Primary renal candidiasis: fungal mycetomas in the kidney

Fungal infections of the urinary tract have a predilection for drainage structures rather than for the renal parenchyma. Of the causal factors, diabetes mellitus, immunosupressed states, AIDS and prematurity are those most commonly encountered. The case of a young, diabetic man whose chief clinical presentation was dysuria is described. On further examination he was found to harbour fungal balls in the right kidney. Radiological manifestations of acute pyelonephritis were also present. Although primary renal candidiasis is often commensurate with systemic fungaemia, he displayed none of the clinical features of disseminate infection and, hence, was treated conservatively with oral antifungal agents. Fortuitously, spontaneous passage of fungal particulate matter in urine was later reported.     

Training and education needs of consumers,families, and front-line staff in behavioral health practice

Much of the behavioral health care delivered to people with serious mental illnesses and chronic addictive disorders is provided by front-line or direct service mental health workers. Issues related to the qualifications, training, and ongoing evaluation of the competencies of this important provider group have received scant attention in the behavioral health field. This paper explores the educational needs and best practices of the consumers and families who carry much of the burden of caring for disabled populations, as well as the front-line staff, many of whom are employed in state psychiatric hospitals and community mental health or addiction treatment systems. Within the overall context of culturally competent behavioral health care, specific recommendations are proposed in an attempt to move the field forward.     

Identification and evaluation of existing nursing homes quality indicators

We summarize work done to identify and evaluate existing quality indicators (QIs) for long-term care (LTC) settings. Indicators operationally defined using routinely collected and computerized patient assessments were identified and then aggregated to characterize the performance of the nursing facility over a specific period of time. Of 143 indicators reviewed, only 22 were recommended for use in comparing performance across facilities. Conceptual and technical issues influence the appropriateness of QIs for different audiences.     

On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles

We investigated the effect of multiple susceptibility alleles at a single disease locus on the statistical power of a likelihood ratio test to detect association between alleles at a marker locus and a disease phenotype in a case-control design. Using simplifying assumptions to obtain the joint frequency distribution of marker and disease locus alleles, we present numerical results that illustrate the impact of historical variation of initial associations between marker alleles and susceptibility alleles on the power of a likelihood ratio test for association. Our results show that an increase in the number of susceptibility alleles produces a decrease in power of the likelihood ratio test. The decrease in power in the presence of multiple susceptibility alleles, however, is less for markers with multiple alleles than for markers with two alleles. We investigate the implications of this observation for tests of association based on haplotypes made up of tightly linked single-nucleotide polymorphisms (SNPs). Our results suggest that an analysis based on haplotypes can be advantageous over an analysis based on individual SNPs in the presence of multiple susceptibility alleles, particularly when linkage disequilibria between SNPs is weak. The results provide motivation for further development of statistical methods based on haplotypes for assessing the potential for association methods to identify and locate complex disease genes.     

The Role of EGFR-Directed Therapy in the Treatment of Breast Cancer

The development of secondary arm lymphoedema after the removal of axillary lymph nodes remains a potential problem for women with breast cancer. This study investigated the incidence of arm lymphoedema following axillary dissection to determine the effect of prospective monitoring and early physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were made preoperatively, at day 5 and at 1, 3, 6, 12 and 24 months postoperatively. Three measurements were used for the detection of arm lymphoedema: arm circumferences (CIRC), arm volume (VOL) and multi-frequency bioimpedance (MFBIA). Clinically significant lymphoedema was confirmed by an increase of at least 200 ml from the preoperative difference between the two arms. Using this definition, the incidence of lymphoedema at 24 mo. was 21%, with a rate of 11% in the TG compared to 30% in the CG. The CIRC or MFBIA methods failed to detect lymphoedema in up to 50% of women who demonstrated an increase of at least 200 ml in the VOL of the operated arm compared to the unoperated arm. The physiotherapy intervention programme for the TG women included principles for lymphoedema risk minimisation and early management of this condition when it was identified. These strategies appear to reduce the development of secondary lymphoedema and alter its progression in comparison to the CG women. Monitoring of these women is continuing and will determine if these benefits are maintained over a longer period for women with early lymphoedema after breast cancer surgery.     

