Giant angiolipoma of the arm in an elderly patient.

Introduction Angiolipoma is a histological variant of lipoma and is the most common neoplasm in the trunk and extremities of young adults. It is extremely rare in elderly people, and its size is ≤4cm. Few data are available for large angiolipomas. Case History An 86-year-old patient was admitted to our surgical department due to a large mass on his left arm, which was resected. The specimen measured 19.5 × 15 × 10.5cm. Histopathological examination revealed a benign non-infiltrating angiolipoma. This is the first report of a giant angiolipoma of the arm reported in an octogenarian patient. Conclusions Giant lipomas of the upper extremities are extremely rare. Resection is associated with cure in most patients, but regular follow-up should be considered.

Parastomal evisceration as an extremely rare complication of a common procedure.

The creation of an abdominal stoma is a common procedure performed as part of the treatment for many conditions. Common complications include poor stoma siting, high output, skin irritation, ischaemia, retraction, parastomal hernia and prolapse. An extremely rare stoma complication is parastomal evisceration. We present a case of a 48-year-old woman who presented to us with parastomal evisceration as a late complication of a transverse colostomy. It is the second case reported as a complication of this procedure but the first that occurred after such a long postoperative period (almost 18 months).

Mechanisms of ketamine action on lipid metabolism in rats.

BACKGROUND AND OBJECTIVE: This study was conducted to determine the effect of ketamine on metabolic homoeostasis and particularly in lipoprotein lipase (LPL) activity in adipose tissue. METHODS: Sixty male Wistar rats were divided into six groups of 10 each. Group A served as controls, while Groups B-F received, respectively, ketamine 60, 80, 100, 120 and 140 mg kg(-1) intraperitoneally. The animals were sacrificed 20 min after the administration of ketamine. Insulin concentrations in plasma and total cholesterol, triglyceride, high-density lipoprotein (HDL) and free fatty acid (FFA) concentrations in serum were measured. LPL activity in adipose tissue and medium-chain acyl-CoA dehydrogenase (MCAD) content in muscle were determined. RESULTS: FFA concentrations in serum significantly increased from the second lowest dose of ketamine. Insulin concentrations in plasma did not exhibit any significant difference between groups. MCAD levels were 0.5-fold more in Group F than in Group A, while there were no significant differences between control group and Groups B-E. Furthermore, high concentrations (120 and 140 mg kg(-1)) of ketamine interfered with in metabolic homoeostasis by significantly reducing LPL activity, thus elevating triglyceride concentrations in serum without affecting cholesterol and HDL metabolism. CONCLUSIONS: Ketamine induces various metabolic effects due to changes in adipose LPL activity and MCAD levels in muscles. These findings seem to be significant only at high doses.

Germ cell transplantation: a review and progress report on ICSI from spermatozoa generated in xenogeneic testes.

Results from the transplantation of donor male germ cells into xenogeneic recipient seminiferous tubules indicate that donor spermatogonia are capable of differentiating to form spermatozoa morphologically characteristic of the donor species. Germ cell transplantation procedures combined with developments in freezing, culturing or enriching germ cell populations have applications of paramount importance in medicine, basic sciences and animal reproduction. Additionally, these techniques can serve as an alternative approach for gonadal protection and fertility preservation in patients with cancer. This article is a chronological critical review of the technological advances that followed the initial successful transplantation of mouse germ cells into recipient mice. Furthermore, the factors responsible for the immunological privilege properties of the testis and the parameters influencing the potential of mammalian germ cells to undergo mitosis and meiosis within a xenogeneic testis are described. Finally, the role of human germ cell transplantation procedures in the therapeutic management of non-obstructive azoospermia is discussed.

Effect of losartan on insulin plasma concentrations and LPL activity in adipose tissue of hypertensive rats.

The aim of this study is to determine the effect of losartan on insulin and angiotensin II (Ang II) concentrations in plasma as well as on lipoprotein lipase activity (LPL) and angiotensin II content in the adipose tissue of hypertensive rats. Fifty male rats were divided in five groups. Group A served as controls. Group B underwent renal artery stenosis. Group C were administered losartan (10 mg/kg/day) per os, while rats in group D were submitted to renal artery stenosis and were treated with losartan as above. Group E was used as sham-operated control. The animals were sacrificed at day 21. Blood samples were collected, and perirenal adipose tissue was isolated. Furthermore, adrenal's were removed and their relative weight (adrenal weight/body weight) was used as an index of sympathetic stimulation. According to our results, renovascular hypertension resulted in lower insulin concentrations and higher Ang II content in plasma. In hypertensive rats, LPL activity was decreased, while the adrenals' relative weight was elevated. On the other hand, losartan administration resulted in normalization of insulin concentrations in plasma and adrenals' relative weight, with consequent up regulation of LPL activity in adipose tissue. In conclusion, renovascular hypertension interferes in lipid metabolism by reducing LPL activity in adipose tissue, while losartan administration reverses this effect by enhancing insulin release and reducing sympathetic nervous system (SNS) stimulation.

