Hospital admission for neurologic disorders among 5-year survivors of noncentral nervous system tumors in childhood: A cohort study within the Adult Life after Childhood Cancer in Scandinavia study

Large, comprehensive studies of the risk for neurologic disorders among long-term survivors of noncentral nervous system (CNS) childhood cancers are lacking. Thus, the aim of our study was to assess the lifetime risk of Nordic non-CNS childhood cancer survivors for neurologic disorders. We identified 15,967 5-year survivors of non-CNS childhood cancer diagnosed in Denmark, Iceland, Finland and Sweden in 1943–2008, and 151,118 matched population comparison subjects. In-patient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). A neurologic disorder was diagnosed in 755 of the survivors while 370 were expected, yielding a RR of 2.0 (95% confidence interval (CI) 1.9–2.2). The highest risks were found among survivors of neuroblastoma (4.1; 95% CI 3.2–5.3) and leukemia (2.8; 95% CI 2.4–3.2). The AER decreased from 331 (278–383) excess neurologic disorders per 100,000 person-years 5–9 years after diagnosis to 82 (46–118) ≥ 20 years after diagnosis. Epilepsy was the most common diagnosis (n = 229, 1.4% of all survivors), and significantly increased risks were seen among survivors of eight out of 12 types of childhood cancer. Survivors of neuroblastoma had remarkably high risks (RR ≥ 10) for hospitalization for paralytic syndromes and hydrocephalus, while survivors of leukemia had additional high risks for dementia and encephalopathy. In conclusion, survivors of non-CNS childhood cancer are at high risk for neurologic disorders, especially within the first decade after diagnosis. Therefore, intensive follow-up to identify those who require close management is needed.     

Flexible Thoracoscopy may Facilitate Video-Assisted Thoracoscopic Lobectomy

Background  

Video-assisted thoracoscopic lobectomy was introduced in the early 1990s but has not yet gained widespread acceptance. The VATS approach is still controversial although several studies suggest less postoperative morbidity compared with open thoracotomy. Nevertheless, some patients report long-lasting chest wall pain following VATS procedures, and, in theory, such pain may be related to intercostal nerve injury. The present study presents our experience with a commercially available flexible thoracoscope.     

MDA435/LCC6 and MDA435/LCC6MDR1: ascites models of human breast cancer.

We have established a novel ascites tumour model (MDA435/LCC6) from the oestrogen receptor-negative, invasive and metastatic MDA-MB-435 human breast cancer cell line. MDA435/LCC6 cells grow as both malignant ascites and solid tumours in vivo in nude mice and nude rats, with a tumour incidence of approximately 100%. Untreated mice develop ascites following i.p. inoculation of 1 x 10(6) cells and have a reproducible life span of approximately 30 days, with all animals dying within a 48 h period. The in vivo response of MDA435/LCC6 ascites to several cytotoxic drugs, including doxorubicin, etoposide (VP-16), BCNU and mitomycin C, closely reflects the activity of these single agents in previously untreated breast cancer patients. MDA435/LCC6 cells also retain the anchorage-dependent and anchorage-independent in vitro growth properties of the parental MDA-MB-435 cells, and can be used in standard in vitro drug screening assays. The drug resistance pattern of the MDA435/LCC6 cells suggests that they may have few active endogenous drug resistance mechanisms. To generate a model for the screening of MDR1-reversing agents, MDA435/LCC6 were transduced with a retroviral vector directing the constitutive expression of the MDR1 cDNA, producing a cell line with a classical MDR1 resistance pattern (MDA435/LCC6MDR1). THese ascites models may be a viable alternative to the murine leukaemia ascites (L1210, P388) and, in conjunction with other breast cancer cell lines, facilitate the in vitro and in vivo screening of new cytotoxic drugs and drug combinations.     

Laparoscopic enucleation of an insulinoma: advantages of using the curved laparoscopic coagulating shears

Laparoscopic excision is a widely accepted and well-described approach to islet cell tumors of the pancreas. We report the case of a patient with biochemically proven insulinoma who underwent successful enucleation using the curved laparoscopic coagulating shears. We discuss the advantages of using laparoscopy to manage these tumors and the increased benefit of using the curved instrument for this type of procedure.     

Treatment strategies in patients with major depression not responding to first-line sertraline treatment

