Elevated fibrinogen, von Willebrand factor, and Factor VIII confer resistance to dilutional coagulopathy and activated protein C in normal pregnant women.

BACKGROUND: Gestational changes in coagulation factor concentrations include elevations in fibrinogen, Factor VIII, and von Willebrand factor (vWF). We hypothesised that blood samples from term pregnant (TP) subjects are less prone to coagulation disturbances from haemodilution compared with those from non-pregnant (NP) females. METHODS: Blood samples were collected from 15 NP and 15 TP subjects. In vitro haemodilution with normal saline was assessed by modified Clauss fibrinogen assay, factor activity, flow-chamber assay, and thromboelastometry. The impact of human fibrinogen concentrate (hFC), cryoprecipitate, and vWF/Factor VIII (FVIII) concentrate replacement in diluted TP and NP blood was compared. Thrombin generation and activated protein C sensitivity were assessed. RESULTS: TP blood contained twice the concentrations of fibrinogen, FVIII, and vWF relative to NP blood (P<0.0001). Platelet thrombus formation (PTF) under flow was reduced by 99.2% and 69.2% in diluted NP and TP blood, respectively. Platelet thrombus formation was partially restored by adding vWF/FVIII, but not hFC or cryoprecipitate. Fibrin clot firmness approached the threshold of 10 mm in diluted NP blood, and clot firmness was effectively restored by hFC, but not by vWF/FVIII. In the presence of thrombomodulin, peak thrombin generation was decreased by 86.7% in NP plasma, but by 31.8% in TP plasma (P<0.0001 vs NP plasma), indicating reduced activated protein C sensitivity in TP plasma. Both elevated FVIII and haemodilution contributed to activated protein C insensitivity. CONCLUSIONS: Our in vitro model showed relative resistance of TP blood to dilutional coagulation changes with respect to platelet adhesion, fibrin polymerisation, and thrombin generation. Careful therapeutic monitoring for different pro-haemostatic agents in pregnant women is warranted.

Constitutive variants of the pC194 cat gene exhibit DNA alterations in the vicinity of the ribosome binding site sequence.

The chloramphenicol-inducible regulation of the expression of cat genes from two Gram-positive bacteria, Staphylococcus aureus and Bacillus pumilus has been suggested to result from the presence of inverted repeat sequences that span the ribosome-binding site (RBS) for cat. In support of this hypothesis, we demonstrate that two derivatives of the pC194 cat gene which are constitutively expressed in Bacillus subtilis are deleted for all or a major portion of the inverted-repeat sequences.

Radiation pneumonitis after selective internal radiation treatment with intraarterial 90yttrium-microspheres for inoperable hepatic tumors.

PURPOSE: To investigate the clinical, histopathological, and radiological features of radiation pneumonitis arising as a complication of selective internal radiation treatment for liver tumors. To correlate the development of radiation pneumonitis with the degree of lung shunting as assessed by 99mTechnetium-labeled macroaggregated albumin (Tc-MAA) scan. METHODS AND MATERIALS: Five out of 80 patients who had inoperable hepatic tumors and underwent treatment with intraarterial 90Yttrium- (90Y)-microspheres, developed progressive restrictive ventilatory dysfunction without an infective or cardiovascular cause. Histopathological evidence of a pneumonitis and the presence of microspheres in the lung tissue suggested a diagnosis of radiation pneumonitis. The clinical course, radiological and histopathological findings, percentage tumor shunting to the lungs (lung shunting, as predicted by gamma camera scanning after intraarterial Tc-MAA), and the estimated radiation dose to the lungs were analyzed. In an attempt to reduce pulmonary shunting of the microspheres, three patients received partial hepatic embolization with inert particles before selective internal radiation therapy. RESULTS: In the five patients who developed radiation pneumonitis, lung shunting percentages (as predicted by Tc-MAA scan) ranged from 13.1 to 45.6% (median 23.7%). The estimated whole lung radiation dose ranged from 10.43 Gy to 36.44 Gy (median 25.04 Gy). Among 75 patients who did not develop radiation pneumonitis, the percentage lung shunting ranged from less than 1% to 15% (median 6%). Nine patients had lung shunting greater than 13% and five of them developed radiation pneumonitis, whereas this developed in none of those in whom shunting was below 13%. The onset of radiation pneumonitis ranged from 1 to 6 months after internal radiation treatment. All five patients exhibited characteristic plain radiographic and computerized tomographic changes comprising extensive consolidation with well-defined lateral margins. Clinical improvement after corticosteroid treatment was seen in two patients. Three patients died from respiratory failure and two from other causes. Partial hepatic arterial embolization reduced the degree of lung shunting to less than 13%, but did not prevent the development of radiation pneumonitis. CONCLUSION: Radiation pneumonitis may become a complication after intraarterial 90Y-microspheres treatment when lung shunting, as assessed by Tc-MAA scan, is high (above 13%). Prescribed activity of 90Y and lung shunting of Tc-MAA should be considered together before giving selective internal radiation (SIR) therapy for hepatic tumors, and preferably avoided if the lung shunting is above 13%.

