Heavy metal pollution and co-selection for antibiotic resistance: A microbial palaeontology approach.

Frequent and persistent heavy metal pollution has profound effects on the composition and activity of microbial communities. Heavy metals select for metal resistance but can also co-select for resistance to antibiotics, which is a global health concern. We here document metal concentration, metal resistance and antibiotic resistance along a sediment archive from a pond in the North West of the United Kingdom covering over a century of anthropogenic pollution. We specifically focus on zinc, as it is a ubiquitous and toxic metal contaminant known to co-select for antibiotic resistance, to assess the impact of temporal variation in heavy metal pollution on microbial community diversity and to quantify the selection effects of differential heavy metal exposure on antibiotic resistance. Zinc concentration and bioavailability was found to vary over the core, likely reflecting increased industrialisation around the middle of the 20th century. Zinc concentration had a significant effect on bacterial community composition, as revealed by a positive correlation between the level of zinc tolerance in culturable bacteria and zinc concentration. The proportion of zinc resistant isolates was also positively correlated with resistance to three clinically relevant antibiotics (oxacillin, cefotaxime and trimethoprim). The abundance of the class 1 integron-integrase gene, intI1, marker for anthropogenic pollutants correlated with the prevalence of zinc- and cefotaxime resistance but not with oxacillin and trimethoprim resistance. Our microbial palaeontology approach reveals that metal-contaminated sediments from depths that pre-date the use of antibiotics were enriched in antibiotic resistant bacteria, demonstrating the pervasive effects of metal-antibiotic co-selection in the environment.

The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders - a life-long perspective.

OBJECTIVE: It is generally accepted that one of the most important predictors of recurrence in depressive and bipolar disorders is the number of previous episodes. However, very few studies have considered the individual tendency toward recurrence in analyses of the effect of the number of episodes on the risk of subsequent recurrence in affective disorder. METHOD: Frailty models were used to estimate the effect of the number of episodes on the rate of recurrence taking into account the individual frailty toward recurrence. The study base consisted of 406 patients, 186 patients with depressive disorder and 220 patients with bipolar disorder, who were admitted between 1959 and 1963 to the Psychiatric Hospital University of Zurich with an affective episode and followed up to 1997. RESULTS: The individual rate of subsequent recurrence was found to increase with the number of episodes even when the effect was adjusted for the individual frailty toward recurrence. The effect of episodes was the same in depressive and bipolar disorders and for men and women. CONCLUSION: It seems increasingly valid that in depressive and bipolar disorders, the risk of subsequent recurrence increases with the number of episodes.

Intussusception due to Yersinia enterocolitica enterocolitis in a patient with beta-thalassemia.

Patients who are homozygous for thalassemia major are at risk for Yersinia enterocolitica infections. We present a case of a 4-year-old child with intussusception of the terminal ileum whose past medical history was significant for beta-thalassemia. His monthly blood transfusions for this condition may have put him at risk for Y enterocolitica enterocolitis. The pathogenesis of this disease relates to the role of iron as an essential growth factor for Yersinia, and this patient's transfusions left him in an iron-overloaded state, despite treatment with Desferal. Our patient's unusual presentation of intussusception was secondary to the mass effect caused by lymphoid hyperplasia, specifically hypertrophied Peyer's patches in the ileum caused by Y enterocolitica infection. To our knowledge, this is the first such case of intussusception caused by Yersinia to be reported.

[Quality development at a medical department]. / Kvalitetsudvikling på medicinsk afdeling.

Organization on medical wards have an impact on patient continuity, both regarding contact with physicians and nurses. Highest continuity was found in teams with approximately 20 beds. Members ought to spend most of their time in the team. This was found to be especially important for the internal medical specialists. The amount of blood samples taken was lowest in the team with the highest patient-specialist continuity. Teams with or without continuity had the same high level of patient satisfaction.

Severe nodal arrhythmia following direct current cardioversion for atrial flutter.

