Human CRY1 variants associate with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a common and heritable phenotype frequently accompanied by insomnia, anxiety, and depression. Here, using a reverse phenotyping approach, we report heterozygous coding variations in the core circadian clock gene cryptochrome 1 in 15 unrelated multigenerational families with combined ADHD and insomnia. The variants led to functional alterations in the circadian molecular rhythms, providing a mechanistic link to the behavioral symptoms. One variant, CRY1Δ11 c.1657+3A>C, is present in approximately 1% of Europeans, therefore standing out as a diagnostic and therapeutic marker. We showed by exome sequencing in an independent cohort of patients with combined ADHD and insomnia that 8 of 62 patients and 0 of 369 controls carried CRY1Δ11. Also, we identified a variant, CRY1Δ6 c.825+1G>A, that shows reduced affinity for BMAL1/CLOCK and causes an arrhythmic phenotype. Genotype-phenotype correlation analysis revealed that this variant segregated with ADHD and delayed sleep phase disorder (DSPD) in the affected family. Finally, we found in a phenome-wide association study involving 9438 unrelated adult Europeans that CRY1Δ11 was associated with major depressive disorder, insomnia, and anxiety. These results defined a distinctive group of circadian psychiatric phenotypes that we propose to designate as "circiatric" disorders.

Carboplatin and vindesine in advanced non-small cell lung cancer. A feasibility study.

Twenty-eight patients affected by advanced non-small cell lung cancer (NSCLC) were enrolled in a feasibility study evaluating toxicity and activity of carboplatin-vindesine combination chemotherapy, according to two different schedules. Fourteen patients were treated with carboplatin 350 mg/m2 monthly and vindesine 3 mg/m2 weekly for 5 doses, then every other week (schedule 1). The activity observed was promising with 3 partial remissions, but the toxicity was substantial, preventing full dose administration in 11 out of 14 patients. The subsequent 14 patients were treated with carboplatin 350 mg/m2 monthly and vindesine 3 mg/m2 on days 1 and 8 of each cycle. Activity was maintained with 4 partial remissions and toxicity was quite tolerable, allowing all patients to receive the planned treatment. The combination of carboplatin 350 mg/m2 on day 1 and vindesine 3 mg/m2 on days 1 and 8 seems active and well tolerated in advanced NSCLC patients and deserves further evaluation in a larger phase II study.

Intracavitary cisplatin in malignant cardiac tamponade.

A case of lung cancer presenting with cardiac tamponade is reported. Lasting control of the malignant effusion was achieved by means of intracavitary cisplatin following pericardiocentesis. The patient presented an objective response to subsequent systemic chemotherapy and died 10 months after the diagnosis because of disseminated cancer, without clinical or instrumental findings of pericardial effusion.

[CT assessment of encephalic and suprarenal spread of "operable" pulmonary neoplasms. Preliminary results]. / Valutazione TC della diffusione encefalica e surrenale nelle neoplasie polmonari "operabili". Risultati preliminari.

Computed Tomography (CT) was employed to evaluate the incidence of brain and adrenal gland metastases in 74 patients (not-small cell lung cancer) staged for surgery. Nine patients presented one or more asymptomatic brain metastases, 4 adenocarcinomas, 3 epidermoid, 2 adenosquamous. In 6 cases adrenal gland masses were found, only one of which was confirmed as a secondary lesion at biopsy. The authors conclude that brain CT is useful in the preoperative staging of lung cancers, independent of the histology of the primary lesion. An accurate assessment of the utility of CT of the adrenal glands requires a larger sample of patients due to the high incidence of benign adrenal gland masses.