Extracellular matrix fragmentation in young, healthy cartilaginous tissues.

Although the composition and structure of cartilaginous tissues is complex, collagen II fibrils and aggrecan are the most abundant assemblies in both articular cartilage (AC) and the nucleus pulposus (NP) of the intervertebral disc (IVD). Whilst structural heterogeneity of intact aggrecan ( containing three globular domains) is well characterised, the extent of aggrecan fragmentation in healthy tissues is poorly defined. Using young, yet skeletally mature (18-30 months), bovine AC and NP tissues, it was shown that, whilst the ultrastructure of intact aggrecan was tissue-dependent, most molecules (AC: 95 %; NP: 99.5 %) were fragmented (lacking one or more globular domains). Fragments were significantly smaller and more structurally heterogeneous in the NP compared with the AC (molecular area; AC: 8543 nm2; NP: 4625 nm2; p < 0.0001). In contrast, fibrillar collagen appeared structurally intact and tissue-invariant. Molecular fragmentation is considered indicative of a pathology; however, these young, skeletally mature tissues were histologically and mechanically (reduced modulus: AC: ≈ 500 kPa; NP: ≈ 80 kPa) comparable to healthy tissues and devoid of notable gelatinase activity (compared with rat dermis). As aggrecan fragmentation was prevalent in neonatal bovine AC (99.5 % fragmented, molecular area: 5137 nm2) as compared with mature AC (95.0 % fragmented, molecular area: 8667 nm2), it was hypothesised that targeted proteolysis might be an adaptive process that modified aggrecan packing (as simulated computationally) and, hence, tissue charge density, mechanical properties and porosity. These observations provided a baseline against which pathological and/or age-related fragmentation of aggrecan could be assessed and suggested that new strategies might be required to engineer constructs that mimic the mechanical properties of native cartilaginous tissues.

Self-assembling peptide/thermoresponsive polymer composite hydrogels: effect of peptide-polymer interactions on hydrogel properties.

We have investigated the effect of doping the self-assembling octapeptide FEFEFKFK (F, phenylalanine; E, glutamic acid; K, lysine) hydrogels with various amounts of thermoresponsive conjugate of FEFEFKFK and poly(N-isopropylacrylamide) (PNIPAAm) in order to create novel hydrogels. The samples were characterized using a range of techniques including microdifferential scanning calorimetry (µDSC), oscillatory rheology, transmission electron microscopy (TEM), atomic force microscopy (AFM), and small angle neutron scattering (SANS). The peptide from the conjugate was shown to be incorporated into the peptide fiber, resulting in the polymer being anchored to the peptide fiber. The conjugation of the polymer to the peptide and its anchoring to the peptide fibers did not affect its lower critical solution temperature (LCST). On the other hand, it did result in a decrease in the LCST enthalpy and a significant increase in the G' of the hydrogels, suggesting the presence of hydrogen bond interactions between the peptide and the polymer. As a result, the polymer was found to adopt a fibrillar arrangement tightly covering the peptide fiber. The polymer was still found to go through a conformational change at the LCST, suggesting that it collapses onto the peptide fiber. On the other hand, the fibrillar network was found to be mainly unaffected by the polymer LCST. These changes at the LCST were also found to be fully reversible. The nature of the interaction between the polymer and the peptide was shown to have a significant effect on the conformation adopted by the polymer around the fibers and the mechanical properties of the hydrogels.

The effect of monosodium glutamate on parotid salivary flow in comparison to the response to representatives of the other four basic tastes.

Parotid salivary flow was recorded from eight fit and healthy subjects using modified Lashley cups connected to an instantaneous flow meter in response to gustatory stimuli. The gustatory stimuli were monosodium glutamate (MSG), sodium chloride, sucrose, magnesium sulphate and citric acid. Stimuli were applied for 30 s, and repeated after the flows had returned to baseline following the rinse. Subjects were a significant source of variation for salivary response to each different test stimuli (p<0.001). The normalised salivary flow showed a strong correlation to concentration for all test stimuli (p<0.0001). The parotid salivary flow to MSG (umami) showed a dose-dependant response in which both Na(+) and glutamate ions contributed. The overall order of relative salivary flow responses from highest to lowest flows was citric acid (sour)>MSG (umami)>NaCl (salt)>sucrose (sweet)>=magnesium sulphate (bitter). The relative responses of the peak salivary flows showed the same ordered relation. The peak salivary flow provided a greater contribution to the response to citric acid, NaCl and MSG compared to the response to sucrose and magnesium sulphate.

Treatment of invasive thymoma with single-agent ifosfamide.

