Assessing the needs of women and clinicians for the management of menopause in an HMO

Objective: To determine the perceived needs of perimenopausal women regarding the management of menopause and the resource needs of the clinicians who treat them. Setting: A large staff and group network model health maintenance organization (HMO) in New England. Participants: A random sample of 790 perimenopausal women aged 45–60 years who were members of the HMO in 1991, and a random sample of 180 clinicians in internal medicine, family practice, and obstetrics/gynecology practicing in the HMO during 1991. Method: Mailed surveys of women and clinicians were designed to assess possible needs and attitudes that could lead to the improvement of care for menopausal women. The chi-square test was used to determine differences in perceived needs and satisfaction levels among women with differences in self-reported menopausal status. The Kruskal-Wallis one-way analysis of variance and the Mann-Whitney U test were used in the clinician survey to test for differences among specialties and between genders. Results: The key findings include that: 1) most (81%) of the women wanted to see a woman clinician, 2) many (50%) were interested in a menopause support group, 3) 30% reported that their care for menopause had been fair to poor, 4) only 55% of the primary care specialists (including internal medicine and family practice) reported high confidence in their abilities to treat menopause, compared with 68% of the obstetric/gynecology clinicians, and 5) 56% of the clinicians surveyed said that support from the HMO to their practices for the treatment of menopause was fair to poor. Conclusions: There is an opportunity for better care for perimenopausal women as reported by two sources, HMO clinicians and members. To provide this care, clinicians may need explicit guidelines as well as administrative supports such as educational materials and specialty access. Since the capability for menopausal care from clinicians in obstetrics/gynecology is perceived to be higher than that from primary care clinicians, an opportunity for cross-specialty collaboration and training may exist.     

Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.     

Characterization of a dopamine receptor (DA2K) in the kidney inner medulla.

Dopamine (DA) produces a natriuretic/diuretic response in the kidney by mechanisms that are still not well understood. There is some indication that DA2 receptors may be involved in mediating the effects of DA, but little is known regarding the nature of this receptor in the kidney. Autoradiographic localization of [3H]spiperone, a DA2 antagonist, indicated that high-density binding was restricted to inner medullary collecting ducts (IMCDs). [3H]Spiperone binding was saturable, high affinity (Kd, 17.2 +/- 1.65 nM), and high density (Bmax, 935 +/- 83 fmol per mg of protein). The photosensitive spiperone analogue N-(p-azido-m-[125I]iodophenethyl)spiperone labeled similar sized proteins of Mr = 120,000 in membranes prepared from the kidney inner medulla, striatum, and pituitary. However, the rank-order competition profile for the [3H]spiperone binding in the kidney inner medulla differed from the DA2 receptor in striatum and pituitary and, furthermore, RNA (Northern) blot analyses of kidney inner medullary RNA with brain DA2 receptor oligonucleotide probes were negative. Functionally, DA stimulated prostaglandin E2 production by IMCD cells, an effect that could be blocked by the DA2 antagonist domperidone. These results indicate that the kidney inner medulla expresses a functional DA receptor that may represent a newly identified DA receptor subtype (here designated DA2K). Moreover, these results suggest that the kidney inner medulla may be a significant site at which DA, either directly or indirectly, influences water and electrolyte excretion.     

Psoriatic arthritis quality of life instrument: an assessment of sensitivity and response to change

OBJECTIVE: To assess responsiveness of the Psoriatic Arthritis Quality of Life tool (PsAQoL) and add further data regarding the construct validity of PsAQoL. METHODS: Twenty-eight patients with PsA underwent clinical assessment over a period of 6 months after change of disease modifying therapy, usually to methotrexate. Measures of outcome included PsAQoL, Health Assessment Questionnaire (HAQ), and assessment of disease activity. RESULTS: PsAQoL revealed significant change at 3 and 6 months. Standardized response mean was large at 3 months and small at 6 months. There was strong correlation with other patient-derived measures such as the HAQ and Patient Global at all timepoints. Disease Activity Score-28 and Physician Global showed a relationship with PsAQoL at 3 and 6 months, while a tender joint count relationship was seen only at 6 months. CONCLUSION: The PsAQoL now has responsiveness data and a measure of construct validity to sit alongside previously demonstrated reliability data. Our study has compared the change characteristcs within a group of patients. The next step in the development will require a placebo controlled trial to test discrimination between patients undergoing active treatment or taking placebo.     

