysfunction with coma led to intubation on the 13th day. A diagnosis of MSUD was immediately made and CAVHF was initiated and continued for 19 hours. The plasma leucine, valine and isoleucine levels fell from 2,248 to 275, 640 to 91 and 298 to 13 mumol/l, respectively. Neurologic improvement was dramatic, except for moderate hypertonia which lasted for the 2 following days. CAVHF is an appropriate treatment for very young patients with inborn errors of metabolism. It appears safer and more rapidly effective for eliminating branched-chain amino acids than other techniques, such as peritoneal dialysis with or without exchange transfusions. It also permits more rapid introduction of the specific diet.


[Mirror movements. Preliminary therapeutic study].

Mirror movements are a specific type of synkinesis. The pathogenesis is unknown. Three types have been identified: 1) a hereditary form, 2) a form associated with other neurological diseases, 3) a sporadic form, as is this case. A girl was born at term after cesarean section for fetal anoxia. Psychomotor development seemed normal, but mirror movements of fingers, hands, wrists and forearms were noticed when she was 8-9 months old. There were no other neurological manifestations and the imaging techniques were normal. Rehabilitation was begun when she was 20 months old. The girl is now 4 1/2 years old and writes, draws and cuts up normally. Mirror movements that are not associated with other neurological disorders usually remain unchanged and can be a professional handicap for adults. Prolonged rehabilitation offers a good functional prognosis.


[Medical treatment of chylous effusions in newborn infants. Apropos of 3 cases].

Chylous effusions are the most frequent cause of non immunologic hydrops fetalis. They can be recognized antenatally by ultrasonography. Their evacuation is sometimes necessary and medical treatment often effective. Case n. 1: fetal ascites was detected by ultrasonography at the 30th week of gestation. Paracentesis was performed at 36 weeks, followed 3 days later by spontaneous delivery. The newborn was fed milk formula. A second paracentesis showed a milky fluid, rich in cholesterol, triglycerides and chylomicrons. The child was fed formula rich in medium-chain triglycerides and the chylous ascites disappeared completely within 2 weeks. Case n. 2: a diagnosis of bilateral hydrothorax and hydramnios was made at the 27th week of gestation. An in utero evacuation of the hydrothorax performed at the 30th week was ineffective and a pleuro-amniotic drainage was performed 2 weeks later. The baby was born at the 35th week, and presented a moderate respiratory distress due to the hydrothorax and ascites. Aspiration of the thoracic fluid confirmed its chylous origin. The chylous effusions completely disappeared when the child was fed a high medium chain triglycerides diet. A lymphedema of legs appeared at the age of 1 month. Case n. 3: ascites, hydramnios, hydrothorax and peripheral edema were found at the 21st week of a third pregnancy (the 2 first pregnancies were complicated by lethal hydrops fetalis). Bilateral hydrothorax and peripheral edema were found again after birth at the 37th week. Diuresis and albumin-infusion led to recovery, but chylothorax and chylous ascites reaccumulated after introduction of milk formula, despite repeated evacuations and feeding medium-chain triglycerides formula. The thoracic fluid remains chylous at the age of 9 months. In utero, and sometimes post-natal, evacuation of fluid present in the thoracic and peritoneal cavities can be necessary, depending of the functional tolerance. Medical management including feeding a low fat and/or high medium-chain triglycerides diet, and sometimes temporary total parental nutrition, is necessary, together with salt restriction, diuresis and albumin infusion as required. Most cases recover spontaneously or as a result of therapy within a few weeks.


[Phlebothrombosis revealing Behçet's disease in a 13-year-old adolescent].

Behçet's disease is rare in children and is exceptionally revealed by thrombophlebitis at this age of life. A girl, aged 13 years, was admitted after having suffered from thrombophlebitis of the right leg for 6 weeks. Her medical history included frequent attacks of aphthous stomatitis and conjunctivitis and one episode of iritis. At admission, thrombophlebitis with venous thrombosis was confirmed by Doppler; it was associated with aphthous gingivitis and two similar erosive lesions in the genital area. Technetium 99 perfusion scintiphotography revealed a right pulmonary embolism. The erythrocyte sedimentation rate was elevated but there was no change in coagulation factors or immunologic abnormalities, except for the presence of immune complexes and increased complement C3 component. Biopsy of the skin lesions showed vascularitis. There was no involvement of the eyes. The condition progressively improved with anticoagulant treatment for 1 year, followed by low doses of acetylsalicylic acid. Phlebothrombosis, a classic complication of Behçet's disease in adults, revealed the disease in this girl. Its mechanism remains unclear and duration of anticoagulant treatment is still debated.


Tissue distribution of MHC class II--positive cells, their down-manipulation by monoclonal antibodies and potential role in organ allograft immunogenicity.

This review article presents current state of knowledge of tissue distribution of MHC class II antigens in rat kidney. Our attention focuses particularly on down manipulation of these antigens by monoclonal antibodies. The results of organ perfusion procedure on prolongation of graft survival and perspectives of further studies are also discussed.


Macrophage activating factors produced in the course of murine tularemia: effect on multiplication of microbes.

