Uncaria tomentosa for Reducing Side Effects Caused by Chemotherapy in CRC Patients: Clinical Trial.

To evaluate the effectiveness of Uncaria tomentosa in minimizing the side effects of chemotherapy and improving the antioxidant status of colorectal cancer (CRC) patients, a randomized clinical trial was conducted. Patients (43) undergoing adjuvant/palliative chemotherapy with 5-Fluorouracil/leucovorin + oxaliplatin (FOLFOX4) were split into two groups: the UT group received chemotherapy plus 300 mg of Uncaria tomentosa daily and the C group received only FOLFOX4 and served as a control. Blood samples were collected before each of the 6 cycles of chemotherapy, and hemograms, oxidative stress, enzymes antioxidants, immunologic parameters, and adverse events were analyzed. The use of 300 mg of Uncaria tomentosa daily during 6 cycles of FOLFOX4 did not change the analyzed parameters, and no toxic effects were observed.

Could calcium hypochlorite and grape seed extract keep the mechanical properties of root dentin and fracture resistance of weakened roots?

OBJECTIVES: To evaluate the effect of different endodontic irrigation protocols on dentin mechanical properties and fracture resistance of roots with 0.5 mm (weakened roots) and 1.5 mm of thickness. METHOD: Irrigation protocols were the following: Distilled water (DW) + Ethylenediamine tetraacetic acid (EDTA); grape seed extract (GSE) + EDTA; sodium hypochlorite (NaOCl) + EDTA; NaOCl + EDTA + GSE; calcium hypochlorite (Ca(ClO)2) + EDTA; Ca(ClO)2 + EDTA + GSE; chlorhexidine (CHX) + EDTA; CHX + EDTA + GSE. The samples were prepared and the values of microhardness, ultimate tensile strength (UTS), and flexural strength were obtained. Further, fracture resistance of roots with dentin thickness of 0.5 mm and 1.5 mm, and restored with fiberglass post relined with composite resin and metal crowns, were evaluated with same irrigation protocols previously described; the failure mode was evaluated as well. All tests presented normality in data distribution (Kolmogorov-Smirnov), and Analysis of Variance and Bonferroni test (α = 0.05) were performed. RESULTS: Higher reduction of dentin microhardness was observed in the NaOCl and NaOCl + EDTA + GSE groups (p < 0.0001). An increased in the UTS values was obtained in the CHX groups (p < 0.0001), while similar values were observed between the control and other groups (p > 0.05). The reduction of dentin flexural strength was observed in the NaOCl groups (p < 0.0001), while no significant changes were observed in the other groups (p > 0.05). With regard to fracture resistance, no statistical difference was obtained among the irrigation's protocols (p > 0.05), except for CHX (p = 0.0031) and CHX + GSE (p = 0.0001) that showed increased in fracture resistance values in roots with 1.5-mm thickness. An increased rate of irreparable failure was obtained in the NaOCl groups, whereas there was a predominance of repairable failure in the other groups. CONCLUSIONS: The endodontic irrigation protocol has a significant impact on the dentin mechanical properties; on the other hand, do not reduce the fracture resistance of root with 0.5 mm and 1.5 mm of thickness.

Hepatitis C and HIV prevalence using oral mucosal transudate, and reported drug use and sexual behaviours of youth in custody in British Columbia.

BACKGROUND: Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population was assessed in British Columbia (BC) in 1994 but hepatitis C virus (HCV) prevalence has never been measured. We sought to determine: 1) the performance of the OraSure, a non-invasive device for oral mucosal transudate (OMT) specimen collection, to detect HCV and HIV antibodies; 2) the prevalence of HCV and HIV among youth in custody; and 3) the factors associated with intravenous drug use and sex for trade. METHODS: OraSure was validated in 110 adults with known HIV and HCV sero-status. Nurses administered an anonymous survey and collected OMT samples from youth aged 14-19 years in BC youth custody centres. RESULTS: Antibody detection in OMT had 96.4% sensitivity for HIV and 94.6% for HCV. 417 youth were enrolled; 22% were female; 48% reported Aboriginal ethnicity. Although 98.3% reported ever using drugs, <8% reported injection drug use (IDU). IDU was independently associated with age of first sexual intercourse (inverse association) and sex for trade (sex in exchange for money, drugs, food or shelter) (OR 4.28; 95% CI: 1.56-11.75). Females were >9 times more likely to report sex for trade. Five Aboriginal youth were identified with HCV; prevalence estimate 1.2% (95% CI: 0.53-2.77%); 3 reported injecting drugs, the other 2 reported using cocaine/crack and sharing non-injection drug paraphernalia. Two youth were identified with HIV, prevalence estimate 0.48% (95% CI: 0.14%-1.72%). CONCLUSION: IDU, HCV and HIV prevalence remain low. Interventions are needed to prevent transition to IDU and further opportunities for prevention and harm reduction should be explored while the youth are in custody.

