The father of hematologic oncology Jean Bernard (1907-2006) and his contribution to the research and treatment of leukemia.

Through his medical research and scientific work Jean Bernard dominated for half century in medicine and literature and he was honored as no other scientist. He excelled in different medical fields and is rightly considered as the founder of hematology, oncology and bioethics.

Noncanalized horns of uterus didelphys with prolapse: a unique case in a young woman.

The authors report the unique case of a 20-year-old patient with prolapsed uterus didelphys with noncanalized horns, who complained of primary amenorrhea. Clinical examination revealed a rudimentary noncanalized cervix with a third degree prolapse and no palpable uterus. A small prolapsing remnant of a uterus didelphys with 2 noncanalized uterine horns was excised by laparotomy. Ultrastructural examination of subepithelial cervical connective tissue revealed collagen of normal structure, but of low concentration. The etiologies of both the Mullerian ducts anomalies and the genital prolapse are probably multifactorial. Low collagen concentration indicates a constitutional tissue weakness contributing to the development of genital prolapse.

Pentasomy 49,XXXXY diagnosed in utero: case report and systematic review of antenatal findings.

OBJECTIVES: Pentasomy 49,XXXXY is a rare sex chromosome polysomy usually diagnosed postnatally by the combina- tion of mental retardation, facial dysmorphism, and genital, cardiac and skeletal malformations. Prenatal detection of 49,XXXXY is unusual and may be incidental due to non-specific ultrasound (US) findings. We report a case of 49,XXXXY diagnosed prenatally and present a literature review of the few prenatally diagnosed cases. METHODS: We searched the PubMed electronic database without year and language restriction, using the keywords 'Prenatal', 'Diagnosis', and '49,XXXY', performing a systematic review. RESULTS: We report a 35-year-old patient with normal first-trimester US but increased combined risk for trisomies 18 and 13. Amniocentesis at 16 weeks of gestation revealed a 49,XXXXY karyotype. Pregnancy was terminated at 19 weeks' gestation, and a male fetus with facial dysmorphism and hypospadia was delivered. A total of 12 articles were identified in the systematic review. All were case reports and dated from 1980 until 2008. The mean maternal age was 34.8 years (range 30-41). The most common prenatal US feature was cystic hygroma, present in 5 cases. Hypogenitalism was the most common macroscopic clinical feature identified after pathology examination in 7 cases. In 2 cases, there was an increase in first-trimester combined risk for trisomy 21. CONCLUSIONS: Pentasomy 49,XXXXY is associated with a variety of non-specific US findings, of which cystic hygroma was the commonest. No specific sequence of findings could be identified in this review.

Leptomeningeal melanoma of unknown primary site: two cases with an atypical presentation of acute meningitis.

Primary melanoma of the central nervous system accounts for only 1% of the cases of melanoma, having a relatively rare frequency of being reported in the literature. We report two cases of leptomeningeal melanoma of unknown primary site diagnosed after post mortem examination. In the first case, the patient presented with resisting epilepsy, whereas in the second with persisting fever and mental slowness. Cranial CT in the first patient showed postgadolinium enhancement of the ependyma and the infundibulum, while in the second there was diffuse enhancement of the leptomeninges. Analyses of the CSF in both cases did not establish the presence of malignant cells but revealed altered CSF glucose and increased CSF protein levels. There were no extracranial abnormalities. Both patients were treated for infectious meningitis and died a few days afterwards. At autopsy, all body cavities including oral cavity and the entire integument were examined. In both cases the leptomeninges were diffusely covered with brownish material. Histological examination of the brain specimens revealed the presence of a malignant neoplasm of low differentiation. Diagnosis was established with the results of immunohistochemistry, tumor cells were positive for HMB-45 and S-100 whereas they were negative for cytokeratins, CD45 and GFAP. In conclusion, both patients, although presenting with symptoms and signs highly suggestive of meningitis, suffered from leptomeningeal melanomas of unknown primary site. Clinical, radiological and histological findings are discussed with a review of the literature.

Frequency of impalpable prostate adenocarcinoma and precancerous conditions in Greek male population: an autopsy study.