Epstein-Barr virus-associated gastric lymphomas are distinct from mucosa-associated lymphoid tissue-type lymphomas: genetic abnormalities of p53 gene.

The authors studied 46 primary gastric lymphomas for expression of the p53 gene by immunohistochemistry and screened for mutations in p53 exon 5-8 by polymerase chain reaction-single strand conformation polymorphism. Twenty-five specimens cases were also analyzed for loss of heterozygosity (LOH) of chromosomal region 17p12-13.1. In 36 lymphomas negative for Epstein-Barr virus (EBV) infection, of which 29 were of mucosa-associated lymphoid tissue (MALT) type, p53 genetic changes were found in 47.2% but correlated poorly with overexpression. Only 20% of the mutations involved exon 7. There were recurrent mutations of intron 7, intron 6, and exon 6. In contrast, the 10 EBV-positive cases, none of MALT type, had a much higher rate of mutation, and all showed both p53 overexpression and p53 mutation and/or LOH, and 87.5% had mutations involving exon 7. Four of these involved codon 242, not seen in the EBV-negative group. Splicing mutations of intron 8 were seen in three specimens, two involving the same nucleotide position. In four of five specimens, LOH analysis identified microsatellite instability, allelic loss, or both. The Helicobacter pylori infection rate in the EBV-positive group (20%) was much lower than in the EBV-negative group (91.7%). These differences between the two groups suggest involvement of different carcinogens. Mutation of codon 242 has not been specifically associated with other tumors and may represent a mutational hot spot in the EBV-positive lymphomas.

Chromosome 11 copy number gains and Epstein-Barr virus-associated malignancies.

Epstein-Barr virus (EBV) genome can be found in many malignant tumors in China. Previous data of interphase cytogenetics, by comparative genomic hybridization and/or fluorescence in situ hybridization, on nasopharyngeal carcinomas and natural killer cell-type non-Hodgkin lymphomas in Hong Kong have noted gains in chromosome 11. This study compares the frequency of chromosome 11 copy number gains in three different types of EBV-associated tumors in Hong Kong. Using alpha-satellite probes, the authors studied by fluorescence in situ hybridization 31 EBV-positive tumors comprising 10 EBV-positive gastric carcinomas, 8 lung lymphoepithelioma-like carcinomas, and 13 non-Hodgkin lymphomas. Trisomy or polysomy 11 was detected in 10 of 10 (100%) EBV-positive gastric carcinomas, 6 of 8 (75%) lung lymphoepithelioma-like carcinomas, and 4 of 13 (30.8%) non-Hodgkin lymphomas. Compared with the EBV-positive gastric carcinomas, the 10 EBV-negative gastric carcinomas that were also studied showed chromosome 11 copy number gains in 3 of 10 (30%), a significantly lower frequency. The authors conclude that gains in chromosome 11 are common in EBV-associated malignancies in Hong Kong, with the strongest association found in gastric carcinoma. There seems to be differences between EBV-associated tumors of different locations, and between gastric carcinomas with and without EBV.

Gastric choriocarcinoma shows characteristics of adenocarcinoma and gestational choriocarcinoma: a comparative genomic hybridization and fluorescence in situ hybridization study.

