Pectus deformities: tomographic analysis and clinical correlation

Objective  

To assess, with computed tomography (CT) studies, features of anterior chest wall development that can be related to different types of pectus deformities.     

Dedifferentiated endometrial cancer: an atypical case diagnosed from cerebellar and adrenal metastasis: case presentation and review of literature

Dedifferentiated endometrial cancer (DEC) is microscopically characterized by the presence of high-grade areas emerging from low-grade tumour. DEC is an aggressive tumour even when the dedifferentiated component represents only 20% of the entire neoplasm. A proper histological diagnosis is essential to define the most appropriate therapeutic approach for these tumors, since they are characterized by a particularly aggressive trend and by an extremely poor prognosis. We report a single case of DEC associated with dedifferentiated and adrenal metastasis, for which the patient underwent both abdominal-pelvic and cerebellar surgery. Dedifferentiated carcinoma of the endometrium is a poorly recognized neoplasm since they have not been clearly defined the histological features discriminating this neoplasm from high-grade endometrioid adenocarcinoma. Revising existing literature we found 79 described cases of central nervous system secondary involvement and 13 cases where the onset of the disease was characterized by neurological signs and symptoms. We could only find two reported cases of adrenal metastases originating from endometrial neoplasia but in no case of dedifferentiated endometrial carcinoma previously described has been reported the concomitant adrenal-cerebellar involvement.     

Intraventricular hemorrhage in preterm infants: declining incidence in the 1980s

Ultrasound has been routinely used since late 1979 to diagnose periventricular-intraventricular hemorrhage in infants whose gestational age was 34 weeks or less. During the years 1980 to 1987 the ultrasound scans were interpreted by one person, and a steady decline in incidence of periventricular-intraventricular hemorrhage was observed. Both for infants of 34 weeks or less and for very low birth weight (less than 1500 g) infants, periventricular-intraventricular hemorrhage incidence decreased, respectively, from 34% and 39% in 1980 to 1981 to 19% and 25% in 1986 to 1987. This decrease was confined to true intraventricular hemorrhages, which decreased from 22% in 1980 to 1981 to 7% in 1986 to 1987 for infants of less than or equal to 34 weeks' gestation. These results were not influenced by a change in the distribution of birth weights or gestational ages of the infants evaluated nor by a change in the inborn to outborn ratio. The incidence of periventricular-intraventricular hemorrhage was lower in infants born by cesarean section than those delivered vaginally, but the decrease could not be attributed to an increased number of deliveries by cesarean section. Although there were undoubtedly changes in neonatal care during this time period, no planned intervention occurred. It was concluded that pharmacologic intervention studies must be interpreted with caution.     

Increased nucleated red blood cell counts in small for gestational age infants with very low birth weight

We evaluated the nucleated red blood cell (NRBC) counts in all infants with very low birth weight admitted to our neonatal intensive care unit from 1983 to 1986. There were 374 infants with birth weights of 500 g to 1500 g admitted in the first 24 hours after birth, but 31 died before studies were obtained. Of the remainder, 282 were appropriate for gestational age (AGA) and 61 were small for gestational age (SGA). Over 80% of both AGA and SGA infants were inborn and were evaluated within three hours of delivery. Nucleated red blood cell counts were significantly increased in SGA infants compared with AGA infants. The percent of infants with NRBC counts higher than 4.0 and 10.0 x 10(9)/L were 48% and 26%, respectively, in SGA infants compared with 19% and 6%, respectively, in AGA infants. Similarly, the percent of SGA infants with more than 40 or 100 NRBCs per 100 white blood cells were 62% and 36%, respectively, compared with 25% and 6%, respectively, in AGA infants. Data for specific weeks of gestation are provided and the differences were present at each gestational age. Recent data in fetuses with growth retardation, when blood was obtained directly from the fetal umbilical vein, showed an association between elevated NRBC counts and chronic hypoxemia. When increased NRBC counts are seen soon after birth, the possibility of a chronic intrauterine insult should be considered.     

