Telomere length, comorbidity, functional, nutritional and cognitive status as predictors of 5 years post hospital discharge survival in the oldest old.

BACKGROUND: Telomere length has been considered in many cross-sectional studies as a biomarker of aging. However the association between shorter telomeres with lower survival at advanced ages remains a controversial issue. This association could reflect the impact of other health conditions than a direct biological effect. OBJECTIVE: To test whether leukocyte telomere length is associated with 5-year survival beyond the impact of other risk factors of mortality like comorbidity, functional, nutritional and cognitive status. DESIGN: Prospective study. SETTING AND PARTICIPANTS: A population representative sample of 444 patients (mean age 85 years; 74% female) discharged from the acute geriatric hospital of Geneva University Hospitals (January-December 2004), since then 263 (59.2%) had died (December 2009). MEASUREMENTS: Telomere length in leukocytes by flow cytometry. RESULTS: In univariate model, telomere length at baseline and cognitive status were not significantly associated with mortality even when adjusting for age (R²=9.5%) and gender (R²=1.9%). The best prognostic predictor was the geriatric index of comorbidity (GIC) (R²=8.8%; HR=3.85) followed by more dependence in instrumental (R²=5.9%; HR=3.85) and based (R²=2.3%; HR=0.84) activities of daily living and lower albumin levels (R²=1.5%; HR=0.97). Obesity (BMI>30: R²=1.6%; HR=0.55) was significantly associated with a two-fold decrease in the risk of mortality compared to BMI between 20-25. When all independent variables were entered in a full multiple Cox regression model (R²=21.4%), the GIC was the strongest risk predictor followed by the nutritional and functional variables. CONCLUSION: Neither telomeres length nor the presence of dementia are predictors of survival whereas the weight of multiple comorbidity conditions, nutritional and functional impairment are significantly associated with 5-year mortality in the oldest old.

Peptidylarginine deiminase (PAD) 6 is essential for oocyte cytoskeletal sheet formation and female fertility.

Peptidylarginine deiminase 6 (PAD6) is an enzyme that is uniquely expressed in male and female germ cells. To study the function of this enzyme in vivo we generated mice deficient for PAD6. Here we show that inactivation of the PAD6 gene in mice leads to female infertility whereas male fertility is not affected. The absence of the PAD6 protein and consequently absence of citrullination activity in oocytes results in dispersal of the cytoskeletal sheets in oocytes, indicating an essential role of these germ cell-specific structures in zygote/embryo development. PAD6 deficient mice do not show any other overt phenotype. Thus, we identify citrullination as a new regulator of fertility.

Life-threatening intracranial hypotension after diagnostic lumbar puncture.

Intracranial hypotension syndrome as a complication of diagnostic lumbar puncture is a rarely observed entity. Intracranial hypotension syndrome is characterized by postural headache, neck pain/stiffness, blurred vision, nausea, vomiting, clouding of consciousness, dizziness and vertigo. The majority of cases resolve spontaneously with conservative treatment. Rarely, epidural blood patch is required. We report a 41-year-old man with multiple sclerosis, who developed intracranial hypotension syndrome after diagnostic lumbar puncture and who did not respond to conservative treatment. A subdural hematoma was subsequently found, when the patient showed considerable worsening of clinical conditions with life-threatening symptoms. Surgical evacuation of the subdural hematoma was not sufficient to improve significantly the patient's conditions, while complete symptoms remission was achieved 12 hours after epidural blood patch. We stress the need for epidural blood patch in any case of post-diagnostic lumbar puncture postural headache which does not resolve with conservative therapy.

Inhibitory effects of cadmium on carbonic anhydrase activity and ionic regulation of the estuarine crab Chasmagnathus granulata (Decapoda, Grapsidae).

This work was aimed at evaluating the gill carbonic anhydrase (CA) activity of the estuarine crab Chasmagnathus granulata exposed in vivo to cadmium, at different salinities. The in vivo effect of the specific inhibitor acetazolamide (AZ) was also assayed. Besides, the inhibition of CA activity by different heavy metals (cadmium, copper, zinc) and AZ were evaluated under in vitro conditions. For the in vivo assays, adult males were acclimated to salinities of 2.5 or 30/1000. The corresponding 96-h LC50 of cadmium was 2.69 mg l-1 at 2.5/1000, and > 50 mg l-1 at 30/1000. Cadmium only caused a significant lower CA activity than control at 2.5/1000. EC50 for CA inhibition was estimated to be 1.59 mg l-1 at 2.5/1000. Statistical differences in Na+ hemolymphatic levels (P < 0.05) were only detected at 2.5/1000, between 0 and 1.25 mg l-1 of cadmium, but no statistical differences were observed for Cl- levels at any assayed salinity. As CA inhibition registered at 2.5/1000 was followed by only changes in Na+ concentration, it is likely that cadmium exposure could differentially affect ions permeability, among others factors. The concentrations that inhibited in vitro 50% of enzymatic activity (IC50) were 2.15 x 10(-5), 1.62 x 10(-5), 3.75 x 10(-6) and 4.4 x 10(-10) M for cadmium, copper, zinc and AZ, respectively. The comparison with IC50 values of other aquatic species, indicates a higher CA sensitivity for C. granulata to pollutants.

