False-negative serological HLA-B27 typing results may be due to altered antigenic epitopes and can be detected by polymerase chain reaction

Serological typing with the microlymphocytotoxicity test (MLCT) and flow cytometry (FC) using HLA-B27 antisera is commonly used for the determination of HLA-B27. However, in some patients tested more than once, negative results have turned out to be positive at following investigations. We retested by polymerase chain reaction (PCR) samples from 20 randomly selected patients with reactive arthritis or Reiter's syndrome who had now been followed for 20 yr. Ten of the patients were originally tested to be HLA-B27 positive and 10 HLA-B27 negative by the MLCT. All 10 serologically HLA-B27 positive individuals were also positive in the PCR. However, 2/10 patients interpreted as being HLA- B27 negative were positive by PCR. At this time, the same two patients were also positive in the routine MLCT and FC using four different monoclonal antibodies against HLA-B27. PCR is superior to serological techniques to determine HLA-B27 positivity unequivocally, since it is based on the detection of HLA-B27 gene sequences.      

Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony- stimulating factor

We administered recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM-CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM-CSF added to chemotherapy in patients with newly diagnosed AML.     

2-chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia

A number of effective treatments are available for patients with hairy cell leukemia (HCL). 2-Chlorodeoxyadenosine (2-CdA) induces more than 80% complete responses, but is associated with profound suppression of CD4+ lymphocyte counts. However, the duration of each is uncertain. We have analyzed a previously reported cohort of 40 patients who had responded to 2-CdA. Eight patients (20%) have relapsed at a median of 16 months (range, 3 to 23 months). The remaining 32 patients were observed for a median of 30 months (range, 7 to 43 months). No patients have died. At 3 years, the actuarial disease-free survival rate is 77% (95% confidence interval, 70% to 84%). The median CD4+ lymphocyte count before therapy was 743/microL (range, 58 to 2,201/microL). The median CD4+ nadir after treatment was 139/microL (range, 25 to 580/microL). There was a single opportunistic infection and no second malignancies observed. Although there was evidence of some improvement in CD4+ lymphocyte counts on sequential testing, CD4+ counts remained significantly lower than baseline (P < .0001) at a median of 23 months after therapy (median, 237/microL; range, 25 to 514/microL), and were also lower than baseline (P < .002) in those patients with more than 1 year of follow-up (median, 27 months; range, 13 to 42 months). The median time to reach an absolute CD4+ lymphocyte count of 365/microL, the lower limit of the normal range, was 40 months. Although responses to 2-CdA are durable in the majority of patients with HCL, the uncertain long-term consequences of the observed CD4+ lymphocytopenia suggest caution in the broad application of this therapy.     

Management of oral complications of disease-modifying drugs in rheumatoid arthritis

Stomatitis is a troublesome adverse effect of disease-modifying anti- rheumatic drug (DMARD) therapy in rheumatoid arthritis (RA) patients. This review presents data to examine the incidence, clinical features and consequences of DMARD-related stomatitis, and suggests an algorithm for its clinical management. The specific objectives of the two studies presented here were to determine the incidence of DMARD-related stomatitis and its effect on DMARD continuation, and secondly to identify the clinical and laboratory risk factors. We investigated two cohorts of patients: (i) a retrospective survey of data collected from drug monitoring clinics run for patients on DMARDs from 1987 to 1994 involving 1539 patients and 2394 drug exposures; (ii) a prospective study of 25 consecutive RA patients presenting with DMARD-related stomatitis compared to 29 RA controls with no history of DMARD stomatitis. The retrospective survey showed that 2% of DMARD patients stopped therapy because of stomatitis, but 55% of these were able to resume the same therapy. In the case control study. 24% of patients discontinued temporarily and 8% permanently. Cases of DMARD-related stomatitis differed from controls in that they had a higher incidence of previous mouth ulcers (40% vs 14%), they smoked less (8% vs 31%) and Schirmer's test was more often abnormal (44% vs 21%). There were no differences in RA severity, disease activity or oral hygiene. Haematinic deficiencies were equally common in cases and controls: 30% for iron, 8% for vitamin B12 and 24% for folic acid. Herpes simplex virus was involved in a minority (8%) of cases. In conclusion, the occurrence of stomatitis in RA patients on DMARD should not lead to cessation of drug therapy, but to a careful evaluation so that patients may be maintained on effective treatment.      