Concomitant effect of topical ubiquinone Q10 and vitamin E to prevent keratocyte apoptosis after excimer laser photoablation in rabbits

PURPOSE: To investigate in vivo whether ubiquinone Q10 together with vitamin E protects rabbit corneas from keratocyte apoptosis after excimer laser irradiation. METHODS: Photorefractive keratectomy (PRK) was performed in both eyes of three New Zealand white rabbits. During 3 days before surgery, each right eye received four-times-daily instillation of an eye-drop solution containing ubiquinone Q10 0.20% and vitamin E 0.04%; each left eye was treated with a solution that did not contain ubiquinone or vitamin E. The central cornea was analyzed after surgery using the in situ end labelling (ISEL) technique of nicked DNA to detect DNA fragmentation. To determine the number of ISEL positive nuclei, an average of 70 random microscopic fields (five for each de-epithelialized tissue section) of 138,000 mu2 were examined in the right and left cornea samples at 250X by two different observers. RESULTS: Light microscopic examination of the sections from corneas treated before PRK showed that cells committed to apoptosis by PRK were about 50% compared to those of untreated controls. CONCLUSION: Treatment of rabbit eyes before PRK with ubiquinone Q10 lowered the number of apoptotic events.     

A phase II trial of combination chemotherapy and surgical resection for the treatment of metastatic adrenocortical carcinoma: continuous infusion doxorubicin,vincristine, and etoposide with daily mitotane as a P-glycoprotein antagonist

BACKGROUND: Adrenocortical carcinoma (ACC) is rare, nearly always fatal, and to the authors' knowledge has few nonsurgical treatment options. Based on in vitro studies demonstrating the efficacy of mitotane as a P-glycoprotein (Pgp) antagonist, and expression of high levels of Pgp in ACC, the authors conducted a study of infusional doxorubicin, vincristine, and etoposide with oral mitotane +/- surgical resection in patients with metastatic ACC. METHODS: Thirty-six patients with metastatic ACC received daily oral mitotane (mean, 4.6 g/day) and 96-hour infusional doxorubicin (10 mg/m(2)/day), etoposide (75 mg/m(2)/day), and vincristine (0.4 mg/m(2)/day). Four responding patients (11%) underwent surgery. RESULTS: Thirty-five patients were evaluable; all had metastatic disease. Eleven patients had not undergone resection of the primary tumor. Approximately 53% of patients had functional tumors. A total of 190 cycles were administered to 36 patients. Responses were observed in 8 patients (22%): 1 complete, 4 partial, and 3 minor responses. The mean duration of response was 12.4 months. Using a landmark method, the median survival of patients who did not respond to chemotherapy was 11.6 months from a point 4 months after the initiation of therapy, whereas that of 8 patients who demonstrated a response to chemotherapy was 34.3 months from that same landmark. High levels of Pgp expression were documented in nine of nine tumors. Mitotane levels > 10 microg/mL, previously shown to antagonize Pgp in vitro, were achieved in 25 of 36 patients (69%). However, rhodamine efflux from CD56-positive cells was not impaired, suggesting poor in vivo Pgp inhibition. The predominant Grade 3/4 toxicity (according to the Common Toxicity Criteria of the National Cancer Institute) was neutropenia in 66% of cycles; however, fever occurred in only 3% of cycles. Daily mitotane was associated with Grade 1/2 nausea, diarrhea, fatigue, and neuropsychiatric changes in 31 of 36 patients (86%). CONCLUSIONS: Using a combination regimen of daily mitotane with infusional doxorubicin, vincristine, and etoposide in patients with metastatic ACC, responses were observed in 22% of patients. The superiority of this combination over single-agent mitotane is uncertain. The side effects of mitotane made treatment difficult. More effective Pgp antagonists are needed.     

Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics

The tumor suppressor protein p53 localizes to microtubules (MT) and, in response to DNA damage, is transported to the nucleus via the MT minus-end-directed motor protein dynein. Dynein is also responsible for MT-mediated nuclear targeting of adenovirus type 2 (Ad2). Here we show that treatment with low concentrations of MT-targeting compounds (MTCs) that do not disrupt the MT network but are known to suppress MT dynamics enhanced p53 nuclear accumulation, and the activation of the p53-downstream target genes. p53 nuclear accumulation required binding of MTCs to MTs and enhanced the induction of p53-up-regulated modulator of apoptosis (PUMA) mRNA and apoptosis on challenging cells with the DNA-damaging drug adriamycin. Low concentrations of MTCs enhanced the rate of movement of fluorescent Ad2 to the nucleus and increased the nuclear targeting efficiency of Ad2. We propose that suppression of MT dynamics by low concentrations of MTCs enhances MT-dependent trafficking toward the minus ends of MTs and facilitates nuclear targeting.     

The role of genetic susceptibility in head and neck squamous cell carcinoma

Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at −80°C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).