An observational study of women with positive HPV-DNA tests and normal cytology and colposcopy.

PURPOSE: High risk human papillomaviruses (HPV) are implicated in the aetiology of malignant cervical disease. The usefulness of HPV DNA tests in identifying women at risk of cervical cancer as an adjunct to cervical cytology is under evaluation. PATIENTS AND METHODS: This is a retrospective analysis of 47 women positive for high risk HPV but with negative cytology and negative colposcopy at the start of the study. Women were observed for three years or more (in 96% cases) using six-monthly combined HPV DNA tests, cytological and colposcopic evaluation. RESULTS: At the end of follow-up, 29/47 (62%) women were still positive for high risk HPV, 45/47 (96%) women had normal cytology and 47/47 (100%) women continued to have normal colposcopy. CONCLUSIONS: Normal colposcopy has an excellent negative predictive value for HPV positive women with normal cytology. These women can be safely screened cytologically on a three-yearly basis.

Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women.

BACKGROUND: During the last decade, transvaginal ultrasonography (TVS) has become a widely-used technique for the evaluation of endometrial histology. The purposes of this study were to compare transvaginal sonographic evaluation of the endometrium with histology obtained by endometrial biopsy in asymptomatic postmenopausal women and to determine whether screening transvaginal sonography might be useful in the evaluation of postmenopausal women. MATERIALS AND METHODS: The study included 59 unselected asymptomatic postmenopausal women who attended the outpatients' clinic for annual cervical cytology at Ioannina University Hospital, Greece. The women were evaluated by transvaginal scans, performed immediately before endometrial biopsy. RESULTS: In the 43 women with a histopathological diagnosis of normal endometrium/inadequate for assessment/atrophy, the mean endometrial thickness was 5.1 +/- 3.3 mm (range 0.8-13.8 mm) whereas the corresponding value in the 16 women with abnormal findings was 17.6 +/- 4.3 mm (range 9.4-24.6 mm) (p<0.001). If a 9-mm cut-off limit was used for endometrial thickness, the sensitivity, specificity and positive predictive value were 100%, 90.69% and 80%, respectively. CONCLUSION: TVS is a sensitive test for determining endometrial disease in asymptomatic postmenopausal women. However, well-designed studies should be conducted, completed, analysed and validated before a mass-screening program using TVS is implemented.

Transvaginal uterine ultrasonography compared with endometrial biopsy for the detection of endometrial disease in perimenopausal women with uterine bleeding.

BACKGROUND: Almost 70% of all gynecological consultations in perimenopausal women are related to irregular uterine bleeding. In this prospective study, we compared endometrial assessment by transvaginal ultrasonography (TVS) in perimenopausal women with irregular uterine bleeding to histological assessment and tested whether the TVS was effective as a diagnostic tool for the detection of endometrial pathology in these women. MATERIALS AND METHODS: Eighty consecutive perimenopausal women complaining of irregular uterine bleeding participated in the study. The women were evaluated by transvaginal scans, performed immediately before endometrial biopsy. The ultrasonographic results were compared with the histological diagnosis obtained from the endometrial biopsy. RESULTS: Sixty-seven out of 80 women (83.7%) had normal histological findings, whereas 13 (16.3%) had abnormal findings. No endometrial cancer was diagnosed in this cohort of women. In the 67 women with a histological diagnosis of normal endometrium, mean+/-SD endometrial thickness was 10.5+/-4.0 mm (range 4.0-18.5 mm), whereas the corresponding value in the 13 women with abnormal findings was 18.7+/-3.8 mm (range 13.5-22.5 mm). If a 13 mm cut-off limit was used for endometrial thickness, which would include all abnormal cases, the sensitivity, specificity and positive predictive values were 100%, 71.64% and 40.62%, respectively. CONCLUSION: TVS can identify women with perimenopausal bleeding in which the likelihood of endometrial pathology is high and in which tissue sampling should be performed. Thus, TVS can be a primary method of selecting women with perimenopausal bleeding who must be further investigated with more invasive methods such as endometrial biopsy.

Screening transvaginal uterine ultrasonography for identifying endometrial pathology in postmenopausal women.

