Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.

OBJECTIVE: To examine the relationship between growth rate of vestibular schwannomas and the expression of various growth factor receptors. STUDY DESIGN: Retrospective case review of clinical growth rate in conjunction with a histopathologic and immunohistochemical reexamination of archival specimens. SETTING: A tertiary referral neurotologic center. PATIENTS: Three groups: a historical group to act as controls, consisting of 30 patients with sporadic vestibular schwannomas removed before the unit adopted an initial interval scan policy; a group of 14 patients with sporadic vestibular schwannomas who had undergone an initial interval scan policy, showed radiologic evidence of growth, and therefore had their schwannoma removed; and a group of 16 schwannomas removed from 11 neurofibromatosis Type 2 patients. MAIN OUTCOME MEASURES: A comparison between the three clinical groups using immunohistochemical studies to determine the level of expression of the proliferation factor Ki-67, c-erbB-2, and c-erbB-3 receptors and fibroblastic growth factor receptors 1 and 4. RESULTS: The level of expression of the proliferation factor Ki-67 was very low and similar in all three groups. C-erbB-2 and c-erbB-3 receptors were not expressed in any of the groups. fibroblastic growth factor receptor 4 expression was not significantly different, but there was a variation in the expression of fibroblastic growth factor receptor 1 between the three groups that correlated well with the differing incidence of growth in the groups. The increase in expression of fibroblastic growth factor receptor 1 in the neurofibromatosis Type 2 group was not statistically significant, but the increase in expression of fibroblastic growth factor receptor 1 in the growing sporadic group was statistically significant when compared with the historical controls. The level of fibroblastic growth factor receptor 1 expression correlates significantly with the rate of growth as measured on interval magnetic resonance imaging. CONCLUSIONS: Overexpression of fibroblastic growth factor receptor 1 has a positive correlation with the incidence and the rate of growth of sporadic vestibular schwannomas.     

Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension

The renin-angiotensin system is involved in control of blood pressure and salt and fluid homeostasis. Genes for components of this system have been of major focus in research on the causation of the common, complex, polygenic trait, essential hypertension (HT). Association of an A→C variant at nucleotide 1166 of the angiotensin II type 1 receptor (AT₁R) gene with HT, but an absence of linkage of this locus with this disease, has been reported recently. Since confirmation in a different setting is imperative, we performed a cross-sectional case-control study of the A1166C variant in a well-characterized group of 108 Caucasian HT subjects with a strong family history (two affected parents) and early onset disease. Genotyping was by mismatch polymerase chain reaction/ Bfr I restriction fragment length polymorphism analysis. Frequency of the C¹¹⁶⁶allele was 0.40 in HTs and 0.29 in normotensives. The difference in genotype (χ²= 13, P = 0.0015) and allele (χ²= 5.3, P = 0.02) frequencies between the two groups was significant (odds ratio for CC vs AA+AC = 7.3 [95% CI, 1.9–31.9). The present results implicate the AT₁R gene, or a locus in linkage disequilibrium with the variant tested, in the causation of essential HT.     

Immunoassays for proteins alkylated by nicotine-derived N-nitrosamines

Polyclonal antibodies recognizing the pyridyloxobutyl (POB) moiety of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were produced in rabbits immunized either with POB-bovine albumin or POB-Sepharose. The POB intermediates necessary to modify the protein were generated by alkaline (pH 9.0) treatment of the synthetic precursor 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone. In a competitive enzyme linked immunoabsorbent assay (ELISA), 70 pmole NNK inhibited 50% of the binding of the anti-POB antibodies to POB-protein absorbed on microtiterplates. This 50% inhibition varied from 70 pmole to 200 nmole using a series of NNK analogues, depending on the integrity of the POB moiety. Immunological techniques initiated in this study detect NNK-protein conjugates or measure the quantity of POB groups liberated upon alkaline or acid treatment of NNK modified protein.     

