Iatrogenic secondary infertility caused by residual intrauterine fetal bone after midtrimester abortion

Eleven women with secondary infertility had ultrasonographic findings of intrauterine calcification. Infertility developed in all women after operative termination of midtrimester pregnancy. Dilation and curettage or hysteroscopic removal confirmed residual fetal bony fragments. The removal of these bony fragments was associated with therapeutic success for infertility.     

Characterization of adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice

Microvascular hyperaemia is decreased in subjects at risk of developing non-insulin-dependent diabetes mellitus (NIDDM) who have fasting hyperglycaemia. Such microvascular abnormalities may be involved in the pathogenesis of diabetic microangiopathy. To investigate the relationship of reduced microvascular hyperaemia to metabolic and blood pressure abnormalities associated with the prediabetic state, we studied 24 subjects with fasting hyperglycaemia and 24 age- and sex-matched control subjects. The microvascular hyperaemic response to local heating of the skin on the dorsum of the foot measured by laser Doppler fluximetry was reduced in the subjects with fasting hyperglycaemia (1.18 [0.87-1.83] volts vs 1.51 [1.30-2.14] volts normal subjects; p = 0.0002) and was negatively correlated with fasting plasma insulin concentration (Rs = 0.70; p = 0.001) and positively related to insulin sensitivity determined by continuous infusion of glucose with model assessment (CIGMA) (Rs = 0.52; p = 0.01), but showed no association with fasting plasma glucose, beta-cell function 24 h ambulatory blood pressure profiles or serum lipid concentrations. These results suggests that hyperinsulinaemia, as a result of insulin resistance, may have a detrimental effect on microvascular function in the prediabetic state.     

Propagation of genetically altered tumor cells derived from fine-needle aspirates of primary breast carcinoma

Because primary breast tumors are diagnosed earlier in the clinic, procurement of sufficient amounts of tumor tissue for in-depth biological characterization is becoming increasingly difficult. We demonstrate here that relatively small numbers of tumor cells within samples of fine-needle aspirates (FNA) can be propagated in culture. Of 25 cases attempted, 12 were passageable, resulting in up to 10(7) viable cells. FNA-derived cultures were evaluated for anchorage-independence, c-erb-B2 overexpression, aneusomy, and pattern of allelic loss. In every case examined, the cultured cells closely resembled the original tumor tissue and displayed one or more tumor phenotypes. The incidence of erb-B2 overexpressing tumors was similar in passageable and nonpassageable cases (33% versus 31%, respectively). FNAs that are expanded from a wide range of clinical breast material could be useful for functional studies presently limited to rare established cell lines, such as aberrant signal transduction and gene regulation, and for testing potential anticancer vaccines and drugs.     

High-throughput assay for G2 checkpoint inhibitors and identification of the structurally novel compound isogranulatimide

Treatment of cancer cells lacking p53 function with G2 checkpoint inhibitors sensitizes them to the toxic effects of DNA damage and has been proposed as a strategy for cancer therapy. However, few inhibitors are known, and they have been found serendipitously. We report the development of a G2 checkpoint inhibition assay that is suitable for high-throughput screening and its application to a screen of 1300 natural extracts. We present the isolation of a new G2 checkpoint inhibitor, the structurally novel compound isogranulatimide. In combination with gamma-irradiation, isogranulatimide selectively kills MCF-7 cells lacking p53 function.     

The intravenous administration of tumor necrosis factor alpha, interleukin 8 and macrophage-derived neutrophil chemotactic factor inhibits neutrophil migration by stimulating nitric oxide production

1. The i.v. administration of tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and the recently described macrophage-derived neutrophil chemotactic factor (MNCF) inhibits the recruitment of neutrophils to the inflammatory site. 2. Pretreatment of mice with the NO synthase antagonist, NG-monomethyl-L-arginine (L-NMMA, 15-60 mg kg(-1)), but not the inactive enantiomer D-NMMA (30 mg kg(-1)), prevented in a dose-dependent manner the TNF-alpha, IL-8 and MNCF-mediated inhibition of neutrophil migration into thioglycollate-challenged peritoneal cavities. 3. Treatment of the neutrophils with TNFalpha (10(-7) M), IL-8 (10(-7) M) or MNCF blocked their migration towards FMLP in the chemotaxis assay. The pretreatment of the neutrophils with L-NMMA (50-200 microM) prevented in a dose-dependent manner the inhibition of FMLP-induced chemotaxis by IL-8, but did not alter the inhibition caused by TNF-alpha or MNCF. Different concentrations of the NO donors, S-nitroso-N-acetylpenicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1), did not alter this chemotaxis. 4. Preincubating the neutrophils with L-NMMA (200 microM) significantly increased the TNF-alpha (10(-7) M) and MNCF-mediated neutrophil adhesion to unstimulated endothelial cells, but had no effect on IL-8 (10(-7) M)-mediated adhesion. 5. Although NO donors did not directly affect the mechanisms of neutrophil motility, NO is involved in the in vitro inhibitory action of IL-8 on chemotaxis. The TNF-alpha and MNCF-mediated inhibition of neutrophil migration seems to be indirect, by affecting the mechanisms of adhesion. It was concluded that TNF-alpha-, IL-8- and MNCF-mediated inhibition of neutrophil migration is associated with the stimulation of NO production.     

