Susceptibility of penicillin-susceptible and -resistant pneumococci to CFC-222, a new fluoroquinolone

Rotavirus (RV) strains infecting newborns often have unique neutralization antigens (P serotypes) on their outer capsids that are distinct from those found on RV strains that cause diarrhea in older children. We examined the hypothesis that unusual RV strains preferentially infect newborns because the newborns lack maternal neutralizing antibodies to these strains. To test this hypothesis, sera and saliva samples collected from neonates infected with 116E-like (P[11]G9) strains in the maternity ward of the All India Institute of Medical Sciences (AIIMS) hospital in New Delhi were tested for neutralizing antibodies against common RV strains and those infecting newborns and these titers were compared with those of newborns who did not become infected (controls). The infected neonates had significantly lower levels of cord blood neutralizing antibodies to 116E than the controls, suggesting that immunity to neonatal RV infection is acquired transplacentally through maternal antibodies. Further, this study confirmed the immunogenicity of the AIIMS neonatal strain 116E, a vaccine candidate, in its ability to evoke a potent RV-specific immunoglobulin A and neutralizing antibody response in serum and saliva among the infected babies. Our findings have important implications for the development of an effective RV vaccine. In India, where G9 strains are common in the community, the use of 116E as a vaccine, together with the rhesus tetravalent vaccine, may provide a broader protection against all the circulating RV serotypes, including serotype G9, which is not represented in the current rhesus RV tetravalent vaccine (G1-G4).     

Pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy: outcome and prognostic factors

STUDY OBJECTIVE: To determine predictors of mortality from pulmonary infiltrates in neutropenic patients with acute leukemia during chemotherapy, and the significance of those factors related to the underlying malignancy and its therapy as well as of those related to the severity of the illness associated with pulmonary infiltrates. DESIGN: A historical cohort study. SETTING: A university teaching hospital and tertiary referral center. PATIENTS AND METHODS: Overall, 53 patients with neutropenia during chemotherapy and with first episodes of pulmonary infiltrates during a 4-year period were studied. Prognostic analysis included 38 variables. Multivariate analyses were performed by logistic regression. RESULTS: The survival rate from pneumonia was 57% (30/53). The following eight parameters were significantly associated with death in univariate analysis: comorbidity present; development of "late" pulmonary infiltrates (> or = 14 days after hospital admission); heart rate > or = 100 beats/min; a ratio heart rate/systolic blood pressure (HR/SBP) > or = 1.2; urea nitrogen > 7 mmol/L; radiographic score > or = 3; neutropenia < 1.0x10(9)/L at the treatment end point; and failed complete remission. In a multivariate model including only parameters available at diagnosis of pulmonary infiltrates, the presence of a ratio HR/SBP > or = 1.2 and of a radiographic score > or = 3 remained independently associated with death. In a second model also including the evolutionary parameter neutropenia < or = 1.0x10(9)/L at the treatment end point, both parameters remained significant together with neutropenia <1.0x 10(9)/L at the treatment end point. The presence of a ratio HR/SBP > or = 1.2 was a strong marker of early death. CONCLUSION: Both therapy- and malignancy-associated neutropenia as well as the severity of illness associated with pulmonary infiltrates are independent prognostic factors. Patients with a ratio HR/SBP > or = 1.2 at diagnosis of pulmonary infiltrates suffer from potentially reversible acute illness, are at risk for early death and, therefore, may be appropriate candidates for treatment in an ICU.     

The artificial heart and neuromonitoring? Technical and clinical aspects

There is a steady progress in the development of artificial heart and circulatory assist devices. There is also no doubt that further advances in energy systems, materials, and electronics will provide for smaller and more reliable electrically driven blood pumps, but the present engineering design appears to be adequate to provide devices satisfactory for initial clinical use. Due to problems in the availability of suitable donor hearts, the concept of replacing the natural heart with an artificial heart as a "bridge to transplantation" has gained attention in recent years. The present paper shows technical and clinical aspects of multivariable electrophysiologic neuromonitoring in a patient with an artificial heart assist device in the intensive care unit. The data (EEG, 40 Hz brain oscillations, brainstem auditory- and somatosensory evoked potentials) are discussed with respect to the influence of the artificial heart on their quality and reliability. Reasons for artifacts and problems of interpretation are shown.     

Proteinase activity in the isolates of Trichomonas vaginalis according to their pathogenicity

Ten axenic isolates of Trichomonas vaginalis were subcutaneously injected to the BALB/c mice in order to assess their pathogenicity by means of so-called "mouse assay" method. All the isolates revealed neutral and acid proteinase activities both in their lysates and in culture media, but the specific activities of both proteinases in the severely pathogenic group were significantly higher than the mildly pathogenic group (p < 0.05). In the SDS-PAGE system in which the electrophoretic gels contained 0.4% gelatin as the substrate, five different banding patterns of trichomonal proteinases were detected, and the patterns were closely related with the pathogenicity of the isolates of T. vaginalis. All five bands might be regarded as cysteine proteinases group in the inhibitor assays. The cytotoxicity of the lysates of T. vaginalis to the target Chinese hamster ovarian (CHO) cell line was also significantly different according to the pathogenicity of the isolates, and generally lower in the lysates treated with cysteine proteinase inhibitors than in the control lysates. In summarizing the results, it might be considered that the proteinases of T. vaginalis showing five electrophoretic banding patterns are closely related with the pathogenicity and cytotoxicity of the isolates of T. vaginalis.     

