Cystic fibrosis mortality trends in France.

BACKGROUND: In 1992 France set up a national cystic fibrosis observatory (Observatoire national de la mucoviscidose, ONM) to monitor the state of health of patients on an annual basis. Using the ONM data, this study estimates the main indicators for life expectancy and assesses the total number of cystic fibrosis patients. METHODS: The data for the years 1994 to 2003 are divided into 3-year periods. Life tables are drawn up for these periods, from which mean and median lengths of life are determined. Using the most recent life table, the number of births in 2003 and the incidence of the disease, the total population of patients can be estimated, assuming a stationary population. RESULTS: In 2001-2003, life expectancy at birth of patients registered with the ONM was 39.1 years and median length of life was 36.4 years. These results, substantially better than those of 1994-1996, are linked to improved conditions of patient inclusion in the ONM database, to improvements in their healthcare, but also to the limitations of the life tables. Based on the 2003 data, the total theoretical number of patients is 6490, and coverage by the ONM database is thus 63.2%. CONCLUSIONS: These provisional results demonstrate the need to convert the ONM observatory into a registry providing exhaustive coverage of all patients.     

Selective hepatic artery ligation for hepatic haemangioendothelioma: case report and review of the literature.

Although benign, hepatic haemangioendotheliomas (HHE) are rare vascular tumours of the infant which have a high mortality rate secondary to high output congestive heart failure. The management of these tumours is still controversial and none of the different medical or surgical options has been unanimously accepted. We report the case of a neonate with congestive heart failure (CHF) due to a localized HHE, treated successfully by selective ligation of the left hepatic artery branch irrigating the tumour, under perioperative ultrasound Doppler control. A review of the literature showed 35 cases of HHE treated by hepatic artery ligation (HAL) with a survival rate of 80 %.     

On the subject of the cyclic vomiting syndrome]

The cyclic vomiting syndrome is defined by episodes of vomiting lasting from hours to days with free intervals between episodes. Various symptoms can be associated with vomiting: nausea, abdominal pain, photophobia, fever, pallor, dehydratation, excess salivation, social withdrawal. Some factors often precipitate the crisis: infection, psychological stresses, menstruation. Excluding a medical condition, especially a gastro-intestinal or a neurological disease is compulsory for the diagnostic of cyclic vomiting syndrome. The cyclic vomiting syndrome shares many common features with migraine including treatment. Due to negative paraclinical testing, a psychiatric disease is often suspected in these children. Pathophysiology of cyclic vomiting syndrome is unknown. As for migraine, mitochondrial and ionic channels abnormalities are thought to play a role. Overactivation of hypothalamic-pituitary-adrenal axis and autonomic dysfunction seem to be involved too. Three clinical vignets will illustrate these aspects.     

Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage.

As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were produced with these three excipients (60% w/w) and theophylline as drug model (40%). On the one hand, in vitro dissolution studies were performed with the rotating paddle method displaying the different release behaviour of these three matrices (immediate release for MCC, steady release for HPMC and sustained release for EC). On the other hand, the evolution of the T2m spin-spin relaxation time in NMR experiments during granules hydration was recorded. NMR findings shore up dissolution data, both depending on interactions between the matrix and water. NMR spectroscopy appears to be a valuable tool for obtaining, at an earlier stage of drug development, more information about drug release mechanism.     

Broad ligament hernia-associated bowel obstruction.

BACKGROUND AND OBJECTIVE: We present the case of a female patient 29 years of age with antecedents of laparoscopic laser ablation for endometriosis, laparoscopic appendectomy, and umbilical hernioplasty. METHODS: The patient was admitted to the hospital's emergency room for abdominal pain in the epigastrium, transfixing, irradiating to both upper quadrants and to the lumbar region, accompanied by nausea and gastrobiliary vomiting. Lipase determination was 170 mg/dL. Other laboratory findings were normal. Plain abdominal films on the patient's admission were normal, and computed tomography (CT) showed data compatible with acute pancreatitis. Without improvement during the patient's hospital stay, pain and vomiting increased in intensity and frequency. RESULTS: New abdominal x-rays revealed dilatation of small bowel loops. Management was begun for intestinal obstruction, with intravenous hydration and placement of a nasogastric tube without a good response. At 48 hours, a diagnostic laparoscopy was performed, revealing a 3-cm internal hernia in the left broad ligament in which a 20-cm segment of terminal ileum was encased. We performed liberation of the ileal segment and closed the hernial orifice by using the laparoscopic approach. CONCLUSION: The patient's evolution was excellent.     

