A generalized film technique for the verification of vertex fields used in the treatment of brain tumors

With the availability of commercial three-dimensional (3D)-treatment planning systems, more and more treatment plans call for the use of noncoplanar conformal beams for the treatment of brain tumors. However, techniques for the verification of many noncoplaner beams, such as vertex fields which involve any combination of gantry, collimator, and table angles, do not exist. The purpose of this work is to report on the results of an algorithm and a technique that have been developed for the verification of noncoplanar vertex fields used in the treatment of brain tumors. This technique is applicable to any geometric orientation of the beam, i.e., a beam orientation that consists of any combination of gantry, table, and collimator rotations. The method consists of superimposing a central plane image of a correctly magnified vertex field on a lateral or oblique field port film. To achieve this, the 3D coordinates of the projection of the isocenter onto the film for lateral (or oblique) as well as the vertex fields are determined and then appropriately matched. Coordinate transformation equations have been developed that enable this matching precisely. A film holder has been designed such that a film cassette can be secured rigidly along the side rails of the treatment table. The technique for taking a patient treatment setup verification film consists of two steps. In the first step, the gantry, table, and collimator angles for the lateral (or oblique) field are set and the usual double exposures are made; the first exposure corresponds to that of the treatment portal with the isocenter clearly identified and the second one a larger radiation field so that the peripheral anatomy is visible on the film. In the next step, the gantry, table, and collimator angles are positioned for the vertex field and the table is moved laterally and vertically and the film longitudinally to a position that will enable precise matching of the isocenter on the film. A third exposure is then taken with the vertex portal. What is seen on the film is a superposition of a central plane image of the vertex field onto the image of the lateral or oblique field. This technique has been used on 60 patients treated with noncoplanar fields for brain tumors. In all of these cases, the coincidence of the projection of the isocenter for the lateral (or oblique) and the vertex fields was found to be within 3 mm.     

Interferon-gamma increases expression of chemokine receptors CCR1, CCR3, and CCR5, but not CXCR4 in monocytoid U937 cells

Chemokine receptors (CR), which can mediate migration of immune cells to the site of inflammation, also function as coreceptors for human immunodeficiency virus (HIV) entry into CD4+ T lymphocytes and antigen-presenting cells. We demonstrate here that interferon-gamma (IFN-gamma) increases the expression of chemokine receptors CCR1, CCR3, and CCR5 in monocytoid U937 cells as detected by cell surface molecule labeling and mRNA expression, as well as by intracellular calcium mobilization and cell migration in response to specific ligands. The increased expression of these chemokine receptors also results in an enhanced HIV-1 entry into cells. Our data provide evidence for a relationship of cellular pathways that are induced by IFN-gamma with those that regulate chemokine receptor expression.     

Treatment and prophylaxis of some infectious diseases of swine and cattle using of natural alpha-interferons

On the basis of experimental studies which proved stimulating action on absorbing and bactericidal function of blood phagocytes and antibody genesis the methods of therapy and prophylaxis of wide spread infections in modern live-stock (transmissive gastroenteritis of pigs, parainfluenza of calves, colibacteriosis of swine and cattle) were created. It was established, that optimal one-time therapeutical dose of homologous alpha-IFN for intramuscular administration to new-born pigs was 2000-4000 IU per head, prophylactic dose was 1000-2000 IU. Therapeutical doses of alpha-IFN for calves did not exceed 4000-6000 IU, prophylactic--4000 IU. As a rule, it is necessary to introduce the preparation three times with 48 h intervals. With the account of these data the large-scale commissional trials of these preparations were carried out.     

