Radiation-induced cell death and dendritic cells: potential for cancer immunotherapy?

Dendritic cells are key orchestrators of the immune system. There is considerable interest in their use for treating cancer. Whether they initiate an effective cytotoxic response against antigen-bearing cells, or produce tolerance, depends on the context in which those antigens are presented. Ionising radiation, and the cell death it causes, has several properties that may facilitate such an effective response. A range of in-vitro and in-vivo data supports this, although potential problems exist that may require concurrent strategies.     

Treatment of recurrent head and neck cancer: re-irradiation or chemotherapy?

For most patients with head and neck cancer, locoregional disease recurrence carries an extremely poor prognosis and has severe adverse effects on quality of life. Only a few patients are suitable for salvage surgery and, even in selected cases, the success rate is low. Most patients are managed by supportive palliative care, or with palliative chemotherapy. In the UK, re-irradiation is rarely used because of concerns about treatment-related toxicity and lack of efficacy. Despite this, a significant body of evidence suggests that re-irradiation may have a higher probability of achieving local control than other treatments. In this review, we discuss the use of re-irradiation in patients with locally recurrent head and neck cancer, and present the pertinent data.     

Platelet inhibitor therapy for patients with cardiovascular disease: looking toward the future

Understanding platelet function and the role of platelets in the response to vascular injury has led to the development of novel platelet-inhibiting therapies that have been proven effective in the treatment of acute and chronic vascular disease. Antiplatelet therapies are cornerstone treatments for patients with acute coronary syndromes and have been essential in reducing the acute and subacute ischemic complications of percutaneous coronary intervention. Furthermore, an increased understanding of the pathobiology behind the platelet's role in atherothrombosis has offered up many new avenues of research and many new targets for therapeutic drug development. This review briefly summarizes the state of available anticoagulant and antiplatelet treatments in cardiovascular disease management and provides a perspective on the key issues in developing new antiplatelet strategies in the future.     

Percutaneous Testis Biopsy: An Alternative to Open Testicular Biopsy in the Evaluation of the Subfertile Man

Purpose

We evaluated the safety and efficacy of percutaneous testis biopsy by comparing the ultrasound appearance and histological status of testicular parenchyma obtained to those noted after open testis biopsy.

Materials and Methods

A total of 51 consecutive infertile men with azoospermia or severely impaired semen quality, in whom ductal obstruction was suspected, underwent percutaneous (31) or open (20) testis biopsy, with 58 and 34 procedures performed, respectively. Scrotal ultrasound was performed preoperatively, and at 2 weeks and 1, 3 and 6 months after biopsy. In addition, immunoglobulins G and A antisperm antibody assays were obtained preoperatively and postoperatively. Two biopsy specimens were obtained from each testis for formal histological evaluation. A touch preparation was also performed and examined immediately for mature spermatozoa using phase contrast microscopy.

Results

All biopsies yielded adequate tissue for diagnosis and morphometric analysis. Of 58 percutaneous biopsies 4 (7 percent) demonstrated sonographic evidence of intratesticular bleeding, characterized by a hypoechoic region within the testicular parenchyma, which resolved by 6 months postoperatively. In contrast, 10 of 34 open biopsies (29 percent) showed evidence of intratesticular bleeding or a new area of increased echogenicity at 1 month after the procedure (intraparenchymatous scar). All intraparenchymatous scars persisted to 6 months postoperatively. No patient undergoing percutaneous or open testis biopsy had antisperm antibodies in the seminal fluid or serum (azoospermia cases) or on sperm postoperatively. Of the 32 and 20 patients undergoing percutaneous and open testis biopsy 3 (9 percent) and 14 (70 percent), respectively, required narcotic analgesia. All patients returned to routine activities within 24 hours after percutaneous testis biopsy. No postoperative infections or extratesticular hematomas were noted. Pathological study was diagnostic in all specimens.

Conclusions

Percutaneous testis biopsy is well tolerated by the patient, with fewer apparent complications than and diagnostic value equal to open testis biopsy. Percutaneous testis biopsy should be considered an alternative to open biopsy.     

