Diabetes and HIV.

The co-existence of diabetes mellitus and HIV infection poses significant challenges for both patient and physician. This article reviews the clinical problems, the implications for treatment plans and potential confusions that can arise when managing patients who have both conditions.

Combined (99m)Tc-methoxyisobutylisonitrile scintigraphy and fine-needle aspiration cytology offers an accurate and potentially cost-effective investigative strategy for the assessment of solitary or dominant thyroid nodules.

Purpose: Fine-needle aspiration (FNA) has revolutionised the care of patients with thyroid nodules and is the initial investigation of choice. However, as a result of nondiagnostic (Thy1) and nonneoplastic (Thy2) specimens, it remains an imperfect sole solution with a range of sensitivities and a high inadequate ratio. Therefore the British Thyroid Association (BTA) guidelines recommend a second FNA immediately for Thy1 specimens and 3-6 months later for Thy2 specimens.

Erectile dysfunction in general medicine.

Erectile dysfunction (ED) affects millions of men worldwide with implications that go far beyond sexual activity. ED is now recognised as an early marker of cardiovascular disease, diabetes mellitus (DM) and depression. The risk factors that are associated with ED (sedentary lifestyle, obesity, smoking, hypercholesterolaemia and the metabolic syndrome) are very similar to those for cardiovascular disease (CVD).

Highly selective 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase.

We report the SAR around a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. 2-Aminophenethyl analogs demonstrate excellent potency but moderate kinase selectivity, while 2-aminobenzyl analogs that fill the Ala571 subpocket exhibit good inhibition activity and excellent kinase selectivity.

Psychological and quality of life changes in patients using GLP-1 analogues.

Aims: Using psychological and quality of life assessment tools, we prospectively studied changes in health-related quality of life and emotional well-being in patients who had commenced GLP-1 analogue therapy (exenatide) and compared them with new insulin starters.

Methods: Two matched groups of patients with type 2 diabetes who had suboptimal glycaemic control on oral medication were assessed using a battery of well-validated psychological and quality of life tests at baseline, prior to commencement of treatment and then again after 6 months of continuous therapy, along with body mass index (BMI) and hemoglobin A1c (HbA1c) measurements.

Results: In the exenatide-treated patient group (n=71), treatment satisfaction was greater (P<.

Unusual initial manifestation of metastatic follicular carcinoma of the thyroid with thyrotoxicosis diagnosed by technetium Tc 99m pertechnetate scan: case report and review of literature.

Objective: To report a case of metastatic thyroid cancer diagnosed on a technetium Tc 99m pertechnetate (TcO4-) thyroid scan.

Methods: We present the clinical findings, laboratory results, imaging studies, and surgical pathology report in a man with thyrotoxicosis in whom metastatic well-differentiated thyroid cancer was diagnosed incidentally on a routine TcO4- thyroid scan in the setting of a presumed diagnosis of benign toxic thyroid disease. In addition, we review the literature regarding coexistence of metastatic thyroid cancer and thyrotoxicosis.

4-anilino-5-carboxamido-2-pyridone derivatives as noncompetitive inhibitors of mitogen-activated protein kinase kinase.

A new series of MEK1 inhibitors, the 4-anilino-5-carboxamido-2-pyridones, were designed and synthesized using a combination of medicinal chemistry, computational chemistry, and structural elucidation. The effect of variation in the carboxamide side chain, substitution on the pyridone nitrogen, and replacement of the 4'-iodide were all investigated. This study afforded several compounds which were either equipotent or more potent than the clinical candidate CI-1040 (1) in an isolated enzyme assay, as well as murine colon carcinoma (C26) cells, as measured by suppression of phosphorylated ERK substrate.

Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases.

A series of N-6 substituted 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones were prepared from N-substituted (5-methoxyphenyl)ethenylindoles. The target compounds were tested for their ability to inhibit the G2/M cell cycle checkpoint kinases, Wee1 and Chk1. Analogues with neutral or cationic N-6 side chains were potent dual inhibitors.

Binding thermodynamics of substituted diaminopyrimidine renin inhibitors.

Renin is an aspartyl protease involved in the production of angiotensin II, a potent vasoconstrictor. Renin inhibitors can prevent blood vessel constriction and therefore could be useful for the treatment of hypertension. High-throughput screening efforts identified a small molecule renin inhibitor with a core substituted diaminopyrimidine ring.

Evaluation of an ethnic media campaign on patterns of HIV testing among people from culturally and linguistically diverse backgrounds in Australia.

Objective: To evaluate a 2-week pilot ethnic media campaign that was implemented in 14 languages to promote awareness of HIV/AIDS and HIV testing among selected non-English speaking populations in Australia in November/December 2000.

Methods: The main outcome measure was clinic attendances for the purpose of HIV testing by individuals from the target populations at one ofthree public sexual health clinics in Sydney and Melbourne prior to and immediately after the campaign.

Results: The number of HIV tests on members of the 14 target language communities attending the clinics almost doubled from 66 to 122 tests.

Pyrido[2,3-d]pyrimidin-7-ones as specific inhibitors of cyclin-dependent kinase 4.

Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, and good potency against Cdks has been reported for representative examples. Obtaining selectivity for individual Cdk enzymes, particularly Cdk4, has been challenging.

Mean cell volume (MCV) changes in HIV-positive patients taking nucleoside reverse transcriptase inhibitors (NRTIs): a surrogate marker for adherence.

To assess whether changes in mean cell volume (MCV) could be used as a surrogate marker of adherence, the percentage rise from the baseline MCV (%MCV rise) was compared to an independent marker of adherence, the number of days of medications dispensed in a 24-week period. Nucleoside analogues were found to differ in the extent to which they affect the MCV. The correlation between zidovudine (AZT) (30 subjects) and stavudine (D4T) (41 subjects) with adherence based on prescriptions was 0.