Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis

Atherosclerosis is the underlying pathology of most cardiovascular disease and it represents the major cause of premature death in modern societies. Current therapies target risk factors being hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycemia when diabetes is present however the maximum efficacy of these strategies is often 30% or less. Areas of vascular biology that may lead to the development of a complementary vascular wall directed therapy are: inflammation, oxidation, endothelial dysfunction, diabetes-specific factors--hyperglycemia and advanced glycation endproducts and lipid retention by vascular matrix specifically proteoglycans. The major structural features of proteoglycans that determine low-density lipoprotein (LDL) binding are the length and sulfation pattern on the glycosaminoglycan (GAG) chains. Emerging data discussed in this review indicates that these structural properties are subject to considerable regulation by vasoactive substances possibly using novel signaling pathways. For example, GAG elongation stimulated by platelet-derived growth factor is not blocked by the receptor tyrosine kinase antagonist, genistein suggesting that there may be a previously unknown signaling pathway involved in this response. Thus, modifying proteoglycan synthesis and structure may represent a prime target to prevent LDL binding and entrapment in the vessel wall and thus prevent the development and progression of atherosclerosis.     

Family caregivers' and professionals' experiences of supporting people living with dementia’s nutrition and hydration needs towards the end of life

The aim of this paper was to understand the needs of family caregivers and professionals supporting people living with dementia with eating and drinking difficulties towards the end of life and the strategies they use to overcome them. A total of 41 semi-structured interviews with family caregivers (n = 21) and professionals (n = 20) were conducted in London and surrounding areas of England. Interviews were audio-recorded and transcribed verbatim. Four themes were identified: caregivers accessing and seeking help, perceived priorities of care, professionals' supportiveness and educational role, and strategies. Caregivers often struggle as they are not aware of the eating and drinking difficulties associated with dementia's progression. Care can change over time with families prioritising a person's comfort towards the end of life rather than ensuring a particular level of nutrition. Mutual support is required by both professionals and caregivers to enhance the care of the person living with dementia. Cognitive difficulties are often behind initial eating and drinking challenges in dementia, whereas physical challenges take over towards the later stages. Flexibility and creativity are key to adapting to changing needs. There is a need to raise awareness of the eating and drinking challenges associated with the progression of dementia. Professionals can help caregivers embark on the transition towards focussing on comfort and enjoyment of eating and drinking near the end of life rather than nutrition. This is particularly relevant for those caring for a relative living at home. Caregivers' input is needed to tailor professionals' recommendations.     

Seminal plasma prostate-specific antigen level in benign prostatic hyperplasia

INTRODUCTION: We evaluated the role of the seminal plasma PSA level in the prediction of the response to alpha-blocker treatment in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: 18 male patients with lower urinary tract symptoms were enrolled in the study. After their blood was sampled for PSA, ejaculates of all the subjects were obtained. Serum and seminal plasma PSA levels were calculated by Active PSA IRMA kit. Patients were given 4 mg/day doxazosin for a period of 6 weeks, following which their International Prostate Symptom Score (IPSS) evaluation was repeated. The correlation between serum PSA, seminal plasma PSA and PSA density levels and the percentage improvement in IPSS was investigated. RESULTS: The mean serum PSA level, the mean PSA density and the mean seminal PSA level of the patients were 2.7 +/- 1.2 ng/ml, 0.05 +/- 0.02 ng/ml/cm(3) and 0.7 +/- 0.39 g/l, respectively. The percentage improvement in IPSS varied from 26.9 to 53.5%. Serum PSA and serum PSA density were not useful in the prediction of the response to alpha-blocker treatment, but the seminal PSA levels correlated with the percentage improvement in the IPSS (p = 0.017). CONCLUSIONS: Seminal plasma PSA has been found to be a better predictor of the response to alpha-blocker treatment when compared to serum PSA and PSA density.     

Optimizing bexarotene therapy for cutaneous T-cell lymphoma

BACKGROUND: Bexarotene (Targretin oral capsules), the first RXR-selective retinoid "rexinoid" approved for all stages of cutaneous T-cell lymphoma (CTCL), had a response rate (RR) of 45% at the optimal dose of 300 mg/m(2) per day in 2 multicenter trials. With hypertriglyceridemia reported at 79%, bexarotene is often administered with lipid-lowering agents (LLAs). Statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) may modulate class II major histocompatibility class expression and T-cell responses. OBJECTIVE: We attempted to optimize the clinical response to bexarotene by controlling dose-limiting hypertriglyceridemia and combining bexarotene with other active agents. METHODS: We prospectively evaluated 70 patients with CTCL at M. D. Anderson Cancer Center who were treated with oral bexarotene as monotherapy or in combination with other active agents. RESULTS: Fifty-four patients receiving bexarotene monotherapy achieved an overall RR of 48%. Thirteen had stage IA-IIA disease (RR = 53%, 1 complete response [CR]); 41 had stage IIB-IVB disease (RR = 46%, 2 CRs). Forty-two (77%) of these also required one or more LLAs: atorvastatin (n = 29, RR 43%), atorvastatin plus fenofibrate (n = 10, RR 90%), or gemfibrozil (n = 3, RR 33%). Gemfibrozil was discontinued because it increased bexarotene and triglyceride levels. Patients taking 2 LLAs had a significantly higher RR of 90% during monotherapy than those taking one or no LLAs (P <.0001). Forty of 54 patients (74%) received thyroid hormone replacement to normalize thyroxine levels. Four patients receiving monotherapy have complete CRs of >3 years' duration and received maintenance dosing. Sixteen patients with advanced disease treated with bexarotene (225-750 mg/d) in combination with other CTCL therapies achieved an overall RR of 69% (11/16) with concomitant statin therapy. Bexarotene was safely combined with psoralen ultraviolet A (PUVA) plus interferon alfa (IFN-alpha) (n = 2, RR = 50%), with extracorporeal photopheresis (ECP) (n = 8, RR = 75%, 1 CR), with ECP/IFN-alpha (n = 4, RR =50%), with ECP/IFN-alpha/PUVA (n = 1, RR = 100%), and with IFN-alpha/PUVA/topical nitrogen mustard (n = 1, RR = 100%). Two patients receiving IFN-alpha had slight leukopenia, but rhabdomyolysis associated with multiple LLAs did not occur. CONCLUSION: This single-center study supports the safety and efficacy of bexarotene as both a monotherapy and a combination therapy for CTCL. Long durable CRs may be achieved with oral monotherapy. Use of statins with bexarotene may also increase RRs by permitting higher doses to be administered without interruption, by modulating the immune response, or both. When bexarotene is combined with other active CTCL therapies, higher RRs were achieved in patients with advanced disease, without unacceptable side effects.     

