Assessment of neuropsychological impairments in regular cannabis users.

BACKGROUND: Cannabis is the most widely used illicit drug in the world. It is responsible for cognitive dysfunction of memory, speed of information processing, attention, and executive functions. Cognitive performance depends on the level of study, tolerance, and duration of abstinence from cannabis use. This study analyses cognitive function in a large population of regular cannabis consumers taking into account level of education. METHODS: A battery of neuropsychological tests using the Cambridge Neuropsychological Test Automated Battery was performed on a population of 58 cannabis users categorized into two groups according to their level of education with a threshold of 12 years of study, and 25 non-users. RESULTS: In Attention Switching Task percent correct trials, significant differences were found between the group of cannabis smokers with less than 12 years of study and the non-smoker group (P=0.022), and between the cannabis users with more than 12 years of study and the non-smoker group (P=0.008). A significantly lower performance in the Rapid Visual Information Processing (Mean latency, Probability of hit, Total hits, Total misses, Correct rejections) was found in the cannabis users with less than 12 years of study compared with the non-user group. CONCLUSION: In our population, chronic cannabis users presented divided and sustained attention and working memory disorders. Rapid Visual Information Processing performance may be influenced by education level in cannabis smokers.

Mindfulness-based relapse prevention for cannabis regular users: Preliminary outcomes of a randomized clinical trial.

Mindfulness-based approaches have shown their effectiveness in caring for patients with substance use disorders (SUD). Mindfulness-based relapse prevention (MBRP) integrates practices from mindfulness-based interventions and cognitive-behavioral relapse prevention (RP) approaches. This article presents the preliminary results of a study that measures the effectiveness of an MBRP protocol for volunteer cannabis users willing to reduce or stop their consumptions. Twenty cannabis users were randomly assigned to either receive an eight-week outpatient MBRP program or treatment as usual (TAU). Cannabis use was assessed weekly through the timeline follow back (TLFB). Eighty percent of individuals received MBRP treatment and 60% of individuals received TAU completed treatment. Preliminary results did not find significant difference at the end of treatment (week 8) regarding the number of joints smoked. Despite the absence of any significant difference between the two groups, the contribution of mindfulness in the caring of SUD seems encouraging and promising. Many MBRP group participants reported qualitative changes in the way they consumed. This study will be continued in order to evaluate the effectiveness of MBRP on a larger number of subjects.

[Characteristics of chronic wounds in substance abuse: A retrospective study of 58 patients]. / Caractéristiques des plaies chroniques chez les toxicomanes : étude rétrospective de 58 patients.

BACKGROUND: Drug addiction causes chronic wounds (CW) responsible for severe complications. Very few studies are available on this topic. The aim of our study was to describe the demographic, clinical and etiological characteristics as well as the course of CW in drug addicts. PATIENTS AND METHODS: This was a retrospective and prospective multicenter study including all drug addicts with CW. RESULTS: We included 58 patients (17 prospectively), 84.5% of whom were male, of median age 43 years, presenting multiple CW as a result of intravenous (78.2%), inhaled (41.1%) and/or snorted (20%) drug abuse. Addiction to opioids (68.4%), cocaine (47.4%) and/or cannabis (40.4%) was ended and/or treated through substitution in 79.3% of patients. CW were fibrinous and necrotic (42.9 to 53.6%), recurrent (54.2%), and in some cases had been present for more than 1 year (61.5%). Intravenous drug addiction was associated with large, fibrinous, ulcers in a setting of venous and lymphatic insufficiency (74%). Only 23% of these wounds involved the upper limbs. Necrotic ulcers associated with clinical arteriopathy were described mainly with inhaled addiction. Abscesses (50%) and erysipelas (29.3%) were the most common cutaneous complications. After 3 months, 50% of CW were improved and 29.2% of patients were lost to follow-up. DISCUSSION: Drug abuse-related CW occurred preferentially in young men with history of intravenous abuse. For the most part, CW were seen on the legs and were associated with venous and lymphatic insufficiency, and the resulting major risk for cutaneous infection increased morbidity and mortality in this population in whom medical follow-up is inherently complicated.