A series of 212 prostate specimens of men dead between August 2002-August 2004, have been sectioned in consecutive autopsies and subjected to whole mount analysis in purpose to determine the epidemiology of impalpable prostate cancer in Greece. Impalpable prostate carcinomas were found in 40 cases (18.8%) most in the peripheral region. In all, 29 of 40 impalpable cancers (70.7%) had volume less than 1 cm3. Most of impalpable carcinomas were of favorable (Gleason score 2-4) or intermediate (Gleason score 5 and 6) histological type (55 and 27.7%, respectively) while only five (12.5%) were undifferentiated (Gleason score 7 and 8). In all, 24 (60%) of the 40 impalpable carcinomas were multifocal and consisted of two or more foci, most of small size (<0.5 cm3). Most of the impalpable cancers found in this autopsy study were potentially insignificant tumors (relatively low volume, favorable or intermediate histological pattern and absence of invasiveness). Prostate intraepithelial neoplasia (PIN) coexisted with impalpable carcinomas, in almost half of the cancer-positive specimens. There was a positive correlation between PIN foci and coexistent cancer foci in most of the cases. Frequency rate and pathological features of both entities show significant variations in medical literature. Since the incidence of clinical prostate cancer in Greece is relatively low, and according to our autopsy findings, it is plausible that the frequency of clinical prostate cancer in a certain population could be related to the prevalent model of impalpable cancer as well as to the frequency and extend of the precancerous lesions.

Solitary hydatid cyst in the pelvis: a case report.

Hydatid disease mainly affects the liver and the lungs. Pelvic involvement have been rarely reported in the literature. Herein we present a rare case of isolated hydatid cyst of pelvis attached to the urinary bladder.

Hydatid disease of the seminal vesicle: a rare presentation of hydatid cyst.

Seminal vesicle belongs to the unusual sites of the hydatid cyst presentation. Even though the patient had a history of surgically treated hydatid disease of the liver, however, solitary echinococcal cyst of the seminal vesicle is a rare condition. Surgical removal of the cyst intact is the treatment of choice.

Colonic duplication in adults: report of two cases presenting with rectal bleeding.

Gastrointestinal duplication is an uncommon congenital abnormality in two-thirds of cases manifesting before the age of 2 years. Ileal duplication is common while colonic duplication, either cystic or tubular, is a rather unusual clinical entity that remains asymptomatic and undiagnosed in most cases. Mostly occurring in pediatric patients, colonic duplication is encountered in adults only in a few cases. This study reports two cases of colonic duplication in adults. Both cases presented with rectal bleeding on admission. The study was focused on clinical, imaging, histological, and therapeutical aspects of the presenting cases. Gastrografin enema established the diagnosis in both cases. The cystic structure and the adjacent part of the colon were excised en-block. The study implies that colonic duplication, though uncommon, should be included in the differential diagnosis of rectal bleeding.

Indium-111 monoclonal antimyosin cardiac scintigraphy in men with idiopathic dilated cardiomyopathy.

This study examined the prognostic value and the evolution of the heart-to-lung ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA occurs when the myocytes become irreversibly damaged. The study included 29 men with IDC followed up for 3 years. The diagnosis was verified by endomyocardial biopsy in all patients. Patients who survived beyond 1 year were restudied. Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression analysis revealed that MAA and New York Heart Association class were independent predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval 1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003), respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York Heart Association class was >11. When these patients were divided into those with chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]), baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p = NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time in subacute IDC and remains stable in chronic IDC.

A valveless high stroke volume counterpulsation device restores hemodynamics in patients with congestive heart failure and intractable cardiogenic shock awaiting heart transplantation.

The paraaortic counterpulsation device is a round pumping chamber with one valveless opening 20 mm in diameter and a 100 ml stroke volume. The paraaortic counterpulsation device was implanted on the ascending aorta of three male patients with intractable cardiogenic shock. Patients were assisted for 4 hours and 8 and 54 days, respectively; the first patient died as a result of nonresponding peripheral vasodilation and the other two died of septic shock. The two patients who were assisted for 8 and 54 days were conscious and able to function in a limited manner during the mechanical assistance. Discontinuation of the mechanical support for a few seconds was followed by low systolic arterial pressure (30 to 60 mm Hg) and syncopal episodes. Biochemical tests and autopsy results in these patients showed no evidence of blood cell destruction, thrombus formation, brain infarction, or other distal emboli. In conclusion, satisfactory hemodynamic effects, excellent biocompatibility, and simplicity of the implantation procedure in these patients encourage the use of the paraaortic counterpulsation device as a bridge to heart transplantation.

Lung squamous cell carcinoma presenting with brain metastases in an HIV-positive patient.

The case history of a patient with squamous cell carcinoma of the lung and HIV infection is described, who presented clinically with CNS symptomatology. No association of the tumor with human papilloma virus was found.

Evaluation of the cyclin-dependent kinase inhibitor p21Cip1 in epithelial ovarian tumors of low malignant potential and adenocarcinomas.

