PubMed Health⌕ Search

Biomedical subjects

S Gebhard

Publications and source records attributed to S Gebhard.

At least 19 recordsLinked to original sources
PubMed2004

4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models.

Since the pioneering work by Gossen and Bujard in 1992 demonstrating the usefulness of the Escherichia coli derived tet resistance operon for regulating gene expression a large collection of doxycycline-controlled transgenic mice has been established. Gene switching in eukaryotic tissue culture cells or mice requires administration of tetracycline, anhydrotetracycline or doxycycline to efficiently inactivate the transactivator protein tTA (TET-OFF system) or alternatively to activate the reverse transactivator protein rtTA (TET-ON system). However, the antibiotic activity of doxycycline can create an imbalance of the intestinal flora, resulting in diarrhoea and in a smaller number of animals in colitis. Previous studies reported that 4-epidoxycycline (4-ED), a hepatic metabolite of doxycycline, does not function as an antibiotic in mice. This gave us the idea that 4-ED might be useful for controlling gene expression in mice without the unwanted antibiotic side effect. To study the applicability of 4-ED for control of gene expression we used cell lines expressing the oncogene HER2 under control of tTA (TET-OFF) as well as rtTA (TET-ON). 4-ED and doxycycline were similarly efficient in switching on or -off HER2 expression. In vivo we used a conditional mouse model that allows switching off HER2 in tumor tissue. We show that (i) doxycycline, 7.5mg/ml in drinking water (used as a positive control), (ii) 4-ED, 7.5mg/ml in drinking water, (iii) 4-ED, 10mg/kg body weight, s.c., and (iv) anhydrotetracycline, 10mg/kg, s.c. (used as a second positive control), were similarly efficient. Using mice with tumor volumes of 1.6cm(3) all four schedules led to a tumor remission of more than 95% within 7 days. In conclusion, 4-ED is similarly efficient as doxycycline to control gene expression in vitro and in mice. Since 4-ED lacks the antibiotic activity of doxycycline it may help to avoid adverse side effects and selection of resistant bacteria.

Administration, Oral↗
PubMed2002

Downregulation of beta2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem cells?

Adherently growing, non-hematopoietic somatic stem cells isolated from human cord blood were stained with the fluorescent dye PKH26 and transplanted into livers of SCID-mice to examine a possible cell fate transition. Already 7 days after transplantation stem cells were well integrated into the liver tissue. Human albumin that was not expressed by the stem cells before transplantation was detectable in the host's livers after injection of cord blood stem cells. Human alpha1-antitrypsin was detectable in stem cells already before transplantation and remained positive in the mouse liver. The most interesting observation in this study was the downregulation of human beta2-microglobulin (beta2M) in the stem cells after transplantation: beta2M is expressed constitutively in our cord blood stem cells. However, beta2M was no longer detectable by RT-PCR in all tissues where human albumin and alpha1-antitrypsin were expressed after stem cell transplantation. beta2M is known to participate as an integral part of the major histocompatibility complex. Absence of beta2M makes the residual heavy chain inactive as an antigen. Thus, downregulation of beta2M may represent an escape mechanism from killer-T cells and may be a molecular mechanism explaining the recently described "immunological blindness" [37] of stem cells. In contrast to the results obtained after direct injection of stem cells as a suspension, no consistent downregulation of beta2M was observed after transplantation of stem cells encapsulated in alginate beads to generate a compartment where stem cells are protected from the host's natural killer cells. No expression of human genes was observed after transplantation of human cord blood derived mononuclear cells (MNC) that were used as a negative control. In conclusion, we have shown that human cord blood somatic stem cells survive and are reprogrammed after transplantation into mouse livers, although a complete transdifferentiation to hepatocytes did not occur within 7 days, since some marker genes (GATA4 and alpha-fetoprotein) were still negative. Switching off expression of beta2M may be part of an intriguing and novel mechanism explaining why stem cells escape the host's immune system.

Aged↗
PubMed2001

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I-IV), the most relevant clinical parameters. Similarly, a significant association between c-erbB-2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly, c-erbB-2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II-IV), median survival of patients with undetectable c-erbB-2 expression was 274 days compared with only 23 days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p = 0.0031; log-rank test). Similar results were obtained for patients with extensive disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c-erbB-2 expression was not associated with survival in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent prognostic factor of survival. The effect of c-erbB-2 expression seems to become more important in advanced stages of the disease. Since c-erbB-2 is a therapeutical target in other types of cancer, further studies to identify the role of c-erbB-2 in SCLC are clearly warranted.

