Drug-associated interstitial lung disease: a diagnostic challenge

Drugs are frequently incriminated as the cause of interstitial pneumonia. There are two major mechanisms of drug-associated interstitial lung disease: direct toxicity and immunoallergic reaction. When a drug is suspected, the difficulty lies in obtaining proof. The chronology of the disease and its manifestations together with earlier evidence reported in the literature can lead to a tentative diagnosis of drug-associated interstitial pneumonia. Proof is obtained through surveillance during the disease course. In nearly all patients, therapeutic decisions must be taken on the basis of suspected drug involvement.     

Long-term behavioural alterations in female rats after a single intense footshock followed by situational reminders

Post-traumatic stress disorder (PTSD) affects a vulnerable sub-population of individuals exposed to a traumatic event. This psychopathology induces long-lasting hypothalamo-pituitary-adrenal (HPA) axis hypoactivity, hyperarousal and avoidance of trauma-like situation. PTSD also manifests a high co-morbidity with anxiety disorders. The aim of the present study was to characterise long-term biobehavioural alterations in female rats in an animal model of PTSD consisting in an intense footshock (2 mA, 10s) followed by three weekly situational reminders. This procedure induced several long-term alterations: increased anxiety behaviour, reduced time spent in an 'aversive-like' context, altered social behaviour and blunted corticosterone response to stress. These results demonstrate that exposure to an intense footshock associated with repeated situational reminders elicited long-term disturbances which lasted more than 1 month after the footshock administration. Our findings suggest that this paradigm could provide a useful animal model of PTSD.     

Prenatal stress affects behavioral reactivity to an intense stress in adult female rats

In rats, prenatal stress has been shown to influence behavioral and neuroendocrinological immediate responsivity to several kinds of mild stress in adulthood. Indeed, prenatal stress increases anxiety-like behavior, depressive-like disturbances and alters the hypothalamo-pituitary-adrenal (HPA) axis response to stress. However, long-term effects of an intense stress on behavior of prenatally stressed rats remain unknown. Moreover, most studies focus on male offspring. The aim of our study was to evaluate long-term behavioral effects of an aversive procedure consisting of an intense footshock (2 mA, 10 s) followed by three weekly situational reminders in prenatally stressed female rats. Prenatal stress was achieved by restraining the pregnant dams under bright light three times per day for 45 min during the last week of pregnancy. The aversive procedure induced long-term behavioral alterations in adult animals: an increase of immobility in the footshock chamber, hypoactivity in a novel environment and decreased avoidance of an "aversive-like" context. Interestingly, the procedure induced opposite effects in control and prenatally stressed females, suggesting bi-directional manifestation in some situations. In conclusion, prenatal stress affects behavioral response to an intense footshock associated with repeated situational reminders. These results suggest that early stress may interact with later ability to cope with intense stress in adulthood.     

Dermatoglyphics and Schizophrenia: a meta-analysis and investigation of the impact of obstetric complications upon a-b ridge count

BACKGROUND: Patients with schizophrenia show deviances in their dermatoglyphics, in particular reductions in palmar a-b ridge counts (ABRCs), which are evidence of an early developmental deviance. However, the severity or the origin of these ABRC changes has not been established. METHOD: (i) We examined the published literature on the ABRC in patients with schizophrenia against controls with a random effects meta-analysis. (ii) We used linear regression to study the ABRC in our sample of families including 125 patients with schizophrenia, 107 of their unaffected relatives and 98 controls. (iii) The effect of obstetric complications on the patient's ABRC was examined using the Lewis Murray scale. RESULTS: The pooled standardised effect size of ABRC differences between patients and controls obtained by our meta-analysis was 0.39 (95% CI: 0.05-0.73; p=0.03). In our sample, there were no significant differences in ABRCs between those with schizophrenia, their relatives and controls. Only those patients with obstetric complications had significantly reduced ABRC compared to controls (p=0.01). CONCLUSIONS: We confirmed the presence of significant yet mild ABRC reductions in schizophrenia. These represent a subtle deviance from the norm and could be present in certain subsets of patients, possibly those who suffered early developmental insults.     

Two unusual chromosome aberrations ascertained by sonographic anomalies

We describe two cases of sonographic abnormalities associated with unusual chromosomal aberrations. Case 1 presented with a cystic hygroma at 12 weeks' gestation. Cytogenetic analysis revealed an unbalanced complex chromosome rearrangement implicating chromosomes 6, 13 and 21 (karyotype: 47,XX,t(6;21;14)(q14;q21;q21)mat,+21) and corresponding to a complete trisomy 21. This anomaly resulted from malsegregation of a maternal balanced three-way translocation. For case 2, an alobar holoprosencephaly was identified by ultrasonography at 23 weeks' gestation. Chromosomal analysis showed a recombinant rec (13), dup q chromosome, secondary to unequal crossing-over of a paternal pericentric inversion of chromosome 13, giving rise to partial trisomy 13q (karyotype: 46,XX,rec(13)dup(13q)inv(13)(p11q21)pat). These two cases illustrate the role of ultrasound in leading to detection not only of foetal chromosomal aberrations but also of rare balanced chromosomal rearrangements presented by one of the two parents.     

