Postoperative Cognitive Dysfunction in Middle-aged Patients

Background: Postoperative cognitive dysfunction (POCD) after noncardiac surgery is strongly associated with increasing age in elderly patients; middle-aged patients (aged 40-60 yr) may be expected to have a lower incidence, although subjective complaints are frequent.

Methods: The authors compared the changes in neuropsychological test results at 1 week and 3 months in patients aged 40-60 yr, using a battery of neuropsychological tests, with those of age-matched control subjects using Z-score analysis. They assessed risk factors and associations of POCD with measures of subjective cognitive function, depression, and activities of daily living.

Results: At 7 days, cognitive dysfunction as defined was present in 19.2% (confidence interval [CI], 15.7-23.1) of the patients and in 4.0% (CI, 1.6-8.0) of control subjects (P < 0.001). After 3 months, the incidence was 6.2% (CI, 4.1-8.9) in patients and 4.1% (CI, 1.7-8.4) in control subjects (not significant). POCD at 7 days was associated with supplementary epidural analgesia and reported avoidance of alcohol consumption. At 3 months, 29% of patients had subjective symptoms of POCD, and this finding was associated with depression. Early POCD was associated with reports of lower activity scores at 3 months.     

Cervical pregnancy complicated with group B streptococcal meningitis.

Maternal group B streptococcal infection is an uncommon entity. Herein we describe a case of a 27-year-old-woman who presented life-threateniing group B streptococcus meningitis with an ectopic cervical pregnancy. No other infectious focus have been found. To our knowledge this is the first time that this association has been reported.     

Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release

The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05–0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca²⁺ concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflamatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1–1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K⁺ current and Ca²⁺-activated K⁺ current in a concentration-dependent manner. Niflumic acid (0.1–1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na⁺ current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K⁺ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca²⁺ with each impulse.     

PTOV-1, a novel protein overexpressed in prostate cancer,shuttles between the cytoplasm and the nucleus and promotes entry into the S phase of the cell division cycle

PTOV1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer. The PTOV1 protein consists of two novel protein domains arranged in tandem, without significant similarities to known protein motifs. By immunohistochemical analysis, we have found that PTOV1 is overexpressed in 71% of 38 prostate carcinomas and in 80% of samples with prostate intraepithelial neoplasia. High levels of PTOV1 in tumors correlated significantly with proliferative index, as assessed by Ki67 immunoreactivity, and associated with a nuclear localization of the protein, suggesting a functional relationship between PTOV1 overexpression, proliferative status, and nuclear localization. In quiescent cultured prostate tumor cells, PTOV1 localized to the cytoplasm, being excluded from nuclei. After serum stimulation, PTOV1 partially translocated to the nucleus at the beginning of the S phase. At the end of mitosis, PTOV1 exited the nucleus. Transient transfection of chimeric green fluorescent protein-PTOV1 forced the entry of cells into the S phase of the cell cycle, as shown by double fluorescent imaging for green fluorescent protein and for Ki67, and also by flow cytometry. This was accompanied by greatly increased levels of cyclin D1 protein in the transfected cells. These observations suggest that overexpression of PTOV1 can contribute to the proliferative status of prostate tumor cells and thus to their biological behavior.     

A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring short attacks of fever and serositis. Secondary AA amyloidosis is the worst complication of the disease and often determines the prognosis. The MEFV gene, on chromosome 16p13.3, is responsible for the disease and around 30 mutations have been reported to date. Colchicine is the standard FMF treatment today, and prevents both attacks and amyloid deposition in 95% of patients. Here we describe a three-generation Spanish kindred with five family members affected by a severe periodic inflammatory disorder associated with renal AA amyloidosis and colchicine unresponsiveness. Clinical diagnosis of definite FMF disease was made based on the Tel-Hashomer criteria set. Genetic analyses revealed that all subjects were heterozygous for the new H478Y MEFV variant, segregating with the disease. In addition, mutations in the TNFRSF1A and CIAS1/PYPAF1/NALP3 genes, related to the dominantly inherited autoinflammatory periodic syndromes, were ruled out. However, the dominant inheritance of the disease, the long fever episodes with a predominant joint involvement, and the resistance to colchicine in these patients raise the question of whether the periodic syndrome seen in this kindred is a true FMF disease with unusual manifestations or rather another MEFV-associated periodic syndrome. We conclude that the new H478Y MEFV mutation is the dominant pathological variant causing the inflammatory periodic syndrome in this kindred and that full-length analyses of the MEFV gene are needed to obtain an adequate diagnosis of patients with clinical suspicion of a hereditary periodic fever syndrome, especially those from non-ancestral populations.     

Are Anti-Beta2-Glycoprotein-I Antibodies Markers for Recurrent Pregnancy Loss in Lupus Anticoagulant/Anticardiolipin Seronegative Women?

Problem  Anti-beta₂-Glicoprotein-1 antibodies (anti-β₂GPI-ab) have been related to recurrent miscarriage (RM) with conflicting results. The aim was to evaluate the role of anti-β₂-GPI-ab as unique biological marker in RM related to antiphospholipid (aPL).
Method of study  A cohort study that included 59 cases, divided in two groups, was designed: group 1 comprised 43 pregnant women with 'obstetric' antiphospholipid syndrome (APS) and group 2 included 16 cases with similar complaints but only having repeatedly anti-β₂-GPI-ab. Previous thrombosis and/or inherited thrombophilia were excluded. Lupus anticoagulant, anticardiolipin antibodies (aCA), anti-β₂-GPI-ab, and other autoantibodies were analyzed. Miscarriages, premature births, pre-eclampsia, live births, placental and systemic thromboses were studied.
Results  No differences in previous obstetric complications were detected ( P  =   1.00–0.164). After the treatment, differences in number of obstetric complications were not seen ( P  =   1.00). Live births were similar in two groups (88.4% and 93.7%; P  =   1.00). Placental thrombosis was equal in both groups, 93.3% versus 80% ( P  =   1.00).
Conclusion  These results suggest that anti-β₂-GPI-ab may be considered a biological marker for obstetric APS.     

Decreased serum ubiquinone-10 concentrations in phenylketonuria.

BACKGROUND: Ubiquinone-10 is a lipid with important metabolic functions that may be decreased in phenylketonuria (PKU) because patients with PKU consume diets restricted in natural proteins. OBJECTIVE: We studied serum ubiquinone-10 concentrations in PKU patients. DESIGN: This was a retrospective, transversal study in which we compared serum ubiquinone-10, plasma cholesterol, plasma tyrosine, and plasma phenylalanine concentrations in 43 PKU patients with concentrations in a reference population (n = 102). Serum ubiquinone-10 concentrations were analyzed by HPLC with ultraviolet detection. Plasma tyrosine and phenylalanine were measured by ion-exchange chromatography. RESULTS: Serum ubiquinone-10 concentrations in PKU patients were significantly lower than in the reference population (P < 0.01 for patients aged 1 mo to <8 y and P < 0.00005 for patients aged 8-33 y). Moreover, 5 of 18 PKU patients (28%) in the younger age group and 10 of 23 (43%) in the older age group had serum ubiquinone-10 concentrations below the reference interval. CONCLUSIONS: Serum ubiquinone-10 deficiency appears to be related to the restricted diet of PKU patients. Because serum ubiquinone-10 plays a major antioxidant role in the protection of circulating lipoproteins, the correction of ubiquinone-10 concentrations should be considered in PKU patients. Further investigation seems advisable to elucidate whether the deficiency in serum ubiquinone-10 status is clinically significant.