Catheter-associated bloodstream infection in patients with cancer: comparison of left- and right-sided insertions.

BACKGROUND: There is limited research on the relationship between side of insertion of central venous catheter (CVAD) and bloodstream infection risk in patients with cancer. AIM: To conduct an exploratory analysis of data from a randomized control trial (RCT) and data from a prospective cohort study to compare infection rates for right- and left-sided insertions. METHODS: The study populations were patients aged >14 years with cancer from two tertiary hospitals in Brisbane, Australia. The primary endpoint was catheter-associated bloodstream infection (CABSI) adjudicated by blinded assessors. For the RCT, randomized intention-to-treat comparisons were conducted between left- and right-side allocated insertion for early (≤14 days) and late (>14 days) infection using Cox proportional hazards regression. The RCT data were also combined with cohort study data collected from one of the hospitals prior to the RCT and non-randomized comparisons conducted between left- and right-sided insertions. FINDINGS: In 634 randomly allocated CVADs there were 141 CABSIs. Analysis showed strong evidence of right-side allocated insertions having an increased risk of early infection by 2.5 times (95% confidence interval (CI): 1.3-4.7); however, there was no evidence of increased risk for late infection (hazard ratio: 1.06; 95% CI: 0.71-1.59). Results from analysis of the RCT and cohort study data combined (2786 CVADs and 385 CABSIs) were similar. CONCLUSION: There appears to be an increased risk of CABSI in patients with cancer for CVAD inserted into the right-side for around two weeks after line insertion. The mechanism underpinning the increased risk is unknown.

Catheter-associated bloodstream infections in adults with cancer: a prospective randomized controlled trial.

BACKGROUND: A common complication of central venous access devices (CVADs) is catheter-associated bloodstream infection (CABSI). We previously demonstrated that insertion of CVADs on the right side was associated with increased risk of CABSI, and hypothesized that this related to the predominance of right-handedness in the patient population, resulting in greater movement and bacterial contamination. AIM: To perform a prospective randomized, controlled, non-blinded study to determine whether the side of CVAD insertion influenced the incidence of CABSI. METHODS: Adult cancer patients were randomly allocated to either dominant or non-dominant side CVAD insertion. The primary endpoint of the study was the number of line-days until CABSI, determined in a blinded fashion by two assessors. FINDINGS: In all, 640 CVADs were randomized to dominant (N = 322) or non-dominant (N = 318) side of insertion, 60% had haematological malignancies, and 40% solid tumours. CVADs were a peripherally inserted central catheter line (67%), tunnelled CVAD (23%), and non-tunnelled CVAD (10%). Twenty-two percent of CVADs were complicated by CABSI. The rate of CABSI per 1000 line-days was 3.49 vs 3.66 in the non-dominant vs dominant group (hazard ratio (HR): 0.91; 95% confidence interval (CI): 0.65-1.28). By multivariable analysis, the rate of CABSI was increased by: use of tunnelled CVADs compared to peripherally inserted central venous catheter lines (HR: 2.05; 95% CI: 1.45-2.91); having a haematological malignancy compared to non-gastrointestinal solid tumours (5.55; 2.47-12.5); but not dominant compared to non-dominant side of CVAD (0.97; 0.69-1.36). CONCLUSION: CABSI in adult patients with cancer was not impacted by whether CVAD insertion was on the dominant or non-dominant side.

An unusual case of foreskin phimosis after radiotherapy for rectal carcinoma.

Phimosis of the foreskin after radiotherapy for rectal carcinoma is extremely rare and has previously been described only once (2006) in the English-language literature. Combination chemo/radiotherapy is currently the treatment of choice and widely used in the management of various pelvic malignancies. In this report, we describe a rare complication on male genitalia following the radiotherapy for lower rectal cancers. Few days following the completion of radiotherapy, patient developed phimosis of the foreskin, which was successfully treated medically without the need for circumcision. Radiotherapy can bring a great risk of injury to anorectum and its adjacent structures. Risk of phimosis should be considered under the current radiation guidelines and we support the concept of using penile shielding for all radiotherapy procedures in colorectal carcinoma patients.

Catheter-associated bloodstream infection incidence and risk factors in adults with cancer: a prospective cohort study.