Is pentoxifylline therapy effective for the treatment of acute rheumatic carditis? A pilot study

OBJECTIVE: The aim of the present study was to determine whether pentoxifylline has a beneficial effect on the treatment of rheumatic carditis. METHODS: A total of 33 children between the ages 6 and 16 were studied in two groups. The first group (5 boys, 10 girls, mean age: 12.2 +/- 2.9 years) was treated with steroid plus pentoxifylline and the second group (6 boys, 12 girls, mean age; 11.6 +/- 2.8 years) was treated with steroid only for 3-6 weeks until the acute-phase reactants became normal. At admission and on the 7th, 30th, and 90th days of the treatment, laboratory studies including white blood cell count, erythrocyte sedimentation rate, C-reactive protein, throat culture and cytokines (interleukin-1alpha, tumour necrosis factor-alpha) were performed. Cardiac evaluation with chest X-ray, electrocardiography and echocardiography was performed in all patients. In the control group (12 boys, 3 girls, mean age; 10.7 +/- 3.2 years) all parameters were evaluated once only. RESULTS: In both groups, the similar white blood cell count was significantly decreased on the 90th day, and there was no significant difference between the two groups. C-reactive protein, erythrocyte sedimentation rate and interleukin-1alpha were significantly decreased on the 30th and 90th days. In the first group (treated with steroid plus pentoxifylline), the cardiothoracic index was significantly greater at the beginning of the therapy. In the first group, tumour necrosis factor-alpha became normal on the 30th day and in the second group, tumour necrosis factor-alpha became normal on the 7th day of therapy. For all parameters, there was no significant difference between the two groups with respect to the type of therapy used. CONCLUSION: The present study showed that pentoxifylline plus steroid treatment has no beneficial effects on the treatment of acute rheumatic carditis when compared with steroid alone.     

Acute supraglottic laryngitis complicated by vocal fold immobility: prognosis and management

European Archives of Oto-Rhino-Laryngology - Acute supraglottic laryngitis (ASL) is manifested by supraglottic inflammation that has the potential for rapid and fatal airway obstruction....     

Propofol and Propofol–Ketamine in Pediatric Patients Undergoing Cardiac Catheterization

We investigated the effects of propofol and propofol–ketamine on hemodynamics, sedation level, and recovery period in pediatric patients undergoing cardiac catheterization. We performed a prospective, randomized, double-blind study. The study included 60 American Society of Anesthesiologists physical status II or III (age range, 1 month–13 years) undergoing cardiac catheterization for evaluation of congenital heart disease. Propofol and ketamine were prepared in 5% glucose solution to a final concentration of 5 and 1 mg/ml, respectively; similar injectors containing 5% glucose solution only were prepared. Fentanyl (1 μg/kg) and propofol (1.5 mg/kg) were given to both groups. Then, group 1 received 0.5 ml/kg of 5% glucose and group 2 0.5 ml/kg of ketamine solution by an anesthesiologist who was unaware of the groups of patients. Local anesthesia with 1% lidocaine was administered before intervention in all patients. The noninvasively measured mean arterial pressure, heart rate, respiratory rate, and peripheral oxygen saturation were recorded at the baseline, following drug administration, at 3, 5, 10, 15, 20, and 30 minutes and then at 15-minute intervals until the end of the procedure. Additional drug and fentanyl requirements to maintain a sedation level of 4 or 5 were recorded. After the procedure, the time to a Steward recovery score of 6 and adverse effects in the first 24 hours were recorded. The number of patients with more than a 20% decrease in mean arterial pressure was 11 in group 1 and 3 in group 2 (p < 0.05). The number of patients who experienced more than a 20% decrease in heart rate was 12 in group 1 and 5 in group 2 (p = 0.054). Ten patients in group 1 and 3 patients in group 2 required additional fentanyl doses (p = 0.057). The number of additional propofol doses was lower in group 2 (p < 0.05). Propofol combined with low-dose ketamine preserves mean arterial pressure better without affecting the recovery and thus is a good option in pediatric patients undergoing cardiac catheterization.