Management of cerebral hemispherectomy in children

Surgical removal of a cerebral hemisphere may be undertaken in patients with intractable seizure disorders. Anesthetic management of such patients has not been reviewed in detail before. This study retrospectively analyzed hospital records of ten patients undergoing cerebral hemispherectomy at the Johns Hopkins Hospital between July 1983 and February 1988. Patient records were reviewed for diagnosis, physical characteristics, preoperative medications, anesthetic management, and postoperative course in the intensive care unit (ICU). Massive and sudden blood loss was a common finding in these patients, and during the intraoperative and postoperative periods, fluid resuscitation frequently was an ongoing process. In some patients, the blood loss exceeded one blood volume and was associated with coagulopathy, hypokalemia, and hypothermia. Urine output was elevated by a glucose-induced diuresis in some patients, giving misleading information as to intravascular volume status. Seizures and hemorrhage into the hemispherectomy cavity were management problems in the ICU. From this review, the authors conclude that blood loss may be marked and precipitous during surgical removal of a cerebral hemisphere. Monitoring of intra-arterial pressure and central venous pressure (CVP) is necessary for patient management during the intraoperative and postoperative periods. Intravenous (IV) access should allow rapid intravascular volume administration as it becomes necessary. Patients should remain intubated and observed closely during the immediate postoperative period due to difficulties with hemodynamic stability, seizures, and hemorrhage.     

Adverse effects associated with physical restraint.

OBJECTIVE: Restraint use is not monitored in the US, and only institutions that choose to do so collect statistics. In 1999, investigative journalists reported lethal consequences proximal to restraint use, making it a life-and-death matter that demands attention from professionals. This paper reviews the literature concerning actual and potential causes of deaths proximal to the use of physical restraint. METHOD: Searching the electronic databases Medline, Cinahl, and PsycINFO, we reviewed the areas of forensics and pathology, nursing, cardiology, immunology, psychology, neurosciences, psychiatry, emergency medicine, and sports medicine. CONCLUSIONS: Research is needed to provide clinicians with data on the risk factors and adverse effects associated with restraint use, as well as data on procedures that will lead to reduced use. Research is needed to determine what individual risk factors and combinations thereof contribute to injury and death.     

Fine T-Cell Subsets in Alcoholics as Determined by the Expression of l-Selectin, Leukocyte Common Antigen, and β-Integrin

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8^hl lymphocytes that are HLA DR⁺; we now demonstrate that they also have striking alterations in the quantitative relationships of the fine T-cell subsets. Both CD4⁺ and CD8^hl lymphocytes have a sharply reduced percentage of the l -selectin⁺ CD45RA⁺ subset, increased percentages of the CD45RA-subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4⁺ suppressor inducer and CD4-dependent CD8⁺ suppressor effector cells are reduced, whereas other subsets, including CD8⁺ CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal. In other results, the percentage of CD8^hl lymphocytes expressing CD11b (β-integrin) is shown to be reciprocal with the percentage expressing l -selectin both in normals and alcoholics. However, the regression function of CD11b vs. l -selectin on CD8^hl cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion-dependent functions, and a shift in the balance of regulatory interactions.     

PULMONARY RESECTION FOR METASTATIC BREAST CANCER

Background : A patient with a solitary pulmonary metastasis who had breast cancer in the past may benefit from pulmonary resection. Methods : Between 1984 and 1996, 17 patients underwent metastatectomy for metastatic breast cancer. There were 15 females and two males whose average age was 59 (range: 40–74 years). The median tumour-free interval after the primary breast-cancer operation was 5.1 years (range: 8 months-18.2 years). Sixteen patients had complete resections, which included six lobectomies and 10 lesser resections. Results : The postoperative mortality was nil and the morbidity rate was 6%. Follow-up was complete in all patients. Recurrent disease developed in four patients and two patients died of their disease. The 5-year survival was 62%. Conclusion : An aggressive surgical approach is warranted in patients with isolated resectable pulmonary metastases from breast cancer.