It has been estimated that the majority of patients with type 2 diabetes mellitus will need treatment with insulin eventually if they are to keep their blood sugar levels within recommended limits. Whilst much is known about the physiological benefits of insulin, far less is known about the 'lived experience' of going onto insulin therapy. The purpose of this study was to elucidate the range of subjective experiences of men and women with type 2 diabetes who have recently gone onto insulin. It was specifically concerned with their expectations and experiences of insulin and the impact they felt it made on their lives.A purposeful sample of six people with type 2 diabetes mellitus, who had recently commenced on insulin therapy, was taken. Data were collected using semi-structured interviews which were audiotape-recorded and transcribed. The transcripts were analysed together with the researcher's observational notes and documentary evidence, using interpretive phenomenological analysis.The data showed that patients experienced a range of initial reactions (from shock and anger, to relief) and perceptions of insulin, sometimes resulting in an altered selfimage. However, perceptions were shown to change over time, with some patients eventually accepting insulin and becoming empowered.It was concluded that patients starting on insulin need a programme of education and support which is not solely directed at imparting knowledge and new skills. Health care professionals must first establish patients' health beliefs, expectations and fears regarding insulin, if this knowledge is to be accepted and new skills are to be used effectively.
We have examined the antipneumococcal mechanisms of a series of novel fluoroquinolones that are identical to ciprofloxacin except for the addition of a benzenesulfonylamido group to the C-7 piperazinyl ring. A number of these derivatives displayed enhanced activity against Streptococcus pneumoniae strain 7785, including compound NSFQ-105, bearing a 4-(4-aminophenylsulfonyl)-1-piperazinyl group at C-7, which exhibited an MIC of 0.06 to 0.125 g/ml compared with a ciprofloxacin MIC of 1 g/ml. Several complementary approaches established that unlike the case for ciprofloxacin (which targets topoisomerase IV), the increased potency of NSFQ-105 was associated with a target preference for gyrase: (i) parC mutants of strain 7785 that were resistant to ciprofloxacin remained susceptible to NSFQ-105, whereas by contrast, mutants bearing a quinolone resistance mutation in gyrA were four-to eightfold more resistant to NSFQ-105 (MIC of 0.5 g/ml) but susceptible to ciprofloxacin; (ii) NSFQ-105 selected first-step gyrA mutants (MICs of 0.5 g/ml) encoding Ser-81-to-Phe or -Tyr mutations, whereas ciprofloxacin selects parC mutants; and (iii) NSFQ-105 was at least eightfold more effective than ciprofloxacin at inhibiting DNA supercoiling by S. pneumoniae gyrase in vitro but was fourfold less active against topoisomerase IV. These data show unequivocally that the C-7 substituent determines not only the potency but also the target preference of fluoroquinolones. The importance of the C-7 substituent in drug-enzyme contacts demonstrated here supports one key postulate of the Shen model of quinolone action.The renewed interest in antibacterial fluoroquinolones derives from the recent development of agents active against gram-positive pathogens, particularly Streptococcus pneumoniae, the main cause of community-acquired pneumonia (4,7,29). Several new fluoroquinolones, e.g., clinafloxacin, gatifloxacin, gemifloxacin, and moxifloxacin, which are more potent in vitro than ciprofloxacin or levofloxacin, are at various stages of clinical development. With the likely increase in clinical use of antipneumococcal fluoroquinolones, attention has concentrated on their mechanisms of action and resistance in S. pneumoniae.
Epithelioid hemangioendothelioma (EHE) isan uncommon tumour of endothelial origin having borderline malignant potential which frequently is initially misdiagnosed when occurring in the liver, often as cholangiocarcinoma, metastatic carcinoma or veno-occlusive disease. The authors report two cases of hepatic EHE. The fi rst case presented in a 33-year-old female and was originally misdiagnosed as cholangiocarcinoma. Only after re-evaluation of the case seven years later, because of an unexpectedly indolent clinical course, was the correct diagnosis made. The second case presented in a 26-year-old female having nonspecific gastrointestinal complaints. The diagnosis of hepatic EHE was made from a wedge biopsy of liver taken during an exploratory laparotomy. In both cases, immunohistochemical reactivity of the tumour cells for von Willebrand factor (FY1IIR:Ag) and Ulex europeaus I lectin was key to the final diagnosis. The first patient, to this time, remains asymptomatic. The second patient underwent liver transplantation and is being followed (now one year since the initial diagnosis). Hepatic EHE can present a diagnostic dilemma. The use of immunohistochemical techniques to demonstrate the vascular origin of this tumour is essential for its diagnosis. Better awareness of this lesion and the features differentiating it from other histologically similar lesions will prevent exposing affected patients to unnecessary investigations and treatments.
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