Primary F. tularensis infection in mice induces the production of macrophage activating factors (MAFs) by spleen cells. The stimulation of macrophage cytolytic activity (MAF-c) and hydrogen peroxide production (MAF-H2O2) dominates between days 7 and 10 in the course of tularemia. Three various pools of active fractions (10-11, 14-15, 25-28) were fractionated by two-step chromatography. Typical for 10-11 and 14-15 is MAF-c activity whereas in 25-28 prevails MAF-H2O2. Initial concentrated supernatant (day 7 of infection) and individual fractions have been used to raise antibodies KI (anti 10-11) and KII (anti 14-15). Neutralization reactions with specific antibodies indicate the presence of tumor necrosis factor alpha (TNF alpha) in 14-15 (44% inhibitable), interferon gamma (IFN gamma) and interleukin 2 (IL 2) in 25-28 (65% and 30% neutralization, respectively). Utilizing KI and KII, 99% and 90% inhibition of cytolytic activity is reached in 10-11 and 14-15, respectively, in spite of non-specific cross reaction. Western blot analysis of proteins in supernatant on day 7 detects, besides TNF alpha, further protein bands (13, 15.5, 52 and 72 kDa) that seem to be associated with macrophage activation. Significant protective effect against in vivo multiplication of tularemic microbes indicates a certain role of TNF alpha, however, cooperation of other molecules is worth to be taken into consideration.


Two patterns of NK activity changes following blood donation: decrease in the beginners and restoration in regular blood bank donors.

NK cell activity of peripheral blood lymphocytes was determined in voluntary blood bank donors in a standard 4-hr 51Cr-release cytotoxicity assay. When blood donors were divided into groups according to the total amount of blood they had donated in the past, decreased NK activity was found in "moderate" donors who had donated between 3 and 9 l of blood, but not in those who had donated < or = 3 or more than 9 l of blood before testing. This observation was the rationale for a study on the effects of regular blood donations on NK activity in randomly selected voluntary blood bank donors re-tested over a period of time. The study demonstrated decreased NK activity in the second measurement in donors who had donated up to 6 l of blood before the study, and an increase in NK activity between the first and the second testing in those who had donated more than 6 l of blood. This result, together with data obtained at the population level, suggests that some compensatory mechanism(s) regulate NK activity in the course of regular blood donation.


T lymphocyte subsets and NK cell cytotoxicity in chronic hemodialysis patients. The effect of recombinant human erythropoietin (rHu-EPO) treatment.

We investigated subpopulations of T lymphocytes, NK cell number and cytotoxic activity in 14 chronic uremic patients on regular hemodialysis treatment. We observed a significantly decreased absolute lymphocyte number and percentage of CD3 cells. Relative numbers of CD16 cells were significantly elevated, but NK cell cytotoxic activity was within a normal range. Nine patients with chronic renal anemia on maintenance hemodialysis were enrolled in rHu-EPO treatment trial. The treatment was continued till the hematocrit level reached 30%. Each of the patients had corrected anemia and well-being. After 12 weeks of the treatment we observed in these patients decreases in CD3, CD4, CD8 and CD16 cell numbers and elevation of CD4/CD8 ratio. Cytotoxic activity of NK cells did not change significantly. Presented results indicate that chronic hemodialysis patients have significantly diminished lymphocyte number. rHu EPO treatment affects the T lymphocyte subsets inducing a deep decrease of CD8 and CD16 cell percentage leading to normalisation of the CD4/CD8 ratio.


The influence of tuftsin partial sequences on histamine level in guinea pig and rat tissues.

We investigated the influence of tuftsin partial sequences (Thr-Lys, Lys-Pro, Lys-Pro-Arg and Pro-Arg) on histamine concentration in selected tissues (lungs, kidneys, liver, duodenal wall and arterial blood) of guinea-pigs and rats. The peptides were administered in 1 mg/kg dose intravenously (single dose) or intraperitoneally (single dose or three doses at one-hour intervals). Histamine concentration was determined spectrofluorimetrically. Tissues used in the determination were taken 1 hour after the last injection. It was found that Pro-Arg and Lys-Pro-Arg (similarly to tuftsin), lower histamine concentration in lungs, and elevate it in kidneys.


Immunosuppressive activity of tyrosine analogues of cyclolinopeptide A.

Immunosuppressive properties of six tyrosine analogues of cyclolinopeptide A were studied and compared with the activity of cyclosporin A. The peptides were investigated using PFC (in vitro) and DTH tests.


The activity of two immunotoxins composed of monoclonal antibody MoAb-16 and A-chain of ricin (MoAb-16-RTA) or A-chain of mistletoe lectin I (MoAb-16-MLIA).

The A-chains of ricin obtained from Ricinus communis or mistletoe lectin I from Viscum album were coupled to the monoclonal, anti-L1210V antibody MoAb-16, using SPDP as a cross linking agent. The cytotoxic activity in vitro of these immunotoxins was compared. Each of two immunotoxins tested, applied in vitro for 1 h in appropriate doses, caused irreversible inhibition of leukemic L1210 cells proliferation. Unexpectedly, MoAb-16-MLIA immunotoxin appeared to be cytotoxic to normal bone marrow progenitor cells, as observed in NCFUS tests. Moreover, this immunotoxin revealed cytotoxic effect to the P388 leukemia cells which do not share the antigen, common within L1210 leukemia cells, detected by MoAb-16 antibody.


Simultaneous induction of interferon gamma and tumor necrosis factor alpha by different seleno-organic compounds in human peripheral blood leukocytes.