Hospital at home or acute hospital care? A cost minimisation analysis

OBJECTIVE: To compare, from the viewpoints of the NHS and social services and of patients, the costs associated with early discharge to a hospital at home scheme and those associated with continued care in an acute hospital. DESIGN: Cost minimisation analysis. SETTING: Acute hospital wards and the community in the north of Bristol (population about 224 000). SUBJECTS: 241 hospitalised but medically stable elderly patients who fulfilled the criteria for early discharge to a hospital at home scheme and who consented to participate. MAIN OUTCOME MEASURES: Costs to the NHS, social services, and patients over the 3 months after randomisation. RESULTS: The mean cost for hospital at home patients over the 3 months was 2516 pounds, whereas that for hospital patients was 3292 pounds. Under all the assumptions used in the sensitivity analysis, the cost of hospital at home care was less than that of hospital care. Only when hospital costs were assumed to be less than 50% of those used in the initial analysis was the difference equivocal. CONCLUSIONS: The hospital at home scheme is less costly than care in the acute hospital. These results may be generalisable to schemes of similar size and scope, operating in a similar context of rising acute admissions.     

Renal angiomyolipoma: embolotherapy with a mixture of alcohol and iodized oil

A monoclonal antibody, D5G2, which reacts in a balloon angioplasty damage model with unfixed damaged but not with unfixed undamaged human endothelial cells, was used to screen a human endothelial cDNA library in an Escherichia coli/lambda gt11 expression system. Sequences of DNA inserts in D5G2+ phage clones matched those reported for a laminin-binding protein, LBP-32. Both D5G2 and purified laminin bound to a polypeptide of 55 kD on PVDF membranes carrying electrophoretically separated endothelial cell lysates, D5G2 also bound to recombinant LBP expressed in E. coli, and showed similar staining patterns on human and bovine endothelial cells to another characterized anti-LBP antibody. Increased staining of unfixed endothelial cells on detergent permeabilization suggests that D5G2 binds to intracellular laminin-binding protein made accessible by cell membrane injury. Antibodies to intracellular targets exposed by cell damage may be useful in anchoring therapeutic agents at sites of vascular damage.     

Experimentally induced pulmonary arterial occlusion with detachable balloon in pigs: thin-section CT findings

RATIONALE AND OBJECTIVES: The authors evaluated changes of lung attenuation in pigs, with special attention to the mosaic pattern of low attenuation, at thin-section computed tomography (CT) after obstruction of the proximal pulmonary artery with a detachable balloon. MATERIALS AND METHODS: In seven pigs, nine sites of the descending pulmonary artery were obstructed with detachable balloons. This-section CT scans of the lungs were obtained immediately (n = 9) and at 1 week (n = 5), 2 weeks (n = 1), 3 weeks (n = 2), 4 weeks (n = 1), 6 weeks (n = 1), 8 weeks (n = 1), and 12 weeks (n = 1) after pulmonary artery obstruction. RESULTS: No statistically significant difference was found between the measured lung attenuation of the normal lung and that of the lung distal to the obstruction. Of the nine sites of pulmonary artery obstruction, five (56%) showed an irregular area of increased lung attenuation without lobular architecture. The diameter of the pulmonary artery after obstruction, compared with the diameter before obstruction, decreased by a range of 13%-57% (mean, 35%) and by 0-67% (mean, 44%) at levels 1 cm and 2 cm distal to the obstruction, respectively. CONCLUSION: This experimental study reveals that regional low-attenuation areas do not develop for up to 12 weeks after the obstruction of proximal pulmonary artery, despite a marked decrease in the diameter of the pulmonary artery distal to the obstruction.     

The immunohistological diagnosis of E. coli O157:H7 colitis: possible association with colonic ischemia

OBJECTIVE: E. coli O157:H7 may cause hemorrhagic colitis resembling ischemic colitis. Diagnosis is usually made by finding sorbitol-negative colonies on MacConkey agar that react with O157 and H7 antisera. Most ischemic colitis is idiopathic, but some may be caused by E. coli O157:H7, inasmuch as this organism can produce fibrin thrombi in colon vasculature. The objectives of this study were to determine whether E. coli O157:H7 infection can be diagnosed retrospectively from paraffin blocks of colon sections and whether an association exists between E. coli O157:H7 infection and colonic ischemia. METHODS: Paraffin-embedded sections of normal colon (n = 2) and various colitides [ischemic (n = 11), E. coli O157:H7 (n = 2), IBD (n = 8) and pseudomembranous (n = 3)] were used. Sections were deparaffinized, rehydrated, incubated with 3% peroxide in methanol, rinsed, and incubated with peroxidase-labeled antibody isolated from goats immunized with whole E. coli O157:H7. Sections were stained with peroxidase chromagen reagent and counterstained with hematoxylin. Coarse, granular, orange-brown staining was considered positive. To determine the localization of the chromagen deposits, three cases that stained positive, including one of the culture-proved E. coli O157:H7 colitis and two of colonic ischemia, were processed for electron microscopy. RESULTS: Both cases (100%) of E. coli O157:H7 colitis and three of 11 (27.3%) cases of ischemic colitis stained positive by light microscopy. In one culture-proved case, electron microscopy demonstrated staining of bacillary structures; in two cases of colonic ischemia, extensive deposits of chromagen material were present that were associated neither with inflammatory cells nor with bacterial forms. CONCLUSIONS: Immunoperoxidase staining of archival sections may be used to diagnose E. coli O157:H7 infection. An etiological role for this organism is possible in some cases of colonic ischemia.