The international criminal tribunal for the former Yugoslavia (ICTY) and the forensic pathologist: ethical considerations.

Since 1991, war crimes in the former Yugoslavia have been the subject of several international medico-legal investigations of mass graves within the framework of inquiries led by the International Criminal Tribunal for the former Yugoslavia (ICTY). Forensic pathologists involved in the ICTY missions could be subjected to ethical tensions due to the difficulties of the missions, the emergent conflicts between forensic scientists of the investigating teams and the original nature of the ICTY proceedings. In order to study the nature of such ethical tensions, we sent a questionnaire to 65 forensic pathologists who have been involved in the ICTY missions. The rate of response was 38%. The majority of forensic pathologists questioned (n=18) did not know how the medico-legal data was exploited by the ICTY. Three of them have been subjected to pressures. Three of them were aware of mass grave sites knowingly not investigated by the ICTY. Fifteen considered that the ICTY respected the elementary rules of the law and four of them questioned the impartiality of the justice led by the ICTY. Two conflicting types of ethics can be drawn from these results: conviction ethics, which are shared by most of the forensic pathologists questioned, and responsibility ethics. In the former, the forensic pathologist completely agrees with the need for an international war crimes tribunal, even if such justice can be challenged regarding the respect of human rights and impartiality. In the latter, he or she needs to conduct him or herself in ways that do not infringe impartiality. As medical deontology duty requires impartiality ethics, discursive ethics are needed to ease ethical tensions and to suggest ethical guidelines. Alternatives to international justice, through a truth and reconciliation commission and by way of humanitarian missions combining victims' identification with forensic investigations for historical purposes, could be considered.

Zidovudine therapy and HIV encephalitis: a 10-year neuropathological survey.

OBJECTIVE: To assess the effect of zidovudine on productive HIV infection of the brain. DESIGN: To correlate the incidence of HIV-specific neuropathology with zidovudine therapy. PATIENTS: We examined 192 AIDS cases neuropathologically; 97 had never been treated with zidovudine, 72 had received zidovudine for over 3 months and until death, 23 had their treatment terminated more than 1 month before death. RESULTS: The incidence of HIV encephalitis/HIV leukoencephalopathy (HIVE/HIVL) and of multinucleated giant cells (MGC) was significantly lower in patients who had received zidovudine than in those who had never received zidovudine. The yearly incidence of HIVE/HIVL increased between 1982 and 1987 probably because of improved survival, and decreased between 1987 and 1990 although the percentage of patients treated with zidovudine increased. Since 1991 the incidence of HIVE/HIVL and of MGC increased slightly. The percentage of patients treated with zidovudine until death decreased and that of patients whose treatment was terminated increased concomitantly. In 1989 and 1990, most patients whose treatment was terminated had MGC and HIVE/HIVL. In 1991 and 1992 this incidence decreased markedly, coinciding with the introduction of dideoxyinosine therapy. CONCLUSION: Zidovudine treatment significantly reduces the occurrence of productive HIV infection of the brain in AIDS. Discontinuing zidovudine therapy may favour the occurrence of HIV encephalitis. Substitution therapy with dideoxyinosine also appears to protect against HIV-specific brain pathology.

Early brain changes in HIV infection: neuropathological study of 11 HIV seropositive, non-AIDS cases.