The authors report two cases of the rare primary gastric choriocarcinoma. These tumors showed an overwhelming predominance of cytotrophoblast- and syncytiotrophoblast-like tumor cells that were positive for beta-human chorionic gonadotrophin, with small foci of glandular differentiation. Beta-human chorionic gonadotrophin was also detected serologically in one patient. Comparative genomic hybridization study was performed on one specimen. Copy number gains of chromosomes 12, 17, 20, 22, and X, together with losses on 18q, were the major findings. Except for the gain of chromosome 12, which is known to be uncommon in primary gastric adenocarcinoma but frequently associated with choriocarcinoma, the remaining genomic imbalances were among the most common comparative genomic hybridization findings reported in primary gastric adenocarcinoma. Fluorescence in situ hybridization on paraffin sections of both specimens confirmed the presence of polysomy 17 and trisomy 12. These results suggest that primary gastric choriocarcinoma genetically possesses characteristics of both adenocarcinoma and gestational choriocarcinoma. The authors believe this is the first interphase cytogenetics study on this rare tumor, and that the results support the theory that gastric choriocarcinoma arises from alternate differentiation pathways of adenocarcinoma.

Aggressive primary natural killer cell lymphoma of the caecum: a case report and literature review.

An unusual case of aggressive Stage IIE(B) primary natural killer cell lymphoma of the caecum is described in a 16-year old Chinese girl. The immunophenotype of the tumour cells was CD2+, CD3-, CD4-, CD5-, CD7+, CD8-, CD45RO+, CD45RA-, CD56+, CD57-. Southern blot analysis showed a normal germline arrangements of the T-cell antigen receptor and immuno-globulin heavy chain genes. This lymphoma pursued a highly aggressive clinical course, with the rapid development of an extensive local recurrence after an apparently complete resection and combination cytotoxic therapy. The patient died 7 months after diagnosis, despite receiving salvage treatment. Given the aggressiveness and poor prognosis in this biologically distinct primary gastrointestinal lymphoma, a more vigorous systemic therapy should be considered in addition to surgery.

Head and neck manifestations of the acquired immunodeficiency syndrome in children.

The head-and-neck manifestations of HIV infection in children are very different from those in the adult population. Recurrent bacterial and viral infections are common manifestations, and persistent sinusitis or otitis media should make the otolaryngologist suspicious of HIV infection if the child has been exposed to the virus. Other common problems include mucocutaneous and esophageal candidiasis, recurrent herpes I and II and zoster infections, parotid swelling, and cervical lymphadeopathy.

Aggressive primary hepatic lymphoma in Chinese patients. Presentation, pathologic features, and outcome.

BACKGROUND: Primary non-Hodgkin's lymphoma of the liver is rare. In this study, the presentation, pathologic features, and outcome of seven Chinese patients with primary hepatic lymphoma are described. METHODS: From 1984 to 1994, the clinical records of 14 Chinese patients with non-Hodgkin's lymphoma and histologically proven liver involvement were reviewed. Seven (four males, three females; median age, 54 years) were considered to have primary hepatic lymphoma. Histologic and immunohistochemical studies were performed on paraffin embedded liver tissue. RESULTS: "B" symptoms including fever (86%) and weight loss (57%) were the most striking presenting features. Hepatomegaly was present in all patients, splenomegaly in three (43%), and thrombocytopenia in six (86%). Only one patient was hepatitis B surface antigen-seropositive. None had preexisting liver disease. Histologic subtypes, though heterogeneous, were mostly unfavorable and consisted of diffuse large cell lymphoma (two patients), small lymphocytic lymphoma (one patient), lymphoblastic lymphoma (one case), mantle cell lymphoma (one patient), anaplastic large cell Ki-1 lymphoma (one patient), and hepatosplenic T-cell lymphoma (one patient). Three patients expressed B-cell and 2 expressed T-cell phenotypes. Six patients received cytotoxic chemotherapy. One had resection and one had splenectomy, but none achieved complete remission, and only one remained alive as of this writing. The median survival was 3.7 months (range, 8 days to 47.7 months). CONCLUSION: Chinese patients with primary non-Hodgkin's lymphoma of the liver have prominent "B" symptoms, disease with a highly aggressive course, a poor response to local and systemic treatment, and short survival. Hepatitis B virus infection is not a major etiologic factor for these patients.

Evaluation of prognostic indices based on pulmonary and hemodynamic variables in patients with adult respiratory distress syndrome (ARDS).