Skeletal Muscle Function and Its Relation to Exercise Tolerance in Chronic Heart Failure

Objectives. This study sought to define the relation between muscle function and bulk in chronic heart failure (HF) and to explore the association between muscle function and bulk and exercise capacity.Background. Skeletal muscle abnormalities have been postulated as determinants of exercise capacity in chronic HF. Previously, muscle function in chronic HF has been evaluated in relatively small numbers of patients and with variable results, with little account being taken of the effects of muscle wasting.Methods. One hundred male patients with chronic HF and 31 healthy male control subjects were studied. They were matched for age (59.0 ± 1.0 vs. 58.7 ± 1.7 years [mean ± SEM]) and body mass index (26.6 ± 0.4 vs. 26.3 ± 0.7 kg/m²). We assessed maximal treadmill oxygen consumption (

Full-size image

Full-size image

₂), quadriceps maximal isometric strength, fatigue (20-min protocol, expressed in baseline maximal strength) and computed tomographic cross-sectional area (CSA) at midthigh.Results. Peak

Full-size image

Full-size image

₂ was lower in patients (18.0 ± 0.6 vs. 33.3 ± 1.4 ml/min per kg, p < 0.0001), although both groups achieved a similar respiratory exchange ratio at peak exercise (1.15 ± 0.01 vs. 1.19 ± 0.03, p = 0.13). Quadriceps (582 vs. 652 cm², p < 0.05) and total leg muscle CSA (1,153 vs. 1,304 cm², p < 0.005) were lower in patients with chronic HF. Patients were weaker than control subjects (357 ± 12 vs. 434 ± 18 N, p < 0.005) and also exhibited greater fatigue at 20 min (79.1% vs. 92.1% of baseline value, p < 0.0001). After correcting strength for quadriceps CSA, significant differences persisted (5.9 ± 0.2 vs. 7.0 ± 0.3 N/cm², p < 0.005), indicating reduced strength per unit muscle. In patients, but not control subjects, muscle CSA significantly correlated with peak absolute

Full-size image

Full-size image

₂ (R = 0.66, p < 0.0001) and is an independent predictor of peak absolute

Full-size image

Full-size image

₂.Conclusions. Patients with chronic HF have reduced quadriceps maximal isometric strength. This weakness occurs as a result of both quantitative and qualitative abnormalities of the muscle. With increasing exercise limitation there is increasing muscle weakness. This progressive weakness occurs predominantly as a result of loss of quadriceps bulk. In patients, this muscular atrophy becomes a major determinant of exercise capacity.     

Prevalence of polyhydramnios in the third trimester in a population screened by first and second trimester ultrasonography

AIMS: To determine the prevalence of polyhydramnios in a routine antenatal population, in which first and second trimester ultrasound screening for fetal abnormality had been performed and to examine the outcome in these pregnancies. METHODS: A retrospective analytical survey of all obstetric ultrasound examinations performed in a university teaching hospital over a thirty-six month period. Polyhydramnios was defined as either the measurement of a single deepest pool of liquor > 8 cm (AFV) or according to the amniotic fluid index, the sum of a four quadrant measurement > 24 cm (AFI). Using the stated definitions, polyhydramnios was diagnosed in 37 women, 16 of whom had a raised AFI. The main outcomes of interest included the mode of onset of labour and mode of delivery (rates of spontaneous and induced labour, cesarean section deliveries), birth weight, presence or absence of fetal anomalies, and the perinatal outcome. RESULTS: The prevalence of polyhydramnios in this study is lower (0.15% AFI > 24 cm and 0.36% AFV > 8 cm) than in previous studies. The association between polyhydramnios, maternal diabetes mellitus (10.8%), fetal abnormalities (5.4%) and fetal macrosomia (10.8%) was also lower than in past reports. There was a better overall fetal outcome compared with previous studies and no perinatal deaths were seen. CONCLUSIONS: In this study, the prevalence of polyhydramnios in the third trimester was lower than in previous studies, as well as being associated with a better prognosis. This may have been the result of a combination of several factors. These include the introduction of multi-level ultrasound screening for fetal abnormality, and the improved care of diabetic women, and mothers with rhesus iso-immunisation.