Ultrasonographic endometrial thickness for diagnosing endometrial pathology in postmenopausal bleeding.

We conducted this retrospective analysis of our clinical data to identify the incidence of benign endometrial abnormalities, endometrial carcinoma and to find out the endometrial thickness (ET) cut-off point using trans-vaginal ultrasonography for patients with postmenopausal bleeding (PMB) referred to the Rapid Access Clinic in Northampton General Hospital. All women referred between April 2004 and April 2005 with PMB were included in this analysis. Final diagnostic outcome was classified into benign endometrial polyp, endometrial hyperplasia, endometrial carcinoma or normal (by excluding these pathologies). A total of 142 patients were included in this survey. The incidence of abnormal endometrial pathology was found to be 23.9% and 5% for endometrial carcinoma. Our results suggested that benign endometrial pathology is the most common cause of postmenopausal bleeding. Lowering the endometrial thickness cut-off point from 5 mm to 3 mm will not improve the diagnostic accuracy of endometrial carcinoma.

A novel human stress response-related gene with a potential role in induced radioresistance.

We have isolated a novel gene, DIR1, from L132 cells that is transiently repressed after exposure to low radiation doses and has a potential role in induced radioresistance. Molecular and cellular characterization of this gene reveals that it is unique but has similarities to a family of heat-shock-related proteins known as immunophilins. These have been implicated in various cellular functions including general stress responses and control of the cell cycle. Antisense strategies have demonstrated that the DIR1 gene also appears to have some involvement in the control of the cell cycle. Furthermore, there appears be a potential role for this gene product in the phenomenon of induced radioresistance through a mechanism that increases the rate of DNA repair in cells exposed to X rays and subsequently increases the cells' resistance to radiation. This is the first description of an immunophilin-like gene that has a possible role in adaptive/inducible responses to X rays in mammalian cells.

Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.

The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated through permanent indwelling subarachnoid catheters. Human glioma D-456 MG growing in the subarachnoid space was treated with 8.1 micromol of intrathecal Spartaject Busulfan. Single-dose therapy was also subsequently compared with 4 doses of 8.1 and 2.0 micromol busulfan, respectively, against D-456 MG neoplastic meningitis. Additional experiments evaluated a saline control versus 8.1 micromol x 1, 6.2 micromol x 4 and 4.1 micromol x 4, respectively, against D-456 MG. A single dose of 8.1 micromol of intrathecal Spartaject Busulfan resulted in an increase in median survival of 61.7% compared with the saline control. In experiment 2, all busulfan treatments showed increases in median survival of 142.8% (8.1 micromol x 1), 52.3% (2.0 micromol x 4), and 23% (8.1 micromol x 4) (p < 0.001 for all groups) compared with the saline control. These results suggest that a narrow therapeutic dose range for both toxicity and activity has been defined for intrathecal busulfan in the treatment of human neoplastic meningitis in athymic nude rats. Although busulfan has only limited activity against solid tumors, the high doses achievable in the CSF following intrathecal administration coupled with the steep dose-response relationships of alkylating agents, provide rationale for further evaluation of this agent.

Ectopic pregnancy - laparoscopic management in a district general hospital.

A 2-year retrospective study was carried out in a district general hospital to review the outcome of laparoscopic management versus laparotomy for the management of ectopic pregnancy. Outcome measures included operating time, postoperative analgesia requirements, complications, length of hospital stay, the post-ectopic intrauterine pregnancy rates and the recurrent ectopic pregnancy rates over an observational period of 16 months. Forty-nine consecutive women were seen. Twenty-six were managed laparoscopically and 23 were managed by laparotomy. There was no significant difference between the operating times and complications but the laparoscopy group had significantly fewer doses of opiate analgesia (P<0.05), shorter length of stay (P<0.05), and significantly higher post-ectopic intrauterine pregnancy rates (P<0.05) compared with the laparotomy group. Laparoscopic management of ectopic pregnancy is a viable alternative to conventional laparotomy in district general hospitals.

Conducted vascular responses: communication across the capillary bed.