Ebselen is known as anti-inflammatory and anti-oxidant selenium containing drug. We have synthetized 13 seleno-organic compounds, analogs of ebselen. Seven of them were found to be inducers of interferon gamma (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) in human peripheral blood leukocytes (PBL) cultures. The most active cytokine inducers were: 2-phenyl-1,2-benzisoselenazol-3(2H)-one (1, ebselen), bis [2-(N-phenylcarbamoyl)]phenyl diselenide (7) and bis (2-[N-(2-pyridyl)carbamoyl])phenyl diselenide (8). The amounts of IFN and TNF produced by PBL cultures in response to the seleno-organic compounds were found to be similar to that induced by phytohemagglutinin (PHA). The activities of the seleno-organic compounds were dose-dependent and related to the chemical structure of the drugs suggesting involvement of the specific cytokine-inducer receptor. The simultaneous inductions of IFN-gamma and TNF-alpha were highly correlated, but independent on each other.


Human lymphoid target cells for the cytokine-inducing seleno-organic compounds.

Several seleno-organic compounds including ebselen are known as antiinflammatory and antioxidant agents. They also have glutathione peroxidase-like activity and are inhibitors of leukotrienes and prostaglandins. We have recently discovered that these drugs are inducers of cytokines, mainly interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and mitogenic interleukins in human peripheral blood leukocytes (PBL) but not in the mouse or rat lymphoid cells. We described a production of IFN-gamma and TNF-alpha by various subsets of PBL stimulated with 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) or bis [2-(N-phenyl-carbamoyl)]phenyl diselenide. IFN-gamma was produced mainly by E-rosette positive lymphocytes. However, the presence of monocytes was required for the optimal production of IFN-gamma. Also soluble mediators released by monocytes enhanced IFN-gamma synthesis. On the other hand, TNF-alpha was produced mainly by the adherent monocytes. Its synthesis was enhanced by the addition of T or B lymphocytes or conditioned medium from the culture of the stimulated lymphocytes. The relative concentrations of the subsets of lymphocytes or monocytes was important for the maximum production of both IFN-gamma and TNF-alpha. High concentration of lymphocytes inhibited the cytokine production.


The association between occlusion and attrition.

The purpose of this study was to identify variables of malocclusion that might be associated with attrition and then to quantify the relationship between these variables and attrition. The results of this study indicate that, with all other factors held constant, a patient's attrition score tends to: increase with age, increase with bite depth, decrease initially with overjet until a critical value and then increase, and be unaffected by sex, interincisal angle, U1 to NA angle, Angle classification, posterior or anterior cross bites. Further, we discuss the statistical treatment of data of this kind and emphasize the importance of a professional approach to analysis.


Dentofacial orthopaedic correction of maxillary retrusion with the protraction facemask--a literature review.

The retruded maxilla in the Class III skeletal pattern could be effectively corrected with the protraction facemask in selected cases. A review of the different types of orthopaedic appliances used in Class III treatment, the rationale for facemask therapy, the effect of this treatment and the factors affecting stability is presented.


A novel method of sterilizing orthodontic instruments.

A range of orthodontic instruments was artificially inoculated with a mixed culture of representatives of the oral microflora and a marker bacterium and subjected to dry heat sterilization using a glass bead sterilizer. The shortest time which would guarantee total sterilization of the functional parts of the instruments was thirty seconds.


A new concept in the Begg technique: the separate arch system.

The author reports on the Separate Arch System (SAS) he has devised by adapting basic Begg Technique concepts in the light of his clinical experiences. SAS, a multi-bracket arrangement using reverse light wire brackets, is a method of initiating orthodontic movement in the anterior and posterior segments separately, but completing them at the same time. The method's features include: a) use of thinner wire in segments and in multiple strands, as needed, maximising benefits of light force and differential anchorage; b) one-point rigidity in the wire-bracket relation; c) the method can be applied in both extraction and non-extraction cases; d) the patient's home care is simplified; e) the method is quick, simple, and systematic (thus making estimation of a therapy goal possible).


A procedure for attachment of gold chain for traction of impacted teeth.

There is a need to improve the strength of the attachment of the gold chain to impacted teeth. Dislodgement of the gold chain requires a second surgery for reattachment. Failures have been observed to occur at two interfaces. The authors have devised a method of attaching the gold chain to the mesh pad securely, by ligating them together. This article describes the method and discusses other factors which enhance the retention of the gold chain to the impacted tooth.


Case report--swallowed piece of archwire.

A fifteen year old healthy, male patient contacted our office stating that whilst eating a bread roll he had swallowed a piece of orthodontic archwire. He complained of stomach pain and was advised to contact his local medical practitioner who had the area radiographed. The radiographic examination revealed the piece of archwire to be lodged in the pylorus. The patient was then referred to a consultant physician who, using a gastroscope and with the orthodontist present, to assist with supervision of the orthodontic appliance during gastroscopy and to determine that the piece removed had not undergone further fracture, removed the piece of broken archwire. The piece of wire was forwarded to the Therapeutic Devices Branch of the Department of Community Services and Health for analysis.


[Hidden symmetry of peptide and protein primary structures].

