Cytotoxic effects of Argentinean plant extracts on tumour and normal cell lines.

In the search for possible new anti-cancer agents, we investigated the effects of 75 aqueous and methanol extracts from 41 Argentinean plant species. The effect in cell growth was evaluated in the LM2 mammary adenocarcinoma cells. In a second stage, the highly active selected extracts were assayed in 3 other tumour cell lines: melanoma B16, bladder MB49 and lung A549; and 3 normal cell lines: mammary Hb4a and keratinocytes PAM212 and HaCat. Eight methanol extracts were found to be highly cytotoxic: Collaea argentina leaf, Iochroma australe leaf, Ipomoea bonariensis flower, Jacaranda mimosifolia flower, Solanum amygdalifolium flower, Solanum chacoense leaf, Solanum sisymbriifolium flower and Solanum verbascifolium flower. However, extract inhibition on cell growth was highly dependent on cell type. In general, except for the highly resistant cell lines, the inhibitory concentrations 50% were in the range of 10-150 µg/ml The eight extracts highly inhibited cell growth in a concentration-dependent manner, and in general the methanol extracts were always more active than the aqueous. Murine cells appear to be more sensitive than human cells to the cytotoxic action of the plant extracts. The human melanoma B16 line was the most resistant to four of the extracts. In terms of selectivity, S. verbascifolium was the species which showed most selectivity for tumour cells. Overall, this is one of the first studies focusing on southern South American native plants and their biological effects. Since some species of 5 genera analyzed have been reported to possess different degrees of alkaloid content, we examined microtubule structures after extract treatments. The eight extracts induced destabilization, condensation and aggregation of microtubules in LM2 cells, although no depolarization, typical of Vinca alkaloids damage was observed. In a near future, antitumour activity of purified fractions of the extracts administered at non-toxic doses will be assayed in transplantable murine tumour models.

Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration.

Among brain regions affected in Alzheimer's disease (AD), the posterior cingulate shows the earliest and largest decrement in energy metabolism. Positron emission tomography (PET) studies have shown that these decrements appear before the onset of memory deficits or other symptoms in persons at genetic risk for AD. This study compares in vivo imaging results and in situ postmortem analyses by examining the posterior cingulate (area 23) in 15 AD patients and 13 age-matched nondemented controls using quantitative cytochrome oxidase histochemistry as an intracellular measure of oxidative energy metabolic capacity. Each of the six layers of the posterior cingulate demonstrated a decline in cytochrome oxidase activity in AD relative to controls, whereas adjacent motor cortex showed no significant differences. This decrement did not appear to be mainly secondary to nonspecific decrement in mitochondrial enzymes, oxidative stress, cell loss, or histopathology. The cytochrome oxidase decrement was most severe in the superficial layer I (-39%), which demonstrated a correlation to disease duration. Covariance analyses suggest that superficial laminas undergo a functional uncoupling from the deeper layers of posterior cingulate cortex in AD, whereas no such effects are found in motor cortex or controls. These findings expand on previous results from PET studies by illuminating the layer-specific cytochrome oxidase contributions to energy hypometabolism. The findings suggest a decrement of cytochrome oxidase in posterior cingulate cortex, with progressive reduction within the superficial laminas linked to disease duration. Such decrement could contribute to some of the behavioral symptoms displayed by AD patients. This decrement appeared greater in women.

European multicenter survey on the laparoscopic treatment of gastroesophageal reflux in patients aged less than 12 months with supraesophageal symptoms.