Maternal opioid addiction: A potential cause of elevated 17-OH progesterone in neonatal screening.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is a disease that is part of neonatal screening. There are many causes of false-positive results on neonatal screening, and maternal opioid consumption during pregnancy is suspected to increase 17-hydroxyprogesterone (17-OHP) levels at birth. The aim of this study was to determine the effect of maternal drug consumption on 17-OHP values on neonatal screening. MATERIAL AND METHODS: We studied 17-OHP levels of term newborns with reported maternal drug consumption born at the Maternity Hospital of Nancy between 2002 and 2018. These infants were matched with newborns of mothers without drug addiction. The 17-OHP levels, withdrawal syndromes, birth parameters, and maternal characteristics were compared between the two groups. RESULTS: The study included 241 patients (121 in the drug-exposed group, 120 in the control group). The mean 17-OHP levels in newborns of mothers with substance addiction were 9.83 nmol/L compared to 4.90 nmol/L (p=0.0001) in the control group. Newborns exposed to drugs were smaller (p=0.0001), lighter (p=0.0001), had smaller head circumference (p=0.0001), and had lower Apgar scores (p=0.004 at 1 min and p=0.0001 at 5 min). The 17-OHP level did not differ in cases of withdrawal syndrome in drug-exposed newborn (p=0.911). CONCLUSION: A significant increase in 17-OHP levels was observed in newborns exposed to drugs, with no influence of withdrawal syndrome on 17-OHP levels. Maternal substance addiction may be associated with moderately increased 17-OHP levels during neonatal screening.

Examining men as victims of intimate partner violence in a French forensic department.

OBJECTIVE: Intimate partner violence (IPV) is a particular type of interpersonal violence, in which violence is performed between individuals involved in an intimate relationship. Johnson developed a typology in which he differentiates common couple violence (CCV) from intimate terrorism (IT). We led a descriptive review of the cases of men treated at the victimology unit of the forensic department of Nancy for IPV-related abuse. METHOD: We retrospectively investigated our database to extract every file of male patient treated at the victimology unit of the forensic department of Nancy (France) from 2014 to 2019 for IPV-related abuse. We studied several parameters relating to the protagonists and their relationship, the violence endured, and the statements made during the forensic consultation. An attempt to perform Johnson's typology was made. RESULTS: We had a total of 226 consultations. The age of the patients ranged from 18 to 88 years old. Almost all patients experienced physical violence. Psychological violence was noted in 138 files. Concerning Johnson's typology, we identified 92 cases consistent with the definition of CCV and 46 cases compatible with IT. CONCLUSION: Male victims of IPV are now backed by an ever-growing corpus of studies that sheds an opportune light upon this challenging topic. Sadly, too many remain discredited and unaccounted for. We believe that escaping a gender-opposing conception in favor of a global understanding of this phenomenon would be of benefit to both men and women.

Knowledge assessment of sudden infant death syndrome risk factors in expectant mothers: A prospective monocentric descriptive study.

In France, approximately 500 deaths per year are related to sudden infant death syndrome (SIDS). After a 75% reduction of SIDS-related deaths in the 1990s, thanks to large prevention campaigns directing parents to put their infants to sleep on their back, the number of SIDS-related deaths remains stable. However, we estimate that 100-200 infant deaths per year in France could be prevented with better education on the risk factors for SIDS. In this prospective, descriptive monocentric study, we aimed to evaluate the level of expectant women's knowledge about SIDS. Questionnaires were distributed during a midwife consultation. A score on sleeping conditions, environmental and protective factors was determined with coefficients attributed according to their relevance to SIDS. Of 296 questionnaires distributed, 202 were completed and included in the analysis from March 1 to September 21, 2018. Scores were distributed from 2 to 46/50. The average score was 28.6/50. Information was principally obtained from media and not health professionals. When the information was delivered by a caregiver, in particular by a paediatrician, we observed better knowledge among these women. This study shows that it is important for health professionals to take the time to inform future mothers about the risk factors for SIDS, especially the least informed population groups such as young mothers and those from lower socioeconomic status, in order to reduce the number of avoidable infant deaths.