The internal symmetry of peptide chains was considered. To identify symmetrically located equivalent amino acids, the signatures method and the code of amino acid codon roots were applied. There was revealed the hidden symmetry of amino acid sequences of peptides and proteins as well as of their active centres. Amino acids having common codon roots in primary (and supposedly in the spatial "biologically active") molecular structures, are located symmetrically. Definition of local symmetry of peptide chains was proposed to use as one of the elements of complex analysis to determine location of molecular active centres.


[Approach to studying the structure-activity relationship of native peptides. I. Structural organization of the opioid peptide Tyr-Glu-Gly-Phe-Met-Arg-Gly-Leu and its artificial analogs].

Theoretical conformational analysis was carried out for the octapeptide Tyr1-Gly2-Gly3-Phe4-Met5-Arg6-Gly7-Leu8. Possible structure of the opioid peptide under physiological conditions may be described by a set of low-energy conformations belonging to 14 different forms of the backbone. The solution of the "reverse conformational problem" for the opioid peptide enables one to predict the modified amino acid sequences (Ala2, D-Ala2, Ala3, D-Ala3, Ala7, D-Ala7, MeMet5, MeArg6-analogues) which may assume one of the low-energy states of the native hormone. The influence of the solute was not taken into account in our calculations.


[Approach to studying the structure-activity relationship of native peptides. II. Structural organization of alpha- and beta-neoendorphins].

By means of a semi-empirical method, an a priori conformational analysis of alpha- and beta-neo-endorphins was carried out. Calculations yielded the values of all dihedral angles of the backbone and side chains of the peptide's various forms as well as intra- and inter-residue interaction energies.


[BspLS2I--a new site-specific endonuclease from the thermophilic bacteria Bacillus species LS2].

A new restriction endonuclease BspLS2I was isolated from the thermophilic bacterium Bacillus species LS2 and purified by blue sepharose and hydroxyapatite chromatographies. The enzyme is an isoschizomer of SduI from Streptococcus durans. BspLS2I recognizes the sequence 5' G(G/A/T)GC(C/T/A) decreases C 3' on double-stranded DNA and cleaves it is indicated by the arrow to yield sticky-ended DNA fragments. Maximum catalytic activity of endonuclease was found in 10 mM tris-HCl (pH 7.9) in the presence of 15-30 mM MgCl2 at 50 degrees C. The phage T4 glucosylated DNA is not cleaved by the enzyme.


[Genetically engineered human insulin. 1. HPLC in analyzing products of basic production stages].

Application of some variants of HPLC for the step-by-step analysis of recombinant human insulin production was studied. Chromatographic columns with commercial and specially developed supports for size-exclusion, ion-exchange and reverse phase HPLC were used. Effective combinations of the chromatographic techniques for analysis of products and intermediates at every technological step were found and used for production of insulin. The authenticity of insulin obtained in the Shemyakin Institute of Bio-organic Chemistry by the scheme described in the present paper was confirmed by means of some physical and chemical methods and biological activity analysis.


[Chemical-enzymatic synthesis and cloning of the full-length genome of a DNA-containing plant virus].

The full-length genomic DNA of a small plant virus--coconut foliar decay virus (CFDV)--has been synthesized by a combination of chemical synthesis, ligation and polymerase chain reaction. Three separately cloned DNA fragments of the genomic DNA were sequenced and assembled in the pPCV002 plasmid vector.


[Structure of a single-stranded DNA target as a factor influencing the effectiveness of its modification with a complementary reagent].

Site directed alkylation of three oligonucleotide targets: 41-mer (hairpin structure), 22-mer (loop part of this hairpin) and 10-mer (part of the loop) with 5'-p-(N-2-chloroethyl-N-methylamino)benzylamides of oligonucleotides complementary to the loop region was studied. Thermodynamic parameters of the interaction were estimated using the dependence of the limit modification extent on the reagent concentration at different temperatures. The stability of the complex increases much in the set: 302-mer carrying the above hairpin, 41-mer, 22-mer; data on 22-mer and 10-mer being almost identical. This indicates significant influence of the loop supporting structure on the interaction with antisense reagents.


[Structure of the polysaccharide component of the bioglycan from the sea scallop Patinopecten uessoensis].

A bioglycan, [alpha]20D + 144 degrees (c 0.7, water), was isolated from the mantle of the scallop Patinopecten yessoensis, which is widespread in the Sea of Japan. The bioglycan represents a complex of alpha-D-glucan (83%) and protein (13%) and was homogeneous as judged by gel-filtration and ultracentrifugation. By means of molecular-sieve chromatography on Sepharose CL-4B, its average molecular weight was estimated as 4 MDa. Methylation studies, periodate oxidation and amylolysis showed that the polysaccharide part of the bioglycan consisted of alpha-1,4-linked D-glucopyranose residues, with side chains attached to every fourth sugar unit of the backbone through alpha-1,6-linkages (some side chains seem to be 1,3-linked). The structure of the bioglycan was confirmed by NMR spectral data. Amino acid composition of the protein part of the bioglycan was elucidated. The scallop bioglycan is related to the known bioglycans-immunomodulators of marine invertebrates with regard to the structure and immunological behaviour.


[Mechanism of action of vitamin E. Study of the interaction of vitamin E (alpha-tocopherol) and its analogs with fatty acids and their derivatives by fluorimetry].

Formation of a complex between alpha-tocopherol or its analogues in the excited state and fatty acids or their hydroperoxides has been suggested basing on the fluorescence quenching experimental data. The possible mechanism of the complex formation, its nature and role in the fatty acid peroxidation is discussed.


