2H-[1]benzothiepino [5,4-b]pyran derivatives with local anesthetic and antiarrhythmic activities

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-[1]benzothiepino [5,4-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzothiepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The 4-methylphenylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine and the 4-morpholino derivative showed an antiarrhythmic activity in rats comparable to that of quinidine.     

Upper extremity deep vein thrombosis after suspension of progesterone-only oral treatment.

The intake of steroid hormone contraceptives is a strong and independent risk factor for venous thromboembolism. Several studies have assessed an increased risk of venous thromboembolism in women using oral contraceptives who are carriers of the G20210A mutation in the prothrombin gene. Most trials evaluating the thrombotic risk of oral contraceptives are based on combined oral preparations, but only a few focus on progestogen-only oral preparations. Results from such studies are conflicting and globally assess the thrombotic risk, ranging from modest to slightly increased. Furthermore, little is known about the relationship between the C677T mutation in the methylenetetrahydrofolate reductase gene and the progestogen-based preparations. Herewith we report the case of a 49-year-old woman with a complex genetic thrombosis risk factor who had taken oral progesterone for 15 months without any complication, but then experienced severe left upper extremity deep vein thrombosis 2 months after the drug suspension.     

CXCL10 haplotypes and multiple sclerosis: association and correlation with clinical course

CXCL10 (interferon- γ -inducible protein-10) levels are increased in cerebrospinal fluid of multiple sclerosis (MS) patients with symptomatic attacks of inflammatory demyelination, supporting a role for this molecule in MS pathogenesis. Two hundred and twenty-six patients with MS and 235 controls were genotyped for G  →  C and T  →  C single nucleotide polymorphisms (SNPs) in exon 4 of CXCL10 gene. Haplotypes were tested for association and correlated with clinical variables. The two SNPs studied were in complete linkage disequilibrium. None of the determined haplotypes was associated with MS. However, carriers of the GGTT haplotype (defined as wild type, according to the sequence in National Centre for Biotechnology Information (NCBI) database) had a significantly lower progression index than non-carriers ( P  = 0.016). Furthermore, amongst patients who had an initial relapsing remitting (RR) course of the disease, the time between onset and second episode was significantly longer in GGTT carriers ( P  = 0.021). Considering secondary progressive (SP)–MS patients, the time between the initial RR form and the subsequent worsening to SP was longer in this group ( P  = 0.08). Therefore, the GGTT haplotype of the CXCL10 gene is not a susceptibility factor for the development of MS, but is probably to influence the course of MS, possibly contributing to slow down the progression of the disease.     

The variability of arterial pressure measured by oscillometric methods in premature newborn infants

The variability of blood pressure measured by oscillometry and the validity of this technique were studied in premature infants. Thirty premature babies whose postnatal age was six days or more had their blood pressure measured 11 times over a twenty-minute period for three consecutive days. Movements were found to have a very substantial influence on results that could not be reliably compared with values obtained invasively. No consistent pattern of variations of oscillometric results obtained during the eleven measurements of use for recommending a specific measurement time was found. Diastolic blood pressure fell gradually over the three-day study period. The most reliable of the eleven daily values was the lowest value for which good correlations were found between the three study days; this lowest value was not influenced by neonatal or postnatal factors.     

Cholinergic balance in dementia with Lewy bodies: reversible worsening of Parkinsonism at rivastigmine dosage modulation

We describe a patient with probable dementia with Lewy bodies (DLB) whose Parkinsonism worsened after administration of rivastigmine within the therapeutic dose range. Some extrapyramidal signs (EPS) then reversed to pre-treatment level after rivastigmine dose reduction. We draw attention to the need of EPS monitoring during titration of cholinesterase inhibitors in patients with DLB. This is the first report to our knowledge of iatrogenic worsening of Parkinsonism which was successfully managed by dose reduction.

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Sommario Si descrive il caso di un paziente affetto da Demenza a corpi di Lewy (Dementia with Lewy Bodies, DLB) probabile, in cui si è assistito ad un peggioramento del parkinsonismo dopo somministrazione di rivastigmina a dosi terapeutiche. Alcuni segni extrapiramidali sono regrediti al livello pre-trattamento con una riduzione posologica di rivastigmina. Si sottolinea la necessità di un monitoraggio dei segni extrapiramidali durante la titolazione della terapia con inibitori dell’acetilcolinesterasi cerebrale in pazienti con DLB. Questo è il primo caso descritto, a nostra conoscenza, di un peggioramento iatrogeno di parkinsonismo efficacemente gestito con una riduzione posologica della terapia con rivastigmina.

     

dCTP misincorporation in a Chinese hamster mutator phenotype: the role of GGA genetic context

Clone CSA7 is a CHEF18 hamster cell line that shows an increasedintracellular accumulation of dCTP. To localize the mutationsthat accumulate spontaneously in a functional gene of such amutator phenotype, independent CSA7 mutants of the hypoxanthine–guaninephosphoribosyl transferase (hprt) gene were isolated and screenedby a polymerase chain reaction–single strand conformationpolymorphism technique. Sixty-two percent of mutants produceddetectable changes of the strand migration profile and the mutationswere preferentially localized in the exons 3 (31%) and 6 (62%).The sequencing of such exons revealed that the rate of C baseincorporation was the major mutation pathway and that the Abase of a GGA sequence was the preferential site of misincorporation. ³To whom correspondence should be addressed     

Transposition of the great arteries and isolated origin of the sinus node artery

We report the cases of 2 newborns who underwent at 7 days of age an arterial switch operation for transposition of the great arteries with a rare coronary anomaly: the left and right coronary arteries originated with a single ostium from sinus 1 and the sinus node artery had an isolated origin from sinus 2. The sinus node artery was reimplanted into the new aorta in both patients. Both babies were discharged in sinus rhythm. Preserving the vascularization of the sinus node may avoid the occurrence of postoperative atrial rhythm disturbances.     

The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis

Between March 1976 and June 1985, 1,000 consecutive adults with asymptomatic gross or microscopic hematuria in the absence of proteinuria were evaluated urologically. Lesions that could account for the hematuria were detected in 88.3 per cent of the patients. Life-threatening lesions were diagnosed in 9.1 per cent of the patients, while lesions requiring at least observation were present in 22.8 per cent. The incidence of life-threatening lesions increased with age, with a sharp increase after age 50 years. Life-threatening lesions were more common in men (13.6 per cent) than in women (4.9 per cent). In general, as the degree of hematuria increased so did the yield of life-threatening lesions; however, there was no "safe" lower limit of hematuria. Of the patients with life-threatening lesions 18.6 per cent had at least 1 urinalysis with less than 3 red blood cells per high power field within 6 months of the diagnosis. The direct medical cost of a hematuria evaluation was $777. The difference in direct medical costs to diagnose and treat localized versus metastatic genitourinary cancer was $48,070 in 3 matched pairs of patients. In this study group 77 of 84 patients (92 per cent) diagnosed with genitourinary cancer had localized disease. A hematuria evaluation was cost-effective for all groups studied. A literature-based estimate of the life-threatening risks of diagnostic studies applied to the study data resulted in a 1.1 per cent life-threatening risk per hematuria evaluation. For all categories studied, except for women less than 40 years old with microscopic hematuria, the risk of a hematuria evaluation was less than the incidence of life-threatening lesions discovered as a result of the evaluation. Asymptomatic hematuria, whether gross or microscopic, is a significant finding and warrants evaluation from a risk-benefit and cost-effectiveness standpoint.