[Risk in the elderly home dwelling: a relational object]. / Le risque chez les personnes âgées à domicile: un objet relationnel.

Risk is an unavoidable "partner" of the life course for single home dwelling elderly, especially in the older age. The primary concerned person is not the only one to make decisions, his/her proxy and the community care professionals are also involved. Crisscrossing the point of view of these three types of actors with the same situation shows that risk is a notion which has to be problematized. Due to the large part of underlying life principles its understanding can't easily be objectified nor easy to reach by consensus. The three case studies presented suggest a dynamic grid of interpretation for an approach of risk concept.

Clinical outcomes and complications of enteral nutrition among older adults.

AIM: Several reviews or clinical trials published in the last years have not demonstrated that tube feeding can improve outcomes, including inhalation pneumonia, survival, pressure sores. Further, high rate of risks are recognized. Therefore, this practice should be discouraged for severely demented patients. The aim of this study was to assess the validity of these findings in a sanitary district in the Venetian Region, Italy, characterized by a fully integrated program of territorial-hospital care and where enteral nutrition (EN) is supervised by a specialized nutritional team (NT). METHODS: A distinctive aspect of this study concerns the fact that all patients with tube feeding were followed at home, in hospital, in nursing home by the same NT. The team controls the selection of patients and supports the follow-up, according to the guidelines of the Italian Society of Parenteral and Enteral nutrition. The study provides a prospective evaluation including 108 patients, mean age 78.2 years, followed for 12 months. Each patient underwent multidimensional tests, including activities of daily living, instrumental activities of daily living, Norton, Pfeiffer and Karnofsky scales, and anthropometric and biochemical indicators of nutritional status. RESULTS: The main diagnoses were dementia (72 patients), stroke (23 patients), malignancy (5 patients), amyotrophic lateral sclerosis (3 patients) and miscellaneous disease (5 patients). EN was delivered by PEG (62 patient), NGT (45 patient), jejunostomy in one patient. The main complications of nasogastric tube versus PEG have been inhalation 15.5% and 7.9%, respectively, tube displacement 62.2%, and 4.7%, tube clogging 11.1% and 7.9 %. The first month mortality rate was 7.4% and 23.1% at one year. The mean survival was 674 days. CONCLUSIONS: Almost all complications have been mild and could be managed throughout adequately. Their prevalence is low, with reference to the long period of follow-up, for a whole of 39420 days. Tube displacement is frequent with NGT but not with PEG and may be a cause of physical restraint, compromising in this way patient's quality of life. In this study, survival was nearly three times higher than reported in literature. These positive outcomes may be the result of two factors. First, the selection and follow-up program was supervised by the same nutritional team. Second, the network of integrated services of continuing care, including nursing homes, hospital and home care.

Clinical pathological findings in an owl (Athene noctua) with microfilaraemia in Italy.

We report the first case of microfilaria infection in a free-flying owl Athene noctua in Italy. A macroparasite, about 10.1-mm long, was observed in the right chamber of the heart. On microscopic examination microfilariae were seen in liver, kidney, myocardium and lungs, although no cellular reaction was present in association with the parasites in any of these tissues. Because of the low pathogenicity of this parasite, infection with microfilaria may be not harmful in wild owls.

Reduced Na(+), K(+)-ATPase activity in erythrocyte membranes from patients with phenylketonuria.

Na(+), K(+)-ATPase activity was determined in erythrocyte membranes from 12 phenylketonuric patients of both sexes, aged 8.8 +/- 5.0 y, with plasma phenylalanine levels of 0.64 +/- 0.31 mM. The in vitro effects of phenylalanine and alanine on the enzyme activity in erythrocyte membranes from healthy individuals were also investigated. We observed that Na(+), K(+)-ATPase activity was decreased by 31% in erythrocytes from phenylketonuric patients compared with normal age-matched individuals (p < 0.01). We also observed a significant negative correlation between erythrocyte Na(+), K(+)-ATPase activity and plasma phenylalanine levels (r = -0.65; p < 0.05). All PKU patients with plasma phenylalanine levels higher than 0.3 mM had erythrocyte Na(+), K(+)-ATPase activity below the normal range. Phenylalanine inhibited in vitro erythrocyte Na(+), K(+)-ATPase activity by 22 to 34%, whereas alanine had no effect on this activity. However, when combined with phenylalanine, alanine prevented Na(+) K(+)-ATPase inhibition. Considering that reduction of Na(+), K(+)-ATPase activity occurs in various neurodegenerative disorders leading to neuronal loss, our previous observations showing a significant reduction of Na(+), K(+)-ATPase activity in brain cortex of rats subjected to experimental phenylketonuria and the present results, it is proposed that determination of Na(+), K(+)-ATPase activity in erythrocytes may be a useful peripheral marker for the neurotoxic effect of phenylalanine in phenylketonuria.

