Docetaxel-induced lymphopenia in patients with solid tumors: a prospective phenotypic analysis

BACKGROUND: The quantitative abnormalities of the different peripheral blood lymphocyte subsets during docetaxel administration were prospectively studied. METHODS: Forty-six chemotherapy-naive patients with solid tumors were treated with docetaxel either in a 3 weekly (n = 33) or weekly (n = 13) schedule. Twenty patients with central nervous system (CNS) metastatic disease as the first clinical presentation of cancer and 35 patients with metastatic colorectal carcinoma treated with chemotherapy were enrolled as controls. The phenotype of peripheral blood lymphocytes was determined by indirect immunofluorescence using appropriate monoclonal antibodies and fluorescent-activated cell sorter analysis. RESULTS: After the administration of the first docetaxel cycle, the absolute number of peripheral blood lymphocytes (P < 0.005), CD3(+) (P < 0.01), CD4(+) (P < 0.01), CD8(+) (P < 0.01), and CD56(+) (P < 0. 01) but not CD20(+) (P < 0.3) cells was significantly decreased compared with the pretreatment values. Further treatment resulted in a further decrease of these lymphocyte subsets including CD20(+) cells (P < 0.01). Similarly, after the administration of the first weekly dose of docetaxel, the absolute number of total lymphocytes, CD3(+), CD4(+), and CD8(+) cells was decreased. The administration of the second weekly docetaxel dose resulted in a further decrease of CD56(+) (P = 0.012) and CD20(+) (P = 0.007) cells. The administration of either high dose corticosteroids in patients with CNS metastases or an irrelevant chemotherapy (CPT-11/5-FU) did not result in similar abnormalities. The discontinuation of docetaxel was associated with a recovery of CD3(+) and CD4(+) lymphocytes within a 3-month period. Eight (17%) patients developed nonneutropenic infections during docetaxel treatment. CONCLUSIONS: Docetaxel has an important but reversible nonspecific lymphopenic effect that seems to be associated with an increased risk for nonneutropenic infections.     

Cholangitis revealing an intrahepatic Osler's disease

Osler Weber Rendu Disease is an hereditary haemorrhagic télangectasia habitually revealed by reccurent bleeding (epistaxis). Hepatic involvement in Osler disease is found in 8 to 31%, manifested by cholestasis. We report an original observation of a cholangitis revealing Osler disease.     

Inguinal hernia: Challenging the traditional indication for surgery in asymptomatic patients

Background: It is generally accepted that most inguinal hernias should be operated on electively in order to avoid the high morbidity and mortality associated with incarceration and small bowel obstruction. The present study reassesses the indication for surgery in asymptomatic inguinal hernia patients. Methods: We analyzed profiles, separately, for elective and emergency inguinal herniorrhaphies and compared the morbidity and mortality rates. Results: Two hundred randomly selected elective hernia repairs were compared with 67 incarcerated cases. Postoperative complications were more common following emergency (23.9%) than elective repair (10.5%); however, in both groups, minor complications predominated. The mortality rate in the incarcerated group (6%) was clearly linked with a high preoperative American Society of Anesthesiologists (ASA) score. A bowel resection rate of 4.5% was found in the incarcerated cases, which was not correlated with mortality. Conclusions: Patients with asymptomatic inguinal hernia and unfavorable medical conditions should be recommended an elective repair, preferably under local anesthesia, to avoid the high mortality associated with an emergency operation.     

The stability of human acidic beta-crystallin oligomers and hetero-oligomers

Crystallins are bulk structural proteins of the eye lens that have to last a life time. They gradually become modified with age, denature and form light scattering centres. High thermodynamic and kinetic stability of the crystallins enables them to resist unfolding and delay cataract. Here we have made recombinant human betaA1-, betaA3-, and betaA4-crystallins. The betaA3-crystallin formed higher oligomers that lead to precipitation at ambient temperature. Heat-induced precipitation of betaA3-crystallin was compared with human and calf betaB2-crystallins, showing that the human proteins start to precipitate above 50 degrees C while the calf betaB2-crystallin stays in solution even when unfolded. The stabilities of these human acidic beta-crystallin homo-oligomers have been estimated by measuring their unfolding in urea at neutral pH. BetaA3/1/betaB1 and betaA4/betaB1-crystallin hetero-oligomers have been prepared from homo-oligomers by subunit exchange. The resolution of the methodology used was insufficient to detect a stabilization of the betaA4-crystallin subunit in the hetero-oligomer, the betaA1-crystallin subunit was clearly stabilized by its interaction with betaB1-crystallin. Circular dichroism and fluorescence spectroscopies show that homo-dimer surface tryptophans become buried in the betaA3/1/betaB1-crystallin hetero-dimer concomitant with changes in polypeptide chain conformation.     