BACKGROUND: During the last decade, transvaginal ultrasonography (TVS) has become a widely-used technique for the evaluation of endometrial histology. The purposes of this study were to compare transvaginal sonographic evaluation of the endometrium with histology obtained by endometrial biopsy in asymptomatic postmenopausal women and to determine whether screening transvaginal sonography might be useful in the evaluation of postmenopausal women. MATERIALS AND METHODS: The study included 59 unselected asymptomatic postmenopausal women who attended the outpatient clinic for annual cervical cytology at Ioannina University Hospital Greece. The women were evaluated by transvaginal scans, performed immediately before endometrial biopsy. RESULTS: In the 43 women with a histopathological diagnosis of normal endometrium/inadequate for assessment/atrophy, the mean endometrial thickness was 5.1 +/- 3.3 mm (range 0.8-13.8 mm) whereas the corresponding value in the 16 women with abnormal findings was 17.6 +/- 4.3 mm (range 9.4-24.6 mm) (p<0.001). If a 9 mm cut-off limit was used for endometrial thickness, the sensitivity, specificity and positive predictive value were 100%, 90.69% and 80%, respectively. CONCLUSION: TVS is a sensitive test for determining endometrial disease in asymptomatic postmenopausal women. However, well-designed studies should be conducted, completed, analysed and validated before a mass-screening program using TVS is implemented.

[Abnormal ramification of the axillary artery: sub-scapular common trunk]. / Ramification anormale de l'artère axillaire: tronc commun sous-scapulaire.

In a man's dissected cadaver we observed an unusual branching of the right axillary artery, which gives a large collateral branch. This branch is the origin of several important arteries as the subscapular artery (with its usual branches), the anterior and posterior circumflex humeral arteries, the proDunda brachii a. and the ulnar collateral artery. The frequency of this variation is evaluated to be 0.45% and is comparable to those found in the literature. We propose to name this artery as common subscapular trunk. The trunk described by us possesses a diameter equal to 6.30 mm and is larger than the continuation or the axillary artery, which courses as superficial brachial artery.

Human papillomavirus testing and the outcome of treatment for cervical intraepithelial neoplasia.

OBJECTIVE: To investigate whether human papillomavirus (HPV) testing could be used in the follow-up after large loop excision of the transformation zone (LLETZ) for cervical intraepithelial neoplasia (CIN). METHODS: We performed a retrospective study of 41 women who developed subsequent CIN after LLETZ (group A) and 82 women without CIN for a minimum of 5 years after LLETZ (group B). The first post-treatment cervical smear was retrieved and examined for high-risk HPV deoxyribonucleic acid. The sensitivity, specificity, positive and negative likelihood ratio of HPV testing, first post-treatment Papanicolaou test, and excision margins for the detection of treatment failure were calculated. Multiple logistic regression analysis was also done. RESULTS: The HPV test was positive in 38 of 41 women in group A and 13 of 82 in group B (P <.001). An abnormal cytologic result in the first post-treatment smear was found in 20 of 41 in group A and 11 of 82 in group B (P <.001). Sixteen women in group A and 18 in group B had involved margins (P =.046). Values for the sensitivity, specificity, and positive and negative likelihood ratios of the HPV test were 93%, 84%, 5.8, 0.08; for the Papanicolaou test they were 49%, 87%, 3.9, 0.586; and for margin status they were 39%, 78%, 1.8, 0.782, respectively. Positive HPV test presents significantly high odds ratio for treatment failure (P <.001), independent of cytology and margin status. CONCLUSION: Women who postoperatively have positive HPV testing are at higher risk of treatment failure. This could be performed at the first post-treatment visit and further follow-up could be adjusted accordingly.

Vaginoscopic hysteroscopy and transvaginal sonography in the evaluation of patients with abnormal uterine bleeding.

STUDY OBJECTIVE: To compare accuracy of vaginoscopic hysteroscopy, a new method of outpatient hysteroscopy, with that of transvaginal sonography in diagnosing intracavitary pathology in women with abnormal uterine bleeding. DESIGN: Retrospective comparative study (Canadian Task Force classification II-2). SETTING: Department of gynecology in a tertiary care university hospital. PATIENTS: Three hundred ninety-seven consecutive patients. INTERVENTIONS: Vaginoscopic hysteroscopy, transvaginal sonography, and histologic evaluation of endometrium. MEASUREMENTS AND MAIN RESULTS: Findings at hysteroscopy and sonography were compared with histopathologic results, considered the gold standard diagnosis. Sensitivity, specificity, and positive and negative likelihood ratios were 92%, 95%, 18.4, and 0.08 for vaginoscopic hysteroscopy and 67%, 87%, 5.15, and 0.38 for transvaginal sonography, respectively. CONCLUSION: Vaginoscopic hysteroscopy is quick and well tolerated, and more accurate in detecting intracavitary uterine pathology than transvaginal sonography. More research is required to determine its place in patients with abnormal uterine bleeding, especially premenopausal women.

