Effects of whole blood leukoreduction on platelet function and hemostatic parameters.

AIMS/OBJECTIVES: The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR). BACKGROUND: Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern. METHODS: Twenty-four units of whole blood were assigned to one of the four groups: non-leukoreduced (NLR), leukoreduced at 1 h and a height of 33 in. (LR-1), leukoreduced at 4 h and a height of 33 in. (LR-4(33)), or leukoreduced at 4 h and a height of 28 in. (LR-4(28)). Viscoelastic parameters, platelet aggregation, cell counts, physiological parameters and thrombin potential were evaluated immediately before and after LR, and on days 1, 7, 14 and 21 following LR. RESULTS: The viscoelastic parameters and thrombin generation potential were unchanged between the groups. Platelet aggregation was reduced in the LR-1 group compared with NLR after 7 days. The LR-4(28) group also showed a trend of reduced platelet aggregation compared with NLR. Aggregation in LR-4(33) was similar to NLR throughout the storage time. Physiological and electrolyte changes over the whole blood storage period were not affected by LR. CONCLUSION: Our study shows that whole blood can be LR at 4 h after collection and a height of 33 in. while maintaining platelet count and without altering platelet function and hemostatic performance.

A psychosocial taxonomy of patients with diabetes: validation in a primary care setting.

AIMS: The aims of this study were (i) to extend a psychosocial taxonomy of patients with diabetes to a primary care setting, and (ii) to validate the taxonomy using more sophisticated clustering methods across an array of psychological dimensions independent of demographic and medical variables. METHODS: In a cross-sectional study, 111 adults with Type 2 diabetes seen in a primary care setting completed the Multidimensional Diabetes Questionnaire and the Brief Symptom Inventory (BSI). They also provided diabetes-specific self-report measures along with HbA(1c). RESULTS: Four psychosocial patient profiles were identified using model-based cluster analysis in a US primary care setting. The four profiles represent a replication of two and refinement of a third profile found previously in French-speaking patients at diabetes education centres. Validation of the profiles using the BSI was replicated for depression and extended to other psychological dimensions. The validity and distinctiveness of the four psychosocial profiles were independent of demographic and diabetes-specific medical variables. CONCLUSION: Replication and extended validation of the psychosocial taxonomy into primary care may allow healthcare workers to supplement medical treatments with psychosocial interventions that can improve outcomes for patients with diabetes that are practical, individually tailored, and cost-effective.

Silicone lymphadenopathy associated with augmentation mammaplasty. Morphologic features of nine cases.

Silicone lymphadenopathy (SL)--defined as the presence of silicone in a lymph node--is a rare side effect of mammary augmentation either by injection of liquid silicone or by placement of a bag-gel prosthesis. Nine new cases in eight patients are herein reported and compared with six previously well-documented cases. The available data showed that SL was frequently detected as an incidental finding of no clinical significance during mastectomy and nodal dissection for associated breast carcinoma (nine cases), but may present as a painful or nontender enlarged lymph node (six cases). The latter presentation was almost always associated with a history of injection of liquid silicone or rupture of the prosthesis. All or some of the following findings were present in an affected lymph node: coarse vacuoles, fine vacuoles, and multinucleated giant cells. All lymph nodes contained a variable amount of an unstained, nonbirefringent, refractile material that, in seven of our cases, was shown to contain elemental silicon by energy-dispersive x-ray elemental analysis. In 312 lymph nodes collected from 18 routine cases of breast carcinoma, coarse vacuoles probably representing fat were found in 107 lymph nodes (34%); focal fine vacuoles were found in one (0.3%), and a single multinucleated giant cell was found in one (0.3%). In conclusion, SL probably will be encountered more frequently when cancer-prone age is reached by the susceptible population. In most cases, it is an incidental finding of no clinical significance. However, the histologic diagnosis can be made by observing characteristic light-microscopic changes, which may be supplemented in doubtful cases by energy-dispersive x-ray analysis.

Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome translocation t(X; 18).

The authors report an unusual spindle cell sarcoma that arose in the lung of a 12-year-old girl. This tumor had histologic, immunophenotypic, and ultrastructural features consistent with monophasic fibrous synovial sarcoma. These features included a growth pattern of densely packed spindle cells in irregularly intersecting, broad fascicles, diffuse vimentin immunoreactivity, and focal expression of epithelial membrane antigen and S100 protein. This diagnosis was further supported by cytogenetic studies showing the specific t(X; 18) chromosomal translocation associated with synovial sarcoma. This balanced translocation appears to be an essentially universal characteristic of these sarcomas, regardless of histologic subtype or site of origin. The constellation of morphologic and cytogenetic findings in this case firmly establishes synovial sarcoma as a subtype of pulmonary spindle cell sarcomas. The distinctive features of these neoplasms allow them to be distinguished from a variety of primary and metastatic malignancies in the lung.