Central venous catheter-associated bloodstream infections (CABSIs) cause considerable morbidity in patients with cancer. We determined the incidence and risk factors for CABSI by performing a prospective observational cohort study of all adult patients requiring a central venous access device (CVAD) in a haematology-oncology unit. All CVADs were inserted under ultrasound guidance by trained operators in a dedicated interventional radiology facility. A total of 1127 CVADs were assessed in 727 patients over 51,514 line-days. The rate of CABSI per 1000 line-days was 2.50. Factors associated with CABSI included: type of CVAD, greatest for non-tunnelled lines [hazard ratio (HR): 3.50; P < 0.0001] and tunnelled lines (HR: 1.77; P = 0.011) compared to peripherally inserted central venous catheter (PICC) lines; patient diagnosis, greatest for aggressive haematological malignancies (HR: 3.17; P = 0.0007) and least for oesophageal, colon and rectal cancers (HR: 0.29; P = 0.019) compared to other solid tumours; side of insertion, greatest for right-sided lines (HR: 1.60; P = 0.027); and number of prior line insertions (HR: 1.20; P = 0.022). In patients with aggressive haematological malignancies there was significantly more CABSI with non-tunnelled lines (HR: 3.9; P < 0.001) and a trend to more CABSI with tunnelled lines (HR: 1.43; P = 0.12) compared to patients with PICC lines, as well as increased CABSI for right-sided insertions (HR: 1.62; P = 0.047). This study highlights the utility of a standardised CABSI surveillance strategy in adult patients with cancer, provides further data to support the use of PICC lines in such patient populations, and suggests that the side of line insertion may influence risk of CABSI.

Morphological effects of the catecholestrogens on cells of the seminiferous tubules of Sprague-Dawley rats.

Estradiol-17 beta (E2) and the two catecholestrogens 2-OHE2 and 4-OHE2, when daily administered at low doses of 10-40 ng/rat, were cytotoxic to the seminiferous epithelium. The structural changes seen after seven days exposure included abnormal meiotic type II cells with uneven chromosome distribution, the formation of binucleated and multinucleated giant cells, of which many were sloughed into the lumina of the seminiferous tubules. The effect of the 4-OHE2 metabolites were always more pronounced that that of 2-OHE2 or E2. After 21 daily exposures, 4-OHE2 proved to be very toxic, the seminiferous tubules were markedly denuded and numerous giant cells were present in the lumina. The catecholestrogens also caused a significant lowering (P less than 0.02) of testosterone serum levels after eight days exposure. E2 at 40 ng/rat/day had no effect on testosterone production. At these low doses the catecholestrogens did not affect gonadotropin release after eight days exposure. Our results indicate that the morphological lesions could not exclusively be attributed to testosterone withdrawal and that a direct effect on developing spermatids is also indicated.

Morphological effects of the catechol estrogens on rat epididymal epithelia.

The 2-hydroxy and 4-hydroxyestradiols (2-/4-OHE2) caused marked cytotoxic effects, including vacuolation and nuclear changes, in rat epididymal epithelia, after exposure to very low levels (40 ng/rat/week) for 20 weeks. The effects of the 2-/4-OHE2 metabolites were more pronounced than that of estradiol-17 beta (E2).

The cytotoxic effects of estradiol-17 beta, catecholestradiols and methoxyestradiols on dividing MCF-7 and HeLa cells.