Consanguinity and apnea of prematurity

Consanguinity, marriage between relatives, has been associated with perinatal mortality and morbidity. Apnea of prematurity is defined as the cessation of breathing for longer than 20 seconds or that of any duration if accompanied by cyanosis and sinus bradycardia, for infants born before 37 weeks of gestation. The objective of the study was to examine the association between consanguinity and apnea of prematurity in Greater Beirut, an area having a relatively high prevalence rate of consanguineous marriages. The study was cross-sectional. Between September 1, 1998, and March 31, 2001, 21723 newborn infants were admitted to the National Collaborative Perinatal Neonatal Network in Greater Beirut, Lebanon. The inclusion criteria were infants less than 37 weeks of gestation who were admitted to the intensive care unit, with no congenital malformations, sepsis, or neurologic disorders. Analysis was based on 597 infants of whom 66 had apnea of prematurity. With adjustment for weeks and type of gestation, pregnancy complications, and Apgar score, the odds ratio of apnea of prematurity for first-degree consanguineous parents as compared with other marriages was 2.9 (95% confidence interval: 1.3, 6.4). In addition to the recognized etiologic factors for apnea of prematurity, this study suggests a role played by genetic factors.     

Exhumations procedures for investigating the genetic link in bones

OBJECTIVE: To identify technical problems in exhumations performed for DNA detection in bones and to propose solutions through a protocol. METHODS: A prospective and qualitative study of exhumations was carried out according to the methods proposed in the medical legal literature. From 1995 to 1998, were performed 10 exhumations to collect human remains for DNA extraction. Of them, seven cases were of civil interest and three of criminal. Alternatives were sought to overcome technical difficulties found during the execution of these procedures. RESULTS: For all cases, there was scarcity of useful information to identify the human remains. In half of them, identification was based on the individual's morphological characteristics, given by their relatives. Individual morphological characteristics contributed to identification in 50% of cases. In three cases, it was possible to determine only the sex, and in one of them, only the age. Lack of infrastructure and police security in the cemeteries impaired the examination. CONCLUSIONS: To assure the reliability of the DNA molecular examination, it is necessary to identify the individual to whom the exhumed mortal remains belonged. To an efficacious investigation, it is paramount to have a working protocol that will cover, among other issues, those concerning identification, infrastructure and staff safety at the site of examination.     

Progress in somatic gene therapy of retinal degeneration in the animal model

More than 60 genes responsible for human retinal dystrophies have already been identified. Most of them are either expressed in the photoreceptor or in the retinal pigment epithelium (RPE). Therefore these cells have become the target of new therapeutical strategies on a molecular level. The most promising approach at present is somatic gene therapy, which has been developed over the last years and the principle has now been established in animal models. For gene therapy of inherited retinal degeneration, as for gene therapy in general, gene transfer has to be proven to be not only efficient but also safe. This has recently been achieved using the adeno-associated virus (AAV) as a vector to express a therapeutic gene within the photoreceptor cell. It could be demonstrated in mouse and dog models of retinal degeneration that expression of the therapeutic transgene leads to anatomical and functional restitution of degenerating photoreceptors. A significant immune response to AAV has not been detected so far. In this paper the recent success of gene therapy of retinal degeneration in animal models is reviewed.     

Quantitative analysis of mannitol polymorphs. FT-Raman spectroscopy

Mannitol is a polymorphic excipient which is usually used in pharmaceutical products as the beta form, although other polymorphs (alpha and delta) are common contaminants. Binary mixtures containing beta and delta mannitol were prepared to quantify the concentration of the beta form using FT-Raman spectroscopy. Spectral regions characteristic of each form were selected and peak intensity ratios of beta peaks to delta peaks were calculated. Using these ratios, a correlation curve was established which was then validated by analysing further samples of known composition. The results indicate that levels down to 2% beta could be quantified using this novel, non-destructive approach. Potential errors associated with quantitative studies using FT-Raman spectroscopy were also researched. The principal source of variability arose from inhomogeneities on mixing of the samples; a significant reduction of these errors was observed by reducing and controlling the particle size range. The results show that FT-Raman spectroscopy can be used to rapidly and accurately quantitate polymorphic mixtures.