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.     

Clinical evaluation of biomarkers in Gaucher disease

Novel or candidate biomarkers require thorough evaluation to establish their utility in a clinical setting. This paper describes an evaluation of several established enzyme markers of Gaucher disease and a newly-described chemokine, pulmonary and activation-regulated chemokine (PARC). The ability of the biomarkers to rank patients with Gaucher disease in order of disease severity and organ bulk, and to reflect changes in key clinical parameters in response to enzyme replacement therapy were evaluated. PARC concentrations were found to be reliably correlated with visceral disease and with key clinical responses to enzyme replacement in an unbiased manner. Unlike chitotriosidase and serum angiotensin-converting enzyme activity, genetic variation in serum PARC did not appear to influence its utility as a biomarker.
Conclusion: For each new candidate biomarker of lysosomal storage diseases, a similar clinical evaluation will be required, though the approach will need to be modified according to the clinical features and natural history of each disorder.     

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.     

Hirschprung's disease

Current evidence on the pathogenesis of Hirschprung's disease, then, favours the 'abnormal microenvironment' hypothesis wherein the developing and migrating normal neural crest cells confront a segmentally abnormal and hostile microenvironment in the colon. This hypothesis would account both for the congenital absence of ganglion cells in the wall of colon and also for the range of enteric neuronal abnormalities encountered including neuronal dysplasia, hypoganglionosis, and zonal aganglionosis. The abnormal constitution of the mesenchymal and basement membrane extracellular matrix in the affected segment of colon is presumably genetically determined and further understanding of the pathogenesis of this disorder will emerge as molecular geneticists characterise the specific genes and gene products associated with Hirschprung's disease. Advances in this field should permit gene probes to be developed to facilitate prenatal and postnatal diagnosis.     

The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.