BACKGROUND: This multicenter survey includes neonates and infants who underwent surgery for primary gastroesophageal reflux (GER) who presented with supraesophageal symptoms of unknown origin with a minimum of 12 months postoperative follow-up. METHODS: A total of 726 patients underwent GER surgery in 10 European Centers in the period 1998-2002. Respiratory symptoms were present in 204 patients (28%); 135 patients (17%) had surgery under 1 year of age, and 46 of them (6.3%) because of respiratory symptoms. Surgery was performed without any previous medical treatment in 10 cases (21%). The type of procedure included 37 complete 360 degrees wraps (80%) (Nissen, 12, and Rossetti, 25) and nine partial wraps (20%) (Thal five, Lortat Jacob one, Toupet one, others two). Gastrostomy was associated in 17 cases (37%) (6 PEG and 11 modified Stamm). No gastric emptying procedures were recorded. RESULTS: No major intraoperative complications were reported. Six patients developed complications (13%) and a redo operation was performed in three (6.5%). Respiratory outcome after antireflux surgery was good in 35 patients (76%) and fair with significantly improved respiratory symptoms in 11 (24%). CONCLUSIONS: This multicenter survey underlines that GER has to be suspected and aggressively treated in infants with difficult-to-treat supraesophageal symptoms, and also in high-risk cases, in order to prevent major complications.

Minimally invasive urologic surgery in children: an overview of what can be done.

PURPOSE: Laparoscopy has emerged as a feasible and effective alternative for abdominal pathologies in children. Urological minimally invasive surgery is now commonly used for basic operations in most centres and is just beginning to expand its use in more complex operations in several selected centres around the world. We present the current state of the art of minimally invasive surgery in children. MATERIAL AND METHODS: We first reviewed all the urological pathologies treated with minimally invasive surgery in our institution. Secondly we reviewed the literature in order to highlight and discuss certain relevant articles and compare them with our own experience. RESULTS: Since beginning to use minimally invasive surgery at our institution we have operated more than 550 cases with urological pathologies. We used three approaches: the transperitoneal, the retroperitoneal and the transvesical approach. Our preferred indications for each approach are discussed. DISCUSSION: Non palpable testis, varicocele surgery, nephrectomy and adrenalectomy are, in our opinion, established minimally invasive procedures. Hemi-nephrectomy, pyeloplasty and Cohen antireflux surgery are probably excellent indications when minimally invasive surgery is carried out by expert hands. Stone management should not be forgotten in cases of contraindication or failure of ESWL. Even the most complex urological operations may be safely carried out using a minimally invasive approach, although most of the cases described are case reports. CONCLUSION: More papers are published on ablative or reconstructive urological minimally invasive surgery. Transperitoneal and retroperitoneal approaches are used with the same results. Transvesicoscopic surgery should rapidly grow to become a standard approach for Cohen reimplantation. It is anticipated that technical progress will provide the opportunity for more paediatric urologists to develop a minimally invasive approach.

Inhibition of the in vitro infectivity and cytopathic effect of human foamy virus by dideoxynucleosides.

Human foamy virus (HFV) is a human retrovirus that has not been clearly associated with human disease. In this study, we tested the capacity of nucleoside derivatives to inhibit the infectivity and cytopathic effect of HFV in T-lymphoblastoid cells in vitro. H9 cells showed a dramatic cytopathic effect 3 weeks after exposure to HFV. At this time, viral infection was demonstrated by detection of viral antigens by immunofluorescence staining, release of reverse transcriptase activity (RT) in the supernatant, detection of typical viral particles by electron microscopy, and presence of proviral DNA by Southern blot analysis. H9 cells were pretreated with dideoxycytidine (ddC), dideoxyinosine (ddI), or azidothymidine (AZT) at various concentrations before HFV infection. ddC could not completely suppress viral replication at low concentrations, and inhibited cell proliferation at higher concentrations. ddI partially inhibited the formation of giant cells at 10 microM, with 95% inhibition of RT in the supernatant. AZT induced a complete inhibition of cytopathic effect at concentrations > or = 1 microM, with more than 95% inhibition of RT in the supernatant. Moreover, the synthesis of proviral DNA was completely suppressed by 10 microM AZT. These results show that AZT and ddI can inhibit HFV replication in vitro.

Effects of retinoids on the meiosis in the fetal rat ovary in culture.