A case of long-lasting nodal arrhythmia and severe hypotension following DC cardioversion for atrial flutter is presented. The patient, treated with the selective serotonin reuptake inhibitor sertraline and with sotalol, thiopental and digoxin, showed no sign of organic disease or drug intoxication. We suggest that drug interaction in combination with the DC shock and an altered sympaticus/parasympaticus balance during anaesthesia provoked the incident.

Relative efficiency of solvents used in endodontics.

A root canal model was used to test the relative efficiency of various commonly used endodontic solvents including eucalyptol, eucalyptus oil, orange oil, chloroform, and xylene to dissolve or soften gutta-percha and several different types of sealers (Proco-Sol, AH26, and Sealapex). There was no significant difference in the ability of the solvents to dissolve gutta-percha and the zinc oxide-eugenol-based sealer Proco-Sol. The resin-based sealer, AH26, was only dissolved in chloroform and took considerable time (> 30 min). The calcium hydroxide-based sealer, Sealapex, could not be tested because it was found not to set at all unless in contact with air. All of the solvents for both Proco-Sol and gutta-percha produced clinically acceptable dissolving times.

Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms.

The influence of the sparteine and the S-mephenytoin oxidation polymorphisms on the kinetics of clomipramine were investigated in 25 healthy volunteers: 10 extensive metabolizers of sparteine and mephenytoin (EMs/EMm), nine poor metabolizers of sparteine and extensive metabolizers of mephenytoin (PMs/EMm), five extensive metabolizers of sparteine and poor metabolizers of mephenytoin (EMs/PMm), and one poor metabolizer of sparteine and mephenytoin (PMs/PMm). A single oral dose of 100 mg clomipramine hydrochloride was given to each subject after an overnight fast. Serum and urine levels of clomipramine and its metabolites were monitored after 1, 2, 3, 4, 6, 8, 11, 14, 24, 36, 48, and 96 hours. Additional serum was monitored after 6, 9, 12, and 15 days in the poor metabolizers. 2-Hydroxyclomipramine was undetectable in most subjects before enzymatic hydrolysis of serum and urine. The total median clearance of clomipramine was 99 L.hr-1 (range, 68 to 210) in the EMs/EMm subjects, 56 L.hr-1 (range, 37 to 183) in the PMs/EMm subjects, 66 L.hr-1 (range, 37 to 89) in the EMs/PMm subjects, and 43 L.hr-1 in the PMs/PMm subject. It was significantly lower in PMs/EMm and EMs/PMm subjects compared with EMs/EMm subjects (p = 0.006 and 0.028, respectively; Mann-Whitney). In addition, the formation clearance of 2-hydroxyclomipramine and the hydroxylation indexes were significantly lower in PMs/EMm subjects, as was the demethylation index in EMs/PMm subjects compared with EMs/EMm subjects. Our data thus provide evidence that the 2- and 8-hydroxylation of clomipramine are catalyzed by CYP2D6 and that the N-demethylation is catalyzed in part by CYP2C.

Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms.

The relationship between the metabolism of the selective serotonin reuptake inhibitor citalopram and the sparteine and mephenytoin oxidation polymorphisms was studied in 24 healthy male volunteers, constituting panels of extensive metabolizers of sparteine and mephenytoin (n = 10), poor metabolizers of sparteine (n = 8), and poor metabolizers of mephenytoin (n = 6). Each subject was given 40 mg/day citalopram for 10 days and citalopram, and its des- and didesmethylmetabolites were assayed in serum and urine. Using a nonenantioselective analytical method (high-performance liquid chromatography), it was shown that the citalopram elimination partially depends on the mephenytoin oxygenase, since steady-state serum concentration, half-life, and area under the serum concentration/time curve for citalopram were significantly higher in poor metabolizers of mephenytoin than in extensive metabolizers of mephenytoin. Both citalopram total clearance and demethylation clearance (formation of desmethylcitalopram) were significantly lower in poor metabolizers of mephenytoin compared to extensive metabolizers (median 15.2 vs. 27.3 and 2.6 vs. 5.9 L/h, respectively). It was further indicated that the demethylation of desmethylcitalopram to didesmethylcitalopram depends on the sparteine oxygenase CYP2D6. Didesmethylcitalopram could virtually not be detected in any poor metabolizers of sparteine, contrasting measurable serum levels in all sparteine/mephenytoin extensive metabolizers. The demethylation clearance of desmethylcitalopram was significantly lower in sparteine poor metabolizers compared to extensive metabolizers (0.3 vs. 2.4 L/h, respectively). During administration of citalopram, there was a modest increase in sparteine metabolic ratio from median 0.31 to 0.80 in extensive metabolizers of sparteine, whereas the mephenytoin S/R ratio was unaltered during citalopram treatment. Both the sparteine and the mephenytoin oxidation polymorphism thus appear to contribute partially to the total pharmacokinetic variability of citalopram.