Apolipoprotein E and cholesteryl ester transfer protein polymorphisms in normal and preeclamptic pregnancies

OBJECTIVES: To evaluate the association of apolipoprotein (apo) E polymorphism and a cholesteryl ester transfer protein (CETP) polymorphism (CETP/TaqIB) with preeclampsia and with lipid/lipoprotein profile in pregnancy. MATERIALS AND METHODS: A group of 144 normal pregnant women (67 in the third trimester) were compared with 51 cases of preeclampsia in the third trimester of gestation. Apo E and CETP genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum lipids, lipoproteins and apolipoproteins were evaluated using commercially available kits. LDL size was assessed by gradient gel electrophoresis. RESULTS: No differences were found in the distribution of subjects with respect to genotypes, in the apo E and CETP polymorphisms, between control and pathologic groups. In the third trimester of gestation (both control and case groups considered), apo E polymorphism, but not CETP polymorphism, was associated with different lipid and lipoprotein levels. Patients carrying the E2 allele (E2+) presented with significantly lower values of LDL cholesterol (LDLc) compared with carriers of E4 (E4+) and E3/3 individuals. E2+ also presented with the highest triglyceride (TG) level, although this was not statistically significant. On the other hand, HDL cholesterol (HDLc) and apo A-I levels were significantly reduced in E4+, compared with E3/3. Furthermore, E4+ presented with the highest total cholesterol and LDL and therefore LDLc/HDLc and apo B/apo A-I ratios were significantly higher in this group compared with the other two. CONCLUSIONS: Neither of our candidate genes showed association with preeclampsia. However, apo E genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.     

Effectiveness of epidural administration of saline solutions to prevent or treat postdural puncture headache

Epidural anesthesia is the most versatile and widely used of the techniques for regional anesthesia. The most common complication of epidural or spinal anesthesia is postdural puncture headache. The loss of cerebrospinal fluid through the hole can be an important causative factor of this cephalalgia. Of the many methods recommended for preventing and treating postdural puncture headache, one is bolus administration or infusion of saline solution into the epidural space, by which both epidural and subarachnoid pressures are increased. We have reviewed the literature evaluating the effectiveness of this technique from 1967 to 2004, using the following search terms: anesthesia, spinal; anesthesia, epidural; analgesia, epidural; headache; postdural puncture treatment or prophylaxis; epidural injection; epidural saline. Few articles were found. The studies had small samples and most did not include a control group. The doses and methods of epidural administration of saline solutions were highly variable and the results were often contradictory. We conclude that using this technique to prevent and/or treat postdural puncture headache is difficult to justify.     

Structure of human sperm DNA and background damage, analysed by in situ enzymatic treatment and digital image analysis

DNA breakage detection-fluorescence in situ hybridization (DBD-FISH) is a procedure to detect and quantify DNA breaks in situ, on a cell-by-cell basis. A comparison between sperm nuclei versus peripheral blood leukocytes using this method demonstrated that the nucleoids from mature human sperm are 12.7 times more sensitive to alkaline denaturation than those from human peripheral blood leukocytes. To investigate the origin of this alkali sensitivity, different approaches were employed. First, free 3'-OH ends of background DNA breaks were labelled by Klenow polymerase, or by DNA polymerase I following the in situ nick translation assay. Second, the presence of abasic sites, the other recognized DNA lesions that lends to constitutive alkali sensitivity, and DNA breaks with blocked 3' ends, were determined by in situ exonuclease III digestion prior to the polymerase labelling. The results demonstrated that the sperm nucleoid contains approximately 2.5-fold higher density of background DNA breaks with 3'-OH ends, and also approximately 2.8-fold higher density of basal abasic sites and DNA breaks with blocked 3' termini, than leukocytes. These differences only partially explain the significant alkali sensitivity of sperm DNA. However, in situ digestion with mung bean nuclease before DNA break labelling showed that sperm DNA is 9-fold more enriched in segments of ssDNA than DNA from leukocytes. The high frequency of partially denatured regions may result from a greater torsional stress of DNA loops in sperm chromatin due to its higher degree of compaction. Moreover, these short unpaired ssDNA stretches should be included in the category of alkali-labile sites detected by all techniques that measure DNA breaks through an alkaline unwinding step. These results provide new insights into the nature of DNA packaging in sperm nuclei.