We investigated the effect of retinoids on the entrance of female germ cells into meiotic prophase and their progression through it, using explants of rat ovaries from 14.5 days post coïtum (dpc) fetuses cultured with or without 10(-6) M retinoic acid (RA) or 10(-9) M retinoic acid receptor alpha (RARalpha) specific agonist. The percentages of oogonia and of oocytes at each meiotic stage in the ovary were evaluated at explantation (D0) and after 3 (D3), 5 (D5) and 9 (D9) days of culture and on equivalent stages in vivo (i. e. 17.5 and 23.5 dpc). The number of germ cells per ovary were counted at D0, D3 and D9. Newly explanted (D0) ovaries contained no germ cell in meiosis. In control medium some germ cells had spontaneously reached the stage leptotene and very few the zygotene on D3. The first pachytene were observed on D5 and the first diplotene on D9. This pattern mimicked that which occurs in vivo although with a slight delay. RA reduced the percentage of oogonia by more than half and increased the percentage of zygotene by more than 22-fold on D3, showing that it accelerated entrance into meiosis. This effect was also observed in response to RARalpha agonist. RA increased the percentage of zygotene and reduced the percentage of pachytene on D9, showing that it can also delay the zygotene/pachytene transition. Lastly, RA reduced the total number of germ cells present on D3 but not on D9. This may be the result of a double effect of RA on the number of germ cells: negative when the cells are in proliferation (D0 to D3) and positive when they entered in meiotic prophase (after D3). Thus, RA is a potential regulator of germ cells meiosis and number in the fetal ovary.

Metabolic activation of the subependymal zone after cortical injury.

The subependymal zone (SEZ) of the adult mammalian forebrain contains a population of progenitor cells that proliferate in response to brain injury. This study examined the effect of cortical injury on metabolic activity in the SEZ using quantitative histochemistry of cytochrome oxidase. The SEZ showed significantly enhanced cytochrome oxidase activity in rats with electrolytic cortical injuries relative to sham-operated controls, while other brain regions showed no such changes. The results indicate that the SEZ had increased oxidative energy demands, and thus provide metabolic evidence that SEZ cells are activated in response to brain injury.

Reduced corpus callosum, fornix and hippocampus in PDAPP transgenic mouse model of Alzheimer's disease.

Persons with Alzheimer's disease (AD) have progressive reductions in the relative sizes of the corpus callosum and hippocampus. Homozygotic PDAPP transgenic mice over-expressing a mutant form of the human amyloid precursor protein have more pronounced reductions in these regions, which are apparent prior to the deposition of amyloid plaques and do not progress with advancing age. The length of the corpus callosum was reduced by two-thirds, the fornix commissure was negligible, and the hippocampal volume was reduced by one-third, suggesting a massive disconnection between the cerebral hemispheres and the hippocampi in PDAPP mice. These findings, which might account for the early, nonprogressive behavioral abnormalities observed in these animals, have implications for the study of AD.

Industrial disaster and mental health of children and their parents.

OBJECTIVE: We report the findings of research conducted a year after an industrial disaster (PCB fire), which occurred on Montreal's South Shore in 1988. A total of 1,663 families were evacuated for a period of 18 days. The study evaluated 174 children between the ages of three and eleven years: 87 in the exposed group and 87 in the control sample. METHOD: Structured questionnaires were administered to the children and their mothers and fathers during home visits. RESULTS: Based on the responses of the children and the mothers, children aged 6 to 11 years displayed more overall internalized and post-traumatic stress disorder (PTSD) symptoms than did those in the control group. CONCLUSIONS: The study demonstrates that the mental health of fathers as well as mothers correlates with children's symptoms and that parents are able to accurately observe their child's reaction to a disaster.

The Dominic-R: a pictorial interview for 6- to 11-year-old children.

