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Biomedical subjects

C Zammit

Publications and source records attributed to C Zammit.

15 recordsLinked to original sources

[Intestinal pneumatosis. Right colon cystic form with linear aspect on scan].

INTRODUCTION: Digestive pneumatosis corresponds to the presence of air in a wall of digestive tract. It is common to oppose primary cystic-type pneumatosis, involving the left colon, with linear-type pneumatosis that may affect the whole of the digestive tract. OBSERVATION: In a 41 year-old man presenting with Sharp's syndrome, abdominal pain occurred revealing an isolated right colon pneumatosis. Although abdominal tomodensitometry showed a strictly linear pneumatosis, colposcopy revealed voluminous cysts. CONCLUSION: With this case report, the limits of tomodensitometry in distinguishing linear from cystic forms are apparent. The importance of avoiding surgery is underlined. Our patient presented with a pneumo-peritonitis only requiring medical treatment since this disease generally regresses spontaneously.

Adult↗

[Gemcitabine-induced thrombotic microangiopathy].

INTRODUCTION: Thrombotic microangiopathy (TMA) regroups the hemolytic and uremic syndrome (HUS) and thrombocytopenic thrombotic purpura (TTP). The TMA associated with cancer can be secondary to cancer, hence similar to TTP, or to chemotherapy, creating an HUS. Gemcitabine, used in the treatment of pulmonary, pancreatic and urothelial carcinomas, is generally well tolerated, but has recently been implied in the occurrence of TMA. OBSERVATION: In a patient treated for a metastatic urothelial carcinoma, HUS developed after 8 cues of gemcitabine used alone. After symptomatic treatment and withdrawal of gemcitabine, the hematological abnormalities disappeared and renal function returned to preceding values. DISCUSSION: The incidence of TMA is of around 5 to 6% of metastatic carcinomas. Gemcitabine-induced TMA are of recent occurrence and some twelve cases have been reported. Their occurrence is delayed with regard to the initiation of gemcitabine. They lead to HUS with good prognosis since, on withdrawal of gemcitabine the renal abnormalities regress. Search for TMA should therefore be proposed after more than 10 cycles of treatment with gemcitabine.

Aged↗

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer.

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

Adult↗

Late results of selective axillary surgery based on contact cytology in women with operable breast cancer.

BACKGROUND: Interest in the possibility of intraoperative analysis of sentinel lymph nodes to select patients with operable breast cancer for immediate axillary clearance encouraged this review of a long-term experience of selective axillary surgery based on intraoperative contact cytology of conventionally sampled nodes. Survival was assessed as a potential marker for understaging. METHODS: Records of 437 patients who had surgery between 1991 and 1994 were reviewed to compare rates of axillary recurrence in patients who had contact cytology only with those who had contact cytology and axillary clearance. RESULTS: Axillary recurrence occurred in seven (3 per cent) of 219 patients who had negative contact cytology, three (4 per cent) of 75 patients who had positive contact cytology with axillary clearance and one (1 per cent) of 93 who had axillary clearance alone. In patients with positive contact cytology, 131 (78 per cent) of 168 positive nodes were in the sample specimen, which included all positive nodes on 19 occasions. Survival probability at 36, 72 and 96 months was 92, 87 and 84 per cent respectively for patients with negative contact cytology, and 85, 73 and 71 per cent for patients with positive cytology and axillary clearance. CONCLUSION: A selective approach to axillary surgery based on intraoperative contact cytology of sampled lymph nodes gave good long-term control of axillary disease.

Adult↗

[Spontaneous portal vein thrombosis associated with acute cytomegalovirus infection in an immunocompetent patient].