In this study the cytotoxic effects of high concentrations (greater than or equal to 1 x 10(-6) M) of estradiol-17 beta (E2), 2-/4-hydroxyestradiol-17 beta (2-/4-OHE2) and 2-/3-/4-methoxyestradiol-17 beta (2-/3-/4-MeOE2) were determined on dividing MCF-7 and HeLa cells. The 2-MeOE2 metabolite followed by 2-OHE2 and E2 (in this order) proved to be extremely toxic to dividing MCF-7 and HeLa cells. The cytotoxic effect on these cells comprised uneven chromosome distribution. Indirect immunofluorescent studies, in which monoclonal anti-alpha-tubulin antibodies were used, showed that these compounds (2-MeOE2 greater than 2-OHE2 greater than E2) at high concentrations caused abnormal and fragmented polar formations as well as disorientated microtubule arrangement in the dividing MCF-7 and HeLa cells. The 4-OHE2 and 3-/4-MeOE2 metabolites had little or no cytotoxic effects on dividing cells. The large number of abnormal metaphases seen in HeLa cells exposed to 2-MeOE2 suggested that this metabolite may be the ultimate cytotoxic compound. The reduction in the number of HeLa cells with abnormal metaphase configurations after exposure to 2-OHE2 plus quinalizarin (an inhibitor of catechol-O-methyltransferase) indicated that the production of 2-MeOE2 is necessary for the formation of abnormal spindles in metaphase. Quinalizarin treatment in the presence of 2-MeOE2 had no effect on the large number of abnormal metaphases. We therefore conclude that neither E2 nor 2-OHE2, but a high concentration of 2-MeOE2 is responsible for abnormal spindle formation. In additional experiments the number of normal and abnormal dividing HeLa cells were greatly reduced when simultaneously exposed to E2 and 2-/4-hydroxylase-inhibitor alpha-naphthoflavone.

The isolation and characterization of the aerobic endospore-forming bacteria present in the liquid phase of an anaerobic fixed-bed digester, while treating a petrochemical effluent.

Sixty-nine gram-positive endospore-forming rods were isolated from the liquid phase of an anaerobic digester, while treating a fatty acid-rich petrochemical effluent. These strains, including eight reference strains, were characterized and the similarities between the different strains were calculated using Sokal and Michener's simple matching coefficient. Phenotypic characteristics, determined by the API 20E and API 50CHB galleries, other biochemical tests, and morphological characteristics, were used for the numerical analysis. The strains were grouped into 12 (five major and seven minor) clusters. Nine of the clusters were positively identified asBacillus pumilus, B. subtilis, B. sphaericus, B. laterosporus, B. brevis, B. cereus, B. coagulans, B. megaterium, andB. circulans. Three clusters could not be identified using Gordon's classical system or the API identification system. Most of the aerobic endospore-forming rods (72%) utilized both acetic and propionic acid, and 17% utilized acetic acid as carbon source, but only under aerobic conditions. A small percentage of the strains studied (11%) was unable to utilize the fatty acids present in the petrochemical substrate, and no explanation could be given as to how they obtained their carbon source. Seventy-eight percent of the strains did not show growth in anaerobic agar. It was possible that sufficient oxygen, required for growth by these members of the genusBacillus, was introduced by the substrate. Since ample time had been allowed for population selection, their presence indicates that these aerobic strains can survive, grow, and compete in the digester environment but their relative importance and role in the primary digestion reactions is not clear.

Characterization of aerobic, facultative anaerobic, and anaerobic bacteria in an acidogenic phase reactor and their metabolite formation.

Fifty-two aerobic and facultative anaerobic and 57 anaerobic bacterial isolates were obtained from an acidogenic phase digestion system. These isolates were characterized and the similarities between the different strains were calculated using Sokal and Michener's similarity coefficient. The aerobic and facultative anaerobic strains clustered in two major groups with the strains of the first main group being gram-negative fermentative rods, representing the generaKlebsiella, Enterobacter, Escherichia andAeromonas. Isolates of the second group were gram-positive streptococci similar toStreptococcus lactis. The strict anaerobic isolates also clustered into two main groups with strains of cluster A being identified as members of the genusFusobacterium while strains in cluster B were members of the genusBacteroides. Hypothetical mean organisms were calculated for each cluster and used in further culture studies. The major products of the continuously fed acidogenic phase reactor were ethanol and acetic, propionic, and butyric acids. In batch cultures, ethanol, acetic acid, diacetyl, and 2,3-butanediol were formed by the strains as major products both under aerobic and anaerobic conditions. The ability of the aerobic and facultative anaerobic strains to be metabolically active under anaerobic conditions indicates a prominent role in acidogenic reactors.

Dihydropyridine calcium antagonists depress the amplitude of the plasma melatonin cycle in baboons.