OBJECTIVE: To review the Dominic-R and the Terry questionnaires, respectively, for white and African-American children, both DSM-III-R-based, and more recent DSM-IV-based computerized versions. METHOD: Five papers describing the development, content, validation studies, and establishment of the diagnostic cutpoints of these instruments are reviewed. The instruments are pictorial, fully structured, and designed to assess mental disorders in children 6 to 11 years of age. Symptom descriptions complement the visual stimulus, providing better information-processing than visual or auditory stimuli alone. Cognitive immaturity of young children bars frequency, duration, and age-of-onset measurements, restricting correspondence with DSM criteria. DSM-IV (computerized versions) and DSM-III-R (paper versions) disorders being assessed include specific (simple) phobias, separation anxiety, generalized anxiety (overanxious), depression/dysthymia, attention-deficit hyperactivity, oppositional defiant, and conduct disorder. RESULTS: Test-retest reliability of symptoms and symptom scores and criterion validity against clinical judgment support the visual-auditory combination of stimuli to assess child mental health. CONCLUSION: Intended for clinical, epidemiological, and screening purposes, these instruments are short and simple. Although it only approximates DSM-III-R and DSM-IV criteria, the pictorial format permits young children to be reliable informants about their mental health.

Do children aged 9 through 11 years understand the DISC Version 2.25 questions?

OBJECTIVE: To assess the understanding of Diagnostic Interview Schedule for Children-Version 2.25 (DISC-2.25) questions by children aged 9 through 11 years. METHOD: Two hundred forty children were recruited from four public schools. The cognitive appraisal of 280 questions from the most prevalent DSM-III-R diagnoses was evaluated. The collaboration of four children was necessary to cover one DISC. Sixty DISCs, evenly distributed according to age and sex, were completed. Two child psychiatrists evaluated the children's answers. Nonparametric tests were used to assess understanding of questions as a whole, of time concepts (overall, categories, number), and of questions based on the number of words. RESULTS: Children aged 9, 10, and 11 years understood 38%, 38%, and 42% of the questions as a whole, respectively, and 26%, 24%, and 30% of the overall time concepts, respectively. The understanding rates of questions as a whole were significantly higher than those of overall time concepts. Durations were significantly better understood than periods and frequencies, and questions having one time component were significantly better grasped than those with two or more. Shorter questions were significantly better understood than longer ones. CONCLUSION: Although the DISC has been greatly improved since the initial version, the results suggest that additional revision is needed before clinicians or researchers use the DISC with younger children.

Diagnostic Interview Schedule for Children (DISC-2.25) in Quebec: reliability findings in light of the MECA study.

OBJECTIVE: To examine the reliability of the French Diagnostic Interview Schedule for Children (DISC-2.25) in Quebec in light of other DISC-2 studies conducted in the National Institute of Mental Health's Methods for the Epidemiology of Child and Adolescent Mental Disorders Study. METHOD: Reliability was assessed for DSM-III-R disorders in a community sample comprising 260 parents of youths aged 6 to 14 years and 145 adolescents aged 12 to 14 years. The DISC was completed at home. The mean test-retest interval was 13.8 days for parents and 12.8 days for adolescents. RESULTS: Parents' reports: Internal consistency was acceptable for a majority of disorders. The kappa coefficients were in the fair or good ranges except for depressive disorders and were higher for children than for adolescents, and intraclass correlations were higher than kappa coefficients. Adolescents' reports: Internal consistency was acceptable or nearly acceptable for a majority of disorders. The kappa coefficients were in the fair range, and intraclass correlations were higher than kappa coefficients. The kappa coefficients were significantly higher for the test-retest interval of 7 to 14 days than for 14 to 21 days for adolescents' reports of anxious disorders and internalizing disorders. CONCLUSION: The French DISC-2.25 shows acceptable internal consistency and fair to good test-retest reliability. Across DISC-2 studies, test-retest reliability of the parents' reports improved for anxiety and depressive disorders. Among sources of variation, studies on attributes of questions would be meaningful.

Quantitative cytochemistry of cytochrome oxidase and cellular morphometry of the human inferior colliculus in control and Alzheimer's patients.

