Histological and biological developmental characterization of the human cerebellar cortex

The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex.     

Shifted distribution of cation-related cyst types in post-menopausal patients with gross cystic disease of the breast

Gross cystic disease of the breast (GCD) is rarely seen after the menopause. Recent work has shown that by measuring electrolytes in the breast cyst fluid (BCF) it is possible to identify two principal classes of cyst, designated Type 1 (K+/Na+ greater than 1.5) and Type 2 (K+/Na+ less than 0.66). A smaller, intermediate class (Type 3) also appears to exist. We measured K+, Na+ and dehydroepiandrosterone sulphate (DHA-S) in 38 BCF samples aspirated from 33 women with GCD who had undergone spontaneous menopause at least 1 yr previously. Statistically significant correlations were found between DHA-S and cations (positive in relation to K+, P less than 0.001; negative in relation to Na+, P less than 0.001). The distribution of cyst types was shifted with respect to that characteristic of cases that occur at an earlier age: whereas Type 1 cysts predominate in menstruating women, Type 2 cysts proved more numerous in the post-menopausal subjects. The difference was statistically validated (P less than 0.001). The results seem to indicate a sharp reduction in high K+, high DHA-S cysts after the menopause, which may be paralleled by a decrease in the associated apocrine metaplasia. In view of the major biochemical differences between Type 1 and Type 2 cysts and of the suggested differences as regards cancer risk, classification of post-menopausal patients with GCD by cyst type is critical prior to any clinical trial or follow-up.     

The risk of pneumonectomy over the age of 70. A case-control study.

OBJECTIVE: A higher mortality has been reported after pneumonectomy over the age of 70. The aim of the study was to quantify the additional risk due to age after standard pneumonectomy for lung cancer by a case-control study. METHODS: Our clinical database was reviewed to search for patients aged 70 years or more who underwent standard pneumonectomy for lung cancer between 1998 and 2005. A control group of patients younger than 70 (one case/two controls) was matched for sex, cardiovascular disease, American Association of Anaesthetists score, respiratory function, side of pneumonectomy, induction chemotherapy and stage. Overall mortality and morbidity were compared. Long-term survival data were also analysed. RESULTS: During the considered period, 35 patients aged 70 years or more underwent pneumonectomy (30 males, median age 73 years, 15 right-sided procedures). The control group was composed of 70 patients. The two groups were homogeneous in the variables used for matching. Overall mortality and morbidity were 11.4 and 54.2% in the elderly group as compared to 4.3 and 41.6% in controls (p-value not significant). Elderly patients experienced a higher rate of respiratory complications (25.7%) as compared to controls (8.3%, p=0.01). At univariate analysis, the only risk factor for death was the occurrence of respiratory complications (OR 6.5, CI 1.8-18.2). At multivariate analysis, age >or=70 years (OR 5.36, CI 1.48-19.3) and preoperative chemotherapy (OR 7.65, CI 2.04-28.6) were confirmed as predictors of respiratory complications. Five-year survival was 17.5% in the elderly group and 53.6% in the control group (p=0.003). Elderly patients with a better respiratory function (FEV1>70%) had a 5-year survival of 45.4%. CONCLUSIONS: In the elderly patients, the risk of respiratory complications after pneumonectomy is increased as compared to younger patients with equivalent respiratory function. Age and preoperative chemotherapy are independent risk factors for respiratory complications. A lower mortality and a better long-term survival are obtained in elderly patients with a better respiratory function (FEV1>or=70%).     

Feasibility of interactive videodisc technology to teach minority youth about preventing HIV infection.

Hispanic and African American adolescents are more likely than white Anglo youth to harbor misconceptions about acquired immunodeficiency syndrome (AIDS) and are also more likely to engage in intravenous drug use and sexual intercourse. This paper describes the development of an AIDS prevention curriculum that uses an interactive videodisc program to teach skills for interventions. Focus group and expert panel studies yielded suggests for intervention vignettes and scenes relevant to Hispanic and African American adolescents. The authors then developed and produced a sample curriculum, specifically designed for Hispanic youth. Content was designed to build knowledge, attitudes, and skills in handling situations where young persons are at risk for human immunodeficiency virus (HIV) infection. The feasibility of the finished pilot product was tested with adolescents and with professionals who serve ethnic and racial minority youth. Adults and Hispanic adolescent viewers rated the videodisc as enjoyable, interesting, and likely to achieve positive effects with the intended target population. Findings suggest that the interactive videodisc is a useful way to interest and help Hispanic adolescents learn ways of reducing their risk of contracting and spreading HIV infection through lifestyle practices. This developmental research in the use of interactive videodisc also provides a basis for further investigation.     