Citalopram: interaction studies with levomepromazine, imipramine, and lithium.

The pharmacokinetic interactions between the selective serotonin reuptake inhibitor citalopram, given as an oral dose of 40 mg/day for 10 days, and (1) levomepromazine (50 mg single oral dose), (2) imipramine (100 mg single oral dose), and (3) lithium (30 mmol/day orally for 5 days) were examined in three panels each of 8 healthy young male volunteers (age 20-31). All volunteers were classified as extensive metabolizers of sparteine and mephenytoin. Each subject completed three study phases--one with citalopram alone, one with one of the three other drugs, alone, and one with citalopram combined with the corresponding other drug. For citalopram and its metabolites, a non-enantioselective analytical method (high-performance liquid chromatography) was used. Only two statistically significant interactions were indicated. First, levomepromazine caused a 10-20% increase from the initial steady-state levels of the primary citalopram metabolite, desmethylcitalopram. Second, citalopram caused approximately 50% increase in the single-dose area under the serum concentration/time curve of desipramine (primary metabolite or imipramine) and a corresponding reduction in the level of the subsequently formed metabolite 2-hydroxydesipramine. These findings are in agreement with the recent observations that (1) the demethylation of desmethylcitalopram (to didesmethylcytalopram) is partly mediated via the sparteine/debrisoquine oxygenase (CYP2D6) and that levomepromazine is a potent inhibitor of CYP2D6, and (2) that desmethylcitalopram has a somewhat stronger affinity for CYP2D6 than desipramine, and therefore may inhibit the hydroxylation of desipramine, which is also a substrate of CYP2D6.

[Excessive bile secretion in a patient with cirrhosis after cholecystectomy and choledochotomy]. / Excessiv sekretion af galde hos cirrosepatient efter cholecystectomia og tubulatio ductus choledochi.

The volume of bile collected from a choledochal stoma usually does not exceed 1,000 milliliters during 24 hours. A case of excessive output of bile (drainage of more than 2,000 milliliters in 24 hours) through a T-tube after cholecystectomy and choledochotomy is described. Biopsy of the liver revealed micronodular cirrhosis. The hypotheses and experimental studies concerning excessive biliary out-flow are mentioned. The conclusion of this case-report is that the T-tube can be removed, despite excessive output of bile, when the patient tolerates clamping of the tube without abdominal pain and when and external fistula has been formed.

Ranitidine and high-dose antacid in reflux oesophagitis. A randomized, placebo-controlled trial.

The liquid antacid Novaluzid (10 ml seven times daily) was compared with ranitidine (150 mg twice daily) and with placebo in 57 patients with symptoms and endoscopic signs of oesophagitis and gastro-oesophageal reflux. A randomized three-period change-over design with the double-dummy technique was used. Each treatment period lasted 6 weeks. Only 37 patients (64.9%) completed the entire trial. In retrospect, five patients receiving placebo were withdrawn because of insufficient effect, six patients because of side effects while taking Novaluzid and two while taking ranitidine. The remaining seven dropouts/withdrawals were for reasons without evident relationship to the treatment given. Statistical analyses based both on the 37 completers and on the 43 patients who had at least two treatment periods showed that ranitidine and Novaluzid were superior to placebo with regard to pain score (p less than 0.005) but not with regard to regurgitation, dysphagia, histology, and appearance on endoscopy (p greater than 0.05). It was impossible to distinguish statistically between ranitidine and Novaluzid. In conclusion, ranitidine and high-dose antacids are of equal effectiveness in the short-term treatment of reflux oesophagitis, and both are superior to placebo with regard to symptomatic relief.