Clinical and pathologic characteristics of breast cancer patients carrying the c.3481_3491del11 mutation.

Tumor characteristics are used today to evaluate the possibility of mutation and to target mutation screening in families with high risk of breast and/or ovarian cancer. We studied the breast tumor profile associated to the c.3481_3491del11 French founder effect mutation on the BRCA1 gene to an attempt to identify any particularity or difference when comparing it to that related to other BRCA1 mutations. Within the population who were referred to our oncogenetic clinic at the Lorraine Oncology Institute in France and who underwent genetic testing between 1994 and 2012, we identified 404 women carrying a BRCA1 mutation. Interestingly, 45% (180/404) women had the germline c.3481_3491del11 mutation. These included 91 patients affected by first breast cancer. Clinical and pathologic data were retrieved from medical files. Descriptive statistics were conducted using the SPSS software (version 20.0). For the entire cohort of 91 women, the mean age was 43.64 years (SD 10.04). Tumors were identified in 37.4% of cases aged < 40 years. Estrogen receptor status and progesterone receptor status were reported to 67 patients. Seventy-four percent were ER negative. Hormonal receptors status was negative in 68.6% of tumors. HER2 status was available for 32 tumors. The triple-negative subtype was found in 21 cases, which accounts for 65.6% of the patients. High tumor grade was found in 81% of triple negative breast cancer patients. Based on our results compared to those of previous international studies, we concluded that the breast cancer associated to the c.3481_3491del11 is not different from that associated to other BRCA1 mutations. A larger cohort with complete information on the breast cancer pathologic characteristics and including other BRCA1 mutations would allow us to statistically compare the breast tumor profile associated to the c.3481_3491del11 to that related to other BRCA1 mutations.

Is there a genetic anticipation in breast and/or ovarian cancer families with the germline c.3481_3491del11 mutation?

The aim of the current analysis is to evaluate any differences of breast or ovarian cancer age at diagnosis between mothers and daughters carrying the c.3481_3491del11 mutation in the BRCA1 gene. A study cohort of 38 women carrying the c.3481_3491del11 mutation and affected by first breast or ovarian cancer who reported a first breast or ovarian cancer in their mother carrying the c.3481_3491del11 mutation, was identified in 37 different families including members with breast and/or ovarian cancer at the Oncology Institute of Lorraine. Twelve mothers underwent genetic testing. Twenty-five pairs of the 38 mothers-daughters pairs with c.3481_3491del11 mutation were affected by breast cancer and 13 pairs by ovarian cancer. Clinical and genetic data were collected from medical files and family pedigrees. Analyses were conducted for each cancer type. We investigated an early breast cancer detection effect due to early screening programs and also an increased breast tumor aggression. Since major improvements in breast cancer clinical management and imaging techniques appeared after 1980, we compared the age at breast cancer diagnosis and the age at death in mothers and daughters before and after 1980, first, in the group of women including mothers and daughters taken together and then in mothers and daughters separately. The mean age at breast cancer diagnosis was 45.28 ± 10.27 years in mothers and 39.80 ± 7.79 years in daughters (p = 0.026). The difference of age at ovarian cancer diagnosis in mother-daughter pairs was 8.62 ± 12.76 years (p = 0.032). When considering the group of women including mothers and daughters taken together, no significant difference of age at breast cancer diagnosis was found between women affected before 1980 and those affected after 1980 (p = 0.577). However, the age at death increased in these women after 1980 (p = 0.026). Comparison of age at breast cancer diagnosis in mothers and daughters separately, showed that daughters were affected at an earlier age after 1980 (p = 0.002). Daughters had a poor prognosis and died earlier than mothers after 1980. Our results may have reflected genetic anticipation in c.3481_3491del11 mutation breast and ovarian cancer families. In order to confirm our findings, a larger cohort would provide more precision to the difference of ages at breast or ovarian cancer diagnosis between mothers and daughters and more powerful statistical analyses. Increased aggression in daughters' tumors compared to those of mothers could be also considered as a parameter of genetic anticipation. Complete information on tumor profile and proliferation would allow us to study genetic anticipation by comparing the tumor phenotypes between mothers and daughters in the future.