Solitary cerebral metastasis from tumor of the testis: some observations about treatment in two cases.

The authors describe two cases of solitary cerebral metastasis from non-seminatous germ cell tumors of the testis: in the first case, the histology was teratocarcinoma; in the second, it was embryonal carcinoma. Both patients underwent surgery, whole-brain radiotherapy and chemotherapy, and are still alive and disease-free after respectively 42 and 72 months. Although systemic metastasis from tumors of the testis are relatively common, they rarely involve the nervous system. A review of our cases and those reported in the literature shows that the outcome in these patients can be improved by the combined surgical, radiological and chemotherapeutic treatment of the metastasis.

Idiopathic normal-pressure hydrocephalus in adults: result of shunting correlated with clinical findings in 18 patients and review of the literature.

The authors describe their findings in a study aimed at identifying clinical-prognostic factors in treatment of idiopathic normal-pressure hydrocephalus. The study comprised 18 adult patients submitted to surgery for ventriculo-peritoneal shunting. The findings that emerged from this series of patients were compared with those reported for the 381 published cases. In our group of 18 patients, average age was 65 years and the average duration of clinical history was 47 months (median 18 months). Follow-up ranged from 3 to 5 years (median 4.2 years): 12 patients improved (9 completely) and 6 presented stable neurological deficits. The factors that had a statistically significant influence on outcome were a short clinical history (less than 6 months) (p = 0.05) and a clinical onset without dementia (p = 0.03). Patients with medium-grade preoperative ventricular enlargement always made a complete functional recovery after surgery (p = 0.2).

Occult dysraphism in adulthood. A series of 24 cases.

The results of a retrospective study of 24 adult patients with occult dysraphism are described. There were 15 males and 9 females, with an average age of 31.1 years. Specific circumstances precipitated symptomatic onset in 67% of patients. Pain, often referred to the anorectal region, was the most common presenting symptom. Bladder and bowel dysfunction were also common findings. The most common tethering lesions were intradural lipoma and a short thickened filum terminale. Myelography revealed the diagnosis of tethered conus in most cases, but the addition of CT and MRI images provided valuable structural details. The surgical outcome was gratifying in relation to pain and sensory-motor deficits but disappointing in the resolution of sphincter disorders. Our conclusion is that symptoms and/or signs of TCS with onset in adult life are not invariably irreversible.

Androgen binding in human fetal amnion.

Human fetal amnion cytosol obtained at term is able to bind specifically [3H]testosterone. The cytosol (105,000 g supernatant) from human amnion was used after a 30 min treatment with dextran-coated charcoal and incubated with increasing concentrations of [3H]testosterone, [3H]dihydrotestosterone, [3H]methyltrienolone for 2 h at 4 degrees C and for 16 h at 15 degrees C. To avoid any possible contamination of sex hormone binding globulin we used a Sepharose 4B column. Scatchard plot analysis of the data after incubation at 4 degrees C for 2 h showed that the amnion possesses high affinity (Kd = 0.62 +/- 0.20 nM) and low capacity (95.0 +/- 21.1 fmol/mg protein) binding sites for [3H]testosterone. After incubation at 15 degrees C for 16 h, we obtained a high affinity (Kd = 0.29 +/- 0.14 nM), low capacity (49.5 +/- 12.8 fmol/mg protein) and a low affinity (Kd = 5.55 +/- 2.55 nM), high capacity (181.7 +/- 20.8 fmol/mg protein) binding sites for [3H]testosterone. The values of Kd, calculated from Scatchard plot analysis were 1.03 +/- 0.7 nM with 20.2 +/- 10.4 fmol/mg protein and 1.97 +/- 1.06 nM with 55.6 +/- 15.9 fmol/mg protein for [3H]methyltrienolone and [3H]dihydrotestosterone respectively. These findings suggest that human fetal amnion cytosol at term contains a specific binding protein for androgens.