OBJECTIVE: In view of the controversial information on the significance of the cyclin-dependent kinase inhibitor p21Cip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathological variables and prognosis of epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 82 primary ovarian adenocarcinomas were stained immunohistochemically for p21Cip1, p53 protein and Ki-67 antigen (a marker of cell proliferation). RESULTS: p21Cip1 levels were significantly higher in LMP tumors (p<0.001) as well as in early stage adenocarcinomas (p=0.021) and those associated with minimal residual disease (p=0.008). However, no relationship existed between p21Cip1 expression and the proliferation rate of adenocarcinomas or LMP tumors. In the vast majority of LMP tumors p21Cip1 expression was not accompanied by p53 accumulation. This p21Cip1-positive/p53-negative phenotype prevailed in the early stage (p=0.026), lower grade (p=0.018) adenocarcinomas as well as in those left with minimal residual disease (p=0.059). In patients with lower grade adenocarcinomas, decreased p21Cip1 expression was adversely related to poor overall survival on its own (p=0.0500) and when combined with p53 protein overexpression (p=0.0323). In multivariate analysis, only the stage remained as the independent predictor of survival. CONCLUSIONS: Decreased p21Cip1 expression is related to several indicators of aggressiveness in ovarian adenocarcinomas and seems to be differentially regulated in LMP tumors and adenocarcinomas. On the contrary, deregulation of p21Cip1 expression does not seem to participate in the pathogenesis of LMP tumors. Furthermore, although p21Cip1 alone or combined with p53 is of prognostic significance in lower grade adenocarcinomas, it does not appear to add to the information gained from traditional prognosticators.

Atherosclerosis of the carotid artery: absence of evidence for CMV involvement in atheroma formation.

Several studies suggest that certain viral and bacterial pathogens may contribute to the process of atherogenesis. However, this relation between infectious agents and atherosclerosis has not yet been established with certainty. The aim of this study was to investigate the presence of CMV in carotid endarterectomies from 40 patients suffering from atherosclerosis using immunohistochemistry and the polymerase chain reaction (PCR). None of the specimens examined gave a positive result, indicating absence of CMV particles or CMV DNA sequences in the walls of carotid arteries. This finding suggests it is possible that CMV infection may not play a major role in the formation of atheroma. Therefore, further investigation is required in order to clarify the etiology of atherosclerosis.

Determination of CMV placentitis. Diagnostic application of the polymerase chain reaction.

Cytomegalovirus (CMV) infection constitutes an important cause of intrauterine death. In the present study CMV infection of placentas resulting from intrauterine deaths was assessed by immunohistochemistry and by the polymerase chain reaction (PCR). Among 32 cases of chronic villitis examined, 7 were found by PCR to be associated with CMV infection, although light microscopic examination revealed only 3 of them, while 4 had shown positive immunohistochemical staining. In conclusion, CMV may be considered to be a relatively common cause of placentitis, and PCR is a helpful tool in confirming the nature of the disease.

Myocardial salvage by the use of reperfusion and intraaortic balloon pump: experimental study.

BACKGROUND: Thrombolytic therapy improves left ventricular ejection fraction and survival. The study was undertaken to evaluate the effects of intraaortic balloon pump used in conjunction with reperfusion in reducing infarct size. METHODS: Twenty-two dogs were subjected to proximal left anterior descending coronary artery occlusion. In group 1 (n = 7) occlusion lasted for 6 hours. In group 2 (n = 6) 2 hours of occlusion was followed by reperfusion. In group 3 (n = 9) after 2 hours of occlusion the dogs were assisted with the intraaortic balloon pump throughout the 4 hours of reperfusion. At the end of 6 hours the infarcted myocardium of the left ventricle was determined and expressed as percentage of the myocardium at risk. RESULTS: In group 1, the infarcted myocardium was 79.3 +/- 9.9% of the myocardium at risk, in group 2, 59.0 +/- 19.9% (p < 0.05 versus group 1), and in group 3, 37.1 +/- 16.7% (p < 0.001 versus group 1 and p < 0.05 versus group 2). Endocardial viability ratio was increased by the intraaortic balloon pump; in group 1 it was 1.02 +/- 0.14, in group 2, 1.25 +/- 0.24, and in group 3, 1.47 +/- 0.31 (p < 0.001 versus group 1 and p < 0.02 versus group 2). CONCLUSIONS: Reperfusion and intraaortic balloon pump increased salvage of the ischemic myocardium over that achieved by reperfusion alone in a canine occlusion-reperfusion model.

Histological assessment of apoptotic cell death in cardiomyopathies.

