ABSTRACT
The high resolution of modern DNA arrays has the implification of unintended coincidental detection of gene deletions predisposing to late-onset neurological and oncological disorders. Here, we report the case of an 18-year-old girl with mild intellectual disability, facial dysmorphisms, and a microdeletion of approximately 6.3 Mb on 22q12.1q12.3 including NF2, the gene for neurofibromatosis type 2, and CHEK2, a modifier gene for breast cancer. Subsequent magnetic resonance imaging of the brain showed she had already developed bilateral vestibular schwannomas. The challenge of DNA arrays and the consequences for genetic counselling and informed consent will be discussed in the light of this unique case with a microdeletion including both a high risk and a moderate risk cancer predisposition gene.
Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 22/genetics , Incidental Findings , Neuroma, Acoustic/genetics , Oligonucleotide Array Sequence Analysis/methods , Adolescent , Checkpoint Kinase 2 , Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Female , Humans , Magnetic Resonance Imaging , Neurofibromin 2/genetics , Neuroma, Acoustic/diagnosis , Protein Serine-Threonine Kinases/genetics , Risk FactorsSubject(s)
Cross Infection/etiology , Diseases in Twins , Gram-Negative Bacterial Infections/etiology , Hydrocephalus/surgery , Infant, Premature , Meningitis, Bacterial/etiology , Ralstonia pickettii , Ventriculoperitoneal Shunt/adverse effects , Cross Infection/drug therapy , Gram-Negative Bacterial Infections/drug therapy , Humans , Hydrocephalus/microbiology , Infant, Newborn , Meningitis, Bacterial/drug therapyABSTRACT
We report on two patients with morphine-related seizures associated with either intrathecal or intracerebroventricular administration. Both patients had a history of malignant tumor and both experienced the seizures following bolus application of morphine, while even higher dosages were well tolerated when continuously infused. Seizures occurred without signs of intoxication. Initiation of intrathecal morphine therapy and bolus application should be performed carefully and only when constant monitoring is provided for at least 12 h. Animal data and possible mechanisms for morphine-related seizures are discussed.
Subject(s)
Analgesics, Opioid/administration & dosage , Epilepsy/chemically induced , Morphine/administration & dosage , Adult , Aged , Analgesics, Opioid/adverse effects , Analgesics, Opioid/therapeutic use , Carcinoma, Squamous Cell/physiopathology , Head and Neck Neoplasms/physiopathology , Humans , Injections, Intraventricular , Injections, Spinal , Male , Morphine/adverse effects , Morphine/therapeutic use , Pain, Intractable/drug therapy , Urinary Bladder Neoplasms/physiopathologyABSTRACT
KT-362 is an antiarrhythmic and antihypertensive agent with vasodilating activity. Since it carries a homoveratryl group in the side chain, an obvious relation exists to the verapamil-type calcium antagonists. Replacement of the fused aromatic moiety in KT-362 with thiophene provided 8-[N-[2-(3,4-dimethoxyphenyl) ethyl]-beta-alanyl]-5,6,7,8-tetrahydrothieno[3,2-b][1,4] thiazepine (1). Compound 1 shows a negative chronotropic activity in spontaneously beating right atria (IC50 = 23 microM, n = 7), and a negative inotropic effect in papillary muscles (IC50 = 2.7 microM, n = 7) and left atria (IC50 = 4 microM, n = 6) of the guinea-pig heart. The decrease of contractility in papillary muscles could be antagonized by increasing the extracellular calcium concentration. Compound 1 was found to affect high (IC50: 70 +/- 5 microM) and low (IC50: 129 +/- 34 microM) voltage-activated calcium channel currents as well as voltage-activated sodium channel currents (IC50: 80 +/- 13 microM) in chick dorsal root ganglion neurons. In addition nicotine-induced currents were potently inhibited (IC50: 6 +/- 0.7 microM) in bovine chromaffin cells.