Age Factors↗
PubMed2001

Inhibition of phosphofructokinases by copper(II).

The biochemical inhibition by Cu2+ on eight phylogenetically and biochemically different phosphofructokinases (PFKs) was investigated. The enzymes screened included representatives from thermophilic and mesophilic bacteria, a hyperthermophilic archaeon and a eukaryote, covering all three phosphoryl donor subtypes (ATP, ADP and pyrophosphate). The sensitivities of the enzymes to Cu2+ varied greatly, with the archaeal ADP-PFK being the least and the eukaryote ATP-PFK being the most sensitive. The bacterial ATP- and pyrophosphate-dependent PFKs showed intermediate sensitivity with the exception of the Spirochaeta thermophila enzyme (pyrophosphate-dependent) which was relatively resistant.

Animals↗
PubMed2001

Malacoplakia simulating organ invasion in a rectosigmoid adenocarcinoma: report of a case.

Malacoplakia is a histiocytic inflammatory response that may be associated with colorectal tumors. We report the case of a 65-year-old male taking steroids for a severe pulmonary disease. He presented with a rectosigmoid tumor that seemed to infiltrate the urinary bladder and the sacrum on the preoperative CT scan and echography and at laparotomy. A low anterior resection en bloc with a partial cystectomy was performed. The pathologic analysis showed a pT3pN0 adenocarcinoma with an extensive malacoplakia infiltrating the bladder and the pericolic and perirectal tissues. This case report emphasizes the overstaging that malacoplakia may induce and underlines a situation the surgeon may possibly confront. Our observation confirms the association of malacoplakia, colorectal carcinoma, and steroid treatment.

Abdominal Pain↗
PubMed2001

Polymerase chain reaction in the diagnosis of T-cell lymphoma in paraffin-embedded bone marrow biopsies: a comparative study.

AIMS: In routine histological analysis of bone marrow biopsies, the distinction between reactive T-cell infiltrates and T-cell lymphoma can be difficult, even with the use of extensive immunohistochemistry. The aim of this study was to evaluate the diagnostic contribution of TCR-gamma gene rearrangement analysed by PCR. METHODS AND RESULTS: The samples studied consisted of 46 paraffin-embedded bone marrow biopsies (diagnosis, staging and follow-up) from 26 patients with T-cell lymphoma. The bone marrow biopsies were categorized into three groups according to the morphological and immunohistochemical results. Group 1, positive for T-cell lymphoma (24 bone marrow biopsies), group 2, suspicion of T-cell lymphoma (15 bone marrow biopsies) and group 3, negative for T-cell lymphoma (seven bone marrow biopsies). DNA could be amplified in 45/46 bone marrow biopsies (98%). Clonal rearrangement was detected in 30/45 bone marrow biopsies tested (67%) including 15/24 bone marrow biopsies (62.5%) of group 1, 11/14 (78.5%) of group 2 and 4/7 (57%) of group 3. In total, PCR analysis supported a diagnosis of T-cell lymphoma in 15/45 bone marrow biopsies (33%), in which histological and/or immunohistochemical examination provided inconclusive evidence of malignancy. CONCLUSIONS: TCR-gamma PCR is a complementary tool for the assessment of T-cell lymphoma in bone marrow biopsies. Optimal evaluation of bone marrow biopsies requires an integrative approach of all available results from morphology, immunohistochemistry, molecular biology and clinical data.

Biopsy↗
PubMed2001

Detection of the synovial sarcoma translocation t(X;18) (SYT;SSX) in paraffin-embedded tissues using reverse transcriptase-polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives.

