Comparison of Intermediate-Dose Methotrexate with Cranial Irradiation for the Post-Induction Treatment of Acute Lymphocytic Leukemia in Children

Abstract We compared two regimens with respect to their ability to prolong disease-free survival in 506 children and adolescents with acute lymphocytic leukemia. All responders to induction therapy were randomized to treatment with 2400 rad of cranial irradiation plus intrathecal methotrexate or to treatment with intermediate-dose methotrexate plus intrathecal methotrexate, as prophylaxis for involvement of the central nervous system and other sanctuary areas. Patients were then treated with a standard maintenance regimen. Complete responders were stratified into either standard-risk or increased-risk groups on the basis of age and white-cell count at presentation. Among patients with standard risk, hematologic relapses occurred in 9 of 117 given methotrexate and 24 of 120 given irradiation (P\u3c0.01). The rate of Central-nervous-system relapse was higher in the methotrexate group (23 of 117) than in the irradiation group (8 of 120) (P = 0.01). Among patients with increased risk, radiation offered greater protection to the central nervous system than methotrexate (P = 0.03); there was no difference in the rate of hematologic relapse. In both risk strata the frequency of testicular relapse was significantly lower in the methotrexate group (1 patient) than the radiation group (10 patients) (P = 0.01). Methotrexate offered better protection against systemic relapse in standard-risk patients and better protection against testicular relapse overall, but it offered less protection against relapses in the central nervous system than cranial irradiation. (N Engl J Med. 1983; 308:477–84.

Development of a genotyping microarray for Usher syndrome

BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Health and healing

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The Effect of Acupuncture on Blood Pressure in Hypertensive Patients Treated in a Complementary Medicine Clinic

Background Hypertension is a major health problem with serious medical and financial consequences. Experimental studies in animals and clinical studies in humans have demonstrated that acupuncture can reduce blood pressure significantly in hypertensive patients. The objective was to assess the effect of acupuncture on blood pressure in hypertensive patients treated at a complementary medicine clinic. Methods Blood pressure values measured before and following acupuncture were recorded from the charts of hypertensive patients who came to the clinic for treatment of other problems. The therapy used was the Kiiko Matsumoto technique for blood pressure imbalance. Results Twenty-nine patients were studied (18 [62%] women). The mean age was 58.5 ± 16.3 years. Systolic blood pressure dropped significantly as a result of the treatment and there was a non-significant trend to reduced diastolic pressure. Weekly acupuncture therapy led to a continuous reduction in systolic blood pressure. Conclusions Acupuncture has a beneficial effect on hypertension, particularly on systolic pressure. Further studies with larger study groups for longer periods of time can confirm this observation and contribute to our understanding of combination therapy with acupuncture and conventional medications for hypertension