Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6, and tumor necrosis factor-alpha.

OBJECTIVE: We investigated whether monocyte-derived factors could stimulate the growth of ovarian cancer cells. STUDY DESIGN: Human peripheral blood monocytes or human monocyte-like cell lines THP-1 and U-937 were cultured with or without macrophage colony-stimulating factor, lipopolysaccharide, or phorbol myristate acetate. Culture supernatants or recombinant cytokines were assayed for growth stimulation of ovarian cancer cell lines by tritium-thymidine incorporation and direct cell counts followed by statistical analysis with Student t test. RESULTS: Conditioned medium from peripheral blood monocytes or from THP-1 or U-937 cells stimulated ovarian cancer cell growth. Interleukin-1 alpha, tumor necrosis factor-alpha, and interleukin-6 also stimulated ovarian cancer cell growth, whereas macrophage, granulocyte, and granulocyte-macrophage colony-stimulating factor did not. Concentrations of tumor necrosis factor, interleukin-1, and interleukin-6 in conditioned medium could not account for all the growth stimulation, and activity remained after neutralization of tumor necrosis factor, interleukin-1, and interleukin-6 with antibodies. CONCLUSIONS: Interleukin-1, interleukin-6, tumor necrosis factor, and additional monocyte factor(s) could provide paracrine growth stimulation when monocytes are attracted to ovarian cancers that produce macrophage colony-stimulating factor.     

Recurrent eosinophilic cystitis: a case responsive to steroids.

We report a case of eosinophilic cystitis that was responsive to prednisone but that recurred when the drug was withdrawn. The cause of eosinophilic cystitis remains an enigma but it probably represents a form of allergy. Investigation of etiology and therapeutic options are discussed.     

Relative potency estimates of acceptable residues and reentry intervals after nerve agent release

In the event of an unplanned release of a chemical warfare agent during any stage of the Chemical Stockpile Disposal Program, the potential exists for off-post contamination of drinking water, forage crops, grains, garden produce, and livestock. The more persistent agents, such as the organophosphate nerve agent VX, pose the greatest human health concern for reentry. A relative potency approach comparing the toxicity of VX to organophosphate insecticide analogues is developed and used to estimate allowable residues for VX in agricultural products and reentry intervals for public access to contaminated areas. Analysis of mammalian LD50 data by all exposure routes indicates that VX is 10(3) to 10(4) times more toxic than most commercially available organophosphate insecticides. Thus, allowable residues of VX could be considered at concentration levels 10(3) to 10(4) lower than those established for certain insecticides by the U.S. EPA. Evaluation of reentry intervals developed for these organophosphate analogues indicate that, if environmental monitoring cannot reliably demonstrate acceptable levels of VX, restricted access to suspect or contaminated areas may be on the order of weeks to months following agent release. Planning for relocation, mass care centers, and quarantine should take this time period into account.     

The impact of near-patient testing on the organisation and costs of an anticonvulsant clinic

A near-patient testing facility was provided at an anticonvulsant clinic and compared with the previously offered service. Productivity was increased by over 20%, with savings in medical and nursing staff time. This saving in time is offset by increased consumable costs but still enables a significant net saving.     

Ciprostene and indomethacin partially reverse the mechanisms of distal end necrosis in the rat random skin flap.

Survival of random skin flap distal end depends on hemodynamic, cellular, and coagulation mechanisms. This study was designed to evaluate whether administration of ciprostene, a stable prostaglandin I2 analogue, and indomethacin, a cyclooxygenase-hydroperoxydase enzyme inhibitor, would improve the survival rate of random skin flaps. Forty-five male rats were divided into nine groups and injected with sesame oil (control), ciprostene (20 micrograms/kg/day), and/or indomethacin (2 mg/kg/day). Injections were done before (pretreatment for 4 days), after (posttreatment for 6 days), and before/after (pre/posttreatment for 4 and 6 days, respectively) the elevation of random dorsal skin flaps. In the pretreatment and pre/posttreatment studies, the flap survival rate of all drug-injected groups was significantly higher than that of the control group (p less than 0.02). In addition administration of ciprostene alone yielded a trend of better flap survival rate, which, however, was not statistically significant (p less than 0.12). Of interest in the posttreatment study, only the simultaneous administration of ciprostene and indomethacin significantly increased skin flap viability compared with the other groups (p less than 0.02). Therefore, the results demonstrated that administration of ciprostene and indomethacin either alone or together partially reversed the pathophysiological mechanisms that cause necrosis of random skin flap distal end. These pharmacological changes significantly improved random skin flap survival rate.     

Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia

Multiple reports of cauda equina syndrome and transient radicular nerve root irritation have suggested that lidocaine spinal anesthesia may be responsible. In this case report, a patient with a preexisting diabetic neuropathy received a partial block following a tetracaine spinal, which was followed by a lidocaine spinal. Following block resolution, a new conus medullaris syndrome was diagnosed. Because of the close proximity of the cauda equina and the conus medullaris, differentiation between these syndromes can be difficult. The preexisting diabetic neuropathy may have predisposed this patient to neurologic injury. The choice of a different local anesthetic drug with less neurotoxic potential such as bupivacaine may have prevented this injury.     

Automated neuropsychological assessment metrics (ANAM) measures of cognitive effects of Alzheimer's disease.

Eight individuals with Alzheimer's disease, and eight age-matched controls, were administered the MMSE, the Yesavage GDS, and a customized subset of the Automated Neuropsychological Assessment Metrics (ANAM) Battery. Accuracy (percent correct) and efficiency (number of correct responses per minute) of performance on six ANAM tasks were assessed. The patients' GDS scores indicated no depression. Although their MMSE scores (mean approximately 25) were significantly lower than those of the controls, they nonetheless indicated that the patients were still functioning at a fairly high level. Analysis of ANAM accuracy scores indicated that the patients were significantly impaired on three tasks measuring working memory. A discriminant function analysis revealed 93.8% correct classification. Analysis of ANAM efficiency scores revealed that except for simple reaction time, the patients were significantly impaired on all tasks. A discriminant function analysis correctly classified 100% of the participants. Given the small size of the groups in the present study, this finding especially underscores the sensitivity of ANAM to the cognitive effects of Alzheimer's disease, as indicated by the large effect sizes. The findings further indicate that ANAM might be capable of detecting more subtle effects of the disease at an earlier stage in its progress.     

Loss of Heterozygosity at the α-Inhibin Locus on Chromosome 2q Is Not a Feature of Human Granulosa Cell Tumors

The α-inhibin gene has been shown in knockout mouse models to be a suppressor of granulosa tumorigenesis in the mouse. To determine if α-inhibin has the same function in humans, we have assessed the frequency of loss of heterozygosity (LOH) of the α-inhibin gene locus on chromosome 2q in 17 human granulosa cell tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%) epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data suggest that in contrast to the suggestions from the mouse model α-inhibin does not function as a granulosa cell tumor suppressor gene in the human. Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to detect either LOH or point mutations, indicating that they have a developmental pathway distinct from that of epithelial ovarian tumors.