Interactions between outcomes and tumor response to preoperative cisplatin-sensitized radiotherapy in advanced head and neck cancer. Southern New Jersey Head and Neck Cancer Treatment Group.

BACKGROUND: Whether or not tumor response to chemotherapy-sensitized radiation therapy (CTRT) for head and neck cancer leads to an improved outcome is unknown. METHODS: Forty patients who received preoperative cisplatin plus simultaneous radiotherapy for operable stage III and IV head and neck cancer were reviewed retrospectively regarding clinical demographics, staging, and survival status. RESULTS: Twenty-one (57%) patients had a histologic complete response (HCR) and 16 (43%) had a partial (PR) (9) or clinical complete (7) response (CCR). Tumor response of N1 versus N2-3 nodal disease showed 6 (75%) HCR and 4 (25%). Five-year disease-free survival overall was 82% for HCR versus 38% for PR/CCR (P <0.05). Disease-specific 5-year survival was 100% for HCR versus 27% for PR/CCR (P <0.002). CONCLUSIONS: Histologic complete response to CTRT for head and neck cancer is associated with increased survival and encouraging disease-free status. Response to CTRT is inversely proportional to lymphatic tumor load.

Segmental xanthomatosis of the ileocecal valve with anatomic and functional obstruction.

A case of intestinal obstruction due to segmental xanthomatosis involving the small intestine and colon at the ileocecal valve is described in a patient with acquired immunodeficiency syndrome. Infiltration of the bowel wall with lipid-laden histiocytes is documented and is associated with severe attenuation and disruption of the muscularis propria. This xanthomatous infiltrate resulted in luminal stenosis and dysfunctional motility. Segmental xanthomatosis of the bowel is a rare cause of intestinal obstruction due to an infiltrative process. The clinical, radiologic, and pathologic presentation of xanthomatosis may mimic other causes of bowel obstruction.

Epithelioid leiomyoma of the vulva.

Smooth muscle tumors are uncommon lesions of the vulva and represent a variety of histologic types. When encountered, surgical treatment is guided by the malignant potential of the tumors. This article presents the case of a 45-year-old woman who underwent conservative excision of a 10-cm vulvar lesion consistent with benign epithelioid leiomyoma. This unusual case provides an opportunity to review the clinical and pathologic features of this uncommon variant of leiomyoma and to describe the recently suggested pathologic criteria for determining the malignant potential of smooth muscle tumors arising in the vulva. Knowledge of these criteria can guide the clinician in selecting the appropriate management.

The rim sign in acute cholecystitis. Comparison of radionuclide, surgical, and pathologic findings.

Nonvisualization of the gallbladder associated with the rim sign of enhanced pericholecystic hepatic activity has been established as a useful and highly specific sign of acute cholecystitis. This study's purpose was to determine the pathophysiologic cause of the rim sign. Thirty-seven surgery-bound patients with a clinical diagnosis of acute cholecystitis were studied. A group of 20 patients with a definite rim sign were compared to a group of 17 patients without a rim sign; all with nonvisualization of the gallbladder. Radionuclide, surgical, and pathologic findings were correlated. In patients with the rim sign and in those without the rim sign, microscopic review of all surgical specimens revealed transmural reaction of the gallbladder wall in 95% and 59% of cases, respectively. The surgeon found inflammation extending beyond the gallbladder wall in 75% of rim sign cases, but in only 35% of case without the rim sign. Liver tissue was attached to the gallbladder specimen in three cases, and the findings support the association of hepatic inflammation with the presence of a rim sign. Pathologic correlation and surgical evidence suggest that the rim sign is caused by the spread of inflammation through the gallbladder wall and into adjacent liver tissue. Transmural reaction is required before the inflammatory process can reach the liver. A high-count, high-intensity technique seems to best demonstrate the rim sign. Once demonstrated, further delayed imaging is unnecessary.

Quaternary structure of rice nonsymbiotic hemoglobin.