Resection of metastatic renal cell carcinoma

PURPOSE: Resection of solitary metastases from renal cell carcinoma (RCC) is associated with a 5-year survival rate of 35% to 50%. Selection criteria are not well defined. PATIENTS AND METHODS: We retrospectively analyzed our experience with 278 patients with recurrent RCC from 1980 to 1993. RESULTS: One hundred forty-one of 278 patients underwent a curative metastectomy for their first recurrence (44% 5-year overall survival [OS] rate), 70 patients underwent noncurative surgery (14% 5-year OS rate), and 67 patients were treated nonsurgically (11% 5-year OS rate). Favorable features for survival were a disease-free interval (DFI) greater than 12 months versus 12 months or less (55% v 9% 5-year OS rate; P < .0001), solitary versus multiple sites of metastases (54% v 29% 5-year OS rate; P < .001), and age younger than 60 years (49% v 35% 5-year OS rate; P < .05). Among 94 patients with a solitary metastasis, lung (n = 50; 54% 5-year OS rate) was more favorable than brain (n = 11; 18% 5-year OS rate; P < .05). Survival rates after curative resection of second and third metastases were not different compared with initial metastectomy (46% and 44%, respectively, v 43% 5-year OS rates; P = nonsignificant). Favorable predictors of survival by multivariate analysis included a single site of first recurrence, curative resection of first metastasis, a long DFI, a solitary site of first metastasis, and a metachronous presentation with recurrence. CONCLUSION: Selected patients with recurrent RCC who can undergo a curative resection of their disease have a good opportunity for long-term survival, particularly those with a single site of recurrence and/or a long DFI.     

Association of kinesin with microtubules in diverse cytoskeletal systems in the outer segments of rods and cones

The membranous outer segments of vertebrate photoreceptors are supported by cytoskeletons consisting of microtubules and associated proteins, which occur as the ciliary axoneme in rods and cones, and as a separate cytoskeletal system at the incisures of rod outer segments. We performed an immunocytochemical study of the cytoskeleton in photoreceptors isolated from amphibian retinas and found that immunoreactivity to the heavy chain of the motor protein kinesin was closely associated with the microtubules in each of these outer segment cytoskeletal systems. In the outer segments of cones, kinesin heavy chain immunoreactivity was confined to a streak at the axoneme that extended to the outer segment tip. In the outer segments of rods, kinesin heavy chain immunoreactivity was found as both a short streak at the axoneme and a series of long parallel lines that coincided with the microtubules at rod outer segment incisures. Our findings constitute the first report of kinesin in the axoneme of cones and at the incisures of rods. Closely associated with microtubules, kinesin in photoreceptor outer segment axonemes and at rod outer segment incisures can transport materials longitudinally along the microtubules and/or connect these with each other and/or with other components. Because these cytoskeletal systems differ in fundamental ways, kinesin can play different roles in each case, e.g., kinesin at rod outer segment incisures can have structural and functional roles that are unique to rods. These findings may have clinical relevance because similar cytoskeletal systems are expected to occur in the outer segments of human photoreceptors; thus, a disturbance involving kinesin in the cytoskeletal systems at photoreceptor axonemes and/or at rod outer segment incisures could interfere with the normal structure and function of photoreceptors and contribute to human photoreceptor degenerations.     

Influence of socioeconomic and cultural factors on racial differences in late-stage presentation of breast cancer

