Multiplex ligation-dependent probe amplification to detect subtelomeric rearrangements in routine diagnostics

Subtelomeric rearrangements are believed to be responsible for 5-7% of idiopathic mental retardation cases. Due to the relative complexity and high cost of the screening methods used till now, only preselected patient populations including mostly the more severely affected cases have been screened. Recently, multiplex ligation-dependent probe amplification (MLPA) has been adapted for use in subtelomeric screening, and we have incorporated this technique into routine diagnostics of our laboratory. Since the evaluation of MLPA as a screening method, we tested 275 unselected patients with idiopathic mental retardation and detected 12 possible subtelomeric aberrations: a der(11)t(11;20)(qter;qter), a 19pter duplication, a der(18)t(18;10)(qter; pter), a 15qter deletion, a 8pter deletion, a 6qter deletion, a der(X)t(X;1)(pter;qter), a der(X)t(X;3)(pter;pter), a 5qter duplication, a 3pter deletion, and two 3qter duplications. The patients can be subdivided into two groups: the first containing de novo rearrangements that are likely related to the clinical presentation of the patient and the second including aberrations also present in one of the parents that may or may not be causative of the mental retardation. In our patient cohort, five (1.8%) subtelomeric rearrangements were de novo, three (1.1%) rearrangements were familial and suggestively disease causing, and four (1.5%) were possible polymorphisms. This high frequency of subtelomeric abnormalities detected in an unselected population warrants further investigation about the feasibility of routine screening for subtelomeric aberrations in mentally retarded patients.     

Hypertension in dialysis and kidney transplant patients

For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease.     

Inflammation of unknown origin versus fever of unknown origin: Two of a kind

ObjectivesA vast literature exists on fever of unknown origin (FUO), characterized by prolonged and perplexing fevers > 38.3 °C. In contrast, no studies are available to guide the approach to inflammation of unknown origin (IUO), defined as prolonged and perplexing inflammation with temperatures < 38.3 °C. We aimed to determine the diagnostic yield, the case-mix, and the outcome of patients with IUO, relative to patients with FUO.MethodsWe matched 57 patients with IUO to 57 patients with FUO of the same gender (54% male) and a similar age (median: 67 years).ResultsA diagnosis was established in 35 patients with IUO (61%) and in 33 patients with FUO (58%) (p = .70). The case-mix did not differ significantly (p = .43). Non-infectious inflammatory disorders were the dominant diagnostic category in the IUO group (16 patients), while in the FUO group, similar numbers of malignancies [10], infections [9], and non-infectious inflammatory diseases [9] were diagnosed. ¹⁸F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scan contributed comparably to the diagnosis in both groups (in 18 of 50, 36%, patients with IUO and in 13 of 40, 33%, patients with FUO) (p = .83). In both groups, 7 patients (12%) died during an average follow-up of 1 year.ConclusionDiagnostic yield, case-mix, contribution of FDG-PET scan and vital outcome were similar in patients with IUO and FUO. These data suggest that the 38.3 °C boundary may be arbitrary and that the diagnostic approaches used in FUO can be applied to IUO.     

Inflammation markers in relation to cognition in a healthy aging population

The relation between serum inflammatory protein levels and cognitive performance was investigated in a healthy population.Individuals were tested during 6 years of follow-up. Serum concentrations of 10 inflammatory proteins were correlated to cognitive speed (Letter-Digit Coding Test, LDCT), attention and information processing (Stroop) and memory (Word Learning). Haptoglobin levels at baseline correlated negatively with cognitive performance on the Stroop and Word Learning Recall test over the 6 years follow-up period. C-reactive protein (CRP) levels at baseline correlated negatively with performance on the Word Learning tests over the 6 years follow-up period. Thus, relatively high concentrations of haptoglobin and C-reactive protein may be indicative for impaired cognitive performance.     

Intraoperative scrape cytology of the sentinel lymph node in patients with breast cancer

BACKGROUND: Intraoperative examination of the sentinel lymph node (SLN) may detect metastatic disease, allowing immediate axillary lymph node dissection and therefore avoiding the need for reoperation. The aim of this study was to evaluate the accuracy of scrape cytology of the SLN in patients with early breast cancer. METHODS: Sentinel node biopsy was performed in 148 patients with clinical T1-2 N0 breast cancer. After harvesting, the SLN was bisected and cells from both halves were scraped with a scalpel blade on to a slide and stained with a Papanicolaou and Giemsa stain. Scrape cytology results were compared with the results of paraffin sections stained with haematoxylin and eosin and with immunohistochemistry. RESULTS: The intraoperative diagnosis was correct in 126 patients (85 per cent). Sensitivity and specificity were 67 and 98 per cent respectively; positive and negative predictive values were 95 and 81 per cent. CONCLUSION: Scrape cytology is a useful method for intraoperative evaluation of the SLN in patients with breast cancer.     