Plant nonsymbiotic hemoglobins are hexacoordinate heme proteins found in all plants. Although expression is linked with hypoxic environmental conditions (Taylor, E. R., Nie, X. Z., Alexander, W. M., and Hill, R. D. (1994) Plant Mol. Biol. 24, 853-862), no discrete physiological function has yet been attributed to this family of proteins. The crystal structure of a nonsymbiotic hemoglobin from rice has recently been determined. The crystalline protein is homodimeric and hexacoordinate with two histidine side chains coordinating the heme iron atom. Despite the fact that the amino acids responsible for the subunit interface are relatively conserved among the nonsymbiotic hemoglobins, previous work suggests that this group of proteins might display variability in quaternary structure (Duff, S. M. G., Wittenberg, J. B., and Hill, R. D. (1997) J. Biol. Chem. 272, 16746-16752; Arredondo-Peter, R., Hargrove, M. S., Sarath, G., Moran, J. F., Lohrman, J., Olson, J. S., and Klucas, R. V. (1997) Plant Physiol. 115, 1259-1266). Analytical ultracentrifugation and size exclusion high pressure liquid chromatography were used to investigate the quaternary structure of rice nonsymbiotic hemoglobin at various states of ligation and oxidation. Additionally, site-directed mutagenesis was used to test the role of several interface amino acids in dimer formation and ligand binding. Results were analyzed in light of possible physiological functions and indicate that the plant nonsymbiotic hemoglobins are not oxygen transport proteins but more closely resemble known oxygen sensors.

Hemangiopericytoma of the cervical spine: report of an unusual case.

A hemangiopericytoma of the cervical spine in a 31-year-old woman is possibly the first reported in the orthopedic literature. There is some confusion about the most efficacious treatment. Based on six cases in the medical literature, it would appear that adjunctive radiation, postoperatively, helps to decrease the recurrence rate of the tumor.

Effect of advance directives on the management of elderly critically ill patients.

OBJECTIVE: To evaluate the effects of advance directives on the management of elderly, critically ill patients. DESIGN: Retrospective chart review. SETTING: Teaching hospital medical/surgical, noncardiac intensive care unit (ICU). PATIENTS: The medical records of 401 patients, > or =65 yrs of age, admitted to the ICU between 1992 and 1995 were reviewed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Advance directive statements included refusal of cardiopulmonary resuscitation (CPR), nutrition, intravenous medications, antibiotics, mechanical ventilation, and blood products. Nineteen (5%) patients had advance directives (study group). These patients were compared with 28 case-matched (age, Acute Physiology and Chronic Health Evaluation II score, and diagnosis) critically ill patients without advance directives (control group). We compared the following data: cost per day; number of surgical procedures; number of radiographic studies; number of central venous and pulmonary artery catheter insertions; number of complete blood counts, electrolytes, and cultures sent for laboratory testing; number of days in the ICU/hospital; and mortality rates. Statistical analysis was performed using the Student's t-test for independent means and the chi-square equation. For all observed parameters, quantitative and dichotomous differences between study and control groups were not statistically significant. Two patients received CPR, despite advance directive statements refusing this treatment. CONCLUSIONS: Few critically ill seniors have advance directives. As assessed by objectively documented information, the level of care delivered to elderly ICU patients is not affected by the presence or absence of advance directive statements. Medical personnel need to be aware of whether or not patients have advance directive statements, as unauthorized CPR was administered to 11% of the patients who died with advance directives.

A new percutaneous renal biopsy device for pediatric patients.

A new automated biopsy technique is described for performing percutaneous renal biopsies in pediatric patients. The biopsy device (Bard Biopty Instrument) employs a relatively small needle (18 gauge). We believe this procedure offers a safer and more effective means of obtaining adequate renal tissue for pathological assessment in pediatric patients.

Alcohol-induced testicular atrophy. An experimental model for hypogonadism occurring in chronic alcoholic men.

Elucidation of mechanisms involved in the hypogonadism and feminization observed in chronic alcoholic men requires the development of an experimental animals model system. Such an animal system should be inducible with ethanol feeding and should duplicate endocrine changes known to occur in chronic alcoholic men. We report such an animal model system. Animals fed a diet with ethanol accounting for 36% of total calories develop significant testicular, prostatic, and seminal vesicle atrophy (P less than 0.01) and greatly reduced plasma testosterone levels (P less than 0.01). Animals fed a similar diet with sucrose isocalorically substituted for ethanol do not. Testicular, prostatic, and seminal vesicular mass relative to body mass and plasma testosterone levels in these isocaloric control animals do not vary significantly from those obtained for age-matched control animals fed an ad libitum rat chow diet. These findings indicate that the caloric deprivation associated with chronic ethanol ingestion is not responsible for gonadal injury and atrophy of the sex steroid-sensitive tissues in the alcohol-fed animals. This animal model provides a useful means of directly examining perturbation in gonadal function that occurs in man as a consequence of chronic ethanol ingestion and confirms our previous data which suggest that ethanol is a primary testicular toxin.

Parathyroid carcinoma: clinical presentation and treatment.