Platelet Na+, K+-ATPase activity as a possible peripheral marker for the neurotoxic effects of phenylalanine in phenylketonuria.

The in vitro effects of phenylalanine or alanine alone or combined on Na+, K+-ATPase activity in membranes from human platelets were investigated. The enzyme activity was assayed in membranes prepared from platelet-rich plasma of healthy donors. Phenylalanine or alanine were added to the assay to final concentrations of 0.3 to 1.2 mM, similar to those found in plasma of phenylketonuric patients. Phenylalanine inhibited Na+, K+-ATPase activity by 20-50% [F(4,25)=11.47 ; p<0.001]. Alanine had no effect on Na+, K+-ATPase activity but when combined with phenylalanine prevented the enzyme inhibition. These results, allied to others previously reported on brain Na+, K+-ATPase activity, may reflect a general inhibitory effect of phenylalanine on this important enzyme activity. Therefore, it is possible that measurement of Na+, K+-ATPase activity in platelets from PKU patients may be a useful peripheral marker for the neurotoxic effects of phenylalanine.

Activation of p21ras is not sufficient to ensure a complete G1 phase of the cell division cycle in mouse fibroblasts.

In the mouse BP-A31 fibroblasts, mRNAs coding the three isoforms (Ha, Ki, N) of ras are expressed, and there are no activating mutations in the codons 12, 13 or 61. We have produced a subline (Ras2) expressing an oestrogen-inducible v-Ha-ras gene. The contribution of v-Ha-ras to the overall p21ras-GTP content was evaluated by metabolic labelling with 32P. Surprisingly, p21ras-GTP complexes were predominant in the serum-deprived BP-A31 cells as well as in the Ras2 cells. The excess of p21ras-GTP was not due to the lack of the GTPase activating protein. In transient transfection experiments, the serum response element (SRE)-directed CAT was expressed in serum-deprived BP-A31 cells, and insulin caused a further two- to threefold increase in CAT activity. A dominant negative ras mutant (Ha-Ras Asn-17) cancelled both the basal and insulin-induced CAT expression in the BP-A31 but not in the Ras2 cells. Expression of v-Ha-ras in Ras2 cells did not relax their growth factor-dependence and oestradiol had only a minor mitogenic effect. We conclude that p21ras activation does not ensure a complete cell division cycle in these cells, and does not entirely account for the transduction of the mitogenic signal initiated by insulin.

Local regulation of testicular immunoreactive-arginine vasopressin and steroidogenesis by naloxone.

The effects of intratesticular injection of naloxone, a universal opioid antagonist, on testicular immunoreactive (IR)-arginine vasopressin (AVP) content and on in vitro testosterone production by Leydig cells were investigated in the mouse. Bilateral intratesticular injection of increasing doses of naloxone (0.1-10 micrograms/testis) resulted 24 h later in a dose-dependent increase in testosterone production by Leydig cells incubated for 3 h in the presence or absence of hCG (100 ng/ml). Unilateral intratesticular injection of naloxone (10 micrograms) similarly enhanced basal and hCG-stimulated testosterone production by Leydig cells, but production was not modified in Leydig cells from the contralateral vehicle-injected testis, nor was it changed when the same dose was injected subcutaneously. Unilateral intratesticular injection of 10 micrograms naloxone led to a dose-dependent increase in the hCG-responsiveness without altering the slope of the hCG dose-response curve. In vitro exposure of Leydig cells to increasing doses of naloxone (10(-9) to 10(-7) M) did not alter either basal or hCG-stimulated testosterone production. Testicular IR-AVP content declined in a dose-dependent manner in naloxone-injected testis, but remained unchanged in the contralateral vehicle-injected testis and in testis from animals that received similar doses of naloxone subcutaneously. Since AVP has been shown to locally exert a negative control on testosterone production within the testis, it might be hypothesized that the increased Leydig cell activity after local naloxone administration results from reduced intratesticular IR-AVP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoreactive arginine vasopressin in the testis: immunocytochemical localization and testicular content in normal and in experimental cryptorchid mouse.