PURPOSE: To evaluate single-agent ifosfamide in the treatment of invasive thymoma. PATIENTS AND METHODS: Fifteen patients (eight male and seven female) with histologically confirmed invasive thymoma were treated. The median age was 48 years (range, 23 to 76 years). Four patients had stage III disease, seven patients had stage IVa disease, and four patients had stage IVb disease. The most common histologic type was lymphoepithelial. Seven patients had received prior treatment, including one patient who received chemotherapy. Ifosfamide 1.5 g/m(2) was given on days 1 to 5, with mesna as a uroprotector. RESULTS: Thirteen patients were assessable for response. Five complete responses (38.5%; 95% confidence interval [CI], 17.7% to 64.5%) and one partial response (7.7%; 95% CI, 1.4% to 33.3%) were seen. The median duration of complete response was 66+ months (range, 25 to 87 months), and the estimated survival rate 5 years after ifosfamide treatment was 57% (SE, 32% to 79%). The most frequent toxicities were nausea, vomiting, and leucopenia, but these were well tolerated. CONCLUSION: Single-agent ifosfamide possesses significant activity against invasive thymoma and is comparable to currently used combination regimens. The inclusion of ifosfamide in combination therapy, particularly in place of cyclophosphamide in regimens such as cisplatin, doxorubicin, and cyclophosphamide, needs to be evaluated.

Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group.

PURPOSE: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma. PATIENTS AND METHODS: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients). RESULTS: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation. CONCLUSION: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

A review of dental treatment of head and neck cancer patients, before, during and after radiotherapy: part 1.

The incidence of head and neck cancer is on the rise. Most head and neck cancers are treated with surgery, radiotherapy, chemotherapy or a combination of these modalities. Patients undergoing radiotherapy can experience several unwanted oral side effects, which have both short and long term implications. Dental general practitioners should be aware of these implications and should liaise closely with the restorative consultants and the oncology team to establish the best oral care pathway. This two-part series is a review of the oral changes that occur during and after radiotherapy and the oral management of head and neck oncology before, during and after radiotherapy. This article deals with both immediate sequelae such as cellulitis, mucositis, dysphagia, dysguesia and weight loss as well as long term sequelae such as rampant caries, trismus, xerostomia and osteoradionecrosis. It also encompasses the importance and need for pre-radiotherapy assessment.

A review of dental treatment of head and neck cancer patients, before, during and after radiotherapy: part 2.

The incidence of head and neck cancer is on the rise. Radiation therapy is one of the major treatment modalities for the management of oral malignancies. As with any treatment modality, radiation therapy is associated with various complications. The second part of this series is a review of the oral changes that occur during and after radiotherapy and the oral management of head and neck oncology patients before, during and after radiotherapy. Dental practitioners will encounter patients who have been affected by cancer or who are current cancer patents. General dental practitioners (GDPs) have a vital and proactive role in supporting such patients. The aim of this article is to review the oral management of these patients during and after radiotherapy, and gives practical advice for GDPs and their teams in the long-term care of these patients.

The use of CT in radiotherapy treatment planning.

A prospective study is reported comparing conventional localisation with computed tomography (CT) localisation of tumours for radiotherapy treatment planning. One hundred and five out of 320 (33%) patients had an alteration in treatment plan and details are given according to the tumour site. CT planning enables more accurate localisation of both tumour and normal organs in addition to providing an accurate body contour and inhomogeneity corrections. Implications for integration of CT into radiotherapy planning practice are discussed and the impact of CT on treatment policy evaluated.

Is there a parotid-salivary reflex response to fat stimulation in humans?

The perception of fats in foods may involve gustatory, olfactory or textural cues. There is contradictory evidence as to whether the orosensory perception of fat is as a basic quality of taste or related to the physical characteristics of fat. A dose-response reflex parotid-salivary secretion has, however, been shown for the accepted basic taste qualities. The aim of this study was to establish whether varying fat concentration in two food types causes an associated dose-response reflex parotid secretion in humans. Parotid salivary flow was recorded using Lashley cups and cannulae connected to an instantaneous flow meter. Gustatory stimuli were achieved using 3 ml of skimmed (0.1% fat), semi-skimmed (1.7% fat) or full (3.6% fat) milk (Sainsbury) or 5 g of extra-light (5% fat), light (16% fat) or original (24% fat) cream cheese (Kraft). No significant differences in salivary flow rate were shown within the milk group (n=10, P=.93) or within the cream-cheese group (n=11, P=.82). Furthermore, no correlation was observed between increasing fat concentration and flow within either the milk (P=.98) or the cream-cheese group (P=.69; Pearson Product Moment Correlation). These results do not support the hypothesis that there is a fat-specific dose-response parotid reflex.