A quantitative evaluation of apoptotic bodies in rat liver

The aim of the present study was to determine if data on the number and acinar distribution of apoptotic bodies (AB) in normal liver could help in the understanding of cell kinetics in the liver, and the mechanism of early ethanol-induced liver damage. Normal male Sprague-Dawley rats were studied. They had free access to Purina chow and drinking water. Ethanol-treated rats received the drug at increasing concentration in drinking water for 5 weeks. The following parameters were measured: number of AB in the lobule, topographical localization, distance from terminal hepatic veins (THV), i.e. row of hepatocytes concerned, H1 being the closest to the THV. The results show that AB are rare in the normal liver and are always observed in zone 3, next to the THV. Of 149 THV examined, 56 showed one associated AB, exceptionally two. 74% of the AB were confined to the first row of hepatocytes (H1), 21% to H2, 4% to H3, and 1% to H4. In ethanol-treated rats the mean number of AB was 2 or 3 for each THV. 42% were found in H1, 32% in H2, 15% in H3, 7% in H4, and 4% in H5. The data show that AB are not randomly dispersed in normal liver but show a preferential acinar distribution. In addition, most AB are located in the row of liver cells immediately adjacent to the THV. If apoptosis is indeed an expression of physiological cell renewal, these findings support the concept that zone 3 contains older hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson’s disease

Abstract Idiopathic Parkinson’s disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62±7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1±8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.     

Enumeration of S-phase cells in normal rat liver by immunohistochemistry using bromodeoxyuridine-antibromodeoxyuridine system

The visualization of incorporation sites of the thymidine analog bromodeoxyuridine (BrdU) into DNA, detected by immunocytochemistry, has been proposed as an index of the percentage of S-phase cells in a variety of tissues and as an easy, less expensive alternative to autoradiography. This technique has not yet been applied to the study of physiological cell renewal in the normal liver. In the present study, results obtained with this method in the liver of normal young adult rats is reported. BrdU was administered in vivo and subsequent incorporation was detected by the PAP technique using monoclonal anti-BrdU antibodies. The nuclei exhibiting a positive reaction within the liver were few and accounted for about 0.45% of all hepatocytes. Positive cells were located preferentially in zone 1, which contained 82.7% of the labeled cells. Zone 2 contained 15.4%, while only 1.9% of the labeled cells were found in zone 3. Positive-staining Kupffer cell nuclei were rare (about 0.5% of all Kupffer cells) and were distributed randomly in the hepatic lobule. These findings provide quantitative data about hepatocyte renewal in the normal liver in the absence of a growth stimulus. The simplicity and the reproducibility of this technique suggests that further application of this method in situations assessing hepatic regeneration are indicated.     

A new priority policy for patients with hepatocellular carcinoma awaiting liver transplantation within the model for end-stage liver disease system.

The best prioritization of patients with hepatocellular carcinoma (HCC) waiting for liver transplantation under the model for end-stage liver disease (MELD) allocation system is still being debated. We analyzed the impact of a MELD adjustment for HCC, which consisted of the addition of an extra score (based on the HCC stage and waiting time) to the native MELD score. The outcome was analyzed for 301 patients with chronic liver disease listed for liver transplantation between March 1, 2001 and February 28, 2003 [United Network for Organ Sharing (UNOS)-Child-Turcotte-Pugh (CTP) era, 163 patients, 28.8% with HCC] and between March 1, 2003 and February 28, 2004 (HCC-MELD era, 138 patients, 29.7% with HCC). In the HCC-MELD era, the cumulative dropout risk at 6 months was 17.6% for patients with HCC versus 22.3% for those patients without HCC (P = NS), similar to that in the UNOS-CTP era. The cumulative probability of transplantation at 6 months was 70.3% versus 39.0% (P = 0.005), being higher than that in the UNOS-CTP era for patients with HCC (P = 0.02). At the end of the HCC-MELD era, 12 patients with HCC (29.3%) versus 57 without HCC (58.8%) were still on the list (P = 0.001). Both native and adjusted MELD scores were higher (P < 0.05) and progressed more in patients with HCC who dropped out than in those who underwent transplantation or remained on the list (the initial-final native MELD scores were 17.3-23.1, 15.5-15.6, and 12.8-14.1, respectively). The patients without HCC remaining on the list showed stable MELD scores (initial-final: 15.1-15.4). In conclusion, the present data support the strategy of including the native MELD scores in the allocation system for HCC. This model allows the timely transplantation of patients with HCC without severely affecting the outcome of patients without HCC.     

Gender differences in smoking cessation

Men and women have traditionally consumed cigarettes very differently, demonstrating widely varying patterns of prevalence during the past eight decades. For example, though the prevalence of smoking among men increased dramatically soon after the turn of the century, an analogous though less dramatic increase among women was not observed for another 25-30 years. Similarly, when a dramatic decrease in smoking prevalence among men was observed following the 1964 Surgeon General's Report, a comparable decrease among women was not seen until 15 years later. Such differences in smoking patterns have led to the widespread belief that giving up smoking is more difficult for women than it is for men. This paper reviews various studies which address this issue and suggests areas in which further research is needed.