Sequence-based differentiation of strains in the Mycobacterium avium complex

The complete 16S-23S rDNA internal transcribed spacer (ITS) was sequenced in 35 reference strains of the Mycobacterium avium complex. Twelve distinct ITS sequences were obtained, each of which defined a "sequevar"; a sequevar consists of the strain or strains which have a particular sequence. ITS sequences were identified which corresponded to M. avium (16 strains, four ITS sequevars) and Mycobacterium intracellulare (12 strains, one ITS sequevars). The other seven M. avium complex strains had ITS sequences which varied greatly from those of M. avium and M. intracellulare and from each other. The 16S-23S rDNA ITS was much more variable than 16S rDNA, which is widely used for genus and species identification. Phylogenetic trees based on the ITS were compatible with those based on 16S rDNA but were more detailed and had longer branches. The results of ITS sequencing were consistent with the results of hybridization with M. avium and M. intracellulare probes (Gen-Probe) for 30 of 31 strains tested. Serologic testing correlated poorly with ITS sequencing. Strains with the same sequence were different serovars, and those of the same serovar had different sequences. Sequencing of the 16S-23S rDNA ITS should be useful for species and strain differentiation for a wide variety of bacteria and should be applicable to studies of epidemiology, diagnosis, virulence, and taxonomy.     

A-IMilano apoprotein. Decreased high density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family

Significant hypertriglyceridemia with a very marked decrease of high density lipoproteins (HDL)-cholesterol levels (7-14 mg/dl) was detected in three members (father, son, and daughter) of an Italian family. The three affected individuals did not show any clinical signs of atherosclerosis, nor was the atherosclerotic disease significantly present in the family. Lipoprotein lipase and lecithin:cholesterol acyltransferase activites were normal or slightly reduced. Morphological and compositional studies of HDL in the subjects showed a significant enlargement of the lipoprotein particles (approximately 120 vs. approximately 94 A for control HDL) and a concomitant increase in the triglyceride content. Analytical isoelectric focusing of HDL apoproteins provided evidence for multiple isoproteins in the apoprotein(apo)-A-I range, with nine different bands being detected instead of the usual four bands observed in normal subjects. Two-dimensional immunoelectrophoresis against apo-A antiserum indicated a clear reduction of apo-A in the alpha electrophoretic region, with splitting of the protein "peak." The observation in otherwise clinically healthy subjects of hypertriglyceridemia, reduced HDL-cholesterol, and marked apoprotein abnormalities, without a significant incidence of atherosclerotic disease in the family suggests this is a new disease entity in the field of lipoprotein pathology, very probably related to an altered amino acid composition of the apo-A-I protein (see Weisgraber et al. 1980. J. Clin. Invest. 66: 901-907).     

Grafting of enzymes on collagen films using Woodward''s reagent "K" and a water-soluble carbodiimide derivative

Two new methods of activation were developed to graft enzymes on collegen films. They involved chemical modifications of surface groups of collagen either by Woodward's reagent "K" or by EDC, a water-soluble derivative of carbodiimide. EDC was a better coupling agent and a detailed study was conducted with this agent. It could be used either in a global method of activation and coupling, or in a two-step procedure of activation of collagen, followed by spontaneous coupling of enzyme. All enzymes tested were successfully bound: malate dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, urease, creatine kinase, hexokinase. The influence on the yield of grafted enzyme, of pretreatment of films, time and temperature of EDC activation, concentration of EDC and enzyme, protecting agents was studied. Stability of enzyme activity on storage was greatly increased after grafting. A co-grafted dual system creatine kinase/heoxkinase, was achieved which exhibited a good efficiency. A striking renaturing process at 0-4degreesC after thermal denaturation, was observed with hexokinase.     

Spinal amino acid release and precipitated withdrawal in rats chronically infused with spinal morphine

Glutamate receptors are implicated in the genesis of opioid tolerance and dependence. Factors governing release of amino acids in systems chronically exposed to opiates, however, remain undefined. Using rats, each prepared with a spinal loop dialysis catheter and with a chronic lumbar intrathecal infusion catheter connected to a subcutaneous minipump, the release of amino acids before and during antagonist-precipitated withdrawal in unanesthetized rats was examined. Spinal infusion of morphine (20 nmol/micro l/hr) for 4 d had little effect on resting release of amino acids. In morphine-infused, but not saline-infused, rats naloxone (2 mg/kg, i.p.) evoked an immediate increase in the release of L-glutamate (299 +/- 143%) and taurine (306 +/- 113%) but not other amino acids. The magnitude and time course of the release of these amino acids significantly correlated with behavioral indices of withdrawal intensity. Acute intrathecal pretreatment immediately before naloxone with clonidine (20 microg; alpha2 agonist), MK-801 (3 microg; noncompetitive NMDA antagonist), or aminophosphonopentanoic acid (AP-5; 3 microg; competitive NMDA antagonist) suppressed naloxone-induced increases in spinal L-glutamate and taurine release and behavioral signs of withdrawal in spinal morphine-infused rats. Results point to a correlated increase in spinal L-glutamate release, which contributes to genesis of the opioid withdrawal syndrome. Agents such as clonidine that suppress opioid withdrawal may owe their action to an inhibition of excitatory amino acid release. The effects of MK-801 and AP-5 suggest a glutamate-evoked glutamate release.