The short-term effects of running on the deformation of knee articular cartilage and its relationship to biomechanical loads at the knee.

OBJECTIVE: To investigate the short-term effects of recreational running on the deformation of knee articular cartilage and to examine the relationship between changes in knee cartilage volume and biomechanical modulators of knee joint load. METHOD: Twenty healthy volunteers participated in a two phase cross-sectional study. Session 1 involved Magnetic Resonance Imaging (MRI) of femoral and tibial cartilage volumes prior to and following a 30 min period of relaxed sitting, which was directly followed by a recreational run of 5000 steps. Subsequently, all participants undertook a laboratory study of their running gait to compare biomechanical derived measures of knee joint loading with changes in cartilage volume. Estimates of knee joint load were determined using a rigid-link segment, dynamic biomechanical model of the lower limbs and a simplified muscle model. RESULTS: Running resulted in significant deformation of the medial (5.3%, P<0.01) and lateral femoral cartilage (4.0%, P<0.05) and lateral aspect of the tibial cartilage (5.7%, P<0.01), with no significant differences between genders. Maximum compression stress was significantly correlated with percentage changes in lateral femoral cartilage volume (r(2)=0.456, P<0.05). No other biomechanical variables correlated with volume changes. CONCLUSION: Limited evidence was found linking biomechanical measures of knee joint loading and observed short-term deformation of knee articular cartilage volume following running. Further enhancement of knee muscle modelling and analysis of stress distribution across cartilage are needed if we are to fully understand the contribution of biomechanical factors to knee joint loading and the pathogenesis of knee osteoarthritis (OA).

Soybean genotypic difference in growth, nutrient accumulation and ultrastructure in response to manganese and iron supply in solution culture.

BACKGROUND AND AIMS: The objective of this research was to characterize the physiology and cell ultrastructure of two soybean genotypes subjected to nutrient solutions with increasing concentrations of manganese (Mn) at two contrasting iron (Fe) concentrations. Genotypes 'PI227557' and 'Biloxi' were selected based on their distinctly different capacities to accumulate Mn and Fe. * METHODS: Bradyrhizobium-inoculated plants were grown in hydroponic cultures in a greenhouse. Nutrient solutions were supplied with Mn concentrations ranging from 0.3 to 90 microm, at either 5 or 150 microm Fe as FeEDTA. * KEY RESULTS: For both genotypes and at both Fe concentrations, Mn concentrations from 6.6 to 50 microm did not affect shoot, root and nodule mass, or leaf and nodule ureide concentration. Mn concentrations of 70 and 90 microm did not result in visible toxicity symptoms, but hindered growth and nodulation of 'Biloxi'. An Mn concentration of 0.3 microm was, however, deleterious to growth and nodulation for both genotypes, and caused an accumulation of ureides in leaves and major alterations in the ultrastructure of chloroplasts, nuclei and mitochondria, regardless of the Fe concentration. In 'PI227557', there was also a proliferation of Golgi apparatus and endoplasmic reticulum in the cytoplasm of leaf cells, and nodules showed disrupted symbiosomes lacking poly-beta-hydroxybutirate grains concomitantly with a proliferation of endoplasmic reticulum as well as arrested bacterial division. At 15 microm Fe, ferritin-like crystals were formed in the lumen of chloroplasts of 'PI227557' plants. For both genotypes, there was an antagonism between the Fe and Mn concentrations in leaves, the higher values of both microelements being detected in 'PI227557'. The absence of any detectable relationship between Fe or Mn and zinc, phosphorus and copper concentrations in leaves ruled out those micronutrients as relevant for Mn and Fe nutrition in soybeans. * CONCLUSIONS: The results confirmed the greater capacity of 'PI227557' for Mn and Fe accumulation than 'Biloxi' for most nutrient treatments. Hence, 'PI227557' may be a very useful genetic resource both in developing soybean cultivars for growth on low nutrient soils and in physiological studies to understand differing approaches to nutrient accumulation in plants.

Contrast-enhanced cardiac magnetic resonance in a patient with familial isolated ventricular non-compaction.

