Positive feedback and synchronized bursts in neuronal cultures.

Synchronized bursts (SBs) with complex structures are common in neuronal cultures. Although the phenomenon of SBs has been discovered for a long time, its origin is still unclear. Here, we investigate the properties of these SBs in cultures grown on a multi-electrode array. We find that structures of these SBs are related to the different developmental stages of the cultures and these structures can be modified by changing the magnesium concentration in the culture medium; indicating that synaptic mechanism is involved in the generation of SBs. A model based on short term synaptic plasticity (STSP), recurrent connections and astrocytic recycling of neurotransmitters has been developed successfully to understand the observed structures of SBs in experiments. A phase diagram obtained from this model shows that networks exhibiting SBs are in a complex oscillatory state due to large enough positive feedback provided by synaptic facilitation and recurrent connections. In this model, while STSP controls the fast oscillations (∼ 100 ms) within a SB, the astrocytic recycling determines the slow time scale (∼10 s) of inter-burst intervals. Our study suggests that glia-neuron interactions can be important in the understanding of the complex dynamics of neuronal networks.

Chinese talismans as a source of lead exposure.

We describe a case of lead exposure after prolonged intake of ashes from burnt Chinese talismans. A 41-year-old woman presented with elevated blood lead level during screening for treatable causes of progressive weakness in her four limbs, clinically compatible with motor neuron disease. The source of lead exposure was confirmed to be Chinese talismans obtained from a religious practitioner in China. The patient was instructed to burn the Chinese talismans to ashes, and ingest the ashes dissolved in water, daily for about 1 month. Analysis of the Chinese talismans revealed a lead concentration of 17 342 µg/g (ppm).

Mercury exposure: the experience of the Hong Kong Poison Information Centre.

OBJECTIVES: To review the characteristics of the consultation about the management of mercury exposure and identify the controversial issues on the clinical management of individuals with a history of mercury exposure. DESIGN: Descriptive case series. SETTING: Hong Kong Poison Information Centre, Hong Kong. PARTICIPANTS: Persons consulting the Hong Kong Poison Information Centre about individuals with possible or definitive mercury exposure. MAIN OUTCOME MEASURES: Characteristics of the consultations, including: the demographics of affected individuals, source and reason for the consultation, tissue mercury levels, the source of mercury exposure, specific intervention if any, and clinical outcomes. RESULTS: Forty-one consultations were analysed. Most consultations were from the public sector. Reasons of the consultation were very variable. Individuals with abnormal tissue mercury levels were uncommon. There was only one case of acute mercury poisoning. The majority of identified individuals were not subjected to specific interventions. Chelation therapy was given to three patients, but in one of them it was considered to be contra-indicated. CONCLUSION: The management of mercury exposure is highly variable. Recommendations were made on the approach to an individual with potential mercury exposure or poisoning.

Life-threatening Torsades de Pointes resulting from "natural" cancer treatment.

INTRODUCTION: Nonradioactive cesium chloride (CsCl) is used by some alternative medicine advocates as a treatment for cancer. The therapy was proven to be neither safe nor effective. Chronic use of CsCl has resulted in cases with severe cardiotoxicity. CASE REPORT: A 65-year-old lady presented to our hospital's accident and emergency department with recurrent syncope attacks. Electrocardiogram monitoring showed QT prolongation and transient Torsades de Pointes (TDP) ventricular tachycardia. She was taking anticancer naturopathic drugs for 6 weeks before admission. One of her naturopathic drugs was subsequently confirmed containing 89% CsCl by weight. Besides conventional treatment of QT prolongation and TDP, the patient was given a 4-week course of oral Prussian blue to enhance gastrointestinal elimination of cesium. The serum half-life of cesium was reduced from 61.7 to 29.4 days after the use of Prussian blue. QT prolongation was normalized in 27 days. DISCUSSION: To our knowledge, this is the first published case of nonradioactive cesium poisoning treated with Prussian blue. A transient rise in serum cesium level was observed during Prussian blue therapy. Possible explanations for this observation include poor drug compliance during outpatient treatment and redistribution of cesium from body stores. CONCLUSION: Nonradioactive CsCl poisoning can result in severe cardiotoxicity with QT prolongation and TDP ventricular tachycardia. The key points in the management of nonradioactive cesium poisoning include cessation of cesium exposure, vigorous electrolytes replacement, and oral Prussian blue therapy.