CONTEXT: Breast cancer mortality is higher among African American women than among white women in the United States, but the reasons for the racial difference are not known. OBJECTIVE: To evaluate the influence of socioeconomic and cultural factors on the racial difference in breast cancer stage at diagnosis. DESIGN: Case-control study of patients diagnosed as having breast cancer at the University Medical Center of Eastern Carolina from 1985 through 1992. SETTING: The major health care facility for 2 rural counties in eastern North Carolina. SUBJECTS: Five hundred forty of 743 patients with newly diagnosed breast cancer and 414 control women from the community matched by age, race, and area of residence. MAIN OUTCOME MEASURES: Breast cancer stage at diagnosis. RESULTS: Of the 540 patients, 94 (17.4%) presented with TNM stage III or IV disease. The following demographic and socioeconomic factors were significant predictors of advanced stage: being African American (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9-4.7); having low income (OR, 3.7; 95% CI, 2.1-6.5); never having been married (OR, 2.9; 95% CI, 1.4-5.9); having no private health insurance (OR, 2.5; 95% CI, 1.6-4.0); delaying seeing a physician because of money (OR, 1.6; 95% CI, 1.1-2.5); or lacking transportation (OR, 2.0; 95% CI, 1.2-3.6). Univariate analysis also revealed a large number of cultural beliefs to be significant predictors. Examples include the following beliefs: air causes a cancer to spread (OR, 2.8; 95% CI, 1.8-4.3); the devil can cause a person to get cancer (OR, 2.1; 95% CI, 1.2-3.5); women who have breast surgery are no longer attractive to men (OR, 1.9; 95% CI, 1.1-3.5); and chiropractic is an effective treatment for breast cancer (OR, 2.4; 95% CI, 1.4-4.4). When the demographic and socioeconomic variables were included in a multivariate logistic regression model, the OR for late stage among African Americans decreased to 1.8 (95% CI, 1.1 -3.2) compared with 3.0 (95% CI, 1.9-4.7) for race alone. However, when the belief measures were included with the demographic and socioeconomic variables, the OR for late stage among African Americans decreased further to 1.2 (95% CI, 0.6-2.5). CONCLUSIONS: Socioeconomic factors alone were not sufficient to explain the dramatic effect of race on breast cancer stage; however, socioeconomic variables in conjunction with cultural beliefs and attitudes could largely account for the observed effect.     

Lidocaine toxicity in primary afferent neurons from the rat

Evidence from both clinical studies and animal models suggests that the local anesthetic, lidocaine, is neurotoxic. However, the mechanism of lidocaine-induced toxicity is unknown. To test the hypothesis that toxicity results from a direct action of lidocaine on sensory neurons we performed in vitro histological, electrophysiological and fluorometrical experiments on isolated dorsal root ganglion (DRG) neurons from the adult rat. We observed lidocaine-induced neuronal death after a 4-min exposure of DRG neurons to lidocaine concentrations as low as 30 mM. Consistent with an excitotoxic mechanism of neurotoxicity, lidocaine depolarized DRG neurons at concentrations that induced cell death (EC50 = 14 mM). This depolarization occurred even though voltage-gated sodium currents and action potentials were blocked effectively at much lower concentrations. (EC50 values for lidocaine-induced block of tetrodotoxin-sensitive and -resistant voltage-gated sodium currents were 41 and 101 microM, respectively.) At concentrations similar to those that induced neurotoxicity and depolarization, lidocaine also induced an increase in the concentration of intracellular Ca++ ions ([Ca++]i; EC50 = 21 mM) via Ca++ influx through the plasma membrane as well as release of Ca++ from intracellular stores. Finally, lidocaine-induced neurotoxicity was attenuated significantly when lidocaine was applied in the presence of nominally Ca(++)-free bath solution to DRG neurons preloaded with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Our results indicate: 1) that lidocaine is neurotoxic to sensory neurons; 2) that toxicity results from a direct action on sensory neurons; and 3) that a lidocaine-induced increase in intracellular Ca++ is a mechanism of lidocaine-induced neuronal toxicity.     

Early weaning induces jejunal ornithine decarboxylase and cell proliferation in neonatal rats