Apoptosis in the myocardium is complex and often difficult to recognise. Myocyte apoptosis is scattered across the myocardial wall and is restricted to individual cells. In the present study, we describe the amount of apoptosis in 50 endomyocardial biopsies taken from 50 patients with dilated cardiomyopathy, in 14 hearts with hypertrophic cardiomyopathy and in five hearts with arrhythmogenic dysplasia of the right ventricle. As a control group, 15 endomyocardial biopsies from 15 transplanted hearts (of live patients) were used. Apoptosis was immunohistochemically determined in paraffin sections with the TUNEL method. In each specimen the TUNEL index was calculated as the percentage of TUNEL-positive nuclei among a total number of 200 counted nuclei. Cellular morphology was assessed in conjunction with TUNEL staining. The mean percentage of TUNEL-positive myocardial cells varied from 4% for dilated cardiomyopathy to 17.5% for arrhythmogenic right ventricle dysplasia and 18.5% for hypertrophic cardiomyopathy, whereas no signs of apoptotic myocardial cell death were found in normal subjects. The numbers of apoptotic cells in dilated cardiomyopathy specimens were significantly lower by comparison with both those of hypertrophic cardiomyopathy and those of arrhythmogenic right ventricular dysplasia specimens. It is evident that apoptosis constitutes a major biological phenomenon in the development of at least some heart diseases, but its role in their pathophysiology has yet to be delineated.

Primary causes of perinatal death. An autopsy study of 556 cases in Greek infants.

The primary causes of death in 556 autopsy cases of perinatal death during the six years from 1979 through 1984 are discussed. On the basis of the clinical data and gross and microscopic findings, each case was assigned to one of the following categories of primary causes of death: a pulmonary hyaline membrane disease, infection, malformation, anoxia, immaturity, maternal causes, other causes, and unaccounted for Definitions of perinatal infant diseases, essential points of diagnosis, and statistics relating to perinatal infant death are also discussed.

An immunohistochemical study of normal human neonate and adult parotid gland tissue. Detection of lysozyme, lactoferrin, a1-antichymotrypsin, a1-antitrypsin and carcinoembryonic antigen.

The immunohistochemical detection and distribution of lysozyme (Ly), Lactoferrin (Lf), a1-Antichymotrypsin (a1-AChy), a1-Antitrypsin (a1-AT) and Carcinoembryonic antigen (CEA) were studied in neonate and adult parotid gland tissue, using the peroxidase-antiperoxidase (PAP) method. Ly stain in neonates extended into acini, intercalated ducts and occasional cells of large ducts, whereas in adults Ly was usually confined to the intercalated ducts. The distribution pattern of Lf in neonates varied considerably between individual glands showing three staining patterns. Most of the intercalated ducts, some groups of acini and rare striated duct cells were positive for Lf in adults. a1-AChy and a1-AT in neonates were positive mainly in the large ducts, whereas staining for a1-AChy and a1-AT in adults frequently extended into some intercalated duct cells, although less intensively. Finally, CEA in neonates was localized in the lumina and luminal membranes of the acini, in intercalated ducts, and less frequently in the large ducts. In adults CEA was present predominantly in the lumina and luminal membranes of the intercalated duct cells. These differences may suggest an immunohistochemical postnatal differentiation of the parotid gland.

Liver metallothionein expression in thioacetamide-intoxicated rats.

Metallothioneins (MT), a group of ubiquitous low molecular weight proteins, implicated primarily in metal ion detoxification, are known to be expressed during hepatocellular proliferation after partial hepatectomy in rats. In the present study, we investigated the expression of MT in a rat model of liver injury and regeneration, induced by intraperitoneal administration of thioacetamide (TAA). The animals were killed at 0, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 hours after TAA administration. The rate of tritiated thymidine incorporation into hepatic DNA, the enzymatic activity of thymidine kinase, and the assessment of the mitotic index in hepatocytes were used as indices of liver regeneration. Liver MTs were detected immunohistochemically. TAA administration caused severe hepatic injury, followed by regeneration. MT expression became prominent in hepatocytes as early as 12 hours post-TAA administration. At 24 and 36 hours post-TAA administration intense nuclear and cytoplasmic staining of hepatocytes was found in the vicinity of necrotic areas. The maximal nuclear and cytoplasmic MT expression coincides with the peak of hepatocyte proliferative capacity, occurring at 48 and 60 hours post-TAA administration. MT expression correlated positively with the Zn content of liver tissue, but negatively with serum one, at the time of maximum hepatocyte proliferative capacity. This study suggests that MT participates in hepatocyte replication after toxin-induced liver injury.

Non-Hodgkin lymphoma of brain occurring after cardiac transplantation.

This case report concerns a case of NHL which affected a 56 year-old patient after cardiac transplantation. The patient was hospitalized because of worsening congestive failure. Despite maximal medical treatment the patient continued to be in NYHA Class III-IV and underwent orthotopic cardiac allograft transplantation. The NHL developed in the CNS eighteen months after surgery and had a very quick lethal progression.