[22q11.2 microdeletion syndrome: Analysis of the care pathway before the genetic diagnosis]. / Syndrome de microdélétion 22q11.2 : analyse du parcours patient avant le diagnostic génétique.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a very broad phenotypic spectrum disorder. It can affect many organs or systems. 22q11.2DS is the most common microdeletion syndrome in humans, with a prevalence ranging from one in every 2000 to one in 4000 newborns. It seems to be more prevalent than reported and under-recognized or undiagnosed because of its inherent clinical variability and heterogeneity. In France, 15,000 patients may be affected by this disease, more than half without knowing it. The aim of this study was to analyze the care pathway before the genetic diagnosis of 22q11.2DS. METHODS: We conducted a single-center, retrospective analysis of postnatally diagnosed patients recruited by the cytogenetic laboratory of Nancy (France) from January 2000 to December 2015. Clinical data were first collected by consulting the medical files of patients and then by calling them directly. Written informed consent was obtained and the study was approved by local research ethics boards. Data concerned only clinical features before the diagnosis. RESULTS: The cohort consisted of 32 individuals with 22q11.2DS. The average age at diagnosis was 9 years and 2 months and the median age was 2 years and 11 months. Fetal echography was abnormal in 15 pregnancies. During the neonatal period, the most important features were eating difficulties and congenital malformations (n=20), with a majority of complex heart diseases (n=16), dominated by conotruncal malformations (n=6). In case of malformation, the average age at diagnosis decreased to 2 years and 6 months. A congenital heart disease brought the average age of diagnosis down to 2 years and 6 months. Hypocalcemia and dysmorphism were also classical features (n=14). Before the age of 3 years, speech delay occurred in nine patients. After 3 years of age, rhinolalia was predominant (n=11). Academic disabilities were present in all subjects. At least 14 patients had a de novo deletion. Five patients were diagnosed within genetic counseling, with the deletion was inherited from the mother in three out of four cases. One was the monozygotic twin of a patient. Seven patients were diagnosed as adults. Four of them were diagnosed only because of the clinical presentation of their children or fetuses. Retrospectively, all adult patients had clinical signs suggesting the 22q11.2DS diagnosis. Relational disorders affected eight patients. None of them had been referred to the geneticist for this reason. In most cases, the pediatric cardiologist referred patients to the geneticist (n=9). Physiotherapists (n=15) and speech-language pathologists (n=12) were frequently requested but did not participate in the diagnosis. CONCLUSION: The present study highlights the difficulty of establishing the diagnosis when the major features of the 22q11.2DS are absent during the 1st months of life. This is particularly true when there is no congenital defect. Special attention must be given to speech disorders in childhood and neuropsychological disorders later in life. The association between 22q11.2DS and early-onset parkinson disease implies that adult neurologists should be aware of this diagnosis. For adult patients, familial occurrence is the most frequent cause of diagnosis in spite of clinical signs suggestive of 22q11.2DS. The management of these patients involves better information of medical and paramedical staff in order to refer them to the geneticist earlier in life.

Specific expression of the retinoic acid-synthesizing enzyme RALDH2 during mouse inner ear development.

Retinoid binding proteins and nuclear receptors are expressed in the developing mouse inner ear. Here, we report that the retinaldehyde dehydrogenase 2 (Raldh2) gene, whose product is involved in the enzymatic generation of retinoic acid (RA), exhibits a restricted expression pattern during mouse inner ear ontogenesis. The Raldh2 gene is first expressed at embryonic day (E) 10.5 in a V-shaped medio-dorsal region of the otocyst outer epithelium, which evolves as two separate domains upon otocyst morphogenesis. At E14.5, Raldh2 is expressed in two areas of the utricle epithelium and specific regions of the saccule and cochlear mesenchyme. Later, Raldh2 transcripts are restricted to two cochlear areas, the stria vascularis and Reissner membrane. Raldh2 mesenchymal expression did not correlate with migrating neural crest-derived melanoblasts. These restricted expression domains may correspond to specific sites of RA synthesis during inner ear morphogenesis.