Synovial sarcoma (SS) is a relatively rare sarcoma, which may be confused with several other mesenchymal and nonmesenchymal lesions. It bears the t(X;18) (SYT;SSX) translocation, which seems to be specific for this tumor type and can be detected in paraffin-embedded tissue, using reverse transcriptase-polymerase chain reaction (RT-PCR). However, the specificity and sensitivity of this detection method have rarely been examined in a large series. Using RT-PCR, we examined 250 mesenchymal and nonmesenchymal, benign and malignant, paraffin-embedded lesions for the SS t(X;18) (SYT-SSX) translocation. PCR products were obtained from 221 tumors (88.5%). There were 135 non-SS tumors, 22 biphasic, and 64 monophasic spindle/round cell SS, of which 10 were cytogenetically confirmed as t(X;18)-positive. SYT-SSX gene fusion transcripts were detected in the SS tumor category only (100% specificity), including 100% of the biphasic SS and 86% of monophasic spindle/round cell SS. Nine tumors originally diagnosed as SS were t(X;18) (SYT-SSX)-negative. Following reassessment, only 3 of these tumors showed clinicopathologic, immunohistochemical, and/or ultrastructural features consistent with that diagnosis, thus raising the overall detection sensitivity to 96%. With regard to the potential adverse effect of the fixatives used, PCR products were obtained in 100%, 91.5%, 90.5%, and 0% of tumors fixed with AFA, buffered formalin, Holland Bouin, and conventional Bouin's fluid, respectively. This study shows that the detection of the SS t(X;18) (SYT-SSX) in paraffin-embedded tissue is feasible with a 100% specificity and an overall 96% sensitivity, provided non-Bouin's fluid fixation is used.

Adult↗
PubMed2000

Metastasizing fibrous histiocytoma of the skin: a clinicopathologic and immunohistochemical analysis of three cases.

The clinicopathologic and immunohistochemical features of three metastasizing fibrous histiocytomas of the skin are presented. The first patient had a 1.3-cm nodule in the right thigh, with right inguinal lymph node metastases 19 years later. The second patient, who had a 3-cm nodule excised from his left thigh and inguinal lymph node metastasis after 4 months, had a favorable outcome 14 years after local radiotherapy and chemotherapy. The third had a 2-cm nodule in his neck, which recurred 16 months later. Four months later, cervical lymph node metastases were found. The patient was alive and well 26 months after initial surgery. All three primary skin tumors involved the dermis and subcutis, appeared well-delineated but nonencapsulated, were associated with some degree of epidermal hyperplasia, and showed features of aneurysmal/atypical or cellular fibrous histiocytoma. The number of mitoses ranged from 6 to 11 per 10 high-power fields. Recurrences and metastases showed morphologic features similar to primary lesions. Tumor cells were positive, at least focally, for CD 68, Ki-M1p, and Factor XIIIa, and occasionally for smooth muscle actin. Desmin, CD 34, S-100 protein, and cytokeratin stainings were negative. Primary neoplasms, recurrences, and metastases showed a Mib-1 labeling index of 10% or less. Cellular, aneurysmal, and atypical (pseudosarcomatous) fibrous histiocytomas of the skin can metastasize, yet they often show a protracted clinical course. Risk factors for metastatic dissemination include large size, high cellularity, aneurysmal changes, marked cellular pleomorphism, high mitotic activity, tumor necrosis, and repeated local recurrences.

Adult↗
PubMed2000

Lipomatous hemangiopericytoma: a fat-containing variant of solitary fibrous tumor? Clinicopathologic, immunohistochemical, and ultrastructural analysis of a series in favor of a unifying concept.

The dinicopathologic, immunohistochemical and ultrastructural features of 13 lipomatous hemangiopericytomas are presented. There were 6 male and 7 female patients whose ages at diagnosis ranged from 27 to 75 years (median 48) all presenting with a mass of variable duration. The tumor sizes ranged from 1.7 cm to 19 cm (median 5.5 cm). The locations included the orbit (1), neck (1), mediastinum (1), epicardium (1), retroperitoneum (3), right iliac fossa (1), and upper (1) and lower (4) extremity. Histologically, the lesions were composed of a varying admixture of spindle-shaped to round cells, variably collagenous stroma, adipose tissue, and branched, often thick-walled, hemangiopericytoma-like vessels. For 11 tumors, the mitotic activity ranged from 1 to 3 mitoses per 10 high-power fields (HPF). One tumor which contained hypercellular areas showed 13 mitoses per 10 HPF, and another hypercellular lesion showed up to 43 mitoses per 10 HPF, abnormal mitoses, and necrosis. Immunohistochemically, tumor cells were invariably positive for vimentin and CD99, and mostly for CD34 but negative for desmin, keratin, CD31, CD117 (c-kit), and inhibin. About half of the tumors showed reactivity for bcl-2. Occasionally, focal reactivity was also observed for smooth muscle actin, muscle-specific actin, S100 protein, and epithelial membrane antigen. Ultrastructural examination of seven cases showed features in keeping with fibroblastic, myofibroblastic, or pericytic differentiation. Treatment consisted of simple tumorectomy in 10 cases and wide excision in 3. Follow-up information on 10 patients (range: 6 to 77 months; median: 18 months) showed no recurrence. Lipomatous hemangiopericytoma which share the clinical, pathologic, immunohistochemical, and ultrastructural features of solitary fibrous tumor (SFT) is likely to represent, in most cases, a fat-containing variant of SFT.