We examined 11 brains of human immunodeficiency virus (HIV) seropositive cases who died from unnatural causes (10 intravenous drug abusers who died from heroin overdose and 1 homosexual dead from a gunshot injury); 10 brains of HIV seronegative heroin addicts who died from overdose and 1 seronegative drug abuser who died from gunshot injury served as controls. Complete postmortem examination did not show evidence of acquired immune deficiency syndrome (AIDS) or AIDS related complex. Terminal changes including nerve cell ischemia, edema and diffuse vascular congestion were observed in all cases. Perivascular pigment deposition with macrophages was a constant finding in drug addicts and was probably related to chronic intravenous injection. In contrast, cerebral vasculitis was significantly more frequent and marked in HIV seropositive cases and was often associated with lymphocytic meningitis. Granular ependymitis, myelin pallor with reactive astrocytosis and microglial proliferation were also more frequent and more severe in HIV seropositive cases. Immunocytochemistry was negative for HIV antigens. Our study further supports the view that early central nervous system changes occur in HIV infection.

Neuropathology of early HIV-1 infection.

Early HIV-1 invasion of the central nervous system has been demonstrated by many cerebrospinal fluid studies; however, most HIV-1 carriers remain neurologically unimpaired during the so called "asymptomatic" period lasting from seroconversion to symptomatic AIDS. Therefore, neuropathological studies in the early pre-AIDS stages are very few, and the natural history of central nervous system changes in HIV-1 infection remains poorly understood. Examination of brains of asymptomatic HIV-1 positive individuals who died accidentally and of rare cases with acute fatal encephalopathy revealing HIV infection, and comparison with experimental simian immunodeficiency virus and feline immunodeficiency virus infections suggest that, invasion of the CNS by HIV-1 occurs at the time of primary infection and induces an immunological process in the central nervous system. This includes an inflammatory T-cell reaction with vasculitis and leptomeningitis, and immune activation of brain parenchyma with increased number of microglial cells, upregulation of major histocompatibility complex class II antigens and local production of cytokines. Myelin pallor and gliosis of the white matter are usually found and are likely to be the consequence of opening of the blood brain barrier due to vasculitis; direct damage to oligodendrocytes by cytokines may also interfere. These white matter changes may explain, at least partly, the early cerebral atrophy observed, by magnetic resonance imaging, in asymptomatic HIV-1 carriers. In contrast, cortical damage seems to be a late event in the course of HIV-1 infection. There is no significant neuronal loss at the early stages of the disease, no accompanying increase in glial fibrillary acid protein staining in the cortex, and only exceptional neuronal apoptosis. Although HIV-1 proviral DNA may be demonstrated in a number of brains, viral replication remains very low during the asymptomatic stage of HIV-1 infection. This makes it likely that, although opening of the blood brain barrier may facilitate viral entry into the brain, specific immune responses including both neutralising antibodies and cytotoxic T-lymphocytes, continuously inhibits viral replication at that stage.

Sex-related C cell hyperplasia in the normal human thyroid: a quantitative autopsy study.

We report a prospective quantitative image analysis study of C cells in 57 normal autopsy thyroid glands, serially sectioned and wholly embedded in paraffin; all slides were immunohistochemically stained for calcitonin. Computerized quantitative image analysis was performed on 47 cases to measure C cell surface area and parenchymatous surface area after immunoperoxidase staining for calcitonin. The method was time-effective, with a good reproducibility. C cells were mainly found in the middle third of each lobe. Important inter-individual variations were observed; the maximum C cell surface area in a section (Amax) ranged from 28 x 10(3) to 470 x 10(3) microns2 (mean, 167 x 10(3) microns2) among 42 adults. Of particular interest was the important difference observed between sexes; Amax was twice as high in men (mean, 201 x 10(3) microns2) as in women (mean, 91 x 10(3) microns2; P = 0.0009). Moreover, 14 (33%) adult subjects [2 women (15%) and 12 men (41%)] fulfilled C cell hyperplasia criteria, i.e. at least 3 fields at x 100 magnification containing more than 50 C cells, suggesting that a substantial part of the normal adult population could have C cell hyperplasia.

Improvement of internal dose calculations using mathematical models of different adult heights.