Clinical trial: levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy in the treatment of resistant Helicobacter pylori infection.

BACKGROUND: The efficacy of levofloxacin-based quadruple therapy in resistant Helicobacter pylori infection is not known. AIM: To test the efficacy of levofloxacin-based quadruple therapy and traditional quadruple therapy in resistant H. pylori infection. METHODS: One hundred and two patients with resistant H. pylori infection were randomized to 1 week of either EBAL (esomeprazole 40 mg b.d., bismuth subcitrate 240 mg b.d., amoxicillin 1 g b.d. and levofloxacin 500 mg b.d.) or EBMT (esomeprazole 40 mg b.d., bismuth subcitrate 240 mg b.d., metronidazole 400 mg t.d.s. and tetracycline 500 mg q.d.s.). (13)C-urea breath test was performed at week 12 to assess post-treatment H. pylori status. RESULTS: In intention-to-treat analysis H. pylori eradication was achieved in 37 of 51 (73%) subjects in EBAL and 45 of 51 (88%) subjects in EBMT groups, respectively (P = 0.046). Per-protocol eradication rates of EBAL and EMBT groups were 78% and 94%, respectively (P = 0.030). The intention-to-treat eradication rate was statistically lower for EBAL than EMBT (56% vs. 90%, P = 0.013) among those who had failed more than one course of eradication therapy. Previous levofloxacin triple therapy did not affect the efficacy of either protocol significantly. CONCLUSIONS: Levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy for resistant H. pylori infection.

Update on clarithromycin resistance in Helicobacter pylori in Hong Kong and its effect on clarithromycin-based triple therapy.

AIM: To determine the antibiotic susceptibility of Helicobacter pylori and evaluate the efficacy of a clarithromycin-based triple therapy in relation to antibiotic resistance. METHODS: Consecutive patients referred for upper endoscopy due to dyspeptic symptoms were recruited. Gastric biopsies were obtained for the CLO test, histology and culture. Antibiotic susceptibility was assessed by the E-test. Patients with H. pylori infection received rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days. RESULTS: Of 234 patients recruited, 124 were H. pylori-positive and culture was successful in 102 patients. The updated prevalences of resistance to clarithromycin, amoxicillin and metronidazole were 7.8, 0 and 39.2%, respectively. A total of 86 patients received 1-week triple therapy with rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily, and 81 patients attended the follow-up test. Eradication rates by per-protocol and intention-to-treat analysis were 92.6 and 87.2%, respectively. The eradication rate by per protocol was significantly higher in patients with clarithromycin-susceptible strains than in those with clarithromycin-resistant strains (98.6 vs. 28.6%, p < 0.001). CONCLUSION: Clarithromycin resistance reduces the clinical efficacy of clarithromycin-based triple therapy. However, due to the low prevalence of clarithromycin resistance, clarithromycin-based therapy is still the first choice for clinical use.

Levobupivacaine and fentanyl for spinal anaesthesia: a randomized trial.

BACKGROUND AND OBJECTIVE: Levobupivacaine 0.5% and racemic bupivacaine 0.5% are equally effective in spinal anaesthesia. Fentanyl has been used as an adjunct to racemic bupivacaine in spinal anaesthesia. At the time this study was designed, there was no published study on the intrathecal use of 0.5% levobupivacaine with fentanyl. METHODS: This prospective, randomized, double-blind study compared the clinical efficacy, motor block and haemodynamic effects of using 2.6 mL of 0.5% levobupivacaine alone (25 patients) and 2.3 mL of 0.5% levobupivacaine with fentanyl 15 microg in 0.3 mL (25 patients) for spinal anaesthesia in urological surgery. The study solution was injected into the subarachnoid space at the L3-L4 interspace. RESULTS: There were no significant differences between the two groups in the haemodynamic changes, and quality of sensory and motor block. Anaesthesia was adequate and patient satisfaction was good in all cases. Side-effects were minor and infrequent with both regimes. CONCLUSIONS: We conclude that 2.3 mL of 0.5% levobupivacaine with fentanyl 15 microg is as effective as 2.6 mL of 0.5% levobupivacaine alone in spinal anaesthesia for urological surgery. Further studies may be directed to find the optimal combination of levobupivacaine and opioid with maximal haemodynamic stability and least motor block.

Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens.

OBJECTIVE: To analyze outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) treated with ofloxacin/levofloxacin-containing regimens. MATERIALS AND METHODS: From February 1990 through June 1997, 63 MDR-TB patients (with bacillary resistance to at least isoniazid and rifampin in vitro) were analyzed retrospectively. Twenty-two patients (34.9%) had had no previous antituberculosis chemotherapy. Each patient received either ofloxacin (53) or levofloxacin (10) even though 13 patients had bacilli resistant to ofloxacin in vitro. The other accompanying drugs mainly included aminoglycosides, cycloserine, ethionamide/prothionamide, and pyrazinamide. Sputum smear and culture examinations for acid-fast bacilli (AFB) were performed monthly for the initial 6 months and then at 2- to 3-month intervals until the end of treatment. Comparison was made between clinical successes and failures using univariate and multiple logistic regression analyses for the following variables: age, sex, presence of cavitation, extent of disease, sputum smear positivity, in vitro resistance to ofloxacin, in vitro resistance to streptomycin and/or ethambutol, treatment adherence, and the number of drugs per regimen. RESULTS: Fifty-one patients (81.0%) were cured, nine patients (14.3%) failed, and three patients (4.7%) died. For the entire group, the mean duration of treatment was 14.0 months, and the mean number of drugs was 4.7. Mean durations of chemotherapy in successful and failed patients were 14.5 and 14.2 months, respectively. Mean time for sputum smear and culture conversions were 1.7 and 2.1 months, respectively. Only cavitation, resistance to ofloxacin, and poor adherence were found to be variables independently associated with adverse outcomes (p < 0.05; odds ratios = 15.9, 13.5, 12.8, respectively). Negative sputum cultures after 2 and 3 months of therapy were 100% predictive of cure. Positive sputum cultures after 2 and 3 months were 52.3% and 84.6% predictive of failure, respectively. One patient (2.1%) relapsed after apparent cure. Twenty-five patients experienced adverse drug reactions, but only 12 of them needed drug modifications. CONCLUSION: Most MDR-TB patients can be treated effectively with ofloxacin/levofloxacin-containing regimens. Presence of cavitation, resistance to ofloxacin in vitro, and poor adherence to therapy portend treatment failure. Monitoring monthly sputum culture for AFB in the initial months of chemotherapy helps predict clinical outcomes.

Osteoporosis and lung transplantation: a prospective study.

STUDY OBJECTIVE: Osteoporosis is a well-recognized complication of lung transplantation that may significantly impair the quality of life of transplant recipients. We performed a prospective study of bone mineral density (BMD) before and after transplantation to determine the degree of bone mass loss associated with lung transplantation Patients and design: We conducted a prospective study of BMD in 28 patients with various end-stage respiratory diseases pretransplantation and 6 to 12 months posttransplantation. The BMD of the lumbar spine (LS) and femoral neck (FN) were measured. All 28 patients were treated only with vitamin D and calcium supplementation posttransplant. The primary endpoint was the percentage change in BMD. The secondary endpoint was the incidence of fractures posttransplant. A univariate analysis was conducted to determine the various risk factors associated with bone mass loss pretransplant and posttransplant. RESULTS: Prior to transplantation, moderate to severe bone disease was evident. The mean (+/- SD) pretransplant T score (the number of SDs from the peak bone mass) and Z score (the number of SDs from the age-matched mean) for the LS were -1.72 +/- 1.37 and -1.44 +/- 1.31, respectively. The mean pretransplant T score and Z score for the FN were -2.65 +/- 1.01 and -1.5 +/- 1.43, respectively. Within 6 to 12 months posttransplant, the mean BMD for the LS decreased by 4.76% (p < 0.001), while the mean BMD for the FN decreased by 5.3% (p < 0.001). Five of the 28 patients (18%) suffered osteoporotic fractures posttransplant, while no fractures were documented pretransplant. The cumulative steroid dose posttransplant was associated with a drop in BMD for the LS and FN (r = 0.39, p = 0.039 and r = 0.63, p < 0.001, respectively), while a negative association was found between cumulative steroid use pretransplant and baseline LS and FN T scores (r = -0.4, p = 0. 02 and r = -0.43, p = 0.023, respectively). CONCLUSION: Within 6 to 12 months after lung transplantation, there is a significant decrease in BMD at both the LS and FN levels (approximately 5%) despite vitamin D and calcium supplementation. This drop in BMD is associated with a relatively high incidence of osteoporotic fractures posttransplant.