[Photosystem II of rye. Nucleotide sequence of the psbK gene and regions adjacent to it].

The structure of the rye chloroplast DNA which contains the psbK gene coding for a subunit of photosystem II is determined. The gene psbI encoding an other protein of photosystem II is located 407 bp downstream from the stop codon of this gene. The determination of structure of the intergenic region between the psbI and psbD genes is fully elucidated. The rye BamHI fragment, comprising the psbK gene, is structurally similar to the corresponding fragment of the barley genome.


Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term.

The purpose of this study was to determine the frequency, microbiologic characteristics, and clinical significance of microbial invasion of the amniotic cavity in women with premature rupture of membranes at term. Amniocentesis was performed in 32 women with term premature rupture of membranes and amniotic fluid cultured for aerobic and anaerobic bacteria and Mycoplasmas. The prevalence of positive amniotic fluid cultures was 34.3% (11/32). The most common isolates were Ureaplasma urealyticum, Peptostreptococcus sp., Lactobacillus sp., Bacteroides fragilis, and Fusobacterium sp. Clinical chorioamnionitis occurred only in one patient with a positive amniotic fluid culture. Her neonate had ophthalmitis. Three patients (9.4%) had endometritis. Among women who were delivered vaginally, those with a positive amniotic fluid culture had a significantly higher rate of endometritis than those with a negative culture (33% [3/9] vs 0% [0/20], respectively, p = 0.023). These data indicate that microbial invasion of the amniotic cavity occurs in approximately one third of patients with preterm premature rupture of membranes. Microbial invasion of the amniotic cavity is a risk factor for endometritis in women with term premature rupture of membranes.


Transport parameter estimation from lymph measurements and the Patlak equation.

Two methods of estimating protein transport parameters for plasma-to-lymph transport data are presented. Both use IBM-compatible computers to obtain least-squares parameters for the solvent drag reflection coefficient and the permeability-surface area product using the Patlak equation. A matrix search approach is described, and the speed and convenience of this are compared with a commercially available gradient method. The results from both of these methods were different from those of a method reported by Reed, Townsley, and Taylor [Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1037-H1041, 1989]. It is shown that the Reed et al. method contains a systematic error. It is also shown that diffusion always plays an important role for transmembrane transport at the exit end of a membrane channel under all conditions of lymph flow rate and that the statement that diffusion becomes zero at high lymph flow rate depends on a mathematical definition of diffusion.


Prospective assessment of biofeedback for the treatment of paradoxical puborectalis contraction.

Eighteen patients with chronic constipation were diagnosed as having paradoxical puborectalis contraction (PPC) as the cause for their constipation. The diagnosis of PPC was made after office evaluation, colonic transit study, manometry, cinedefecography, and electromyography (EMG). These 18 patients had a mean duration of symptoms of 26.9 years; none of these patients had unassisted bowel movements. Fourteen patients had a mean of 4.6 laxative-induced bowel evacuations per week, and 11 patients had a mean of 4.4 enema-induced bowel evacuations per week. Patients underwent a mean of 8.9 one-hour EMG-based biofeedback sessions. At a mean follow-up of 9.1 (range, 0.5-12) months, these 18 patients had a mean of 7.3 unassisted bowel actions per week (P less than 0.0001). In addition, persistent laxative use was reported by only two patients, and, in both cases, this was once a week or less (P less than 0.001). Similarly, enema use was reported by only three patients, one once weekly and the other two thrice weekly (P less than 0.002). No biofeedback-related complications were identified. EMG-based biofeedback is a valuable technique associated with an 89 percent success rate in the treatment of PPC.


Prevention and early detection of colorectal cancer.

Adherence to a low-fat, high-fiber diet and regular screening to detect and identify polyps at an early, more treatable stage may reduce deaths from colorectal cancer. Patients should be told that they can reduce their risk of colorectal cancer by increasing their intake of fruits, vegetables and whole grain cereals and decreasing their intake of fat. Although scientific controversy exists regarding the specific methods and intervals of screening for colorectal cancer, family physicians should adopt a regular approach to screening in their patients. In adults 50 years of age or older, annual fecal occult blood testing is recommended. If positive results are obtained, follow-up examination should be performed with either colonoscopy or flexible sigmoidoscopy plus air-contrast barium enema. Persons between 50 and 75 years of age may also benefit from screening with flexible fiberoptic sigmoidoscopic examination every three to five years.


Long-range correlations in nucleotide sequences.

DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.


Is tomography of intervertebral disc calcification useful in children?

In the past ten years, we have found cervical intervertebral disc calcifications in three children on plain films of the cervical spine made because of cervical pain. In each case, we required further radiological investigations, antero-posterior and lateral linear tomography for two children and an axial computed tomography for one child. In each case, tomography revealed no supplementary useful information. On retrospect, we think that these examinations caused unnecessary irradiation and that they should only be carried out in the rare circumstances when disc calcification is associated with neurological symptoms.


Partial ileal bypass in the treatment of hypercholesterolemia.

Partial ileal bypass is a surgical method of lowering circulating cholesterol levels. This article outlines the history of the partial ileal bypass operation and compares the efficacy, durability, compliance, safety, and cost of this operation with currently available diet and drug therapy for hypercholesterolemia. Partial ileal bypass patients have been followed for up to 26 years, and the procedure is employed currently throughout the United States and Europe. Partial ileal bypass has moved beyond the research stage and can be performed in community hospitals by competent general surgeons.