In internal dosimetry for both nuclear medicine and radiation protection, the adult morphology is represented by a limited number of anthropomorphic models that may not be suitable for all patients. To develop more patient-specific dosimetry, we derived six mathematical models for adults of different height. Three male models (160 cm, 170 cm and 180 cm) and three female models (150 cm, 160 cm and 170 cm), based on the MIRD model design, were developed from the statistical analysis of anthropometric data gathered from autopsies. Monte Carlo calculations were used to provide an example of estimations of S value for these new models for iodine 131 uniformly distributed successively in the stomach or in the urinary bladder. On average, for both male and female models, an increase in the model height of 10 cm leads to a mean reduction in the S value for iodine-131 by 20% and 29% when the stomach and the urinary bladder respectively are selected as source regions. Similarly, when the model height increases by 20 cm, the S values decrease on average by 35% and 48%. This study presents the use of anthropometric data to develop new mathematical models for adults of different height, and shows the significant influence of the morphology on dosimetric parameters.

ABO tissue antigens of Egyptian mummies.

ABO groups were investigated on skin (and muscle), bone and hair specimens from 14 Egyptian mummies dating from the Roman period. Samples were tested by the AE (absorption-elution), MA (mixed agglutination) and HIF (histo-immunofluorescence) methods, in order to evaluate the reliability of each method. For half of the mummies (7) the results were concordant on all samples (3-9 samples for each mummy) with all employed methods, suggesting an unequivocal blood group conclusion. For the other seven mummies there were discordant results with the different methods and interpretation of the results was thus inconclusive. HIF seems to be the most reliable method as specific blood group substances are identified on specific histologic structures. Failure to detect tissular ABO antigens was mainly due to excessive resin impregnation.

Multiplex amplification of mitochondrial DNA for human and species identification in forensic evaluation.

We describe a method combining in a single-round polymerase chain reaction amplifications of both cytochrome b and hypervariable D-loop mitochondrial DNA allowing species determination and individual human identification. Following the amplification step, amplicons are first screened on an agarose gel. The presence of only one band indicates that the sample is nonhuman, while the presence of two bands indicates a human origin. Subsequent DNA sequencing of the hypervariable D-loop region DNA allows for individual human identification as the presence of cytochrome b fragment does not interfere with the analysis. Similarly, further species determination on the basis of the phylogenetically variable cytochrome b gene is possible by sequencing of the cytochrome b DNA fragment.

Postmortem interval estimation by creatinine levels in human psoas muscle.

A new method was tested for estimating time after death in the middle range of postmortem interval (weeks). Creatinine muscular concentration in human cadaver is positively correlated to postmortem estimation. Temperature should be mainly related to the creatinine transformation rate. A stronger correlation was found at 11 degrees C up to 30 days and at 20 degrees Celsius up to 15 days.

Organ weight in 684 adult autopsies: new tables for a Caucasoid population.

The weights of normal organs were retrospectively culled for the years 1987-1991 from 684 forensic autopsy cases. All the subjects were Caucasoid adults who died of external causes and showed no pathological changes. The weights of the following organs were available: the heart, the right and the left lung, the liver, the spleen, the pancreas, the right and the left kidney and the thyroid gland. The external parameters used for statistical correlation were the age, the height, the body weight and the body mass index (BMI) of the deceased. The weight of all the organs was shown to correlate with at least one external parameter, with the exception of thyroids in females. Organ weights decreased with age except for the heart and the thyroid, and increased in relation to body height and/or BMI. Except for the heart, the organ weight showed a better statistical correlation with the body height than the BMI. These updated tables of organ weight were compared with the data collected in previous studies. Such tables have to be regularly updated by pathologists in order to keep organ weight as a good criterion to be used in post-mortem diagnosis.

Postmortem interval estimation by biochemical determination in birds muscle.

Experimental postmortem interval estimation was assayed by various biochemical components of hens pectoral muscle. Among them, only percentage of non-protein nitrogen on total soluble protein, asparatic amino transferase activity and creatinine concentration showed significant correlation with time after death. Asparatic amino transferase was negatively correlated and non-protein nitrogen percentage and creatinine were positively correlated to postmortem interval. The stronger correlation (0.925) was found for creatinine.

Increase of pulmonary density of macrophages in sudden infant death syndrome.