Patients admitted to emergency services for drunkenness: moderate alcohol users or harmful drinkers?

OBJECTIVE: Most of the patients admitted to hospital emergency services are drunk. Some of them may need specific treatment after acute intoxication remits. At present, treatment for alcoholism is offered to less than 5% of these patients. The authors evaluated the biological markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) in patients admitted for acute alcohol intoxication (per DSM-IV criteria) supported by blood alcohol assay. These tests distinguished between otherwise moderate alcohol users who were acutely intoxicated and harmful drinkers or alcohol-dependent patients. METHOD: The authors conducted an exhaustive survey 24 hours a day during 2 nonconsecutive months. The study involved 166 patients (124 men and 42 women) who were admitted for acute alcohol intoxication as a principal or additional diagnosis. Their blood was analyzed for alcohol, GGT, and CDT levels. The CAGE questionnaire was administered, and social and demographic data were collected. RESULTS: About 80% of the population studied displayed elevated GGT or CDT levels (65.7% had CDT levels >60 mg/liter; 41.6% had GGT levels >65 IU/liter). Less than 10% of the patients with acute alcohol intoxication revealed results in the normal range for both markers and a negative finding on the CAGE questionnaire. CONCLUSIONS: Patients admitted to emergency services with high blood alcohol levels should not be assumed to be moderate drinkers. Any drunkenness should be interpreted as a sign of likely harmful alcohol consumption or alcohol dependency requiring clinical and biological tests, including GGT and CDT assays. Specific treatment for alcoholism should be systematically offered to these patients.

Interstitial iridium-192 for bladder cancer (a multicentric survey: 205 patients).

Interstitial irradiation is a technique currently used in the treatment of bladder cancer. We report the data on 205 patients (177 men and 28 women) treated in eight French centers. The patients had received the following treatment: a short course of pre-operative pelvic irradiation, followed by surgery consisting of partial cystectomy or tumor resection, and implantation of plastic tubes filled with inactive lead wires, which were replaced by iridium 192 wires. The tumor characteristics were: transitional cell carcinoma, 88.8%; mean size of the tumor, 29 mm; pathological stages: pTis, 1; pT1, 98; pT2, 66; pT3a, 26; pT3b, 9; pT4, 1; unknown, 4 respectively; surgical lymph node status: N+, 3; N-, 118; no node dissection, 84. The mean follow-up was 51 months. Intravesical failures were seen in 35 patients (17.0%), 25 (71.4%) of them without metastases or regional recurrences. Twenty-one patients (10.2%) presented distant metastases, 2/3 of them suffered no bladder relapse. The 5-year survival, calculated according to the Kaplan-Meier method (all causes of death taken together) was 77.4% for the T1, 62.9% for the T2, and 46.8% for the T3. Fifty-three patients had immediate side-effects and three died from surgical complications. Twenty-nine patients had delayed bladder side-effects (haematuria, fistula, chronic cystitis). Six patients presented an ureteral stenosis. Of the disease-free survivors, 96.1% retained the bladder function. Three factors were significantly predictive of delayed side-effects: partial cystectomy, pre-operative radiotherapy total dose, and linear activity of the wires (p < 0.01). Comparing our results to different authors' series interstitial irradiation is likely to provide a high local and general control of the disease and good quality of life in patients with selected tumors.

Comparable uptake of thallium-201 and technetium-99m MIBI in hibernating and "maimed" myocardium.

Thallium-201 and technetium-99m-MIBI uptake are comparable in "maimed" (i.e., partially viable) and hibernating myocardium. The appreciation of myocardial viability should be based not only on the presence of a regional contractility improvement, but also on the evaluation of the initial level of contractility and of tracer uptake in the concerned area.

Prostate cancer treated by radiotherapy: a multivariate study.