Isolated ventricular non-compaction (IVNC) is an idiopathic form of cardiomyopathy. Recent clinical reports have suggested that this form of cardiomyopathy is more frequently associated with complications of congestive heart failure, thromboembolism and malignant ventricular arrhythmias. Contrast enhanced cardiac magnetic resonance imaging with its excellent spatial resolution, its large field of view and its ability to demonstrate thrombus and myocardial scar is an excellent modality to non-invasively assess patients with this form of cardiomyopathy. This paper presents a case of familial isolated ventricular non-compaction. We describe the echocardiographic, X-ray angiographic and cardiac MRI findings. Cine imaging using a steady-state free precession sequence (BFFE) was performed in axial and short axis planes. Left ventricular (LV) mass was estimated both with and without the incorporation of trabeculations from a contiguous stack of short axis images. Trabecular mass was expressed as a percentage of total left ventricular mass. We compared trabecular mass: total LV mass in 10 patients with dilated cardiomyopathy. The mean percentage trabecular mass: LV mass in dilated cardiomyopathy was 11.3% (range 1.5%-19%), and this differed significantly from the trabecular mass of the noncompaction patient (two-tailed Mann-Whitney test, p = 0.028). Trabecular mass of greater than 20% of total myocardial mass may be a useful index to suggest the diagnosis of IVNC. Gadolinium was administered (0.1 mmol/kg). Qualitative analysis of first pass perfusion suggested reduced trabecular perfusion. Early imaging with an inversion recovery sequence and a fixed long inversion time did not demonstrate LV thrombus. Late imaging with the same sequence (TI = 280-300 msec) did not demonstrate myocardial fibrosis.

A phase II study of mitomycin C, cisplatin and protracted infusional 5-fluorouracil in advanced pancreatic carcinoma: efficacy and low toxicity.

BACKGROUND: The effective treatment of unresectable pancreatic carcinoma represents a formidable challenge. There is a need to develop systemic therapies which combine efficacy with acceptable toxicity. The current 'gold standard' gemcitabine gives an objective response rate of the order of 20% and median survival up to 6 months. Here we have evaluated the efficacy and toxicity of mitomycin C, cisplatin and protracted infusional 5-fluorouracil (MCF). PATIENTS AND METHODS: Forty-five patients with locally advanced (13 patients) or metastatic (32 patients) pancreatic carcinoma were treated with mitomycin C 7 mg/m(2) 6 weekly, cisplatin 60 mg/m(2) 3 weekly and protracted venous infusion 5-FU 300 mg/m(2)/day. Patients were evaluated for response after three cycles and received six cycles in total in the absence of progressive disease or poor tolerance. Median age was 62 (45-75) years; 41 patients were World Health Organization performance status 0-1. RESULTS: Treatment was well tolerated with 36 (84%) patients completing three or more cycles. Grade 3 or 4 toxicities were uncommon: anaemia in three patients (7%), mucositis in two (5%), nausea and vomiting in three (7%) and diarrhoea in one (1%). An objective response was seen in 21 (46%) patients. There was one complete response. The median survival overall was 7.1 months and 10.5 months in responders. The median duration of response was 4.3 months. One-year survival was 29%, 2-year survival was 18%. CONCLUSIONS: MCF combines efficacy with low toxicity in the treatment of advanced pancreatic carcinoma. The efficacy is at least comparable and may be superior to single-agent gemcitabine and MCF may therefore provide a cost-effective alternative.

Laparoscopic excision of a triple gallbladder.

Triplication of the gallbladder is a rare congenital anomaly of the biliary tract; there are only nine reported cases to date. We report a case in which laparoscopic cholecystectomy was performed in a patient with biliary colic and choledocholithiasis. Preoperative assessment with ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) failed to reveal the eventual findings of a triple gallbladder. Successful excision of the triple gallbladder was carried out laparoscopically, and the final diagnosis was confirmed by the pathologist. The patient made an uneventful postoperative recovery and was free of gastrointestinal symptoms at follow-up. This case report describes the first laparoscopic excision of a triple gallbladder and highlights the importance of pre-/perioperative imaging to allow for the safe dissection of rare anomalies of the biliary tract via the laparoscopic approach.

