Predictive genetic testing in maturity-onset diabetes of the young (MODY).

INTRODUCTION: Maturity-onset diabetes of the young (MODY) is characterized by autosomal dominant inheritance of young-onset non-insulin-dependent diabetes. It accounts for approximately 1% of Type 2 diabetes (approximately 20 000 people in the UK). Diagnostic and predictive genetic tests are now possible for 80% of MODY families. Diagnostic tests can be helpful as the diagnosis can be confirmed and the subtype defined which has implications for treatment and prognosis. However predictive genetic testing, particularly in children, raises many scientific, ethical and practical questions. METHODS: This is a case report of a family with diabetes resulting from an hepatic nuclear factor (HNF)1alpha mutation, who request a predictive test in their 5-year-old daughter. The scientific issues arising from molecular genetic testing in MODY are discussed, along with the process of genetic counselling. The views of the family and the clinical genetics team involved are presented. RESULTS: The implications of positive and negative predictive test results and the possibility of postponing the test were among many issues discussed during genetic counselling. The family remained convinced the test was appropriate for their daughter and the clinical genetics team fully supported this decision. The family, motivated by their family history of diabetes and personal experiences of the disease, wished to reduce uncertainty about their daughter's future irrespective of the result. CONCLUSIONS: This case emphasizes that decisions on predictive testing are very personal and require appropriate counselling.     

Detection of clonal T cell populations by high resolution PCR using fluorescently labelled nucleotides; evaluation using conventional LIS-SSCP.

AIMS: To detect clonal T cell populations by high resolution polymerase chain reaction (PCR) using fluorescently labelled nucleotides and analysis on an ABI 377 DNA sequencer, and to evaluate this method using low ionic strength single strand conformation polymorphism (LIS-SSCP) analysis. METHODS: DNA samples from 11 patients diagnosed with a T cell disease and 15 with no known T cell disorder were amplified using four multiplex T cell receptor gamma (TCR gamma) PCR reactions containing fluorescently labelled nucleotides. PCR products were analysed using both LIS-SSCP electrophoresis and an ABI 377 DNA sequencer using Genescan software. A Jurkat T cell leukaemia cell line was used to determine the sensitivity of the two methods. RESULTS: Clonal TCR gamma populations were detected in all 11 samples from patients with a T cell disease and no clonal populations were detected in samples from patients without a T cell disorder, using both LIS-SSCP and DNA sequencer analysis. Although the sensitivity of the two methods was comparable, the data generated by the sequencer were easier to interpret than the LIS-SSCP gels, and allowed accurate size determination of every product, which was not possible using LIS-SSCP. CONCLUSIONS: The use of fluorescent labelled nucleotides provides a more flexible and economical alternative to end labelled fluorescent primers for the detection of clonal TCR gamma gene rearrangements. This method allows clonal populations to be sized accurately and reproducibly, permitting the detection of identical clonal populations in different samples, and providing a method of monitoring disease progression and response to treatment.     

污水中汞的微波消解冷原子吸收测定法

目的 改进冷原子吸收法测定污水中汞的消解方法。方法 采用王水（1＋1）微波消解法代替KMnO4-K2S2O8消解法测定污水中的汞。结果 王水（1＋1）微波消解水样测定污水中汞，方法的线性范围为0~10.0μg／L，检出限为0.25μg／L，相对标准偏差小于2.7％，加标回收率为95.0％-102.0%。结论 与KMnO4-K2S2O8消解法相比，该方法具有较高的灵敏度和精密度，操作简单，结果可靠，适用于环境监测分析。     

Peptic ulcer and gastric carcinoma: diagnosis with biphasic radiography compared with fiberoptic endoscopy

