Recognizing Gynecological Cancer in Primary Care: Risk Factors,Red Flags,and Referrals

Early diagnosis of symptomatic gynecological cancer is likely to improve patient outcomes, including survival. The primary care practitioner has a key role to play in this—they must recognize the symptoms and signs of gynecological cancer and make prompt evidence-based decisions regarding further investigation and referral. However, this is often difficult as many of the symptoms of gynecological cancers are nonspecific and are more likely to be caused by benign rather than malignant disease. As primary care is generally the first point of patient contact, those working in this setting usually encounter cancer patients at an earlier, and possibly less symptomatic, stage than practitioners in secondary care. Despite these challenges, research has improved our understanding of the symptoms patients present to primary care with, and a range of tests and referral pathways now exist in the UK and other countries to aid early diagnosis. Primary care practitioners can also play a key role in gynecological cancer prevention. A significant proportion of gynecological cancer is preventable either through lifestyle changes such as weight loss, or, for cervical cancer, vaccination and/or engagement with screening programs. Primary care provides an excellent opportunity to discuss cancer risk with patients and to promote risk reduction strategies and lifestyle change. In this article, the first in a series discussing cancer detection in primary care, we concentrate on gynecological cancer and focus on the three most common forms that a primary care practitioner is likely to encounter: ovarian, endometrial, and cervical cancer. We outline key risk factors, briefly discuss prevention and screening strategies, and offer practical guidance on the recognition of symptoms and signs and the investigation and referral of women with suspected cancer. While this article is written from a UK primary care perspective, much of what is discussed will be of relevance to those working in other healthcare systems.     

Effects of megestrol acetate on circulating interleukin-15 and interleukin-18 concentrations in healthy elderly men

BACKGROUND: Interleukin-15 (IL-15) and interleukin-18 (IL-18) are potential regulators of body composition in humans. The authors previously reported that megestrol acetate ingestion causes a large accumulation of adipose tissue and reduces muscle mass. Therefore, the purpose of this investigation was to evaluate the effects of megestrol acetate ingestion on circulating IL-15 and IL-18 concentrations in healthy elderly men. METHODS: All participants received 800 mg of megestrol acetate per day during this 12-week study. Megestrol acetate was combined with testosterone injections (100 mg/week), placebo injections, resistance training, or resistance training and testosterone. Resting IL-15 and IL-18 concentrations were measured by enzyme-linked immunosorbent assay at week 0 (pre), week 6 (mid), and week 12 (post). RESULTS: The time effect for IL-15 was significant (p = .0008), with the mid and post values being significantly greater than the pre value. The change in IL-15 concentration was not significantly related to the change in muscle mass (r = -.31; p > .05), nor was it related to the change in fat mass (r =.17; p > .05). Differences among groups or over time were not significant for IL-18, nor were correlations between pre body weight and pre IL-18 (r = -.03), pre fat mass and pre IL-18 (r = .14), or the change in fat mass and the change in IL-18 (r = -.07). CONCLUSIONS: IL-15 was increased as a result of megestrol acetate ingestion; however, megestrol acetate did not affect circulating IL-18 concentrations, and the change in IL-18 did not correlate with any body composition variables.     

Antithrombin Sheffield: amino acid substitution at the reactive site (Arg393 to His) causing thrombosis

A Sheffield family with a predisposition towards thrombosis has been shown to have a functional abnormality of antithrombin. The abnormality was detected as reduced heparin cofactor activity, with normal antigenic levels of antithrombin. Crossed immunoelectrophoresis performed in the absence and presence of heparin was normal. The antithrombin was isolated by heparin Sepharose affinity chromatography. It had normal mobility on SDS polyacrylamide gel electrophoresis. However, the second order rate constant of inhibition of thrombin was about half that of normal, and this was compatible with a heterozygous abnormality involving the reactive site. The antithrombin was further purified by chromatography on thrombin-Sepharose (to remove the normal component), reduced, S-carboxymethylated and fragmented with cyanogen bromide. A pool containing the reactive site region was digested with trypsin and the molecular size of peptides generated determined by fast atom bombardment mass spectrometry. The two peptides adjacent to the Arg393-Ser394 bond of mass 2290 and 700 were almost absent from the mass spectrum, but an additional peptide of mass 2952 was present. Subdigestion with V8 protease reduced the mass of this peptide to 1748. These peptides generated by trypsin and V8 protease were almost identical to those obtained when another variant, antithrombin Glasgow, was treated in the same way (Erdjument et al, 1988). It is concluded that the molecular abnormality of antithrombin Sheffield is identical to that of antithrombin Glasgow, Arg393 to His.     

Neurovascular axillary variations: superficial brachial artery and single-corded brachial plexus

Anatomical Science International - Variants of the axillary artery and brachial plexus were found bilaterally in the axilla of an 86-year-old Asian female. On the left, the cadaver donor had a high...     

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.