Osmolyte accumulation: can it really help increase crop yield under drought conditions?

Osmolyte accumulation (OA) is frequently cited as a key putative mechanism for increasing yields of crops subjected to drought conditions. The hypothesis is that OA results in a number of benefits that sustain cell and tissue activity under water-deficit conditions. It has been proposed as an effective tolerance mechanism for water deficits, which could be enhanced in crops by traditional plant breeding, marker-assisted selection or genetic engineering, to generate drought-tolerant crops. However, field studies examining the association between OA and crop yield have tended to show no consistent benefit. The few, often-cited, investigations with positive associations were obtained under severe water deficits with extremely low yields or conditions with special water-supply scenarios when much of the benefit is plant survival. Under conditions where water deficits threaten crop survival, yields are so low that even large fractional yield gains offer little practical benefit to growers. Indeed, the often-cited benefit of turgor maintenance in cells is likely to result in crop behaviour that is exactly opposite to what is beneficial to crops. The one clear mechanism identified in this review for beneficial yield responses to OA is in the maintenance of root development in order to reach water that may be available deeper in the soil profile.

Short photoperiod inhibits winter growth of subtropical grasses.

Grass development is influenced by length of photoperiod, but no direct measurements under natural conditions exist on mass accumulation in response to photoperiod by subtropical grass species. Grasslands of the subtropics are a major resource, but their growth is inhibited substantially during the short-photoperiod months. This research was designed to examine the consequences on grass production under field conditions when the limitation of short photoperiod is artificially removed. Lights, which extended the daylength to 15 h, were placed over plots of four subtropical forage grasses representing three species (Paspalum notatum Flugge; Cynodon dactylon L.; Cynodon nlemfuensis Vanderyst) to measure their mass accumulation in response to extended photoperiod in a 2-year experiment. Forage yields in all grasses at 5-week harvests during the time of shortest daylength were increased up to 6.2-fold more than the yield under the natural daylength. For the 4.5-month period of shortest daylength in each year, forage yields were increased for all grasses with one grass having a yield increase of 3.6-fold under the extended photoperiod as compared to natural daylength. These results demonstrated that selection of grasses that are insensitive to photoperiod could substantially increase forage yield of subtropical grasslands to benefit animal production and enhance carbon sequestration.

Priorities for adult cancer nursing research: a West Australian replication.

Two Delphi surveys have been conducted during the past 20 years to identify cancer nursing research priorities; one in the United States and one in Canada. Sir Charles Gairdner Hospital, the State Cancer Referral Centre in Western Australia, undertook a replication of this Delphi survey to identify nursing research priorities for adult cancer nursing. The aim of this replication was to identify possible changes in priorities and account for cultural difference in the healthcare systems. A total of 45 responses were received from the first Delphi round and 30 from the second. The top ten priorities identified by this sample were different from those identified in prior studies. The top ranked research topic was "What strategies would be most helpful in allowing nurses time to provide emotional support to cancer patients and carers?" These results may stimulate discussion and re-assessment of research priorities in other adult cancer care settings.

Leaf ureide degradation and N(2) fixation tolerance to water deficit in soybean.

Accumulation of ureides in leaves is associated with the sensitivity of N(2) fixation in soybean to soil water deficit. Consequently, ureide degradation in leaves may be a key to increasing soybean tolerance to dry soils. Previous research indicated that allantoic acid degradation is catalysed by different enzymes in cultivars Maple Arrow and Williams. The enzyme found in Williams requires manganese as a cofactor. The first objective of this study was to determine if the two degradation pathways were associated with differences in N(2) sensitivity to soil water deficits. N(2) fixation of Williams grown on low-Mn soil was sensitive to stress, but it was relatively tolerant when grown on soil amended with Mn. N(2) fixation in Maple Arrow was relatively tolerant of soil drying regardless of the Mn treatment. The second objective of this study was to expand the study of the degradation pathway to nine additional genotypes. Based on ureide degradation in the presence and absence of Mn, these genotypes also segregated for the two degradation pathways. Those genotypes with the Mn-dependent pathway tended to have drought-sensitive N(2) fixation, but there was one exception. The genotypes not requiring Mn for ureide degradation were drought-tolerant except for one genotype. These results demonstrated the possibility for increasing N(2) fixation tolerance to soil water deficits in soybean by selection of lines with high ureide degradation rates, which were commonly associated with the Mn-independent pathway.