Inquerito parasitologico pelo exame de fezes em criancas pertencentes a creches no Rio de Janeiro. / Parasitological survey by stool examination in institutionalized children in Rio de Janeiro

Os autores apresentam os resultados de 117 exames parasitologicos de fezes realizados pelos metodos de Faust e Hoffman, Pons e Janner, em criancas de 0 a quatro anos de idade que frequentavam creches no Rio de Janeiro. Foram encontrados 41 (35,04%) casos positivos e 76 (64,96%) casos negativos. Os parasitos mais frequentemente diagnosticados foram Giardia lamblia (23, 93%), Entamoeba coli (11,97%),Ascaris lumbricoides (9,40%) e Trichuris trichiura (8,54%). Foram observados 14 (11,97%) casos positivos em creches particulares e 27 (23,08%) casos positivos em creches que atendiam criancas de nivel socio-economico mais baixo. Dentre os casos positivos 18 (43,09%) eram de monoparasitismo e os restantes 23 (56,10%) eram de poliparasitismo As associacoes mais frequentemente diagnosticadas foram Entamoeba coli e Giardia lamblia (quatro casos), Giardia lamblia e Trichuris trichiura (tres casos) e Ascaris lumbricoides e Trichuris trichiura (dois casos). Os presentes resultados sao comparados com os de outros inqueritos coproscopicos, inclusive quando realizados em criancas de faixa etaria mais elevada

Colonic transport of water and electrolytes in a patient with secretory diarrhea due to collagenous colitis.

Whole colon perfusion studies and measurements of luminal prostaglandin E2 were carried out in a 41-year-old female with collagenous colitis to investigate pathophysiological mechanisms for the diarrhea. Biopsies of the colorectal mucosa had revealed a continuous 25- to 60-micron subepithelial collagenous layer, but normal junctional complexes and capillaries. When the patient fasted, the diarrhea persisted and fecal electrolytes, as estimated from the concentration of sodium, potassium, and their anions, accounted for all the osmolality (284 mosm/kg) of stool water, the pH of which was above 8.0. The lumen-negative electrical potential difference in the rectum was -64 mV vs -45 +/- 2 mV (mean +/- SEM) in healthy controls. Profuse secretion of fluid and electrolytes occurred during colonic perfusion with saline. Transport of sodium appeared to be passive with flux ratios equal to those predicted for passive sodium movements, while chloride transport against a steep electrical gradient indicated active secretion. Perfusion with an "ileal output"-like solution decreased fluid and electrolyte secretion, suggesting that bicarbonate, in addition to chloride, may be a major determinant of secretion rates. Since immunoreactive prostaglandin E2 levels following in vivo equilibrium dialysis of feces ranged from 555 to 650 pg/ml vs 55 to 235 pg/ml (99% confidence limits) in healthy controls, it is speculated that prostaglandins synthesized locally in response to mucosal hypoxia might be the mediators of anion secretion.

Gastrin production following antrectomy. A study on the occurrence of gastrin-producing cells and the serum gastrin response to feeding.

Fifteen patients were studied 3 to 35 years after antrectomy, with a gastroduodenal (Billroth I (BI)) anastomosis in 8, and a gastrojejunal (Billroth II (BII)) anastomosis in 7. The investigations included gastric acid secretion, serum gastrin response to feeding and immunohistochemical search for gastrin-producing cells in gastric remnant mucosal biopsies. All of the patients had hypochlorhydria. The gastrin response to feeding was minimal. Apart from a significantly higher value of serum gastrin 3 hours post-prandial in BI operated as compared to BII operated patients, no greater differences were found in the gastrin production between the two groups of patients. No gastrin-producing cells could be identified in the gastric remnant, not even in areas of pseudopyloric metaplasia. It is concluded that the gastrin production following antrectomy is caused by extragastric G-cells; these cells are poorly stimulated by food, and do not respond to hypochlorhydria with hypergastrinaemia.