Quantitative cytochemistry of cytochrome oxidase (C.O.) was implemented in human brains to measure C.O. activity in the 3 main divisions of the inferior colliculus (IC): central (ICC), dorsal (ICD), and external (ICE). Units of C.O. activity (micromol/min/g tissue wet weight) were quantified in cellular compartments (overall average, neuropil, perikaryon, and dendrites) at the light microscope level using microdensitometry calibrated with C.O. activity standards measured spectrophotometrically. In a non-AD (Alzheimer's disease) control group (mean age = 79.6 +/- 3.1 years, postmortem time = 6.9 +/- 1.6 h), the ICC and ICD demonstrated higher (p < 0.008) overall average activities (mean = 183.40 +/- 18.7 and 184.98 +/- 45.1 units, respectively) relative to the ICE (56.46 +/- 15.9 units). Comparison of cellular morphometry (soma and nucleus area, perimeter, and diameter) revealed that the ICC contained cells of significantly larger soma size than in both the ICD and ICE (p < 0.002). The distribution of soma diameters in the ICC of controls showed a clear bimodality, enabling the typing of the cells into larger and smaller than average soma diameter. Brains from patients with Alzheimer's disease (AD; mean age = 78.3 +/- 2.9 years, postmortem time = 6.5 +/- 1.3 h) were compared with the non-AD controls. Significant group differences were found only in the large cells of the ICC. The AD large cells showed a decrement in C.O. activity relative to the corresponding controls in overall average activity (p < 0.032) and in peak activity of neuropil near the soma (p < 0.012). These findings provide the first quantitative cytochemical data of C.O. activity in humans. They also suggest that cellular alterations in C.O. metabolism in AD affect predominantly specific groups of larger projection neurons while neighboring neurons are spared.

Comparative studies on IL-6 production status in HTLV-1 chronically infected cell lines derived from different HTLV-1 associated pathologies.

We have comparatively studied the qualitative and quantitative status of Interleukin 6 (IL-6) production in several HTLV-1 chronically infected T-cell lines derived from patients suffering either of adult-T-cell leukemia/lymphoma or of tropical spastic paraparesis (TSP). Two other HTLV-1 chronically infected cell lines, coming from healthy seropositive carriers, were also analyzed. Our results demonstrate that, independently of the origin, all these T cell lines, as compared to uninfected HTLV-1 T cell ones, which were always IL-6 non producers, synthesize and yield comparable amounts of IL-6 synthesis, he nosological origin of infecting viral strains does not seem to play a differential role on IL-6 qualitative or quantitative production parameters.

Aortic valve replacement for aortic stenosis in 200 consecutive octogenarians.

From 1978 to 1992, 200 consecutive patients aged between 80 and 90 years had aortic valve replacement for calcified aortic stenosis. Valve replacement was isolated in 187 cases (93.5%), and it was in combination with coronary bypass (n = 12; 6%), mitral valve replacement (n = 1; 0.5%) or surgery of the ascending aorta (n = 4; 2%). These 200 octogenarians represented 7.4% of the 2716 patients operated for aortic stenosis during the study period. One hundred and forty-eight of them (74%) were in NYHA class III or IV. Operative mortality was 11.5% (23 deaths) and the mean duration of hospitalization was 12.7 +/- 4.83 days. After discharge, all 177 surviving patients were followed up for a mean period of 2.8 +/- 2.1 years (range one month to 10.6 years). There have been 49 deaths during the follow up. At the end of the follow up, 127 of the 128 survivors (98.6) were in NYHA classes I or II. Actuarial survival at one, three and five years was 81.7%, 74.8% and 57.14% respectively, which is equivalent to the life expectancy for subjects of the same age without aortic stenosis. It is suggested that despite the increased, yet acceptable, operative risk, valve replacement in octogenarians is justified due to its beneficial effect on life expectancy and quality of life.

Current indications for laparoscopy and retroperitoneoscopy in pediatric urology.