Teaching undergraduates about familial breast cancer: comparison of a computer assisted learning (CAL) package with a traditional tutorial approach.

We have developed a computer assisted learning package for teaching clinical medical students about familial breast cancer. It explains the principles of genetic predisposition to breast cancer, the association with other cancers, the principles of family history taking and confirmation, risk assessment and possible interventions. Clinical medical students were randomised to either conventional teaching or CAL, 48 students attended the evaluation session. Students randomised to conventional teaching received a 20 min mini-lecture, those randomised to CAL completed the package with technical, but not academic support available. At the end of the intervention both groups of students completed a short written assessment of acceptability and knowledge and understanding of breast cancer genetics. There was no significant difference between the CAL and mini-lecture groups in terms of marks or acceptability. Thus CAL appears to be an acceptable and effective method of teaching clinical medical students about familial breast cancer. Although time consuming to develop, CAL can be used in a variety of settings to increase curriculum flexibility. Methods of motivating students to complete the CAL, and of providing educational support are being explored.

Ureide degradation pathways in intact soybean leaves.

Ureides dramatically accumulate in shoots of N(2)-fixing soybean (Glycine max L. Merr.) under water deficit and this accumulation is higher in cultivars that have N(2) fixation that is sensitive to water deficit. One possible explanation is that ureide accumulation is associated with a feedback inhibition of nitrogenase activity. A critical factor involved in ureide accumulation is likely to be the rate of ureide degradation in the leaves. There exists, however, a controversy concerning the pathway of allantoic acid degradation in soybean. Allantoate amidinohydrolase was reported to be the pathway of degradation in studies using the cultivar Maple Arrow and allantoate amidohydrolase was the pathway that existed in the cultivar Williams. This investigation was undertaken to resolve the existence of these two pathways. An in situ technique was developed to examine the response of ureide degradation in leaf tissue to various treatments. In addition, the response of ureide accumulation and N(2) fixation activity was measured for intact plants in response to treatments that differentially influenced the two degradation pathways. The results from these studies confirmed that Maple Arrow and Williams degraded allantoic acid by different pathways as originally reported. The existence of two degradation pathways within the soybean germplasm opens the possibility of modifying ureide degradation to minimize the influence of soil water deficits on N(2) fixation activity.

Distal proctocolitis and n-3 polyunsaturated fatty acids (n-3 PUFAs): the mucosal effect in situ.

It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.

Distal procto-colitis, natural cytotoxicity, and essential fatty acids.

OBJECTIVES: Recently, it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity, in particular natural killer (NK) and lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process. We have shown previously that the essential fatty acids (EFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis. METHODS: In this pilot study patients were randomized into two groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4 g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for 6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic scores) and histological evaluation of mucosal biopsies were carried out. Also, the circulating levels and activities of NK and LAK cells, using flow cytometric analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562), respectively, were monitored. RESULTS: After 6 months' supplementation with EFA, there was improvement in the clinical activity compared with pretreatment evaluation. There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group. Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK cells, compared with the placebo group. CONCLUSIONS: This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis. These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease.

Fertility and pregnancy in inflammatory bowel disease.

OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.

Upper gastrointestinal bleeding in an open-access dedicated unit.

The open-access high dependency bleeding unit in Aberdeen admits all patients with suspected gastrointestinal bleeding from a stable adult population of 468,000. The aim is to reduce mortality, morbidity and hospital stay, and create a prospective whole community database. An agreed management protocol is based on prompt resuscitation and early diagnosis. From October 1991 to September 1993 there were 1,602 consecutive admissions with suspected upper or lower gastrointestinal haemorrhage. Bleeding was confirmed in 1,098 of 1,324 patients with presumed upper gastrointestinal haemorrhage, (117 bleeding episodes per 100,000 per year). The overall 30-day mortality was 3.9%, with all deaths attributable to significant concurrent illness. Mortality from peptic ulcer bleeding was 5.3%, with an operation rate of 17% and surgical mortality of 8%. Rapid diagnosis allowed 48% of 523 patients with trivial bleeds to be discharged after a median stay of 24 hours. Centralised expertise and equipment is the essence of the unit's success. The interests of patient care are better served, nursing skills are better developed and teaching opportunities better structured. The major improvement in clinical care, welcomed by hospital colleagues, management and general practitioners, makes the unit an indispensable part of acute medical provision.