Malignant angioendotheliomatosis (intravascular lymphomatosis) clinically simulating primary angiitis of the central nervous system.

Primary angiitis of the central nervous system (PACNS) and malignant angioendotheliomatosis (MAE) are two unrelated and lethal diseases that frequently affect the brain. Both are uncommon and both require histologic documentation of their characteristic lesions for a definitive diagnosis. Because brain biopsies are not routinely included in the diagnostic workup of non-neoplastic CNS diseases, a number of unconfirmed nonvasculitic conditions may mimic PACNS. To my knowledge, MAE simulating PACNS clinically and angiographically has not been previously reported, and 3 such cases are described herein.


Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor.

A pathological hallmark of Alzheimer's disease is the deposition of amyloid fibrils in the brain. The principal component of amyloid fibrils is beta/A4 amyloid protein, which can be generated by the aberrant processing of a large membrane-bound glycoprotein, the beta/A4 amyloid protein precursor (APP)3. To test whether overexpression of APP generates abnormally processed derivatives that affect the viability of neurons, we stably transfected full-length human APP complementary DNA into murine embryonal carcinoma P19 cells. These cells differentiate into post-mitotic neurons and astrocytes after exposure to retinoic acid. When differentiation of the APP cDNA-transfected P19 cells was induced, all neurons showed severe degenerative changes and disappeared within a few days. The degenerating neurons contained large amounts of APP derivatives that were truncated at the amino terminus and encompassed the entire beta/A4 domain. These results suggest that post-mitotic neurons are vulnerable to overexpressed APP, which undergoes aberrant processing to generate potentially amyloidogenic fragments.


Effect of constituents of burned skin and in vivo skin burning on the respiratory activity of rat liver mitochondria.

The formation of toxic substances in the skin, due to the influence of thermal energy, is supposed to be one possible mechanism responsible for the high mortality rate after severe burns covering large areas of the body surface. The effects of low-molecular-weight volatile substances (dry distillates) generated after burning mouse skin were investigated. They led to reductions of the respiratory activity of rat liver mitochondria. Among other substances carbon disulphide, methylethylketone and pyrrole were isolated and characterized using gas chromatography. All of them had strong uncoupling effects on mitochondrial respiration. In a second study respiratory measurements were made on mitochondria from rats with 20-30 per cent TBSA full skin thickness burns. A decreased respiratory control ratio and thus uncoupling of mitochondrial respiration was found on days 1, 2 and 5 postburn. The basal mitochondrial respiration was significantly decreased on day 5, which could be important for the mortality mentioned above. Finally after cross-transplantations rats having burned skin grafted showed a reduction of the RCR when compared with rats with the unburned graft. Thus it can be concluded that toxic substances must have been present in burned skin.


Oestrogen replacement therapy after hysterectomy.

To identify those women who might benefit from oestrogen replacement after hysterectomy. Targeted health screening. Large group practice. All women aged under 50 who had had a hysterectomy. Concentration of follicle stimulating hormone, symptom profile, uptake of oestrogen replacement therapy. 145 of 1953 women aged 32-49 had had a hysterectomy. 35 of the 41 with bilateral oophorectomy and 27 of 104 with one or more ovaries conserved were taking oestrogen replacement. 62 of the 68 who had ovaries conserved and were not taking oestrogen replacement attended for review, of whom 14 had a follicle stimulating hormone concentration > or = 20 IU/l. 16 of the 19 women identified as potentially able to benefit from oestrogen replacement started treatment and were still on treatment at six months of follow up. Systematic review of women who had had a hysterectomy identified an important group who would potentially benefit from oestrogen replacement therapy.


Another taboo bites the dust.

Squeamishness has too often in the recent past inhibited sensible inquiries into the mechanisms by which AIDS is spread through human populations but now there may be proof that these attitudes are changing.


The role of exocytosis in the apocrine secretion of milk lipid globules in mouse mammary gland during lactogenesis.

Functional relations between exocytotic vesicle membranes, plasmalemma and milk fat globule membranes (MFGM) were studied during the final stages of mouse mammary gland differentiation, in the gland during full lactation and in the postpartum gland in which the synthesis of secretory products was partly inhibited by application of 2-Br-alpha-ergocryptine. Analysis of ultrathin sections, freeze-fracture replicas, scanning electron microscopy and application of a cytochemical marker filipin showed that the apocrine secretion of lipid globules was closely related to the exocytosis of milk proteins. During the last days of gestation the secretion of lipid globules resulted from many exocytotic events of the secretory vesicles that accumulated and fused around the cytoplasmic lipid droplets. Seldom the lipid droplet protruded partly into the gland lumen and a part of its surface became covered with the apical plasmalemma. Although apical plasmalemma became more important in the formation of MFGM in the postpartum period, we could still confirm a direct contribution of secretory vesicle membranes to the final detachment of the lipid globule. The application of 2-Br-alpha-ergocryptine hindered the apocrine secretion of the lipid globules and a situation similar to the situation in the prepartum gland was observed.


Pneumocystosis in patients with acquired immunodeficiency syndrome.