Patients with established ARDS have a high mortality rate. We continuously monitored hemodynamic and respiratory parameters of 30 patients in our ICU, all had acute respiratory failure during admission then progressively developed ARDS. We compared demographic characteristics, APACHE II (acute physiology and chronic health evaluation) score, ALI (acute lung injury) score, associated MSOF (multiple systems organ failure) in the disease process, pulmonary variables, and hemodynamic variables between survivors and nonsurvivors. Six of the 12 female patients and two of the 18 male patients survived. Our female patients had a better outcome than the males (P < 0.02); and, those who were younger than 35 years old and those who had less than two organ failures during the evolution of ARDS also had a better outcome (P < 0.001 vs. P < 0.03). After ARDS had developed, there were significant differences between survivors and nonsurvivors in the APACHE II score (P < 0.03), serum albumin level (P < 0.02), mean airway pressure (P < 0.05), PCWP (P < 0.02) and SaO2 (P < 0.02). Having a higher APACHE (> or = 15, P < 0.003), lower serum ablumin level (Alb < 2.5 gm/dl, P < 0.04), higher mean airway pressure (> or = 25 cm H2O, P < 0.04), higher PCWP (> or = 14 mmHg, P < 0.006), and lower SaO2 (< 93%, P < 0.002) predicted a poorer outcome. All patients received PEEP therapy and there were no significant differences between survivors and nonsurvivors in the PEEP level applied, either at the beginning of respiratory failure, or after development of ARDS. But those who had PEEP of 6 cm H2O or higher applied at the beginning of respiratory failure and those had PEEP of less than 10 cm H2O after development of ARDS had a better outcome (P < 0.04 vs. P < 0.05). Nevertheless, more controlled trials are needed before we make any conclusion about PEEP therapy.

Hypercapnic respiratory acidosis precipitated by hypercaloric carbohydrate infusion in resolving septic acute respiratory distress syndrome: a case report.

Complications may occur when nutritional support is administered either parenterally or enterally. Inappropriate nutritional formulas with high carbohydrate loads can precipitate respiratory failure in patients with compromised lung function, induce respiratory distress which manifests as dyspnea and tachypnea in an originally normal lung condition, produce hypercapnic acidosis in mechanically ventilated patients with chronic obstructive pulmonary disease (COPD) as well as patients recovering from acute respiratory distress syndrome (ARDS) without chronic lung disease, or result in difficult weaning. Hypercaloric mixed substrates administered either parenterally or enterally can also have profound impacts on gas exchange and energy expenditure. This report describes a patient who experienced exacerbation of respiratory distress and hypercapnic acidosis during recovery from septic ARDS as the result of a nutritionally-related increase in CO2 production. As carbohydrate calories were decreased, CO2 production diminished and the hypercapnia was resolved. The importance of indirect calorimetry cannot be overemphasized during tailoring of nutritional support for the critically ill patients.

Adult respiratory distress syndrome in children.

Adult respiratory distress syndrome or ARDS as coined by Ashbaugh et al in 1967, has been a great challenge in the field of critical care since then. It is a clinical entity which can be caused by various insults at any age. There have been several case reports of ARDS involving infants and children in the past 10 years, but pediatric ARDS is still not well recognized in Taiwan. A review of admissions to the pediatric intensive care unit in the past 2 years shows that 11 of the cases were included as pediatric ARDS combined with the expanded definition of Murray et al, and that each patient had an acute lung injury score greater than 2.5. Clinical manifestations also presented acute pulmonary distress indicating ARDS. The distribution of age ranged from 13 months to 11 years. The predisposing insults included sepsis, gastrointestinal bleeding with shock and massive blood transfusion, central nervous system infection, major trauma, near drowning, fulminant hepatitis and chemotherapy for acute leukemia. All received mechanical ventilatory support. The average peak inspiratory pressure was 46.7 +/- 6.4 cmH2O and the mean value of maximal PEEP used was 11.9 +/- 4.4 cmH2 O. Three patients developed barotrauma. Two patients survived and nine expired, a mortality rate of 82%. It is important for physicians caring for infants and children with respiratory failure to consider the diagnosis and initiate adequate ventilatory support and other resuscitation management.