Pathological changes in the brain in equine grass sickness.

Lesions in a wide range of cranial nuclei are described in 11 horses with grass sickness. Similar changes were seen in one horse with laminitis, but not in control animals. It is suggested that such lesions are non-specific in nature.

Penile cancer: a case for guidelines.

INTRODUCTION: Aspects of the management of penile cancer remain controversial. In the management of early T1 N0 disease, treatments are divided between amputation and a variety of penis conserving techniques (PCT); local excision, laser techniques, chemotherapy and radiotherapy. We report on a retrospective series of patients with penile cancer. PATIENTS AND METHODS: Thirty-seven patients were diagnosed between 1987-1996. All patients records were retrieved. Data recorded included TNM stage, histological grade and treatment. The end-points were death, nodal progression and local recurrence. RESULTS: Median survivor follow-up of 42 months was obtained. Twenty-six patients (70%) presented with T1 disease, 7 (19%) T2 and 4 (11%) T3 or T4. Inguinal nodal disease was seen in 11 (30%). The mean age was 63 years. Overall, 13 penile amputations were performed, 13 underwent radiotherapy, 6 were locally excised in combination with radiotherapy and 3 underwent local excision alone. Two patients were unsuitable for treatment. Of the total (37 patients) 15 have died; 12 from penile cancer. Ten have suffered disease progression and 12 remain alive with no evidence of disease. Twenty-three patients presented with early T1 NO disease. They were treated with radiotherapy (12), local excision (2), combined radiotherapy and excision (2) and partial amputation (4). Outcome was not significantly related to treatment modality. Spread to the inguinal nodes or local recurrence has occurred in 10, of whom 2 have died. Only 13 (57%) appear disease-free. CONCLUSIONS: The characteristics of the patients and the disease in this series are similar to published series in Europe and North America. There is significant variability in the modalities of treatment used within this series. Local recurrence and disease progression occurs in 43% of T1 N0 lesions. There would seem to be some room for improvement. International data are retrospective and inconclusive with regard to best practice. There is an urgent requirement for randomised controlled trials to improve the outcome of these patients.

The sympatho-adrenal system and plasma levels of adrenocorticotropic hormone, cortisol and catecholamines in equine grass sickness.

Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and catecholamines were used to study the role of the sympatho-adrenal system in equine grass sickness. Statistical evaluation determined differences of hormone levels between seven horses with grass sickness (one acute, five subacute and one chronic), six horses with colic (one with laminitis) and 16 control horses before and after mild stress. Plasma levels of the hormones were higher in horses with acute and subacute grass sickness than in the other groups. No differences were detected between horses with colic and stressed control horses but some hormone levels differed between control and colic horses and control horses before and after stress. It is possible that hyperactivation of the sympatho-adrenal system is caused by stress but it is uncertain whether the stress is only a result of the severity of the disease or also plays a role in its aetiology.

A 3-year prospective study of the effects of adjuvant treatments on cognition in women with early stage breast cancer.

The neuropsychological performance of 85 women with early stage breast cancer scheduled for chemotherapy, 43 women scheduled for endocrine therapy and/or radiotherapy and 49 healthy control subjects was assessed at baseline (T1), postchemotherapy (or 6 months) (T2) and at 18 months (T3). Repeated measures analysis found no significant interactions or main effect of group after controlling for age and intelligence. Using a calculation to examine performance at an individual level, reliable decline on multiple tasks was seen in 20% of chemotherapy patients, 26% of nonchemotherapy patients and 18% of controls at T2 (18%, 14 and 11%, respectively, at T3). Patients who had experienced a treatment-induced menopause were more likely to show reliable decline on multiple measures at T2 (OR=2.6, 95% confidence interval (CI) 0.823-8.266 P=0.086). Psychological distress, quality of life measures and self-reported cognitive failures did not impact on objective tests of cognitive function, but were significantly associated with each other. The results show that a few women experienced objective measurable change in their concentration and memory following standard adjuvant therapy, but the majority were either unaffected or even improve over time.

Computed tomography of paranasal sinus tumors.

Thirty-two patients with histologically proved malignant disease involving the paranasal sinuses were studied by CT. The radiological features of tumor were sinus opacification, a soft-tissue mass, bone erosion and/or displacement, sclerosis, and new-bone formation. Measurements of tissue densities were not helpful in distinguishing tumor from benign disease. Significantly greater tumor extent was demonstrated by CT than by conventional methods in 15 patients; the additional tumor most commonly involved the pterygoid region or orbit. The clinical importance of various directions of tumor spread is emphasized.