Parathyroid tumors account for only a small percentage of all head and neck neoplasms. The overwhelming majority of these are parathyroid adenomas that result in primary hyperparathyroidism. From 0.5% to 4% of hyperparathyroid patients, however, will be found to have a parathyroid carcinoma. In this paper, the authors relate their recent experience with such a patient and with two other such cases. Parathyroid carcinoma patients usually present with striking hyperparathyroidism and hypercalcemia, with the resultant related symptoms being more severe than those associated with parathyroid adenomas. Parathyroid carcinomas also tend to be large and may be detectable by current imaging techniques. The surgical appearance of these lesions is also distinct; the tumors are frequently multilobulated, gray-tan in color, quite firm, and often invasive. These physical findings are important since frozen section diagnosis may be difficult. The final histologic diagnosis depends on the presence of mitotic figures and capsular and vascular invasions. Preoperative medical problems, surgical approach, and prognostic factors are also discussed.

Cytogenetic characterization of renal cell carcinoma in von Hippel-Lindau syndrome.

We report the case of a 26-year-old man with von Hippel-Lindau syndrome (VHL) and two renal cell carcinomas (RCC), one of which was studied cytogenetically. Chromosomal analysis of the RCC showed a translocation that involved chromosomes 3 and 8 with subsequent loss of the derivative chromosome 8. The patient's peripheral lymphocytes showed a normal karyotype that indicated that there was not a constitutional chromosomal translocation. This is the third reported case of RCC in a patient with VHL in which loss of a portion of the short arm of chromosome 3 (3p) has occurred. Similar chromosomal changes that involve 3p have been reported in both familial and sporadic cases of RCC and have led to speculation that a tumor suppressor gene may be located in this region. Cytogenetic characterization of renal tumors could assume increasing significance in the diagnosis and classification of RCC and potentially may guide therapy. These studies may also lead to a better understanding of the biologic behavior of RCC and result in more informed patient evaluation and counseling.

Endothelial cell surface F1-F0 ATP synthase is active in ATP synthesis and is inhibited by angiostatin.

Angiostatin blocks tumor angiogenesis in vivo, almost certainly through its demonstrated ability to block endothelial cell migration and proliferation. Although the mechanism of angiostatin action remains unknown, identification of F(1)-F(O) ATP synthase as the major angiostatin-binding site on the endothelial cell surface suggests that ATP metabolism may play a role in the angiostatin response. Previous studies noting the presence of F(1) ATP synthase subunits on endothelial cells and certain cancer cells did not determine whether this enzyme was functional in ATP synthesis. We now demonstrate that all components of the F(1) ATP synthase catalytic core are present on the endothelial cell surface, where they colocalize into discrete punctate structures. The surface-associated enzyme is active in ATP synthesis as shown by dual-label TLC and bioluminescence assays. Both ATP synthase and ATPase activities of the enzyme are inhibited by angiostatin as well as by antibodies directed against the alpha- and beta-subunits of ATP synthase in cell-based and biochemical assays. Our data suggest that angiostatin inhibits vascularization by suppression of endothelial-surface ATP metabolism, which, in turn, may regulate vascular physiology by established mechanisms. We now have shown that antibodies directed against subunits of ATP synthase exhibit endothelial cell-inhibitory activities comparable to that of angiostatin, indicating that these antibodies function as angiostatin mimetics.

Identification of differentially expressed genes in hepatocellular carcinoma and metastatic liver tumors by oligonucleotide expression profiling.

BACKGROUND: The characterization of differentially expressed genes between cancerous and normal tissues is an important step in the understanding of tumorigenesis. Global gene expression profiling with microarrays has now offered a powerful tool to measure the changes of thousands of genes in any carcinoma tissues in an effort to identify these key disease-related genes. To compare the gene expression of a primary liver carcinoma, metastatic carcinoma to the liver, and normal liver, the authors analyzed tissue from six primary hepatocellular carcinomas (HCCs), five colorectal adenocarcinoma metastases to the liver, and eight normal livers. METHODS: Samples were processed from total RNA to fragmented cRNA and hybridized onto Affymetrix GeneChip(R) expression arrays. Analyses were performed to determine the consensus pattern of gene expression for primary liver carcinoma, metastatic liver carcinoma, and normal liver tissue and their changes in expression level. RESULTS: In hepatocellular carcinoma, 842 genes were overexpressed, and 393 genes were underexpressed in comparison with genes of normal liver tissue. Of note, 7 of the 20 most increased identified known genes previously have been associated with liver carcinoma or other types of cancers. The 13 additional identified genes until now have not previously shown strong association with cancers. Furthermore, the authors identified 42 genes and 24 expressed sequence tags that are expressed at a significant level in both HCC and metastastic tumors, presenting a list of marker genes indicative of cancerous liver tissue. CONCLUSIONS: In this study, genes that can be involved in the production of and maintenance of hepatic carcinomas were identified. These data offer new insight into genes that are potentially important in the pathogenesis of liver carcinoma, as well as additional targets for new strategies for cancer therapy and treatment.