Normal synthesis and expression of endothelial IIb/IIIa in Glanzmann's thrombasthenia

Glanzmann's thrombasthenia is a bleeding disorder, inherited in an autosomal recessive way and characterized by an absence or deficiency of the platelet glycoprotein (GP) IIb/IIIa complex. Recently, we and others demonstrated that cultured human umbilical vein endothelial cells synthesized a membrane protein complex similar to the platelet GP IIb/IIIa complex. In this article, we demonstrate that endothelial cells isolated from the umbilical vein of a newborn with Glanzmann's thrombasthenia, as compared with normal endothelial cells, show no difference in their ability to synthesize and express this GP IIb/IIIa complex. Our results indicate that Glanzmann's thrombasthenia is not accompanied by an "endotheliopathy."     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Kidney aminopeptidase A and hypertension, part I: spontaneously hypertensive rats

Tissue and plasma levels of aminopeptidase A (APA), the principal enzyme that hydrolyzes angiotensin II (Ang II) to angiotensin III, were measured in spontaneously hypertensive rats (SHR) and their normotensive control strain at 3 different ages corresponding to prehypertensive (4 weeks), developing (8 weeks), and established (16 weeks) phases of hypertension. Plasma APA activity was significantly but modestly elevated in SHR at all 3 ages compared with normotensive Wistar-Kyoto rats. Likewise, levels of APA in brain, heart, and adrenal gland were generally, but again only moderately, elevated in SHR at all ages. However, a large increase in APA activity was seen within the kidney in which APA levels were elevated 41%, 51%, and 68% in SHR at 4, 8, and 16 weeks of age, respectively. Kidney APA levels were also significantly increased in immunoblots from 8- and 16-week-old SHR. Glomeruli isolated from 16-week-old SHR had 57% higher APA activity and increased immunoreactivity compared with Wistar-Kyoto rats. To determine whether the increase in kidney APA activity in SHR was related to Ang II levels, SHR were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril. Captopril treatment reduced blood pressure to normotensive values and resulted in a 25% reduction in kidney APA activity. These results suggest that APA expression in the kidney may be regulated by activity of the renin-angiotensin system. If so, this would further suggest that upregulation of APA during conditions in which Ang II levels were elevated would have a protective effect against Ang II-mediated cardiovascular diseases, whereas a decrease in APA expression or a failure to upregulate would exacerbate such conditions.     

Craniofacial superimposition: a review of focus distance estimation methods and an extension to profile view photographs

International Journal of Legal Medicine - Craniofacial superimposition concerns the photographic overlay of skulls and faces, for skeletal identification. As a phased method that depends on...     

Autochthonous dermal leishmaniasis in Texas.

Over a 2-year period two cases of dermal leishmaniasis of special interest were recognized in Texas. The first occurred in 1972 in a 74-year-old woman who had residences in Dilworth and Gahzales, Gonzales County, and the other was in a 56-year-old man from Kenedy, Karnes County, in 1974. Both cases were biopsy- and culture-positive, and the second patient exhibited anti-Leishmania antibodies by indirect immunofluorescent antibody and direct agglutination tests. Epidemiologic investigation revealed no association between the two cases and suggested that both patients had acquired their infections locally in southern Texas. Moreover, serologic evidence of Leishmania infection was uncovered in a neighbor of the second case and in 3 dogs living nearby. Potential sylvatic reservoirs and arthropod vectors of the disease are resident in the area. Epidemiologic data suggest that dermal leishmaniasis is endemic in south-central Texas.