BACKGROUND: Portal vein thrombosis (PVT) generally results from a local cause (hepatocellular and pancreatic carcinoma). Spontaneous PVT related to a general cause is less common. We report here a case of spontaneous PVT associated with acute cytomegalovirus (CMV) infection in an immunocompetent patient. CASE REPORT: A 31-year-old white female was admitted with fever and lymph node enlargement. The patient was a heavy smoker and was taking oral contraception. Blood tests revealed an inflammatory syndrome. Liver enzymes were elevated (2N) and platelet count was 118 G/l. Abdominal ultrasonography disclosed partial portal thrombosis. Computed tomography did not show any evidence of a hepatic or pancreatic mass. Protein S, protein C, and anti-thrombin III levels were normal. No antiphospholipid antibodies, no mutation for factors II and V and no abnormality suggestive of paroxysmal nocturnal hemoglobinuria at flow cytometry could be demonstrated. Acute CMV infection was diagnosis with positive viremia (PCR). The patient was given anticoagulation treatment and has done well with no relapse. CONCLUSION: Cytomegalovirus, by damaging endothelial cells, is thought to trigger a cascade of events leading to deep vein thrombosis. CMV infection does not appear to act alone on endothelial cells but rather behaves as an associated factor.

Acute Disease↗

Altered intracellular localization of fibroblast growth factor receptor 3 in human breast cancer.

Immunohistochemical staining of human breast tissues, using an antibody against fibroblast growth factor receptor 3 [FGFR-3], showed differences in cellular distribution. Both malignant and non-malignant epithelial cells contained FGFR-3 immunoreactivity, but myoepithelial cells and stroma were negative. The staining pattern in malignant epithelial cells was predominantly nuclear, whereas epithelial cells in normal breast tissue showed both cytoplasmic and nuclear elements. Reverse transcription-polymerase chain reaction (RT-PCR) revealed two isoforms of FGFR-3 corresponding to the FGFR-3-IIIb variant and a previously described exon-deleted nuclear form of FGFR-3, which were present in both malignant and non-malignant epithelial cells. The higher level of nuclear staining and loss of cytoplasmic staining seen in malignant epithelial cells did not correspond to an increase in expression of the exon-deleted form of FGFR-3, nor to any detectable activating point mutations. Since receptor activation can result in its movement to a perinuclear localization, an alternative explanation for the redistribution of FGFR-3-IIIb could be different degrees of activation by a ligand (FGF1 or FGF9). No FGF9 was detected by immunohistochemistry in breast tissues. FGF1, however, is present in the majority of breast cancers and a different tissue distribution of FGF1 was found in breast tissues, showing predominantly nuclear, or a mix of nuclear and cytoplasmic FGFR-3. The difference in FGFR-3 staining patterns may implicate this ligand-receptor pair in breast cancer.

Adult↗

Increased expression of fibroblast growth factor 8 in human breast cancer.

Fibroblast growth factor 8 (FGF8) is an important developmental protein which is oncogenic and able to cooperate with wnt-1 to produce mouse mammary carcinoma. The level of expression of FGF8 mRNA was measured in 68 breast cancers and 24 non-malignant breast tissues. Elevated levels of FGF8 mRNA were found in malignant compared to non-malignant breast tissues with significantly more malignant tissues expressing FGF8 (P=0.019) at significantly higher levels (P=0.031). In situ hybridization of breast cancer tissues and analysis of purified populations of normal epithelial cells and breast cancer cell lines showed that malignant epithelial cells expressed FGF8 mRNA at high levels compared to non-malignant epithelial and myoepithelial cells and fibroblasts. Although two of the receptors which FGF8 binds to (FGFR2-IIIc, FGFR3-IIIc) are not expressed in breast cancer cells, an autocrine activation loop is possible since expression of fibroblast growth factor receptor (FGFR) 4 and FGFR1 are retained in malignant epithelial cells. This is the first member of the FGF family to have increased expression in breast cancer and a potential autocrine role in its progression.

Adult↗

[Treatment of thrombotic microangiopathies].