女性银屑病患者血清性激素浓度测定

对20例女性、非妊娠期、生育年龄的寻常型、进行期银屑病患者检测了雌二醇(E_2)、孕酮(P)和睾酮(T)的血清浓度。结果为:卵泡期E_2平均值为84±61.6pg/ml,黄体期E_2平均值为164.9±115pg/ml,均显著高于正常平均值(P值分别为<0.001,<0.005);黄体期P平均值为2.67±4.62ng/ml,显著低于正常平均值(P<0.005);T平均值在正常范围,提示银屑病可能与血清E_2和P浓度有关。     

Prospective study of the occurrence of monoclonal gammapathies following bone marrow transplantation in young children

We have prospectively studied the occurrence of monoclonal serum immunoglobulins in 38 recipients of BMT. Patients were young children with primary immunodeficiencies (n = 31), other inherited diseases (n = 4), leukemia (n = 2), or aplastic anemia (n = 1). Twenty-nine received an HLA-nonidentical marrow and nine an HLA-identical marrow. Serum monoclonal immunoglobulins were detected by the immunofixation method. Monoclonal immunoglobulins were found in 26 patients. Monoclonal components were more frequently detected in patients with primary severe T cell deficiencies (21/25) rather than in the other patients (6/13). In 7 of 29 recipients of HLA-nonidentical transplants, versus 0 out of 9 recipients of HLA-identical transplants, serum monoclonal immunoglobulins were found associated with a B lymphocyte proliferation syndrome due to an Epstein-Barr virus infection. In this group, monoclonal immunoglobulins were detected early, prior to the onset of the clinical syndrome. The simultaneous occurrence of several monoclonal immunoglobulins was more frequent in these patients, while monoclonal immunoglobulin concentrations increased faster, especially those of IgM isotype. These characteristics may allow in patients at risk (recipients with primary T cell immunodeficiencies and receiving HLA-nonidentical transplantation) an earlier diagnosis of B lymphocyte proliferative syndrome that may eventually lead to early and more efficient therapy.     

PgH2 analogs as potential antiplatelet derivatives.

Previous observations implicating PgH2 as a direct activator of platelets suggested that derivatives of U46619, a well-characterized TxA2 receptor agonist having structural homology with PgH2, might possess antiplatelet activity. The present work describes the synthesis of [1S-(1 alpha,2 beta,3 alpha,4 alpha)]-3-[(tetrahydropyranyloxy)methyl]- 2-[2-[(triphenylmethyl)oxy]ethyl]-5-oxabicyclo[2.2.1]heptane (14) a potentially useful intermediate for the synthesis of various epoxymethano derivatives. The latter was converted to [1S-(1 alpha,2 beta (Z),3 alpha,4 alpha)]-7-[3-[[2- [(phenylamino)carbonyl]-hydrazino]methyl]-5-oxabicylo[2.2.1]hept-2 - yl]-5-heptenoic acid (23), an epoxymethano derivative of PgH2 containing a hydrazide lower side chain as previously used in the TxA2 antagonist, SQ 29,548. The intermediate 14 was also converted to [1S-(1 alpha,2 beta (Z),3 alpha,4 alpha)]-7- [3-[(hexylamino)methyl]-5-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (25) which contained a simple aza side chain as used in earlier antagonists. Derivatives 23 and 25 appeared to be specific antagonists of the human platelet TxA2 receptor as evidenced by their inhibition of U46619 (1.5 microM) induced aggregation of human platelet rich plasma (IC50 = 22 and 7 microM, respectively), while having little effect on ADP (2 microM) induced aggregation at much higher concentrations. In addition, one of these derivatives, the bicycloamine 25, was shown to compete for [3H]U46619 binding to washed human platelets with an IC50 value of 25 microM, supporting the notion that these derivatives were acting at the thromboxane receptor. However, the potency of these derivatives was less than for previously reported TxA2 antagonists, suggesting that simple linear combinations of functionality from molecules active at the human platelet thromboxane receptor will be of limited predictive value.