A 1996 cytodensitometric study found increased cellular density in the pulmonary parenchyma of infants who died of sudden infant death syndrome (SIDS). The present study clarifies these results in quantifying the density of immunohistochemical subtyped inflammatory cells. Histomorphometry was used to compare the density of macrophages, granulocytes and T and B lymphocytes in the lungs of two groups of infants. From the post-mortem records of infant deaths between 1983 and 1995, 29 (mean age = 5 months) were randomly selected including 16 cases of SIDS and 13 who died of other non-pulmonary causes. Densities of immunoreactive cells were measured under blind conditions in the parenchyma. The mean density of macrophages was significantly higher in cases of SIDS compared with the controls (P = 0.0318), but there were no differences for the lymphocytes and the granulocytes. These morphometrical results must be interpreted within the methodological limits of this study, especially the non-uniform level of lung inflation between selected subjects. However, the differences in level of inflation are not sufficient to explain the observed increase of macrophage density. Indeed, the mean values of alveolar surface area, which represent an indirect measure of lung inflation, are not significantly different between the two groups. Increase of pulmonary macrophage density in SIDS agrees with three non-exclusive hypotheses: (1) an abnormal inflammatory reaction by expression of Th1 helper cell phenotype activation; (2) consequence of passive smoking; and (3) post-agonal mechanisms. Bacterial superantigens produced by toxigenic bacteria in the respiratory tract could play a role as a trigger factor that initiates a fatal cascade with overproduction of cytokines leading to death. The significant increase of pulmonary macrophage density would be the morphological expression of this potential mechanism of death.

Y-STR DNA amplification as biological evidence in sexually assaulted female victims with no cytological detection of spermatozoa.

Identification of spermatozoa is the biological evidence most often sought in specimens from rape victims. Absence of spermatozoa usually terminates biological investigations, and the victim's testimony can be contested. We assessed the utility and reliability of PCR amplification using Y-chromosomal STR polymorphisms in specimens from female victims of sexual assault with negative cytology. One hundred and four swabs without spermatozoa detected by cytology were collected from 79 alleged sexually assaulted female victims and amplification of Y-STR and of amelogenin was performed.Overall, Y-chromosome was detected and evidenced sexual penetration in 28.8% of swabs. In the population of victims examined more than 48 h after the sexual assault, Y-STR were still evidenced in 30% of the cases. These results show that swabs should be taken from victims for Y-chromosome DNA typing even after long delays between sexual assault and medical examination.

Age estimation from quantitation of features of "chest plate" X-rays.

This study presents a method for estimating the age at death from the quantitation of roentgenologic features of X-ray films of chest plates obtained during routine autopsies. Multiple linear regression analysis allows estimation of coefficients of regression of features on known age-at-death individuals. The regression equation can be used in turn for age estimation of an unknown age-at-death individual. The accuracy of age estimation is about +/- 8.4 years (standard error) which is in the range of previously published macroscopic methods, though the present method is much faster and simpler.

Skeletal remains presumed submerged in water for three years identified using PCR-STR analysis.

We describe the successful identification of the remains of a saponified body found in a dam by typing of nuclear DNA. Whereas DNA extracted from soft tissues yielded negative PCR results, DNA extracted from the bone by a slightly modified Qiagen procedure allowed the typing of sex (AMG locus) and of 10 additional STR loci. An identity document was found belonging to a man missing for 3 years and comparison of the results to the DNA profiles of his son and wife confirmed the identity. The longest delay reported until now for successful nuclear DNA genotyping after immersion in river water was 18 months. This case demonstrates a delay of up to 3 years.

Frequency of bone lesions: an inadequate criterion for gunshot wound diagnosis in skeletal remains.

A retrospective study was carried out on 130 fatalities due to gunshot wounds to determine whether the combined absence of bone damage and projectile in a skeleton is sufficient to eliminate a diagnosis of gunshot wound. Our findings showed that bone lesions were present in about 90% of the cases and were associated with intracorporeal projectile(s) in about 70% of the cases. The presence or absence of bone lesions seemed independent of the gun characteristics, the shot conditions, and the type of death. The cause of death was predominantly brain injury in cases with bone lesions whereas thoracic, abdominal, and peripheral vascular causes were more frequently encountered in cases without bone damage. We concluded that the combined absence of bone lesions and intracorporeal projectile (about 5% in our series) cannot exclude a diagnosis of death secondary to gunshot wounds.

Suicidal stab wounds of the throat.

Suicide by stabbing one's throat remains very rare and very few cases have been reported in the forensic literature. In such cases, the important distinction is between suicide and homicide. The direction of stab wounds, their depth, site and number have particular importance in helping to recognize suicide. Suicide when attempted by transfixion of the neck in middle aged and elderly adults often reveals a definite resolution to kill oneself.