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome appear as the same expression of thrombotic microangiopathy (TMA), which is a single pathological entity affecting small blood vessels leading to hemolytic anemia, circulatory changes with renal (hemolytic uremic syndrome, HUS) or nervous (thrombotic thrombocytopenic purpura, TTP) involvement. Because of his low incidence, prospective randomized clinical trials are difficult to conduct and apart from plasma exchanges (PE) which appear superior to plasma infusions (PI), other therapeutic recommendations are based on retrospective studies or on anecdotal reports with limited number of patients. In the absence of appropriate therapy, mortality rate was initially above 90% in adults with TTP. Plasma infusions and plasma exchanges have dramatically improved prognosis of the disease, since more than 80% of patients respond to therapy with a survival greater than 80 to 90%. Analysis of data of medical literature shows that plasma exchanges can cure 82% of TMA with 15% of refractory TMA and a mortality rate of 14%. In two randomized trials, PE are more effective than PI with a response rate benefit of 25% and an overall survival increase of 15%. Although severe thrombocytopenia is frequently observed, it is important to avoid platelet transfusions. Platelets infusions induce deleterious effects since they add to the severity and the extend of microvascular thrombi formation. Use of glucocorticoids, heparin, antiplatelet therapy, intravenous immunoglobulin and vincristine are associated with variable results and no controlled study supports their use. Splenectomy is still under discussion but could be of interest in case of relapsing thrombotic microangiopathies as an attempt to reduce the rate of TMA recurrence.

Adrenal Cortex Hormones↗

Detection of Pneumocystis carinii in a rat model of infection by polymerase chain reaction.

The polymerase chain reaction (PCR) was employed to detect Pneumocystis carinii in organs of infected rats. Using a pair of oligonucleotides designed to the dihydrofolate reductase (DHFR) gene of rat P. carinii, specific amplification of an expected 415 bp region of P. carinii DHFR DNA of this organism was achieved, while no amplification occurred with the human, Candida albicans, and Mycobacterium avium and tuberculosis DNAs. Using rat P. carinii isolated from in vitro cultures and infected lung homogenates, the minimum detection level by PCR on an ethidium bromide gel was about 200 organisms and by Southern analysis with radiolabelled DHFR probe the detection level improved to 20 organisms. This level of sensitivity is sufficient to detect P. carinii specific band on the gel in infected rat lung and other organs. This PCR technique is potentially useful for detecting P. carinii in bronchoalveolar lavage (BAL) fluids of AIDS patients and for quantifying the organisms in tissues and in in vitro cultures where a high background with conventional stains makes it harder to determine the number of organisms.

Animals↗

Proliferation patterns of latent Pneumocystis carinii in rat organs during progressive stages of immunosuppression.

Pneumocystis carinii is known to proliferate mainly in the lung of an immunocompromised host. In AIDS and other immune disorders sporadic extrapulmonary presence of this organism has been documented. Occasionally, P. carinii does not appear to infect the lung. These observations have been based on the detection of P. carinii by conventional staining techniques. We have sought to determine the extent of these infections by the polymerase chain reaction (PCR) in a rat model. Harlan Sprague-Dawley rats weighing between 110 and 130 g were immunosuppressed with dexamethasone (1.2 mg/l) in drinking water. During progressive stages of immunosuppression 2 rats were sacrificed at 2, 3, 4 and 5 wk, and the lung, liver, kidney, spleen and bone marrow were taken. Sonicated crude extracts of the tissues were used as template DNA for the amplification of the dihydrofolate reductase (DHFR) gene of P. carinii. All the PCR products were analyzed by Southern hybridization with radiolabelled DHFR DNA. These analyses revealed a general trend of P. carinii proliferation first in bone marrow at 2 wk, followed by liver at 3 wk, and lung at 5 wk on immunosuppression. Kidney and spleen infections were infrequent. Although P. carinii appears to proliferate in the lung at later stages of immunosuppression, the degree of proliferation is several-fold greater than in extrapulmonary organs. The extrapulmonary proliferation of P. carinii, however small, may possibly suppress hematopoietic stem cell differentiation in bone marrow, and may also contribute to the pathology present in various organs.

Animals↗