Structural studies of chemokines that inhibit HIV-1 entry.

The chemokine receptors CCR5 and CXCR4 have emerged as essential mediators of HIV-1 pathophysiology, functioning as co-receptors for viral entry into cells. The physiological agonists of these receptors inhibit HIV-1 infection in vitro. The discovery of small molecules that disrupt the interactions between HIV-1 and chemokine receptors is one strategy to limit the spread of the virus. These compounds will complement already existing therapies that include HIV-1 reverse transcriptase and protease inhibitors. The complete structural elucidation of a chemokine ligand-receptor complex would be valuable for rational drug design, but has yet to be achieved. Structural studies of chemokine agonists and antagonists can also be useful in understanding interactions that may be important for drug optimization. This review examines the surface properties of the chemokine ligands human SDF-1alpha and HHV-8 vMIP-II, with a goal of determining receptor-interacting sites. In combination with site-directed mutagenesis of the chemokines and structure-activity relationships of chemokine-based peptides, this approach will lead to a better understanding of the interactions in the chemokine ligand-receptor system.

Development of chronic colitis is dependent on the cytokine MIF.

The cytokine macrophage-migration inhibitory factor (MIF) is secreted by a number of cell types upon induction by lipopolysaccharide (LPS). Because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria, we investigated the role of MIF in experimental colitis. MIF-deficient mice failed to develop disease, but reconstitution of MIF-deficient mice with wild-type innate immune cells restored colitis. In addition, established colitis could be treated with anti-MIF immunoglobulins. Thus, murine colitis is dependent on continuous MIF production by the innate immune system. Because we found increased plasma MIF concentrations in patients with Crohn's disease, these data suggested that MIF is a new target for intervention in Crohn's disease.

Expanded cytological referral criteria for colposcopy in cervical screening: comparison with human papillomavirus testing.

OBJECTIVE: The goal of this study was to investigate whether expanded cytologic referral criteria for colposcopy or the addition of human papillomavirus (HPV) testing on cervical screening could improve the rates of detection of cervical intraepithelial neoplasia (CIN). METHODS: HPV testing by semiquantitative polymerase chain reaction/ELISA was performed in 1000 women who were self-referred for routine Pap smear. They underwent colposcopy following an abnormal smear result or a positive HPV test. As abnormal smear results were considered reports of low- or high-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance, and even HPV-associated reactive cellular changes (mild koilocytosis, mild dyskeratocytosis, hyperchromatic nuclei, bimultinucleation, and cleared cytoplasm). Loop excision of the transformation zone was performed in women with cytology and colposcopy indicative of CIN, as well as in women with normal cytology but positive HPV test and colposcopic impression of CIN. RESULTS: The Pap test was abnormal in 89% of the cases of CIN 1 (34/38) and 96% of CIN 2/3 (27/28) diagnosed in our population. HPV testing picked up four additional cases of CIN 1 (11%) and one case of CIN 2/3 (4%). Overall the HPV test detected 95% of the cases of CIN 1 (36/38) and 89% of the cases of CIN 2/3 (25/28). CONCLUSION: HPV testing does not appear to add significantly to cytology in terms of positive predictive value or detection rate, if extended cytologic indications for colposcopy are used.

The use of transvaginal sonography and vaginoscopic hysteroscopy in women on tamoxifen.

BACKGROUND AND OBJECTIVES: Long-term administration of tamoxifen causes endometrial changes. The aim of this study was to evaluate the role of transvaginal sonography and vaginoscopic hysteroscopy in the screening of patients on tamoxifen. METHODS: Seventy patients with breast cancer treated with tamoxifen 20 mg daily underwent transvaginal sonography and vaginoscopic hysteroscopy, a modified relatively painless approach, at the beginning of the treatment and at a follow-up visit approximately 9 months after its initiation. RESULTS: At the follow-up visit, the mean uterine dimensions and mean endometrial thickness as measured by ultrasound were significantly larger, and pulsatility and resistance indices of the uterine arteries as measured by Doppler were significantly lower. Sonography revealed abnormal endometrial thickness in 73% (51 of 70) of the patients, and 83% (58 of 70) had hysteroscopical changes. Sonography missed 1 case of endometrial adenocarcinoma. CONCLUSIONS: Vaginoscopic hysteroscopy, an approach that causes reduced pain, can add significantly to the sensitivity of transvaginal sonography for the detection of endometrial changes in patients with breast cancer receiving tamoxifen. It is recommended for every patient prior to the initiation of treatment and at the follow-up visits.