The coeliac iceberg in Italy. A multicentre antigliadin antibodies screening for coeliac disease in school-age subjects

Background : Recent studies suggest that coeliac disease (CD) is one of the commonest, life-long disorders in Italy. The aims of this multicentre work were: (a) to establish the prevalence of CD on a nationwide basis; and (b) to characterize the CD clinical spectrum in Italy. Patients and methods : Fifteen centres screened 17201 students aged 6–15 years (68.6% of the eligible population) by the combined determination of serum IgG- and IgA-antigliadin antibody (AGA) test; 1289 (7.5%) were IgG and/or IgA-AGA positive and were recalled for the second-level investigation; 111 of them met the criteria for the intestinal biopsy: IgA-AGA positivity and/or AEA positivity or IgG-AGA positivity plus serum IgA deficiency. Results : Intestinal biopsy was performed on 98 of the 111 subjects. CD was diagnosed in 82 subjects (75 biopsy proven, 7 not biopsied but with associated AGA and AEA positivity). Most of the screening-detected coeliac patients showed low-grade intensity illness often associated with decreased psychophysical well-being. There were two AEA negative cases with associated CD and IgA deficiency. The prevalence of undiagnosed CD was 4.77 × 1000 (95% CI 3.79–5.91), 1 in 210 subjects. The overall prevalence of CD, including known CD cases, was 5.44 × 1000 (95% CI 4.57–6.44), 1 in 184 subjects. The ratio of known to undiagnosed CD cases was 1 in 7. Conclusions : These findings confirm that, in Italy, CD is one of the most common chronic disorders showing a wide and heterogeneous clinical spectrum. Most CD cases remain undiagnosed unless actively searched.     

Failures of laparoscopic sterilization by Hulka-Clemens clips

The reasons for failure in a series of 544 laparoscopic sterilizations by Hulka-Clemens clips are analyzed. Patients were divided into 2 groups: 1) 327 women sterilized by clips, and 2) 217 women sterilized with clips simultaneous to suction abortion. Most patients were 31-41 years of age. 10 pregnancies were observed in the 4-12 month follow-up, most of which occurred 2-4 months after clip application. None of the pregnancies were ectopic. The higher failure rate in group 2 (7%) compared to group 1 (1.83%) is due to the larger uterine size in the pregnant women. Most failures were attributable to a lack of technical training on the part of operators. In most cases, the clips were applied to a structure other than the tube: round ligament (3 cases), fimbriae (2 cases), utero-ovarian ligament (1 case), twisted spring (3 cases). The cause for failure remains unknown in 1 case. Compared with other sterilization methods (e.g., diathermic coagulation, Yoon ring), the Hulka-Clemens clip procedure has a low rate of method failure. Other studies have noted the following reasons for failure: material, application in already pregnant patients, incomplete nipping of the tubal lumen, application on another structure, and decrease of pressure on the jaws of the clip. Subsequent pregnancies with this method can be avoided by attention to optimal presentation of the uterus during the procedure to facilitate tubal cupping, and adequate supervision when the procedure is done by an inexperienced operator.     

The use of darbepoetin alfa for the treatment of chemotherapy-induced anaemia

Chemotherapy-induced anaemia, with its important consequences on quality of life and social function of cancer patients, can be improved with erythropoietic therapy. Darbepoetin alfa is the first of a novel generation of erythropoietic proteins with a unique molecular structure and a circulating half-life that is threefold longer than that of the previous recombinant human erythropoietin. The efficacy and safety of weekly administration have been confirmed in different Phase II and III randomised trials. In order to optimise the efficacy profile of darbepoetin alfa, extended dosing intervals and front-loading regimens are evaluated, as well the optimal haemoglobin level to initiate therapy. Across all trials, darbepoetin alfa was shown to be a well-tolerated and safe therapy. The possible favourable effect on the outcome of cancer patients needs to be further elucidated.     

Distal renal tubular acidosis and lymphocytic thyroiditis with spontaneously resolving hyperthyroidism. Report of 1 case without nephrocalcinosis

In a 33-year-old woman concurrence of a complete distal renal tubular acidosis (RTA) and lymphocytic thyroiditis with spontaneously resolving hyperthyroidism was observed. Until recently, the rare association of RTA and hyperthyroidism had been thought to be governed by nephrocalcinosis, via hypercalcemia and hypercalciuria. However, in this case, nephrocalcinosis was not present, but there were histological signs of renal interstitial mononuclear cell infiltration, and the RTA persisted despite the resolution of the hyperthyroidism. This observation supports the idea that immunological mechanisms may relate RTA and hyperthyroidism when the latter has an autoimmune origin.     

A study of somatopsychic vulnerability in encopretic children.

In this article the results of a study to determine the degree of somatopsychic vulnerability in children with encopresis are discussed. A checklist was constructed for the registration of somatic and functional data relevant to encopresis. Twenty-five children with encopresis were compared with a control group. The expectation of the authors that a number of somatopsychic phenomena would occur more frequently among encopretics than among non-encopretics could not be confirmed. It appeared that somatic and psychic diseases were more frequent in the families of the children with encopresis than in the control group.