According to respective proportions of evolutive status groups, results of multivariate studies are difficult to interpret. Among the 1099 cases of local form of prostate cancer, treated by radiotherapy from 1975 to 1982 in 16 French Anticancer Institutes, we can observe two homogeneous status groups of patients: disease-free survivors (285 cases) and patients who died of prostate cancer (278 cases). These correspond to 51% of the whole population. Among other things, they are comparable in size, for age at the beginning of radiotherapy and for delay between histologic diagnostic and radiotherapy. We chose to analyse them using multivariate analysis. To take survival into account, we used a Cox model and Kaplan-Meier curves; the group deceased of prostate cancer was further analyzed by a tree-structured regression method. The Cox model and the Kaplan-Meier curves confirmed two main explicative factors: Stage (p < 0.0001) and tumor grade (p < 0.001). Poorer evolution occurs in extracapsular forms and grade I has better survival than others. The tree-structured regression method indicates two other pejorative factors: hormonotherapy prior to radiotherapy and the presence of cardiovascular pathology. Though the pelvic dose does not appear to be a main explicative factor, it seems to improve survival and delay between radiotherapy and recurrence or metastasis in some categories of cases. Other factors such as tumor dose, age and delay between diagnosis and radiotherapy were not found to be significant. These results cannot be extended to the whole population for which they do not constitute a predictive study. We consider them as "baseline data".(ABSTRACT TRUNCATED AT 250 WORDS)

Interstitial brachytherapy for penile carcinoma: a multicentric survey (259 patients).

Although cancer of the penis is a rare disease, we have collected 506 cases through a multicentric study. In the present study we analyse the results obtained from 259 patients treated by interstitial brachytherapy from 1959 to 1989. Among the 259 patients, 184 males had exclusive brachytherapy (group A) while 75 received a combination of surgery and brachytherapy and/or external beam irradiation (EBI) (group B). Five- and 10-year survival rates are, respectively: overall survival, 66 and 52%; cause-specific survival, 88 and 88%; disease-free survival, 78 and 67%. One hundred and forty-three patients in group A (78%) and 48 (64%) in group B avoided mutilation of the penis while late side effects occurred in 137/259 patients (53%). Survival depends on the volume of the tumor and the presence of involved nodes; systematic groin dissection does not however seem advisable.

Loss of heterozygosity of BRCA1, BRCA2 and ATM genes in sporadic invasive ductal breast carcinoma.

The present study was undertaken to analyse the loss of heterozygosity (LOH) of the three genes, BRCA1, BRCA2 and ATM, and their correlation to clinicopathological parameters in sporadic breast cancer. We studied 59 sets of invasive ductal carcinoma, compared to matched normal control DNA. Microsatellite markers intragenic to BRCA1 (D17S1323, D17S1322, D17S855), BRCA2 (D13S1699, D13S1701, D13S1695) and ATM (D11S2179) were simultaneously used. In addition, one marker telomeric to BRCA2 (D13S1694) and four markers flanking ATM were analysed (D11S1816, D11S1819, D11S1294, D11S1818). Thirty-one per cent of the informative cases showed loss of heterozygosity for the BRCA1 gene, 22.8% for BRCA2 gene and 40% for ATM. LOH of BRCA1 correlated with high grade tumors (p=0.0005) and negative hormone receptors (p=0.01). LOH of ATM correlated with higher grade (p=0.03) and a younger age at diagnosis (p=0.03) in our set of tumors. No correlations were detected between BRCA2 LOH and any of the analysed clinicopathological parameters. However, a correlation was detected between allelic loss of the D13S1694 marker, telomeric to BRCA2, and larger tumor sizes and negative estrogen receptors, favoring the hypothesis of the presence of another putative tumor suppressor gene, telomeric to BRCA2, in the 13q12-q14 region. Only 11 tumors had LOH at more than one of the three genes, most of them (6/11) associated LOH of BRCA1 and ATM. One tumor only combined loss of the three genes BRCA1, BRCA2 and ATM.

Localization of neurotrophin-3-like immunoreactivity in the rat cochlear nucleus.