Antiulcer drug prescribing in hospital successfully influenced by "immediate concurrent feedback".

OBJECTIVE: To determine whether immediate concurrent feedback (ICF) focused on inpatient omeprazole prescribing achieved more rational and cost-effective antiulcer drug prescribing and usage. METHODS: In a 1400-bed teaching hospital, an audit (by specially trained personnel) was conducted to monitor inpatient prescribing of omeprazole (1) in preference to H2-antagonists and other drugs according to agreed criteria (Helicobacter pylori eradication, severe reflux esophagitis, rapid ulcer healing deemed urgent because of severe symptoms or complications, high-dose steroid therapy of > or =30 mg/day prednisolone) and (2) appropriateness of intravenous dosing (oral route not feasible or contraindicated). After baseline monitoring for 1 month, followed by relevant antiulcer drug therapy education, ICF was instituted for 1 year. This entailed explanatory memoranda requesting a change in prescribing issued to the respective medical teams of patients whose omeprazole prescription did not "conform." The main outcomes of the study were omeprazole prescription numbers per month and the proportion conforming, defined daily doses of antiulcer drugs used and corresponding expenditures, and pertinent antiulcer drug utilization data from 9 other local hospitals. RESULTS: Baseline omeprazole prescribing conformed in 32 of 173 (18%) of the patients compared with 451 of 546 (83%) during institution of ICF (P < 0001; chi2 test). Correspondingly, average overall omeprazole and ranitidine usage (inpatient and outpatient) and expenditure decreased (44% and 45%, respectively); collectively, use of less expensive alternatives increased about 61%. Estimated savings averaged about HK$150,000 ($20,000) per month. No comparable changes in usage were noted in 9 other local hospitals. CONCLUSION: Regarding hospital antiulcer drugs, this ICF strategy was associated with more rational prescribing and usage, and an important saving of resources.

Supplemental photocoagulation on the buckle for prevention of surgical revision after scleral buckling procedures.

Supplemental photocoagulation on the buckle appears to be a useful therapeutic modality in selected cases of persistent retinal detachment. In a retrospective review, 71 (63%) of 113 eyes were successfully treated with photocoagulation, thus avoiding the need for surgical revision. Median response time between treatment and postoperative subretinal fluid absorption in the successfully treated eyes was two days, with the majority responding within one day. The one favorable prognostic factor was the use of a soft silicone segmental sponge. Unfavorable prognostic factors included the following: contour of subretinal fluid (combined, ie, both anterior and posterior to the buckle); excessive amount of subretinal fluid; inadequate support of break(s); multiple drainages at first operation; rolled edge in association with a giant break; and residual vitreous traction on the break. Postoperative photocoagulation alone on the buckle did not appear to influence the rate of development of premacular fibroplasia or proliferative vitreoretinopathy.

Management of septic thrombosis of the inferior vena cava caused by Candida.

Septic thrombosis of central veins is rarely diagnosed during life and nearly always proves fatal. We have recently successfully treated a patient with a 75% body surface burn in whom septic thrombosis of the inferior vena cava developed associated with high-grade candidemia as a complication of parenteral nutrition. Signs of venous thrombosis and candidemia persisted after catheter removal. Prompt and intensive therapy with amphotericin B, monitored by fungicidal assays of serum, resulted in cure. Generous hydration and directed supplementation of sodium bicarbonate permitted us to administer a large total dose of amphotericin over a relatively brief period of time with no nephrototoxic effect whatsoever. Septic central venous thrombosis mandates a pharmacologic approach to therapy similar to that used for infective endocarditis, with the addition of anticoagulation. Should sepsis prove refractory to this program of it pulmonary embolization occurs, operative intervention is indicated despite the high risks involved.