Increased ornithine decarboxylase (ODC) activity is associated with rapid cell proliferation in many cell types. The cellular effects of early weaning on intestinal development are not well established. To investigate whether ODC is involved in intestinal growth after early weaning, we precociously weaned suckling rats on postnatal d 15 and followed through d 21 (6 d after early weaning). Age-matched suckling pups served as controls. Rat pups were killed 1, 2, 3 and 6 d after early weaning and jejunal mucosa was assayed for ODC and sucrase activities, and protein and DNA contents. Jejunal cell proliferation was monitored by bromodeoxyuridine immunohistochemistry. Elevated jejunal ODC activity 1 d after early weaning was the earliest cellular event that was detected in the current study. ODC activity peaked at d 3 (about 15-fold greater than age-matched unweaned suckling controls). Sucrase activity was elevated at d 2 after weaning and peaked at d 3 (about 10-fold greater than controls). Greater bromodeoxyuridine immunostaining in early weaned rats occurred on d 3. Protein and DNA contents were greater in jejunal mucosa of early weaned rats at d 6. Serum corticosterone levels were elevated on d 1 and d 2 after early weaning compared to controls. To explore whether the intake of nonpurified diet played a role, we also compared the induction of jejunal ODC activity in early weaned pups and pups that were food-deprived for 1 d. ODC activity was not greater in the food-deprived group compared to suckling controls while the early weaned group had 6-fold greater activity 1 d after early weaning. Early weaning stimulates jejunal cell proliferation and differentiation. The temporal sequence of increased ODC activity followed by increases in other growth variables suggests that the induction of ODC activity may act as an early marker of intestinal growth during early weaning.     

The effect of idebenone, a coenzyme Q analogue, on hydrophobic bile acid toxicity to isolated rat hepatocytes and hepatic mitochondria

Oxidant stress induced by hydrophobic bile acids has been implicated in the pathogenesis of liver injury in cholestatic liver disorders. We evaluated the effect of idebenone, a coenzyme Q analogue, on taurochenodeoxycholic acid (TCDC)-induced cell injury and oxidant stress in isolated rat hepatocytes and on glycochenodeoxycholic acid (GCDC)-induced generation of hydroperoxides in fresh hepatic mitochondria. Isolated rat hepatocytes in suspension under 9% oxygen atmosphere were preincubated with 0, 50, and 100 micromol/l idebenone for 30 min and then exposed to 1000 micromol/l TCDC for 4 h. LDH release (cell injury) and thiobarbituric acid reactive substances (measure of lipid peroxidation) increased after TCDC exposure but were markedly suppressed by idebenone pretreatment. In a second set of experiments, the addition of 100 micromol/l idebenone up to 3 h after hepatocytes were exposed to 1000 micromol/l TCDC resulted in abrogation of subsequent cell injury and markedly reduced oxidant damage to hepatocytes. Chenodeoxycholic acid concentrations increased to 5.15 nmol/10(6) cells after 2 h and to 7.05 after 4 h of incubation of hepatocytes with 1000 micromol/l TCDC, and did not differ in the presence of idebenone. In freshly isolated rat hepatic mitochondria, when respiration was stimulated by succinate, 10 micromol/l idebenone abrogated the generation of hydroperoxides during a 90-minute exposure to 400 micromol/l GCDC. These data demonstrate that idebenone functions as a potent protective hepatocyte antioxidant during hydrophobic bile acid toxicity, perhaps by reducing generation of oxygen free radicals in mitochondria.     

Managed care, school health programs, and adolescent health services: opportunities for health promotion

The rapid expansion of managed care creates opportunities and dilemmas for those involved in school health and adolescent health promotion. Managed care organizations (MCOs), public health agencies, and school and adolescent health providers share certain common goals and priorities including an emphasis on prevention, cost-effectiveness, and quality of care--and a willingness to explore innovative approaches to health promotion and disease prevention. However, MCOs often face conflicting challenges, balancing the goals of cost containment and investment in prevention. In considering support for school health programs, MCOs will be interested in evidence about the effectiveness of services in improving health and/or reducing medical expenditures. Mechanisms for improving prevention efforts within MCOs include quality assurance systems to monitor the performance of health plans, practice guidelines from professional organizations, and the contracting process between payers and health care providers. Development of partnerships between MCOs and schools will be a challenge given competing priorities, variation in managed care arrangements, structural differences between MCOs and schools, and variability in services provided by school health programs.