The presence of arginine vasopressin (AVP)-like peptide(s) and AVP receptors has been previously demonstrated in the testis of several species. In this study we examined the immunocytochemical localization of AVP and of its associated neurophysin (NPII) within the mouse testis, and the testicular immunoreactive (IR)-AVP content in normal pubertal and adult mice and in unilaterally cryptorchid animals. Immunostaining was conducted on fresh frozen adult testicular sections and on cultured testicular cells using the avidin-biotin immunoperoxidase technique. Immunoreactivities for AVP and NPII were localized at the periphery of the seminiferous tubules. Staining for AVP and NPII was reduced in testes showing impaired spermatogenesis. AVP and NPII immunoreactivities were present in cultured Sertoli cells, but staining was undetectable in cultured Leydig cells. Negative controls were obtained by applying antiserum that had been preabsorbed with excess peptides in place of primary antiserum. Mouse testes were found to contain IR-AVP, which co-eluted with synthetic AVP on HPLC and diluted in parallel in a specific RIA for AVP. Levels of IR-AVP expressed as pg/mg wet-weight testis were significantly higher (p < 0.05) in pubertal (36.6 +/- 1.5) than in adult animals (27.4 +/- 1.5). Experimental unilateral cryptorchidism in adult animals resulted 2 wk later in a marked reduction (p < 0.01) in IR-AVP levels in the abdominal testis (18.1 +/- 1.0 pg/mg testis) as compared to the contralateral scrotal testis (29.8 +/- 1.1 pg/mg testis).(ABSTRACT TRUNCATED AT 250 WORDS)

Local control of Leydig cell arginine vasopressin receptor by naloxone.

Arginine vasopressin (AVP) and beta-endorphin are present within the testis where they could act as paracrine effectors of steroidogenesis. In this study we investigated the effect of naloxone, an opioid receptor antagonist on Leydig cell AVP receptor. Intratesticular injection of increasing doses of naloxone (0.1-100 micrograms) resulted 24 h later in a dose-dependent increase in Leydig cell AVP binding capacity. This effect occurred locally since s.c. injection of similar doses of naloxone did not alter the testicular AVP receptor content and intratesticular injection enhanced AVP receptor density only in the naloxone-treated testis but not in the contralateral vehicle-treated testis. Scatchard plot analysis of the data revealed that naloxone locally injected altered AVP binding capacity without change in affinity. These results suggest that in addition to their known paracrine effects in the testis, endogenous opioid peptides may locally control the testicular AVP system by modulating AVP receptor capacity.

Steroid sulfatase activity in homogenates, microsomes and purified Leydig cells from adult rat testis.

Steroid sulfatase (STS) activity was studied in the Long-Evans rat testis. The rate of dehydroepiandrosterone sulfate (DHA-S) hydrolysis determined in whole testis homogenates was low compared to that of the corresponding microsomal fractions, which was, in contrast, as high as that expressed in homogenates from purified Leydig cells. Such an increment in STS activity between total homogenates and the corresponding microsomes was not observed for the seminiferous tubules. The STS affinity reported for total testicular microsomes (Km = 3.47 +/- 0.54 microM; mean +/- SEM) was of the same magnitude as that previously reported for Leydig cells, but was about 3 times higher than that measured for whole testis homogenate (Km = 10.11 +/- 0.92 microM). In vivo hCG treatment decreased the STS affinity in total testicular microsomes without affecting this kinetic parameter in whole testis homogenate. These data suggest that the steroid sulfatase expressed in total testicular microsomes (activity and regulation by hCG) could be considered as a good index of Leydig cell STS activity.

Testicular steroid sulfatase in a cryptorchid rat strain.

Steroid sulfatase (STS) activity was studied in scrotal and abdominal testes from genetically unilateral cryptorchid rats. Specific STS activity was significantly increased in microsomes from abdominal and scrotal testes of the cryptorchid animals as compared to that of control ones. When expressed per gonad, STS activity was only enhanced in the scrotal testis. No difference in the enzyme affinity was observed between descended and undescended testes. Testosterone content was markedly reduced in the abdominal testes. Normal plasma testosterone levels together with elevated LH levels were measured in the cryptorchid rats. The existence of differences in STS expression between descended and undescended testes gives additional support for this enzymatic activity being implicated in testicular function.

Ontogenesis and regulation of steroid sulfatase activity in Leydig cells and seminiferous tubules in the Long-Evans rat.

Steroid sulfatase (STS) activity was studied in Long-Evans rat testis. The affinity of the enzyme was shown to increase during postnatal development and to be always higher in purified Leydig cells than in seminiferous tubules. STS activity appeared to be higher in the seminiferous tubules at the earlier stages. In vivo injection of 100 IU hCG resulted in a decrease in the affinity and an increase in the activity of the enzyme expressed in Leydig cells with no such modification in seminiferous tubules. This suggests that STS could play a regulatory role in testosterone production by Leydig cells.

Incidence of placental sulfatase deficiency on the mode of termination of pregnancy.