Consistent copy number gain in chromosome 12 in primary diffuse large cell lymphomas of the stomach.

Fifteen cases of high grade primary gastric non-Hodgkin's lymphomas were studied using comparative genomic hybridization (CGH) and/or fluorescence in situ hybridization (FISH) techniques. A total of 10 cases of diffuse large cell lymphoma (DLCL) with no histologically identifiable or previous history of low grade mucosa-associated lymphoid tissue (MALT) lymphoma components were examined, four by CGH and validated by FISH, and the remaining six by FISH alone. All 10 tumors showed gains in chromosome 12. Other recurring CGH findings in DLCL included copy number gains of 1q and deletions of 6q. Five cases of high grade tumors with low grade MALT components (HGM) were also examined, three by CGH and validated by FISH and two by FISH only. Only one in five HGM showed gains of chromosome 12. Other recurring CGH findings in HGM included +7q and +11q. We conclude that high grade gastric lymphomas of DLCL type were associated with gains in chromosome 12. The change was much less frequent (P < 0.01) in the HGM type, which had a percentage similar to that observed in previously reported cytogenetics/FISH studies on low grade MALT lymphomas. Our findings suggested that many DLCL were not derived from transformation of low grade MALT lymphomas.

Gonadoblastoma in patient with Turner's syndrome.

A 15-year-old phenotypic female referred for the investigation of primary ammenorrhea, was found to have a 45,XO karyotype and an ovarian cyst. She demonstrated some of the features of Turner's syndrome, as well as virilization. On laparotomy, she was found to have bilateral gonadoblastomas. She was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Subsequently, repeated chromosomal analysis detected the presence of Y chromosomes, which was confirmed by the use of polymerase chain reaction (PCR). The difficulties encountered in searching for the Y chromosome in patients with gonadoblastoma are discussed. Prophylactic gonadectomy is suggested in those cases associated with atypical features.

T cell receptor Vbeta repertoire expression reflects gastric carcinoma progression.

Analysis of TCR beta-chain complementarity-determining region size gives an indication of the T cell immune response. We examined CD4+ and CD8+ subgroups of T cells in the peripheral blood (PBL), benign gastric mucosa, and tumor (TIL) lymphocytes of 12 patients with primary gastric carcinomas of both intestinal and diffuse types. The average number of expanded clones in each compartment, expressed by the 24 families of the TCRVbeta repertoire, was analyzed according to tumor histological type, maximal invasive depth, and lymph node metastases. Fewer clones were expressed by the PBL in the cases with lymph node metastases than in those without (CD4+ P = 0.00017, CD8+ P = 0.016). Fewer CD8+ clones were expressed by the PBL in the cases with full thickness tumor infiltration than in those involving only the mucosa and submucosa (P = 0.05). The CD8+ TIL showed significantly fewer clones in the diffuse-type carcinoma than in the intestinal type (P = 0.046).

Multimodality treatment of primary lymphoepithelioma-like carcinoma of the lung.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) of the lung occurs at a higher frequency in Asian compared with Western patients. Its association with Epstein-Barr virus varies among different ethnic groups. METHODS: Nine patients with primary LELC of the lung treated at a single institution with a multimodality approach comprised of surgery, chemotherapy, and radiotherapy are reported. Chemotherapy was comprised of cisplatin, 100 mg/m2, on Day 1 and 5-fluorouracil, 1 g/m2, on Days 2, 3, and 4. RESULTS: Five male and 4 female patients were treated over a 3-year period. Eight patients were non-smokers. Three patients had operable disease. Two of these patients received adjuvant radiotherapy or chemotherapy and remained free of recurrence at 18 and 20 months, respectively; 1 patient received no adjuvant treatment, and palliative chemotherapy was given for subsequent recurrent disease. Six patients had inoperable disease and received palliative chemotherapy +/- radiotherapy. Five patients had distant metastatic disease at presentation. Of the 7 patients who were evaluable for response to chemotherapy, 71.4% had a partial response and 28.6% had progressive disease. One patient who was evaluable for response to radiotherapy achieved a partial response. CONCLUSIONS: Primary LELC of the lung has a high rate of systemic metastasis and is highly chemosensitive. A multimodality approach to the management of this disease is recommended.