Laparoscopy has raised great interest in the past few years in the field of pediatric urology. It has evolved from a simple diagnostic maneuver to complex operative procedures. The aim of this study was to review urologic laparoscopy literature and provide a critical review of this field to establish current indications for videosurgery in pediatric urology. In general, from an anatomic point of view, retroperitoneoscopy seems to be more suitable than the transperitoneal laparoscopic approach for reaching the upper urinary tract. It also is less invasive and complies with the criteria for open renal surgery. With respect to current indications for videosurgery in pediatric urology, the authors have identified several well-established clinical procedures, although no large series have been published for any of the procedures, except for the treatment of varicocele, nonpalpable testis, and nephrectomy. In conclusion, the data reviewed suggest that videosurgery is a safe and feasible technique in pediatric urology if performed by expert surgeons, and that it certainly will develop further in the next few years.

Long-term outcome of laparoscopic Nissen and Toupet fundoplication in normal and neurologically impaired children.

BACKGROUND: Laparoscopic fundoplication is a commonly performed procedure in children. This report describes the incidence of long-term recurrence and complications after laparoscopic Nissen or Toupet fundoplication in neurologically impaired and normal children. METHODS: Fifty-three children operated on before 1999 were reviewed. All children were evaluated clinically and with a barium meal study thereafter. Symptomatic children and those with abnormal barium meal underwent 24 h pH monitoring. RESULTS: A total of 45 patients were included in the study. The mean follow-up was 4.5 years. All, except one asymptomatic child that declined, had a barium meal. Four were abnormal (2 parahiatal hernias and 2 slight episodes of reflux). Four patients had symptoms related to the operation and 2 to clinical recurrence. Only 1 asymptomatic child with slight reflux at barium meal revealed abnormal 24 h pH monitoring. Finally, 6.6% patients were found to have late recurrence (2 clinical and 1 pHmetry). There was an obvious increase in children's weight, especially in neurologically impaired patients. CONCLUSION: Laparoscopic antireflux surgery is of value in children with gastroesophageal reflux disease. The long-term results are comparable with open surgery, and there was no difference in term of wrap failure between neurologically impaired and normal children.

A structured pictorial questionnaire to assess DSM-III-R-based diagnoses in children (6-11 years): development, validity, and reliability.

This paper presents a structured pictorial instrument, the Dominic questionnaire, to assess mental disorders in 6- to 11-year-old children. Ninety-nine drawings represent situations corresponding to DSM-III-R based ADHD, CD, ODD, MDD, SAD, OAD, and SPh. However, cognitive limitation of 6- to 11-year-old children do not allow for time-related measurement. The instrument takes 15-20 min to administer. Reliability and validity of the Dominic questionnaire were studied in Parent DISC-2 positive and negative outpatient and general population samples and against clinical judgement. The pictorial approach provides acceptable test-retest reliability and the instrument makes standardized assessment possible for children as young as 6 years of age.

Correlates of mental disorders in the Quebec general population of 6 to 14-year olds.

Previous epidemiological studies of correlates of child and adolescent mental disorders in the general population have focused more on child/adolescent and socioeconomic/sociodemographic characteristics than on family characteristics. Moreover, there are no generally accepted methods to analyze and interpret correlates. The purpose of the Quebec Child Mental Health Survey in this regard was twofold: (1) to identify correlates of DSM-III-R internalizing and externalizing disorders according to informant (youth, parent, teacher), for three age groups (6-8, 9-11, and 12-14 years), including relevant family characteristics not considered in previous studies; and (2) to interpret the relative importance of risk indicators by ranking correlates according to strength and consistency of association across age groups. Logistic regression models suggest the inconsistency of correlates across informants. The ranking of correlates reveals that individual and family characteristics make a more important contribution than do socioeconomic characteristics, thereby supporting the relevance of proximal variables in the development of psychopathology.

Hepaticoportoappendicostomy.

In one case of extrabiliary atresia, reconstruction of the biliary tract was performed by using the appendix. The child, who was 2 years old, is doing well without ascending cholangitis. This operation seems simple and satisfying because it seems to be more anatomic and more physiologic than the standard Kasai operation. Its efficacy in a large number of cases remains to be proven.