Actin Cytoskeleton↗
PubMed2000

Orbital and extraorbital giant cell angiofibroma: a giant cell-rich variant of solitary fibrous tumor? Clinicopathologic and immunohistochemical analysis of a series in favor of a unifying concept.

The clinicopathologic and immunohistochemical features of one orbital and nine extraorbital soft tissue lesions, the morphology of which overlaps with giant cell angiofibroma and solitary fibrous tumor, are presented. There were 3 male and 7 female patients. Age at diagnosis ranged from 18 to 81 years (median: 45 yrs). Development of a mass was the main presenting symptom. For two patients, the lesion had been evident for several years before excision. Extraorbital tumors were located in the head and neck area (3), back (3), retroperitoneum (1), hip (1), and vulva (1). Tumor size ranged from 1.3 cm to 11 cm (median: 4.5 cm). The lesions presented grossly as well-demarcated, unencapsulated soft tissue masses. Histologically, they were characterized by the presence of alternating cellular and sclerosing areas, keloidal collagen deposition, round- to staghorn-shaped, thick-walled vessels and multinucleated giant stromal cells often lining pseudovascular spaces. Cellular areas were composed of non-atypical spindle to round cells set in a variably collagenous background. Mitotic activity ranged from 1 to 3 mitoses/10 high-power fields. Immunohistochemical studies showed positive staining of the spindle/round cells and multinucleated stromal cells invariably for vimentin, CD34, CD99, and mostly for bcl-2 but negative for muscle specific actin, desmin, CD31, CD117 (c-kit), and inhibin. Occasionally, focal reactivity was observed for smooth muscle actin, S-100 protein, epithelial membrane antigen, and keratin. Treatment consisted of simple tumorectomy in eight patients and wide excision in two. Follow-up information for eight patients (range: 7-32 mos; median: 14 mos), including four with microscopically positive surgical margins, showed no recurrence. These lesions share the clinical, pathologic, and immunohistochemical features of giant cell angiofibroma and solitary fibrous tumor, supporting the view that these tumors are closely related. In addition, it shows that giant cell angiofibroma occurs equally in both sexes and has a wider distribution than initially thought, developing even more often in extraorbital locations than in the orbit.

Adolescent↗
PubMed2000

Induction of DNA single-strand breaks by 131I and 99mTc in human mononuclear blood cells in vitro and extrapolation to the in vivo situation.