Nurses need to be aware that pneumocystosis is one of the most common and lethal opportunistic infections among AIDS patients. They are extremely susceptible because HIV impairs physiological mechanisms for microbial defense. Patients exhibit only minor symptomatology while the unchecked P carinii organisms accumulate and replicate. Eventually as the sporozoans create a physical barrier between the alveolar-capillary membranes, ventilation becomes impaired and severe hypoxemia develops. Early clinical and diagnostic studies mimic the findings characteristic of ARDS. Unless correct staining techniques are used on sputum specimens, the organism often escapes identification. Thus, the diagnosis and specific treatment of PCP is often delayed. While supporting ventilation, the treatment of choice is administration of antimetabolite drugs, either trimethoprim-sulfame-thoxazole or pentamidine isethionate. The search for more effective, as well as safer, treatment of PCP continues. Life-threatening nursing diagnoses such as impaired gas exchange urgently require priority attention. Besides physical care, the severe hypoxemia demands nursing approaches to help the critically ill patient deal with fear and powerlessness. The nurse also assumes a surrogate role to patients abandoned by family and friends. The psychosocial aspects of nursing care require enormous skill and finesse, because the blood and respiratory isolation precautions can communicate mixed messages to lonely, frightened patients.


Cellular localization of Nef expressed in persistently HIV-1-infected low-producer astrocytes.

The characterization and localization of HIV-1 Nef highly expressed in permanently infected astrocytes (TH4-7-5) as a model for latent infection of human brain cells. Immunochemical methods are an appropriate tool to investigate expression and localization of cellular proteins. Nef expression was analysed by Western blot and immunoperoxidase staining using a panel of monoclonal and polyclonal antibodies. Cellular localization studies were performed by indirect immunofluorescence and subcellular fractionation of TH4-7-5 cells. Myristoylation of Nef was investigated by immunoprecipitation of [3H]myristic acid-labelled cell extract. TH4-7-5 nef gene was cloned and amplified by polymerase chain reaction and the nef nucleotide sequence analysed. Reactivities of various Nef-specific antibodies with Nef antigen in TH4-7-5 cells were demonstrated by Western blot analysis. Immunofluorescence revealed cytoplasmic perinuclear staining of Nef with most antibodies. However, one monoclonal antibody against amino acids 168-175 of Nef showed intense homogeneous nuclear staining in TH4-7-5 cells. Reactivity of this Nef antibody was blocked with recombinant Nef derived from TH4-7-5 cells. After subcellular fractionation, Nef was detected in nuclear, membrane and cytosolic fractions of TH4-7-5 cells. No myristoylated Nef antigen was detectable, perhaps because of a serine residue at position 2 of the TH4-7-5 nef gene instead of the glycine residue required for myristoylation. Chronically HIV-1-infected astrocytoma cells with restricted virus production express different antigenic forms of Nef, which can be distinguished by their subcellular localization. Variant subcellular targeting of Nef suggests the existence of multiple activities of Nef within HIV-infected cells.


A sensitive competitive ELISA for 2,4-dinitrophenol using 3,6-fluorescein diphosphate as a fluorogenic substrate.

A competitive ELISA for sensitive detection of 2,4-dinitrophenol (DNP) was established. Certain amounts of bovine serum albumin conjugate of DNP were readily coated on a polystyrene microplate. Free DNP was then quantitated by its competition with the coated DNP for binding to anti-DNP (antibody)-alkaline phosphatase conjugate. The enzyme conjugate remaining on the plate surface as a result of the competition was detected by an enzymatic reaction with a fluorogenic substrate, 3,6-fluorescein diphosphate (FDP), or comparatively with a conventional chromogenic substrate, p-nitrophenyl phosphate (PNPP). The results showed that the ELISA with FDP at the optimal conditions of enzymatic reaction can detect as little as 10 fmol DNP, a detection limit of 50 times less than that with PNPP. The easy and sensitive DNP assay procedures in this work can be generalized to ELISAs for other antigens, particularly small antigens, haptens or drugs.


Structure of (E)-5-(methoxymethylene)-2,4-imidazolidinedione.

C5H6N2O3, Mr = 142.11, monoclinic, P2(1)/n, a = 3.862 (1), b = 16.329 (2), c = 10.088 (1) A, beta = 98.77 (2) degrees, V = 628.7 (2) A3, Z = 4, Dx = 1.50 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 1.18 cm-1, F(000) = 296, T = 296 K, R = 0.035 for 1124 independent reflections with I greater than 3 sigma(I). The structure is a hydantoin derivative with a methoxymethylene group substituted at the 5-position. Excluding the H atoms, the molecule is planar to within 0.032 A. All of the N and O atoms are involved in an intermolecular hydrogen-bonding network via N--H...O and C--H...O interactions. The packing arrangement is a linear ribbon motif with the ribbons stacked to form the short a axis.


Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning.