Bottom-electrode induced defects in self-assembled monolayer (SAM)-based tunnel junctions affect only the SAM resistance,not the contact resistance or SAM capacitance

In large area molecular junctions, defects are always present and can be caused by impurities and/or defects in the electrode materials and/or SAMs, but how they affect the electrical characteristics of junctions has rarely been studied. Usually, junctions are characterized by two-terminal current–voltage measurements where only the total current across the junction is measured, but with these methods one cannot distinguish how the individual components of the junctions are altered by the defects. Here we show that the roughness of the bottom-electrode is a crucial factor in determining the electrical properties of self-assembled monolayer (SAM)-based junctions. We used potentiodynamic impedance spectroscopy to reveal which components of the junctions are altered by defective bottom electrodes because this method allows for direct determination of all components that impede charge transport in the equivalent circuit of the junctions. We intentionally introduced defects via the roughness of the bottom electrode and found that these defects lower the SAM resistance but they do not alter the capacitance of the SAM or the contact resistance of the junction. In other words, defective junctions can be seen as “leaky capacitors” resulting in an underestimation of the SAM resistance of two orders of magnitude. These results help to improve the interpretation of data generated by SAM-based junctions and explain in part the observed large spread of reported tunneling rates for the same molecules measured across different platforms.

In large area molecular junctions, defects are always present and can be caused by impurities and/or defects in the electrode materials and/or SAMs, but how they affect the electrical characteristics of junctions has rarely been studied.     

Undertreatment of Motor Problems in Children with ADHD

Background: Motor problems occur in 30% to 50% of children with ADHD, and have a severe impact on daily life. In clinical practice there seems to be little attention for this comorbidity with the possible consequence that these motor problems go undertreated. Method: Clinical interview and questionnaire survey of treatment by physiotherapy and factors predicting treatment of motor problems in 235 children with ADHD and 108 controls. Results: Half of motor‐affected children had received physiotherapy. Treated children had more severe motor problems, and less frequently presented with comorbid anxiety and conduct disorder. Treated and untreated children were similar in age, and rated similarly on ADHD inattentive and hyperactive‐impulsive scales and parental socio‐economic status. Conclusion: Currently, undertreatment of motor problems in ADHD occurs. Behavioural factors play a role in referral and intervention.     

Short-term Overfeeding Induces Insulin Resistance in Weight-stable Patients After Bariatric Surgery

Background Short time overfeeding of rats rapidly leads to insulin resistance (IR). A study with healthy human volunteers, which we suggest are less susceptible for developing IR after short time overfeeding, did not show these effects on IR. Therefore a study population of weight-stable, former morbidly obese subjects (BMI 31.3 kg/m²), which were treated with bariatric surgery approximately 3 years ago was selected. Methods Eleven subjects were submitted to a 7-day overfeeding study, resulting in a 53% increase in caloric intake (1,227 ± 394.4 to 1,879.2 ± 298.4 kcal/day). During normal diet and after overfeeding, insulin sensitivity was measured using steady state plasma glucose (SSPG) levels. At these time points, BMI and waist/hip ratio together with plasma levels of inflammatory markers (CRP, AGP, LBP, and TNF-α receptors) and plasma leptin values were also measured. Results SSPG levels after overfeeding increased from 8.2 ± 3.2 to 10.6 ± 2.6 mmol/l (P < 0.05), indicating decreased insulin sensitivity after overfeeding. Fasting plasma insulin, glucose, circulating levels of inflammatory markers, BMI, and waist/hip ratio remained unchanged. Conclusions This study shows that overfeeding in a group of weight-stable, former morbidly obese subjects 3 years after bariatric surgery results in decreased insulin sensitivity. The mechanisms behind decreased insulin sensitivity induced by overfeeding are poorly understood, but the present results reveal that a unique human model is available to study these mechanisms, leading to a better understanding of the pathophysiology of IR.     

Maternal cardiac arrest in early pregnancy

A primigravid woman suffered a prolonged cardiac arrest at 18 weeks of gestation. Dilated ischemic cardiomyopathy was diagnosed. After recovery, the patient received an implantable cardioverter-defibrillator. At 38 weeks of gestation she had an elective caesarean delivery. Both mother and child had a favourable outcome. The effect of pregnancy on underlying cardiac disease and the management of maternal cardiac arrest with a pre-viable fetus are discussed. The importance of a multidisciplinary approach is emphasized. Continued neurodevelopmental assessment of the newborn is necessary to detect the long-term effects of fetal hypoxia in early pregnancy.     

The choice of obstetric care by low-risk pregnant women in the Netherlands: Implications for policy and management

In the Netherlands, pregnant women at low risk of complications during pregnancy, have the opportunity to choose freely between giving birth at home or in a hospital maternity unit. This study analyses how various attributes of obstetric care, socio-economic characteristics and attitudes influence the decisions that these women make with regard to obstetric care. The method of discrete-choice experiment was applied in the process of data collection and analysis. The data were collected among low-risk nulliparous pregnant women. The analysis suggests that there are strong preferences among some Dutch women for a home birth. Nevertheless, the absence of a medical pain-relief treatment during home birth, might provide incentives for some women to opt for a birth in a hospital, especially at the end of their pregnancy. If the attractiveness of home birth should be preserved in the Netherlands, specific attention should be paid on the approach to pain during a home birth. Efforts could also be made in offering a domestic atmosphere during hospital births to improve hospital-based obstetric care in view of women's preferences.