The use of noxythiolin (Noxyflex 'S') as an antiseptic irrigant in upper urinary tract drainage following percutaneous nephrolithotomy

Percutaneous nephrostomy drainage for the relief of obstruction or stone removal has become a common procedure. Despite the routine use of prophylactic antibiotics, nephrostomy urine frequently becomes infected (approximately 30% of cases). Noxythiolin irrigation has been used to prevent and treat bladder infections. A double-blind, placebo controlled study was carried out in 20 patients undergoing a single-stage percutaneous nephrolithotomy to evaluate the use of noxythiolin as an upper urinary tract antiseptic. In the patients whose nephrostomy tubes were irrigated with a 2.5% solution of noxythiolin, significant bacterial infection was eliminated from the nephrostomy urine and colonisation of the catheter tip was markedly reduced. Noxythiolin also rendered pre-operative infected bladder urine sterile. There were no untoward local or systemic sequelae in either group of patients. This study indicates that irrigation of the upper urinary tract with noxythiolin solution is safe and may be a useful adjunct to reduce the risk of sepsis in patients undergoing percutaneous drainage procedures.     

Ethanol reduces tolerance, sensitization, and up-regulation of D2-receptors after subchronic haloperidol

To study the interrelationships between dopamine D2-receptor density and behavioral responses after chronic treatment with neuroleptics female Wistar rats received haloperidol (HP; 14 mg/l), ethanol (ETOH; 5 vol.%), a combination of both, or tap water as drinking fluids for one or two weeks. Mean intake doses ranged between 1.28 and 1.48 mg/kg/day (HP) and between 3.7 and 4.8 g/kg/day (ETOH). HP administered for one or two weeks raised the number of [3H]spiroperidol binding sites in the striatum by 55%. Concomitant administration of ETOH diminished the increase of Bmax to 23%. The up-regulation was even reversed when ETOH was added with a delay of one week, although the drug alone had no effect on dopamine-D2-receptor density. KD values were not substantially affected. During HP treatment the rats established a tolerance to the motor sedation which was measured by circadian motility recordings. Coadministration of ETOH reduced the development of tolerance, the activity remained at a depressed level. Acute applications of HP (0.3, 0.6, and 0.9 mg/kg, or saline, respectively) also revealed tolerance to the drug for various behavioral responses (exploratory locomotion, rearing, rotarod performance, catalepsy). The tolerance was reduced in all those animals which had received combinations of ETOH and HP. The reduction was most pronounced for the cataleptic response. Pretreatment with ETOH alone had no effect. Sensitization to dopamine agonists was studied by apomorphine-induced stereotypies (licking, sniffing, and forepaw scratching). As expected, chronic HP enhanced the responses. The increased number of stereotypies was reduced in rats pretreated with the combination, although ETOH alone did not affect the response. The reduction was most pronounced for licks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phosphatidylcholine-Specific Phospholipase C from Listeria monocytogenes Is an Important Virulence Factor in Murine Cerebral Listeriosis

Meningoencephalitis is a serious and often fatal complication of Listeria monocytogenes infection. The aim of the present study was to analyze the role of internalin A (InlA) and B, which are involved in the invasion of L. monocytogenes into cultivated host tissue cells, and that of phosphatidylcholine-specific phospholipase C (PlcB), which mainly promotes the direct cell-to-cell spread of L. monocytogenes, in murine cerebral listeriosis by use of an InlA/B (ΔinlAB2)- and a PlcB (ΔplcB2)-deficient isogenic deletion mutant strain and the wild-type (WT) L. monocytogenes EGD. Listeria strains were directly applied to the brain, a technique which has been employed previously to study the pathogenesis of cerebral listeriosis (D. Schlüter, S. B. Oprisiu, S. Chahoud, D. Weiner, O. D. Wiestler, H. Hof, and M. Deckert-Schlüter, Eur. J. Immunol. 25:2384–2391, 1995). We demonstrated that PlcB, but not InlA or InlB, is an important virulence factor in cerebral listeriosis. Nonimmunized mice infected intracerebrally with the ΔplcB2 strain survived significantly longer and had a reduced intracerebral bacterial load compared to mice infected with the ΔinlAB2 strain or WT bacteria. In addition, immunization with the WT prior to intracerebral infection significantly increased the survival rate of mice challenged intracerebrally with the ΔplcB2 strain compared to that of mice infected with the WT or ΔinlAB2 strain. Histopathology revealed that the major difference between the various experimental groups was a significantly delayed intracerebral spread of the ΔplcB2 mutant strain, indicating that cell-to-cell spread is an important pathogenic feature of cerebral listeriosis. Interestingly, irrespective of the Listeria mutant used, the apoptosis of hippocampal and cerebellar neurons and an internal hydrocephalus developed in surviving mice, indicating that these complications are not dependent on the virulence factors InlA/B and PlcB. In conclusion, this study points to PlcB as a virulence factor important for the intracerebral pathogenesis of murine L. monocytogenes meningoencephalitis.     

Double mutation (A171T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening the the United States. Mutations in brief no. 128. Online

Biotinidase deficiency is inherited as an antosomal recessive trait that, unless treated with pharmacologic doses of biotin, can result in neurologic and cutaneous symptoms. We have identified two new mutations in exon D of the biotinidase gene of children with profound biotinidase deficiency ascertained by newborn screening. Transition 511G->A near the 5' end of exon D results in a substitution of threonine for alanine 171 (A171T) and transversion 1330G->C occurs close to the 3' end of exon D causing a substitution of histidine for aspartic acid 444 (D444H). The D444H mutation was detected in four individuals from our normal population whose mean serum biotinidase activity is 5.25 nmol/min/ml, which is significantly lower than the mean normal activity (7.1 nmol/min/ml). We calculated that this mutation causes a 52% loss of activity in the aberrant enzyme. Twenty-three individuals with the D444H mutation were found by allele specific oligonucleotide analysis of DNA from 296 randomly-selected, anonymous dried-blood spots. We estimate the frequency of this allele in the general population to be 0.039. In contrast, no individuals in 376 have the A171T mutation. Fourteen children (eleven probands and three siblings) out of the 31 enzyme-deficient children have both the A171T and D444H mutations. Both mutations are inherited from a single parent as a double mutation allele. The nine families in which this allele was identified are of mostly European ancestry, although the mutation cannot be attributed to a specific nationality or ethnic group. The serum of a child who is homozygous for the double mutation allele has very little CRM and the aberrant enzyme has very low biotinylhydrolase activity and no botinyl-transferase activity. This double mutation allele (A171T and D444H) is a common cause of profound biotinidase deficience in children ascertained by newborn screening in the United States.     

Clinical comparison of the Roche Septi-Chek and Dupont Isolator blood culture systems

A study was conducted to compare the recovery of clinical isolates by the DuPont Isolator and Roche Septi-Chek blood culture systems. A total of 5,262 blood culture specimens were processed by the two systems. Of these, 358 cultures contained significant isolates: 219 were positive in both systems, 68 were recovered only by Isolator, 71 were recovered by Septi-Chek only (not statistically significant). Of the isolates recovered in both systems, 159 were positive the same day, 55 were recovered first by Isolator, and 5 were recovered first by Septi-Chek. In cases where Isolator recovered organisms first, the average difference in time was one to two days. Regarding particular groups of organisms, there was no difference between the systems in recovery of Enterobacteriaceae, anaerobes, yeast, and gram-positive bacteria, except for Streptococcus pneumoniae. Septi-Chek recovered S. pneumoniae significantly more often. These results suggest that these two systems are essentially comparable, except with S. pneumoniae, although the Isolator frequently provided results more rapidly.