Conducted vasomotor responses are important for the effective distribution of blood flow, although the mechanism by which these responses are initiated is not well understood. ATP, a substance which is released from circulating red blood cells in response to low PO2 and low pH, two conditions which are associated with decreased supply relative to demand, has been shown to initiate conducted vasodilation following its intraluminal application in first and second order arterioles. Since such low PO2 and low pH conditions would most likely occur on the venous side of the vasculature, we evaluated the response of the arteriolar and capillary networks to application of ATP into venules in the Saran-covered hamster cheek pouch retractor muscle using in vivo video microscopy. Intraluminal application of 40 and 400 pl of 10(-6) M ATP resulted in dose-dependent increases in arteriolar diameter > 450 microm upstream from the site of application. These changes in arteriolar diameter were accompanied by significant increases in red blood cell flux. In capillaries, red blood cell flux doubled in response to ATP administration. Since NO was previously determined to be involved in the vascular response to intraluminal ATP in arterioles, we evaluated its role in these responses. We found that systemic administration of l-NAME prior to ATP application eliminated any conducted response and this effect of l-NAME was reversed by the systemic administration of l-arginine. These data suggest that ATP, which is released from red blood cells in response to low PO2 and low pH, conditions which would be found in the venular microvasculature, may serve a role in distributing perfusion in response to alterations in supply.

Arteriolar responses to extracellular ATP in striated muscle.

Blood flow and its distribution must be appropriately regulated to ensure that perfusion is matched to local tissue demands. We investigated the role of ATP in triggering a conducted alteration in arteriolar diameter in the Saran-covered cheek pouch retractor muscle of anesthetized hamsters (n = 60). Vascular responses were observed using in vivo video microscopy upstream from the site of micropressure application of ATP (10(-8)-10(-4) M) either into the lumen or just outside the wall of first- and second-order arterioles. The role of nitric oxide (NO) in the vascular responses to ATP was determined by inhibiting NO synthase activity with N(omega)-nitro-L-arginine methyl ester (L-NAME) with and without coadministration of an excess of L-arginine. Intraluminal application of ATP led to a concentration-dependent vasodilation, which was conducted upstream along the arteriole. The dilatory response was blocked by systemic pretreatment with L-NAME and was maintained in the presence of an excess of L-arginine. In contrast, ATP introduced extraluminally resulted in a conducted vasoconstrictor response that was enhanced by pretreatment with L-NAME. The dilator response to intraluminal ATP, in the context of ATP release from erythrocytes under conditions associated with decreased supply relative to demand, supports a role for the erythrocyte in communicating local tissue needs to the vasculature, enabling the appropriate matching of oxygen supply to demand.

The other side of affirmative action: reactions of nonbeneficiaries to sex-based preferential selection.

Researchers studied 162 male undergraduates in an experiment designed to investigate how the experience of unfair treatment affects the reactions of nonbeneficiaries of sex-based preferential selection in terms of responses to the work task, characterizations of the woman beneficiary, and prosocial orientation to the work setting. The basis of selection (merit or preference), the comparative ability of the participant and the selectee (superior, inferior, equal, or unknown) and the presence or absence of one type of explanatory justification for the selection decision (an ideological account) were systematically varied. Results indicated that preferential selection can produce negative reactions on the part of nonbeneficiaries. However, reactions to preferential selection were not always uniform, and procedural and distributive aspects of unfairness concerns were found to have consequences for different types of nonbeneficiary reactions. In addition, the mitigating effects of the ideological account were found to be limited to situations in which the beneficiary and nonbeneficiary were believed to be equally qualified.

Quantification of DNA damage and repair in amino acid auxotrophs and UV-sensitive mutants of Aspergillus nidulans using an ELISA.

An ELISA used to investigate DNA repair in mammalian cells has been adapted to investigate mutagen-induced DNA damage and repair in protoplasts of Aspergillus nidulans. The assay shows a reduced rate of repair of DNA damage in methionine and arginine auxotrophs (methG and argB), which were shown previously to be hypersensitive to UV radiation and chemical mutagens. The assay also showed a considerably reduced ability to repair mutagen-induced damage in the uv-sensitive mutants uvsB and uvsH. The increased sensitivity of amino acids auxotrophs to mutagens is, therefore, correlated with a reduced capacity to repair mutagen-induced DNA damage.

Germinating conidiospores of Aspergillus amino acid auxotrophs are hypersensitive to heat shock, oxidative stress and DNA damage.

Germinating conidiospores (conidia) of Aspergillus nidulans amino acid-requiring strains are hypersensitive to heat, oxidative stress, UV radiation and chemical mutagens when compared with other strains. They also showed an increased mutation rate. Sensitivity to stress conditions has been correlated with an abnormal RAS/cAMP pathway in mutants of S. cerevisiae. We suggest that the RAS/cAMP pathway is defective in germinating conidia of Aspergillus amino acid auxotrophs and that this is responsible for suppressing DNA repair and conferring sensitivity to oxidative stress and heat shock.