Replacement of the uterus by malignant mesothelioma of the peritoneum: a case report.

Malignant mesothelioma of the peritoneum is a rare tumor that must be distinguished from the more common primary peritoneal serous epithelial neoplasms. We report a case of a 66-year-old female presenting with weight loss, anemia, and a large pelvic mass on ultrasound. At laparotomy a large (9 x 6.5 x 3.5 cm) mass in the anatomical position of the uterus was found in the minor pelvis. The uterus, tubes and ovaries could not be identified. Palpable paraaortic lymph nodes and liver nodules were found. Immunohistochemically the tumor cells were positive for cytokeratin, epithelial membrane antigen and vimentin-CEA, but S-100 protein and Leu-M1 were negative. Remnants of the uterine corpus, fallopian tubes and ovaries could not be identified. The overall features were best regarded as malignant peritoneal mesothelioma. There have been reports of mesotheliomas involving the uterus. However, this is the first reported case of mesothelioma causing total replacement of the uterus.

CCR2 and CCR5 receptor-binding properties of herpesvirus-8 vMIP-II based on sequence analysis and its solution structure.

Human herpesvirus-8 (HHV-8) is the infectious agent responsible for Kaposi's sarcoma and encodes a protein, macrophage inflammatory protein-II (vMIP-II), which shows sequence similarity to the human CC chemokines. vMIP-II has broad receptor specificity that crosses chemokine receptor subfamilies, and inhibits HIV-1 viral entry mediated by numerous chemokine receptors. In this study, the solution structure of chemically synthesized vMIP-II was determined by nuclear magnetic resonance. The protein is a monomer and possesses the chemokine fold consisting of a flexible N-terminus, three antiparallel beta strands, and a C-terminal alpha helix. Except for the N-terminal residues (residues 1-13) and the last two C-terminal residues (residues 73-74), the structure of vMIP-II is well-defined, exhibiting average rmsd of 0.35 and 0.90 A for the backbone heavy atoms and all heavy atoms of residues 14-72, respectively. Taking into account the sequence differences between the various CC chemokines and comparing their three-dimensional structures allows us to implicate residues that influence the quaternary structure and receptor binding and activation of these proteins in solution. The analysis of the sequence and three-dimensional structure of vMIP-II indicates the presence of epitopes involved in binding two receptors CCR2 and CCR5. We propose that vMIP-II was initially specific for CCR5 and acquired receptor-binding properties to CCR2 and other chemokine receptors.

Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery.

Over the past year, human studies have confirmed and expanded the involvement of macrophage migration inhibitory factor (MIF) in a number of diseases that had originally been studied in animals. In addition to sepsis, rheumatoid arthritis, glomerulonephritis and inflammatory lung disease, elevated MIF levels have been described in patients suffering from ulcerative colitis, inflammatory neurological diseases and cancer. Cellular studies indicate that in addition to macrophages, MIF affects the activities of CD4+ and CD8+ T cells, natural killer cells, fibroblasts and endothelial cells, actions that may explain the contribution of MIF to inflammatory diseases and cancer. Molecular studies have identified direct interactions between MIF and several intracellular regulatory proteins (Jab1, PAG and p53) that control cellular growth and proliferation; however, how interactions with these proteins fit into a general scheme to explain MIF's biological activity has not been elucidated. The three-dimensional structure of MIF has offered some surprising clues and if the potential enzymatic sites identified are involved with MIF-associated diseases, they may provide good targets for therapeutic intervention.

Comparison of the structure of vMIP-II with eotaxin-1, RANTES, and MCP-3 suggests a unique mechanism for CCR3 activation.

Herpesvirus-8 macrophage inflammatory protein-II (vMIP-II) binds a uniquely wide spectrum of chemokine receptors. We report the X-ray structure of vMIP-II determined to 2.1 A resolution. Like RANTES, vMIP-II crystallizes as a dimer and displays the conventional chemokine tertiary fold. We have compared the surface topology and electrostatic potential of vMIP-II to those of eotaxin-1, RANTES, and MCP-3, three CCR3 physiological agonists with known three-dimensional structures. Surface epitopes identified on RANTES to be involved in binding to CCR3 are mimicked on the eotaxin-1 and MCP-3 surface. However, the surface topology of vMIP-II in these regions is markedly different. The results presented here indicate that the structural basis for interaction with the chemokine receptor CCR3 by vMIP-II is different from that for the physiological agonists eotaxin-1, RANTES, and MCP-3. These differences on vMIP-II may be a consequence of its broad-range receptor recognition capabilities.