The diagnostic value of biphasic radiographic examination of the stomach and duodenum was compared with that of fiberoptic endoscopy in a prospective, blinded study of 385 patients with dyspepsia. This investigation was directed at gastric malignancies and peptic ulcers. Methodologically there is no absolute standard for a study of this kind because histologic examination is useful for detection of cancer but inadequate for ulcers. As an alternative, kappa indexes and the sensitivity and specificity, as derived by Hui and Walter, were calculated and compared. For the detection of gastric carcinoma, radiographic and endoscopic findings had almost perfect agreement beyond chance. For gastric ulcers, radiography and endoscopy had substantial agreement, which became perfect if small ulcers (less than 5 mm) were excluded. For duodenal ulcers, radiography had a lower sensitivity than endoscopy; this disagreement disappeared if small ulcers were excluded. Both methods have equal merit; choice of the initial diagnostic procedure will therefore depend on cost, discomfort to the patient, and risk of complications.     

Heterogeneity in young adult onset diabetes: aetiology alters clinical characteristics.

AIMS: To describe the characteristics of hepatocyte nuclear factor (HNF) 1 alpha mutation carriers diagnosed with diabetes after 25 years and compare them with young-onset Type 2 diabetic patients (YT2D) diagnosed at the same age. SUBJECTS AND METHODS: We studied 44 (21 male, 23 female) patients with HNF-1 alpha mutations diagnosed with diabetes at ages 25-45 years and 44 YT2D subjects matched for sex and age of diagnosis. RESULTS: Median age of onset of diabetes was 35 years in both groups. The HNF-1 alpha group demonstrated: lower body mass index (25.1 vs. 30.7 kg/m2; P < 0.001) and lower fasting triglycerides (1.37 vs. 2.96 mmol/l; P = 0.001) with similar fasting cholesterol level. They had lower glycated haemoglobin A1c (7.3 vs. 8.5%; P = 0.015) despite greater duration of diabetes (24 vs. 16 years; P = 0.02) and less frequent treatment with insulin (21% vs. 55%; P = 0.002). They were less likely to be treated for hypertension (13.3% vs. 56.3%; P = 0.009). Importantly, no difference was observed in reported parental history of diabetes between the two groups (65.9% vs. 63.6%; P = 0.92). Logistic regression showed that triglyceride levels and presence of anti-hypertensive treatment were the most important independent variables. CONCLUSIONS: Patients with HNF-1 alpha mutations may present with diabetes as young adults between the ages of 25-45 years. In this age range a wide differential diagnosis of diabetes is observed. Conventional criteria of age of onset and family history will not differentiate HNF-1 alpha mutation carriers from YT2D subjects in this age range, but features of the metabolic syndrome, in particular fasting triglycerides and hypertension, are helpful. In patients diagnosed before 45 years without features of insulin resistance the diagnosis of HNF-1 alpha should be considered.     

An approach to evaluating the drug and alcohol problem in prisoners

In this paper a perspective on the drug and alcohol problems experienced in a specific group, namely, prisoners, is offered. The roles of the medical profession as assessors of drug and alcohol problems, and as educators, is briefly discussed.     

Parathyroid imaging: comparison of double-tracer (T1-201, Tc-99m) scintigraphy and high-resolution US

Parathyroid scintigraphy using a double-tracer (T1-201, Tc-99m) subtraction technique depicted 17 of 23 (74%) parathyroid adenomas in patients with and without previous neck operations. High-resolution (10-MHz) ultrasound (US) depicted 18 (78%) of these adenomas. Average tumor size depicted by US was 17 X 10 X 8 mm (excluding a giant adenoma) and 19 X 10 X 9 mm by scintigraphy. Alone, neither modality was particularly sensitive in the depiction of primary hyperplasia of the parathyroid glands, but combined techniques were more effective than the use of a single modality. With both US and T1-201 scintigraphy, only two of 23 cases of parathyroid adenoma in the neck were missed, and none of the eight cases of secondary hyperplasia were missed. In 11 patients who had previously undergone neck surgery, parathyroid tumors were identified in eight by either US or double-tracer scintigraphy. Preoperative parathyroid imaging with double-tracer scintigraphy and high-resolution US is suggested for patients with hyperparathyroidism, particularly in those patients who have had previous parathyroid surgery.