The role of an open-access bleeding unit in the management of colonic haemorrhage. A 2-year prospective study.

BACKGROUND: Major colonic haemorrhage poses difficult diagnostic and therapeutic problems and, in contrast to upper gastrointestinal bleeding, has no generally accepted plan of management. METHODS: We report community-based prospective data accumulated over 2 years (1991-93) on 1602 patients referred to an open-access bleeding unit with suspected gastrointestinal haemorrhage. RESULTS: Of 278 (17%) admissions with suspected lower GI haemorrhage, 252 were confirmed. Forty-eight per cent were defined as "significant' bleeds, with a decrease in haemoglobin and cardiovascular compromise. Of 102 significant bleeds in subjects more than 60 years old, 29% rebled, and 12.6% required emergency surgery. Diverticular disease (24%) was the commonest diagnosis, with tumours, infective colitis, and inflammatory colitis each at 10%. The overall 30-day mortality for colonic bleeding was 5.1% (13 of 252), with only 1 death occurring in the group less than 60 years old. CONCLUSIONS: This study provides a unique database for the natural history of colonic bleeding and its management within the setting of a specialized bleeding unit.

Developing a condition-specific measure of health for patients with dyspepsia and ulcer-related symptoms.

A patient-administered instrument for dyspepsia and symptoms suggestive of duodenal or gastric ulcer, based on the type of questions asked when taking a patient's history, was developed and tested using the following steps: literature reviews, devising the questions, testing the responses to the questions using factor analysis and internal consistency, assessing test-retest reliability, and validating the questionnaire by comparing patient responses to the SF-36 health survey questionnaire. The main sample consisted of 135 patients referred to an outpatient clinic with dyspepsia, and 152 patients in general practice who were not referred to a specialist. The final instrument produced a Cronbach's alpha of 0.72 and an intraclass correlation coefficient of 0.69. Patient scores on the dyspepsia questionnaire had small to moderate correlations with the SF-36 health survey, the largest correlation being with the SF-36 scale of pain. Patient scores were significantly related to general practitioner perceptions of symptom severity, family history of gastric ulcer disease, and whether the patient was referred. The questions asked in taking a clinical history from a patient with dyspepsia and other symptoms suggestive of ulcer disease can be used to construct a valid and reliable measure of the effect of dyspepsia on health.

Biodegradation of polyurethane foam, revisited, in the rat model.

In a prospective, randomized, controlled animal study, we systematically analyzed implanted polyurethane foam to determine the rate of degradation in the rat and to compare it to our previous human data. Sixteen 1-cm2 silicone-backed pieces of polyurethane foam were randomly implanted into dorsal subcutaneous pockets in each of 16 Sprague-Dawley rats. Eight animals had polyurethane implants removed at 3 and 6 months and the remaining 8 animals at 9 and 12 months. Specimens were examined either by histology or by scanning electron microscopy of recovered foam after collagenase digestion of the capsule. Histologically, there was evidence of foam degradation and a multinucleated giant cell inflammatory response surrounding the implants. With the scanning electron microscope, the strut width of the polyurethane foam upon implantation measured 51.4 +/- 1.3 microns (mean+SEM). This progressively decreased to 29.1 +/- 1.3 microns at 3 months, 16.6 +/- 0.6 micron at 6 months, 14.9 +/- 0.5 micron at 9 months, and 13.2 +/- 0.3 micron at 12 months (p < 0.0001). Duration of implantation has a significant impact on polyurethane degradation as measured by scanning electron microscopy in the rat animal model. The rate of degradation in the rat is much faster than in our human study, indicating that the rat studies cannot be used to draw conclusions regarding rate of biodegradation in humans.