The mode of termination of pregnancy in case of placental sulfatase deficiency (PSD) has been considered in a 28-case series from our laboratory. After comparison with 75 other cases collected from the literature and also with reports concerned with normal pregnancies it appears that in the case of PSD: first, the gestation length is not increased; second, the parity of the patients has no influence on the mode of delivery; third, spontaneous vaginal delivery can occur (67.8% in our series, 43% in the literature series); fourth, the failure rate of labor, especially when induced, is higher than in a normal population; fifth, the high rate of C-section, largely due to the failure of labor, is enhanced by untimely interventions mostly in case of isolated PSD. If a pejorative incidence of PSD on the mode of delivery exists it must be at a moderate level, and intervention is unnecessary in absence of associated fetal and/or maternal complications.

[Steroid sulfatase and placental deficiency. Current data as instigators of new research]. / Stéroïde sulfatase et déficit placentaire. Données récentes instigatrices de nouvelles investigations.

Arylsulfate sulfohydrolases, ubiquitously distributed, mediate the hydrolysis of sulfoconjugated steroids found in large amounts in a variety of human tissues and fluids. The sterol sulfate sulfohydrolase (steroid sulfatase), bound to the microsomal fraction, is capable of hydrolyzing natural substrates such as cholesterol and dehydroepiandrosterone sulfates. The placenta is the richest source of the enzyme. The physiological interest of this enzymatic activity became apparent when placental steroid sulfatase deficiency was described in pregnancies with strikingly low oestrogen levels in the maternal plasma and urine. This enzymopathy appears to have only a moderate pejorative incidence on the mode of delivery, thus intervention is unnecessary unless dictated by fetal and/or maternal associated pathology. The disorder is transmitted on the X-linked recessive mode of inheritance and affected individuals, all males, present with ichthyoses of the sex-linked type. The gene coding for the steroid sulfatase enzyme has been assigned to the distal part of the X-chromosome in the Xp22.3-Xpter region which is known to escape the inactivation process. The lack of enzymatic activity in the somatic tissues of the patients is followed by an increase of the circulating sulfated steroid levels and by an accumulation of cholesterol sulfate in blood and skin. The modified electrophoretic mobility of the low-density lipoproteins, which might result from the excess of cholesterol sulfate bound to these lipoproteins, is a new diagnostic clue for the enzymopathy. Apart from the modification recognized to be systematically associated to the steroid sulfatase deficiency, numerous cases of hypogonadism and cryptorchidism have been recently described and may be considered as new clinical manifestations of this genetic disorder. Recent cloning of the gene coding for the steroid sulfatase should allow the molecular study of the etiology of this inborn error of metabolism.

[Should we still explore placental sulfatase deficiencies? Reflections apropos of a case report]. / Faut-il encore explorer les déficits en sulfatase placentaire? Réflexions à propos d'une observation.

The finding of low or very low levels of oestrogen during pregnancy should suggest the diagnosis of placental sulfatase deficiency, which is confirmed by performing dynamic biochemical tests. These biochemical tests also enable sulfatase deficiency to be differentiated from other conditions which may be accompanied by an abnormal decrease in oestrogens. The authors report one case and stress the harmlessness of sulfatase deficiency and the associated ichthyosis in boys and they question the value of the dehydroepiandrosterone sulfate test which only confirms an abnormality which is now well known and benign.

Biochemical evidence for the non-inactivation of the steroid sulfatase locus in human placenta and fibroblasts.

Steroid sulfatase activities are significantly higher in placentas obtained after the birth of girls than after the birth of boys, and also in female fibroblasts compared to male strains. This constitutes biochemical evidence for the non-inactivation of the X-linked sulfatase locus. No hydrolytic activity is found in the fibroblasts of ichthyotic boys. Heterozygosity is demonstrated in the fibroblasts of the four mothers studied, as they have steroid sulfatase activity of less or equivalent to the normal male value.

Placental sulfatase deficiency: clinical and biochemical study of 16 cases.

Clinical and biochemical data of 16 typical cases of placental sulfatase deficiency have been observed. In vivo loading tests with DHA-S allowed us to make a prenatal diagnosis. In vitro experiments gave confirmation, showing zero or virtually zero placental sulfatase activity towards delta 5P or DHA sulfates Aromatase activities, when tested, were normal or more often less than standard values, the latter showing themselves rather large individual variations. All pregnancies were associated with the delivery of male neonates in good health but 3. The 15 living babies have been developing normally since then. These results, together with those reported in the literature, suggest that placental sulfatase deficiency is under control of an X-linked recessive character, this being supported by the recent observation of such a disorder in two sisters simultaneously pregnant. As to the high frequency problem of cesarian section, pointed out by several authors, we cannot conclude, from our own observations, that the defect has an obvious influence on the good outcome of labor, as 10 out of the 16 women delivered vaginally near term.