Lipid-cholesterol interactions in the P beta' phase. Application of a statistical mechanical model.

We describe a statistical mechanical model for lipid-cholesterol mixtures in the P beta' (ripple) phase of lipid bilayers. The model is a simple extension of an earlier model for the ripple phase in pure lipid bilayers. The extension consists of adding a degree of freedom to allow for the occupation of underlying lattice sites by cholesterol molecules, and adding a lipid-cholesterol interaction term to the model Hamiltonian. The interaction term was constructed based on numerical calculations of lipid-cholesterol energies for several different packing juxtapositions of the two molecules. Other than the lipid-cholesterol interactions, the extended model uses the same parameter set as the earlier model, so that comparison of the properties of the extended model with experimental data serves as a test of the validity of the original model. Properties of the model were calculated using the Monte Carlo method. Results are displayed as snapshots of the ripple configurations at different cholesterol concentrations. The spacing of the ripples increases with increasing cholesterol concentration and the rate of increase compares very well with experimental data. The success of this model supports the conclusion drawn earlier that frustration arising from anisotropic packing interactions is responsible for the ripple phase in lipid bilayers. In the extended model these packing interactions are responsible for the selective partitioning of cholesterol in the regions between the ripples.

Properties of genes involved in the control of isocitrate lyase production in Aspergillus nidulans.

The interaction between genes of Aspergillus nidulans conferring constitutive synthesis of isocitrate lyase (iclc A and iclcB) and fluoroacetate resistance (facB) has been investigated. Although facB mutants are unable to induce the glyoxylate cycle enzyme isocitrate lyase in response to acetate as sole carbon source, this phenotype was suppressed in recombinants of the type iclc;facB. The iclcA and iclcB mutations do not alter significantly the activities of eight enzymes of intermediary metabolism assayed. We conclude that the iclc genes are probably bona fide isocitrate lyase regulatory genes.

An acetate-sensitive mutant of Neurospora crassa deficient in acetyl-CoA hydrolase.

The predicted amino acid sequence of the product of the acetate-inducible acu-8 gene of Neurospora crassa, previously of unknown function, has close homology to the recently published sequence of Saccharomyces cerevisiae acetyl-CoA hydrolase. An acu-8 mutant strain, previously characterized as acetate non-utilizing, shows strong growth-inhibition by acetate, but will use it as carbon source at low concentrations. The mutant was shown to be deficient in acetyl-CoA hydrolase and to accumulate acetyl-CoA when supplied with acetate. As in Saccharomyces, the Neurospora enzyme is acetate-inducible.

A comparison of an innovative four-hour EMT-D course with a 'standard' ten-hour course.

A study was conducted to determine if a four-hour emergency medical technician-defibrillation (EMT-D) course could produce student skills equivalent to a "standard" ten-hour EMT-D course. Two matched groups of EMTs were established, one of which was instructed by a four-hour course (study group) while the other (control group) entered a "standard" ten-hour course. On both written and practical testing, one week and 18 months after the completion of the course, the study group was comparable to the control group. These results indicate that the more cost-effective four-hour course can be used, thus encouraging the widespread availability of cardiac defibrillation by EMTs.

Palliative pelvic exenteration--futility revisited.

In a retrospective review of 23 pelvic exenterations performed at Miami Valley Hospital, 8 were considered to be palliative procedures because of pelvic or paraaortic lymph node metastases, pelvic peritoneal involvement, pelvic sidewall extension, or distant spread. Following palliative exenteration, morbidity and mortality were high, survival was low, and quality of life was uniformly poor. With rare exceptions, pelvic exenteration as a palliative procedure should not be deliberately performed.

Recurrent ileal mucinous adenocarcinoma in an ileostomy.

We report an adenocarcinoma arising in an ileostomy after colectomy for ulcerative colitis and discuss the treatment of a localized recurrence.

Bereavement--an etiologic factor in peptic ulcer in childhood and adolescence?

Bereavement in childhood and adolescence is a relatively common experience. This case report and two studies suggest that the ulcer-prone adolescent may develop clinically significant symptoms under the stress of adapting to a recent loss of a loved one.