The radionuclides (131)I and (99m)Tc are frequently used for therapy of benign and malignant thyroid disease ((131)I) and for diagnosis of thyroid and other diseases ((99m)Tc). However, the levels of DNA single-strand breaks (SSBs) induced in cells of patients after administration of (131)I and (99m)Tc are not known. In this study, we measured the number of SSBs per cell induced by (131)I and (99m)Tc in vitro, extrapolated the results to the clinical situation, and assessed their biological relevance by comparing levels of SSBs induced after therapeutic administration of (131)I and (99m)Tc to those induced by endogenous processes or by occupational exposure to genotoxic substances. A linear dose-response relationship between the radioactivity concentrations of (131)I and (99m)Tc and SSBs in human mononuclear blood cells (determined by alkaline elution) was obtained after incubation at 4 and 37 degrees C. At 4 degrees C, where almost no repair of SSBs takes place, (131)I and (99m)Tc induced 81 and 7 SSBs per cell per hour/(MBq/ml), respectively. At 37 degrees C, only 20 and 1.6 SSBs per cell per hour/(MBq/ml) were observed after incubation with (131)I and (99m)Tc. To estimate the induction of SSBs in vivo in cells of patients after administration of 3700 MBq (131)I (oral) or 60 MBq (99m)Tc (i.v.), the rates of induction of SSBs obtained in vitro were extrapolated to the concentrations of (131)I and (99m)Tc measured in blood of patients. The total number of SSBs (mean +/- standard deviation) accumulated after oral administration of 3700 MBq (131)I up to 70 h after administration was calculated as 200 +/- 59 SSBs/cell. After administration of 60 MBq (99m)Tc (i.v.), 0.032 +/- 0.009 SSBs per cell (total SSBs up to 2 h after administration) were cumulated. The induction of SSBs by endogenous processes (estimated 2,000 SSBs per cell per hour) and by occupational exposure to genotoxic substances (125-430 SSBs per cell) has been estimated in earlier studies. In conclusion, the frequency of SSBs induced by thyroid diagnosis with 60 MBq (99m)Tc is approximately 5 orders of magnitude smaller than the frequency of spontaneous SSBs and thus is most probably without biological relevance. Since the frequency of induction of SSBs by therapy with (131)I (3700 MBq) is about 6000-fold higher compared to thyroid diagnosis by (99m)Tc, its biological relevance is more difficult to assess. Nevertheless, the number of SSBs induced by therapy with (131)I is substantially lower than that induced by endogenous processes.

DNA Damage↗
PubMed1999

Activity of O6-methylguanine DNA methyltransferase in mononuclear blood cells of formaldehyde-exposed medical students.

A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the repair-enzyme causing agent but with respect to all carcinogens causing lesions subject to repair by the enzyme in question. Thus, we examined whether formaldehyde exposure of 57 medical students during their anatomy course at two different Universities in Germany influenced MGMT activity in mononuclear blood cells. Mean formaldehyde exposure of 41 students was 0.2 +/- 0.05 mg/m3 for 6 h per week. MGMT activity was 133.2 +/- 14.9 fmol MGMT/10(6) cells before the beginning of the formaldehyde exposure, 131.1 +/- 15.8 fmol MGMT/10(6) cells after 50 days (P = 0.56) and 128.2 +/- 19.0 fmol MGMT/10(6) cells after 111 days of exposure (P = 0.92). Similarly, no significant influence of formaldehyde exposure was observed, when smoking habits, alcohol consumption, allergic disease and sex of students were considered. In addition no significant difference was obtained in MGMT activity between 16 students with mean formaldehyde exposure of 0.8 +/- 0.6 mg/m3 and students without formaldehyde exposure (n = 51; P = 0.37). In conclusion, exposure of the medical students in western Europe to formaldehyde did not decrease MGMT activity in mononuclear blood cells.

Adult↗
PubMed1998

Localized fibrous tumours of the pleura: 15 new cases and review of the literature.

OBJECTIVE: To present a series of localized fibrous tumours of the pleura (LFTP), to define the clinical and histopathological diagnostic criteria of this tumour, and to determine the optimal treatment and follow-up. METHODS: Review of the charts of the patients with the diagnosis of LFTP (formerly called benign fibrous mesothelioma), as well as of all the histological sections, including immunohistochemical stains. Review of the literature with special emphasis on the clinical and histological criteria of malignancy. RESULTS: During the last 30 years, we found 15 patients with a complete clinical chart and histological material, particularly paraffin blocks of the tumour. The mean age was 57 years (range 27-79). Eight patients were asymptomatic, and the remaining seven presented with non-specific symptoms. All but one had complete resection of the tumour, including partial lung resection in two and partial chest wall resection in three. The diagnosis was confirmed by histological review in 15 cases. Immunohistochemical stainings showed positivity for vimentin in all cases, for CD 34 in 80%, but were consistently negative for cytokeratins. Nine tumours were histologically classified as malignant. Among them, five recurred, two of which were responsible for death. One benign tumour recurred after 1 year, and was treated successfully by repeat resection and radiotherapy. Overall, 13 patients (86%) were alive with no evidence of disease between 10 months and 27 years after the first resection. CONCLUSIONS: LFTP is a rare tumour which has a benign clinical course in over 80% of the cases, and is asymptomatic in half the patients. The diagnosis is difficult to establish before operation. Treatment consists of complete resection including adjacent structures if necessary. The clinical behaviour of LFTP cannot be predicted on the basis of histological aspects only. If histologically malignant tumours are more prone to recurrence and poor outcome, broad-based and locally invasive tumours bear a higher risk of recurrence. Long term follow-up is therefore mandatory in all cases in order to perform early re-resection when recurrence occurs.