RATIONALE: A large proportion of patients with major depression do not respond sufficiently to any first-line treatment. OBJECTIVES: The aim of this study was to compare a strategy of sertraline dose increase with a strategy of adding mianserin in patients with major depression insufficiently responding to 6 weeks of open treatment with sertraline, controlling for the effect of an extended duration of treatment. METHODS: One thousand six hundred and twenty-nine patients, 18-65 years of age, with major depression scoring at least 18 on the 17-item Hamilton depression scale (HDS) were treated openly with 50 mg/day sertraline, and patients who after 4 weeks had not responded (achieving at least a 50% reduction in score on the HDS) were treated with 100 mg/day sertraline for an additional 2-week period. The patients who had still not responded were then randomised to double-blind treatment for an additional 5 weeks with either 100 mg/day sertraline plus placebo, 200 mg/day sertraline plus placebo or 100 mg/day sertraline plus 30 mg/day mianserin. RESULTS: After 6 weeks of open treatment, 60% had responded and 22% had dropped out, leaving 295 non-responding patients (18%) for randomisation. In the intention-to-treat-analysis, continuing the treatment with 100 mg/day sertraline resulted in response in 70% of the non-responders, similar to the response rate (67%) obtained in the patients who had mianserin added. However, increasing the sertraline dose to 200 mg/day resulted in a lower response rate at 56% ( P<0.05). Similar results were seen in the completers. A substantial increase in the accumulated response rate from week 6 to week 8 was seen. There was no influence of baseline variables, including the presence of melancholic features on the overall post-randomisation response rate. CONCLUSION: After 6 weeks of insufficient antidepressant treatment with 50-100 mg/day sertraline, a continued treatment with 100 mg/day sertraline can be considered until at least week 8 before considering changing strategy, unless the condition deteriorates.     

Transient neonatal myasthenia gravis

Ten to twenty percent of the offspring of mothers suffering from myasthenia gravis (MG) also develop transient neonatal MG, since maternal antibodies are able to cross the placenta. We report the course of two newborns of a mother with MG and a healthy father. The first pregnancy was complicated during the 3rd trimester by a hydramnion. The newborn presented with generalized muscle weakness, respiratory distress, weak sounding, anaemia, and poor sucking. Mechanical ventilation was necessary. Confirmation of the diagnosis was achieved by the result of repetitive muscle stimulation, showing a typical decrement in the EMG, and measurement of serum antiacetylcholin receptor antibodies. For 3 months, the infant was treated with neostigmin (cholinesterase inhibitor). After 26 days of hospitalization, the patient was released and followed up regularly. Myasthenic symptoms completely resolved. Side effects of the treatment were not observed. The course of the second pregnancy was normal. This second newborn was healthy. Our case report is remarkable for the very different presentation of two children of the same mother with MG during pregnancy and after delivery, with one child developing severe transient neonatal MG, initially requiring intensive care unit (ICU) treatment followed by quick recovery, and one child being healthy. We also present a score for monitoring the clinical course and adjusting anticholinesterase therapy accordingly.     

Interferon-gamma modifies cytokine release in vitro by monocytes from surgical patients

BACKGROUND: Treatment with interferon-gamma (IFN-gamma), a key mediator for adequate forward-regulatory monocyte immune capability, has been advocated to overcome posttraumatic mononuclear leukocyte paralysis. Conversely, IFN-gamma also is a potent proinflammatory mediator contributing to capillary leakage in sepsis-driven organ failure. The objective of this investigation was to further define the potential of IFN-gamma as a modifier of monocyte activity before and after injury. METHODS: Whole blood samples from 19 patients (7 female and 12 male patients; age, 68 +/- 5 years) before and after cardiac surgery with extracorporeal circulation were incubated under continuous rotation with lipopolysaccharide for 12 hours in the presence or absence of human recombinant IFN-gamma. Pro- and anti-inflammatory cytokines were determined in the plasma. RESULTS: Lipopolysaccharide-induced release of tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-1Ra, and prostaglandin E2 was clearly augmented with IFN-gamma most strikingly postoperatively (p < 0.05). There was no effect on IL-1beta, neopterin, and soluble tumor necrosis factor-R release. CONCLUSION: Thus there is a wide spectrum of IFN-gamma activity on monocyte activation including anti-inflammatory properties. Since cellular preactivation facilitates monocyte reactivity toward IFN-gamma, we conclude that exogenous administration should be effective but must be carried out with great caution in patients with profound inflammation.     

Ketoacidosis at the diagnosis of type 1 (insulin dependent) diabetes mellitus is related to poor residual beta cell function. Childhood Diabetes in Finland Study Group

The determinants of the degree of metabolic decompensation at the diagnosis of type 1 (insulin dependent) diabetes mellitus (IDDM) and the possible role of diabetic ketoacidosis in the preservation and recovery of residual beta cell function were examined in 745 Finnish children and adolescents. Children younger than 2 years or older than 10 years of age were found to be more susceptible to diabetic ketoacidosis than children between 2 and 10 years of age (< 2 years: 53.3%; 2-10 years: 16.9%; > 10 years: 33.3%). Children from families with poor parental educational level had ketoacidosis more often than those from families with high parental educational level (24.4% v 16.9%). A serum C peptide concentration of 0.10 nmol/l or more was associated with a favourable metabolic situation. Low serum C peptide concentrations, high requirement of exogenous insulin, low prevalence of remission, and high glycated haemoglobin concentrations were observed during the follow up in the group of probands having diabetic ketoacidosis at the diagnosis of IDDM. Thus diabetic ketoacidosis at diagnosis is related to a decreased capacity for beta cell recovery after the clinical manifestation of IDDM in children.