Sequential extension of proliferative lifespan in human fibroblasts induced by over-expression of CDK4 or 6 and loss of p53 function

Replicative senescence is thought to be a significant barrier to human tumorigenesis, which in human fibroblasts, and many other cell types, can be overcome experimentally by combined loss of function of p53 and Rb 'pathways'. To avoid the confounding pleiotropic effects of HPVE7 frequently used in such studies, here we have employed retroviral vectors over-expressing CDK4 or CDK6 as a more representative model of naturally-occurring mutations targeting the Rb pathway. We show that these can extend fibroblast lifespan by approximately 10 population doublings, ending in a viable senescence-like state which contrasts with the apoptotic end-stage seen with E7. Compared with 'normal' senescence, this growth arrest was, in most cases, not accompanied by any further increase in p21(Waf1) levels but with up to a 19-fold increase in p16(Ink4a). Surprisingly however, this could not explain arrest, since expression of mutant CDK4 and/or CDK6, incapable of binding p16(Ink4a), did not confer any greater lifespan extension than the wild-type CDKs. Subsequent abrogation of p53 function by a second vector, encoding HPVE6, downregulated p21(Waf1) and conferred a second lifespan extension, ending in a crisis-like state, consistent with full escape from senescence. These data: (i) point to a back-up 'senescence' mechanism distinct from induction of p21(Waf1) or p16(Ink4a); and (ii) provide an in vitro model of clonal evolution through successive dysfunction of Rb and p53 pathways in a relevant human cell context.     

The need to know: informal carers and information

There is a growing recognition that the carers of cancer patients require information. A key source of this information is the formal health care system that patients, and thus carers, encounter. However, the research literature suggests a lack of clarity on the part of service providers concerning the type, amount, timing and purpose of information for carers. This lack of clarity is reflected in the ways carers have been 'tacked on' to patients and thus are often treated as co-clients. That carers are also an active participants in the illness scenario is not always fully recognized, resulting in failure to provide appropriate information. Carers' interactions with health service providers are complex and context bound, and entail potential tensions of allegiance in the arena of information exchange. This article suggests that the following research and practice is required: a clearer understanding of the informational needs of carers in variable situations, specific ways to address these needs, where carers 'fit in' to the health care system, and how processes of information exchange with carers can be improved.     

Clinical applications of proton MR spectroscopy in oncology

Proton magnetic resonance spectroscopy (H1-MRS) has been increasingly receiving more attention from radiologists, neurosurgeons, radiation and medical oncologists in the "in situ" clinical evaluation of human tumors. The utilization of H1-MRS, especially in human brain tumors, coupled to both routine magnetic resonance imaging (MRI) and functional MRI techniques provides greater information concerning tumor grading and extension and characterization of the normal surrounding tissue than what is possible with any other imaging technique alone. In this paper, we will review the current status of proton MR spectroscopy with emphasis on its clinical utility to diagnose tumors, its utility in planning surgical and radiation therapy interventions, and in its use in monitoring tumor treatment.     

Testosterone recovery following prolonged adjuvant androgen ablation for prostate carcinoma

BACKGROUND: This study was conducted to describe the rate and completeness of the recovery of testosterone production following prolonged temporary androgen ablative therapy in men with prostate carcinoma undergoing curative radiation therapy. METHODS: Two-hundred and sixty-seven men treated with between 3 months and 3 years of adjuvant androgen ablation (AA) were followed at 6-month intervals following cessation of their androgen deprivation therapy. A comparative group of 518 men not undergoing AA were also followed. RESULTS: Drugs used included low dose cyproterone/stilboestrol (CPA/DES) in combination (56%) and 1 month depot (18%) and 3 month depot (25%) leutinizing hormone releasing hormone agonist (LHRHa). Seventy-nine percent of men in the current study recovered normal testosterone levels (10nmol/L), and 93% recovered levels of at least 5nmol/L. In comparison, men who had never received androgen ablative therapy showed a fall of testosterone, with 17% having sub-normal levels after 3 years. Median time to testosterone recovery was 10 months. Factors associated on multivariate analysis with delayed testosterone recovery included advanced age (P = 0.008), low pre-therapy testosterone (P = 0.04), and the use of 3 month LHRHa preparations as compared with CPA/DES (P = 0.002) or 1 month LHRHa preparations (P = 0.015). The duration of drug use was not significantly associated with time to testosterone recovery. CONCLUSIONS: Long-acting LHRHa preparations appear to have a more prolonged action than previously supposed. Most men treated for up to 2 years recover normal testosterone levels after cessation of adjuvant androgen ablation, and the limited data available in the current study on patients treated for 3 years also suggests most will recover.