Female↗
PubMed1998

Ectopic ACTH Cushing's syndrome: V3 vasopressin receptor but not CRH receptor gene expression in a pulmonary carcinoid tumor.

In the etiological diagnosis of ACTH-dependent Cushing's syndrome, it may be difficult to distinguish pituitary disease from ectopic ACTH production, specially when this is due to a benign neuroendocrine tumor. We describe a patient with partial dexamethasone suppression consistent with Cushing's disease, an absent response to CRH suggesting ectopic ACTH production and an atypical, apparent circadian rhythm. Bilateral cavernous sinus catheterization suggested a nonpituitary source of ACTH and, in the search of an ectopic tumor, somatostatin receptor scintigraphy, abdominal CT scan, and duodenopancreatic endoscopic echography were performed and failed to reveal any abnormality. Thoracic CT scan disclosed a tiny right lung nodule that showed a definite tracer uptake on MIBG scintigraphy. After resection, the nodule proved to be an 8-mm typical pulmonary carcinoid, with positive immunostaining for the classical neuroendocrine markers and for ACTH, and showing tissue expression of the POMC gene. However, the CRH receptor gene was not expressed, explaining the absent CRH response in vivo, whereas the V3 vasopressin receptor gene was expressed in the tumor tissue. The latter feature appears to be characteristic of benign carcinoids and may contribute to explaining the CRH-independent circadian rhythm observed in this case.

ACTH Syndrome, Ectopic↗
PubMed1995

Nausea and vomiting in fractionated radiotherapy: a prospective on-demand trial of tropisetron rescue for non-responders to metoclopramide.

A prospective trial was performed to better assess the risk of nausea and vomiting and the rescue value of tropisetron (TRO), a 5-HT3 receptor antagonist, in 88 patients undergoing fractionated radiotherapy to the abdomen or to large supradiaphragmatic fields and failing a first anti-emetic trial with metoclopramide (MET). Nausea was graded 0 (absent), 1 (mild), 2 (moderate) and 3 (severe). Nausea requiring anti-emetics (> or = grade 2) was present in 64% of the patients. MET was able to control nausea (< or = grade 1) in 26 of 58 patients (45%) who developed > or = grade 2 nausea during radiation treatment (2 patients vomiting without nausea included). 34 patients required TRO, and 31 experienced immediate relief. However, nausea (> or = grade 2) recurred in 7 patients from 1 to 3 weeks after starting TRO. Sex, age, field type and field size (cm2) did not influence the incidence and severity of nausea and vomiting. Only 24/88 patients vomited after starting radiotherapy. MET helped to eliminate emesis in one third of these patients. TRO helped to control vomiting in 73% of the salvaged patients. Constipation was observed in 8 patients on TRO and was a reason to stop the medication in 4 cases.

Abdominal Neoplasms↗
PubMed1995

Gynecomastia with unusual intraductal "clear cell" changes mimicking pagetoid ductal spread of lobular neoplasia.

This report describes a case of unusual intraductal "clear cell" changes of male breast that mimicked pagetoid ductal spread of lobular neoplasia. The lesion developed inside a nodule of gynecomastia of the left breast in a 56 year-old man. Immunohistochemically, the enlarged clear cells reacted positively with epithelial membrane antigen, low molecular weight cytokeratin and three breast markers (i.e.: gross cystic disease fluid protein-15 and -44 and estrogen receptors). They were negative for high molecular weight cytokeratin, muscle-specific actin, desmin and vimentin. Differential diagnoses included pagetoid ductal involvement by lobular neoplasia (i.e.: lobular carcinoma in situ and/or atypical lobular hyperplasia), pagetoid growth of intraductal carcinoma, atypical intraductal hyperplasia, and unusual intraductal myoepithelial proliferative lesion.

Diagnosis, Differential↗