Several recent studies suggest that activation of ATP-dependent potassium (K(ATP)) channels in the myocardium plays an important cardioprotective role during ischemia. The present study was undertaken to examine further the role of this ion channel in vivo in a model of "stunned" myocardium. Barbital-anesthetized dogs were subjected to 15 minutes of left anterior descending (LAD) coronary artery occlusion followed by 3 hours of reperfusion. Regional myocardial blood flow was measured by radioactive microspheres and segment function by sonomicrometry. Intravenous administration of the potassium channel opener aprikalim (RP 52891) at a dose that produced no significant systemic hemodynamic effects (10 micrograms/kg plus 0.1 microgram/kg/min) resulted in a marked improvement in segment shortening in the ischemic/reperfused myocardium compared with control animals (p less than 0.05) when given before the ischemic insult. However, administration of aprikalim immediately before reperfusion had no beneficial effect. Furthermore, pretreatment with the K(ATP) channel antagonist glibenclamide antagonized the recovery of contractile function afforded by aprikalim when administered at a low dose (0.3 mg/kg) that alone had no effect on postischemic recovery. In contrast, pretreatment with either a higher dose of glibenclamide (1.0 mg/kg) or the related sulfonylurea K(ATP) channel antagonist tolbutamide (100 mg/kg) resulted in a worsening of segment function after reperfusion. The ability of aprikalim and the K(ATP) channel antagonists to alter postischemic wall function occurred independently of differences in systemic hemodynamics, area at risk, and collateral blood flow during occlusion, the major determinants of the extent of myocardial stunning. These results suggest that opening myocardial K(ATP) channels in the ischemic heart results in a marked cardioprotective effect in stunned myocardium and that these channels may serve an endogenous function, which is to provide protection from ischemic insults.


Synthesis of serine-AMC-carbamate: a fluorogenic tryptophanase substrate.

A new fluorogenic substrate for the pyridoxal 5'-phosphate-dependent enzyme tryptophanase is described. L-Serine, which is linked to 7-amino-4-methylcoumarin through an O-carbamoyl tether, serves as a substrate for the enzyme. The released moiety, 7-amino-4-methylcoumarin (AMC), can be detected by either absorbance (355 nm) or fluorescence (excitation 365 nm/emission 440 nm). Kinetic constants were measured using each of these techniques: Km = 85 +/- 20 microM, Vmax = 2.9 +/- 0.4 mumol/min/mg (fluorescence) and Km = 129 +/- 21 microM, Vmax = 3.1 +/- 0.3 mumol/min/mg (absorbance). The Vmax for serine-AMC-carbamate is approximately 1.9 times faster than that of the natural substrate, tryptophan. Using fluorescence detection, solutions containing 10(-3) units of activity could be routinely assayed.


Effects of oxidizing and reducing analogs of acetylcholine on neuronal nicotinic receptors.

The synthesis and pharmacological characterization of dithiobisacetylcholine and dithiobis-N,N-dimethyl-4-acetylpiperazinium (two oxidizing analogs of acetylcholine), as well as those of their reduced counterparts, are described. Both the oxidizing and reducing analogs stimulate nicotinic receptors in the chick retina and block the binding of 125I-labeled neuronal bungarotoxin to retinal homogenates (IC50 values of 2 x 10(-6) to 6 x 10(-5) M). Both oxidizing compounds reverse the physiological effects of reduction by dithiothreitol on nicotinic function in intact chick retina, when applied for 2 sec (EC50 values of about 10(-5) M). This effect is selective, insofar as neither agent alters the effects of dithiothreitol treatment on receptors for N-methyl-D-aspartate. Reoxidation takes place at the disulfide located near the nicotinic receptor agonist binding site, inasmuch as reoxidation by these agents prevents affinity alkylation by bromoacetylcholine, and occupation by the competitive antagonist d-tubocurarine prevents reoxidation. Unlike thiocholine, a weak agonist with a free sulfhydryl that, paradoxically, is reported to oxidize nicotinic receptors in electroplax, the reduced forms, mercaptoacetylcholine and N,N-dimethylamino-4-mercaptoacetylpiperazinium, have no direct redox effects on retinal receptors, but they do protect the receptors against reduction by dithiothreitol.


Inactivation of new carbapenem antibiotics by dehydropeptidase-I from porcine and human renal cortex.

The stability of the new carbapenem antibiotics, panipenem, meropenem and LJC 10,627, against porcine and human renal dehydropeptidase-I (DHP-I) was compared with that of imipenem. The order of stability to hydrolysis by renal DHP-I was: LJC 10,627 greater than meropenem greater than panipenem greater than imipenem. After incubation of the drugs with porcine or human enzyme at 30 degrees C for 4 h, the percentages of residual activity were as follows: LJC 10,627, 73.7% and 95.6%, respectively; meropenem, 0.2% and 28.7%, respectively; panipenem, 0% and 4.3%, respectively; and imipenem, 0% and 0.1%, respectively. These results demonstrate that LJC 10,627 has extremely high stability against renal DHP-I.


Determination of (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5- tetrahydro-1H-3-benzazepin-7-ol (NNC 01-0687), a novel dopamine D-1 receptor antagonist, in plasma by solid-phase extraction and high-performance liquid chromatography.

A fast and reliable method has been established for the determination of the dopamine D-1 receptor antagonist (+)-5-(2,3-dihydrobenzofuran-7-yl)-3-methyl-8-nitro-2,3,4,5-tetrahydro-1 H-3- benzazepin-7-ol (NNC 01-0687) in plasma. A combination of reversed-phase extraction on C18 columns and straight-phase high-performance liquid chromatographic analysis with ultraviolet detection at 287 nm resulted in very clean chromatograms. The limit of quantitation was about 1 ng/ml of plasma. Validation of the method showed good selectivity, linearity, recovery, accuracy and precision. Several modifications of the method were possible with little or no influence on the assay.