An investigation into the effects of verapamil and some dihydropyridine derivatives on plasma melatonin levels was undertaken in baboons. In a number of separate experiments, groups of young male chacma baboons (mean body weight 13 kg) received intraperitoneal injections of the drugs, under ketamine anaesthesia, roughly 30 minutes prior to the following time points: 1200, 1800, 0000, 0200, 0600 and 1200 h. Lights went off at 1800 h and came on at 0600 h. The drugs used, and their respective dosages (expressed per kg body mass), were verapamil up to 4 mg/kg, nifedipine at 0.2 mg/kg, nitrendipine at 0.5 mg/kg and nisoldipine at 0.1 mg/kg. Blood samples, taken at the said time points, were assayed for melatonin. The nighttime peak of the plasma melatonin cycle was significantly depressed by all three dihydropyridine calcium antagonists (up to 40%), while verapamil, even at the relatively high total dose of 24 mg/kg per day, had no significant effect on the circulating plasma melatonin levels.

The effect of harmine on the localization of the nucleolar proteins C23 and B23.

In this study we show that harmine treatment (10 mg/l for 2 or 24 h) of PtK2 cells had a marked effect on the localization of the nucleolar phosphoproteins C23 and B23. C23 was localized with silver staining in the fibrillar areas of completely segregated nucleoli. B23 was localized mainly on the periphery of the nucleoli with the aid of immunofluorescence.

Effect of chlorpromazine on the localization of cAMP phosphodiesterase.

Chlorpromazine (CPZ) at dosages of 10 mg/kg body weight (b.wt.) affected the cytochemical localization of cAMP-dependent phosphodiesterase (cAMP PDE) activity in the synapses of the rat frontal cortex. Postsynaptic cAMP PDE activity was inhibited, and presynaptic activity increased. CPZ also inhibited membrane-bound ATPase activity in the frontal cortex. The activity of Na+-K+-ATPase was significantly (P less than 0.005) inhibited in isolated plasma membranes from the rat frontal cortex. CPZ exposure also affected the cytochemical localization of cations with potassium pyroantimonate. Precipitate, which could be removed with 5 mm EGTA, was decreased in the mitochondria and synaptic vesicles in presynaptic areas after CPZ treatment. The incorporation of 45Ca2+ into slices of the rat frontal cortex was also significantly (P less than 0.001) inhibited by CPZ. This ultrastructural study shows that CPZ may affect biochemical events in an opposite manner in the pre- and post-synaptic areas of some neurons of the frontal cortex.

The effect of allantoin on cellular multiplication in degenerating and regenerating nerves.

Injury to a peripheral nerve is, among other things, followed by degeneration of axons and myelin, as well as by a sharp increase in the number of cells (especially Schwann cells) in the part distal to the injury. The effect of allantoin--a cell proliferant--was tested on the above-mentioned reactions in the sciatic nerve of rats. The nerves were crushed and re-exposed 7, 14, 21, 35 and 90 days after the injury, and removed for histological examination. The results obtained in a group of rats treated with allantoin were compared with those obtained in a control group of rats. The results showed that allantoin had a statistically significant effect on the cellular multiplication seen in the nerve 7 and 14 days after the injury. Myelin degeneration was also found to be more advanced in the allantoin-treated nerve preparations examined 14 and 21 days postoperatively than in the control nerve preparations.

A silver impregnation method for nervous tissue suitable for routine use with mounted sections.

A simple, reliable silver impregnation method for nervous tissue is described for tissues fixed in various fixatives including formalin, Bouin, and Susa. Sections are impregnated in a solution containing 1 g Protargol, 2 ml of a 1% Cu(NO3)2 solution, 2 ml of a 1% AgNO3 solution, and 2-4 drops 30% H2O2 in 100 ml distilled water. Sections are impregnated 2-5 days at 37 C and thereafter reduced in a hydroquinone-formalin solution. This is followed by gold toning and subsequent reduction, dehydration and mounting. This method has been found to be very reliable and selective.

Experimental microsurgery in peripheral nerves.

A surgical technique for the reconstruction of severed peripheral nerves is described. This technique reduces the mechanical manipulation and trauma to the nerve during suturing. Histological studies revealed that scar formation at the suture site was reduced to a minimum. The suture material did not prevent the downgrowth of regenerating axons. Nerves in which suturing was either inaccurately or accurately done, were compared. Histological examination of these nerves revealed that axonal regeneration in nerves with 8 or more sutures was superior to that in nerves with only 2 sutures.