Immunohistochemistry as well as immunohistofluorescence were used to investigate the distribution of the neurotrophin-3 (NT3) in the adult rat cochlear nucleus. We found a widespread distribution of NT3 immunolabeled neurons throughout the three divisions of this nucleus. NT3-like immunoreactivity was clearly population-specific, with some cell groups heavily (various small neurons and granule cells) or moderately (large neurons of the ventral cochlear nucleus) stained, while others remained negative (a major fraction of medium and large neurons of the dorsal cochlear nucleus). Double-labeling experiments were performed using antibody against the glial fibrillary acid protein, a classic marker for mature astrocytes. This colocalization study revealed that NT3 immunoreactivity was also present in a subpopulation of astrocytes, particularly in the glia limitans and their projections. Numerous small cells also colocalized NT3 together with the glial marker in the granule cell domain and in the molecular cell layer of the dorsal cochlear nucleus. These results suggest that NT3 may exist in widespread populations of adult cochlear nucleus neurons as well as in glial cells. This abundant distribution of NT3-like immunoreactivity implies that this neurotrophin may have an important role in the continued maintenance of mature cochlear nucleus and makes it an attractive candidate for playing a role in regulation or stabilization of neuronal circuits in this nucleus.

Distribution of glial fibrillary acidic protein (GFAP) in the cochlear nucleus of adult and aged rats.

The age-related change in glial fibrillary acidic protein (GFAP) immunoreactivity was analyzed in young (3 months) and old (24 months) adult rat cochlear nuclei (CN). Quantitative analyses show a significant increase with age, in the number of GFAP positive astrocytes and processes in the old adult when compared with the young adult rat. There was also a differential distribution of GFAP immunoreactivity in the young adult CN where it predominates in the granular cell region, whereas in old rats, the GFAP immunoreactivity distribution was homogeneous in all parts of the nucleus. There was no change in the total number of neurons between these two stages in any part of the nucleus except for the antero-ventral CN, where a decrease in neuronal number was observed in the aged rats. The increase in GFAP immunoreactivity was related to an increase of both GFAP positive astrocyte number and processes. The increase of GFAP positive astrocytes may be due either to an alteration of auditory nerve fibers, changing the trophic interactions with post-synaptic cells, or to intrinsic alterations of CN neurons and local circuits reflecting aging of the CN.

Peripheral progenitor cells (CFU-GM, BFU-E, CD34) are increased in untreated chronic lymphocyte leukemia patients: stage B and C display a particularly high CD34+ cell count.

No treatment has proved its efficiency in CLL. Autologous transplantation is now under consideration for the youngest patients. We assayed progenitor cells (CFU-GM, BFU-E, CD34) in the peripheral blood of 28 untreated CLL patients and found an increase of all these progenitors in CLL compared to controls. There was no statistical difference between stage A versus stages B and C for CFU-GM and BFU-E. In contrast, CD34 cells were higher in stages B and C as compared to stage A. This finding could be explained by a high number of circulating clonal cells in advanced stages of the disease.

Age-related changes in GFAP-immunoreactive astrocytes in the rat ventral cochlear nucleus.

The age-related changes in the ventral cochlear nucleus (VCN) as revealed by glial fibrillary acid protein (GFAP) immunoreactivity were analyzed in the following age groups: 3-, 6-, 12-, 18-, and 24-month-old Sprague-Dawley rats. A cartographic and a quantitative analysis showed a significant increase in the number of GFAP positive astrocytes during the first year of life and a significant decrease in older rats. We also observed an age-induced modification in the spatial distribution of GFAP positive astrocyte. In the anterior part of the VCN of the 3- and 6-month-old rats, we observed a significant decrease in the rostro-caudal as well in the dorso-ventral axes. In the posterior part of the VCN, a significant decrease in the dorso-ventral axis could be also observed, but no significant difference in the spatial distribution was obtained in the rostro-caudal axis. In older rats, the distribution appeared homogeneous throughout the nucleus. Additionally, aging was associated with a significant increase in GFAP positive astrocyte sizes, except for immunolabelled astrocytes in the granule cell layer. The different levels of GFAP expression occurring in the VCN during normal aging could reflect a progressive decline of cellular activity in the VCN, without severe cell degeneration or synaptic loss.