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Biomedical subjects

M Green

Publications and source records attributed to M Green.

At least 109 records · Page 6Linked to original sources

Bacteremia after intestinal transplantation in children correlates temporally with rejection or gastrointestinal lymphoproliferative disease.

BACKGROUND: Bacteremia occurs frequently after intestinal transplantation (ITx) in children. During our initial experience with this procedure, we noted that bacteremic episodes tended to occur simultaneously with the presence of rejection and/or gastrointestinal (GI) posttransplant lymphoproliferative disease (PTLD). AIM: To document the association of bacteremia with rejection and GI PTLD in pediatric ITx recipients. METHODS: Retrospective analysis of all medical records from 62 children who underwent ITx between July 1990 and January 1998 at Children's Hospital of Pittsburgh. A bacteremic episode was defined as two positive blood cultures from different sites at the same time or from the same site at different times. Rejection and PTLD were defined using previously published criteria. RESULTS: A total of 39/62 ITx recipients had 133 blood stream infections (2.1 episodes/patient) including 121 episodes of bacteremia and 12 of fungemia. Enteric organisms were the most frequently recovered pathogens (Gram negative rods, n=76; enterococci, n=36). Enteric organisms were recovered as a single organism (n=57), with another enteric bacteria (n=23), or with coagulase negative staphylococci (CONS) (n=24). CONS were recovered as a single organism on 21 occasions. An obvious source of bacteremia was not found for 115/121 episodes. Endoscopy was performed for 107 of the 115 bacteremia episodes; an abnormal histology was identified in 74 revealing rejection (n=36), GI PTLD (n=21), or both (n=17). When endoscopy showed GI pathology, enteric organisms alone or in combination with CONS were recovered on 63/107 occasions, although CONS were recovered alone only 11 times. CONCLUSIONS: Bacteremia accompanies GI rejection and intestinal PTLD in ITx recipients. Endoscopy should be performed to inspect the allograft when bacteremia occurs without an obvious source in these patients. This is especially true for patients with bacteremia due to enteric organisms.

Adolescent↗

Lithium regulation of aldolase A expression in the rat frontal cortex: identification by differential display.

BACKGROUND: Substantial evidence indicates that lithium may exert its therapeutic effects through progressive adaptive changes at the level of gene expression; however, the study of lithium-regulated genes has been primarily undertaken with the "candidate gene" approach based on a specific testable hypothesis. The aim of our study was to identify lithium-regulated genes that would not be predicted a priori by the candidate gene approach. METHODS: Differential display polymerase chain reaction was used to isolate and identify messenger RNAs (mRNAs) that are differentially expressed in the frontal cortex of rats given lithium for 5 weeks to achieve plasma lithium concentrations of 0.6 to 0.9 mmol/L. RESULTS: A putative lithium-regulated complementary DNA fragment (LRG1) was identified. Northern blot analysis revealed that 5 weeks of lithium treatment, but not 1 week, significantly reduced LRG1 mRNA levels. LRG1 mRNA levels were similarly reduced by 5 weeks of carbamazepine, but not valproate administration. Sequence analysis and search of the GenBank database revealed that LRG1 is analogous to the sequence of the gene for rat aldolase A. CONCLUSIONS: These results demonstrate that chronic administration of lithium, but not short-term administration, down regulates the levels of aldolase A mRNA, suggesting this effect may play a role in mediating the therapeutic action of this agent.

Animals↗

Long-term results after conversion from cyclosporine to tacrolimus in pediatric liver transplantation for acute and chronic rejection.

UNLABELLED: Tacrolimus is beneficial in liver transplantation for reversing steroid-resistant acute rejection, and for controlling the process of chronic rejection in allograft recipients receiving Cyclosporine- (CyA) based regimens. Very little is known about the long-term efficacy of tacrolimus in pediatric transplantation after conversion from CyA. Our study examines the long-term outcome after conversion to tacrolimus for acute or chronic rejection in pediatric liver transplant (LTx) recipients. METHOD: Seventy-three children (age < 18 years) receiving their primary LTx under CyA between August 1989 and April 1996 were converted to tacrolimus for ongoing acute rejection (n=22, group I) or chronic rejection (n=51, group II). Mean age at the time of conversion was 10.2+/-5.5 years with a mean interval from LTx to conversion of 3.5+/-2.9 (range 0.5-10.1 years). There were 33 boys and 40 girls. All patients were followed until June 1999. Mean follow-up was 97.3+/-17.4 months (range 62.4-118.9 months). RESULTS: Overall 5-year actual patient survival was 78.1% and 8-year actuarial survival was 74.6%. Patients converted to tacrolimus therapy to resolve acute rejection (group I) experience significantly better patient and graft survival at 5 and 8 years than those converted to resolve chronic rejection (group II). Eight-year patient survival and graft survival was 95.5 and 90.9% for group I compared to 74.6 and 53.5% for group II, respectively (long rank P=0.035 and 0.01, respectively). Nearly 75% of children were weaned off steroids after conversion. There was a marked improvement in hypertension, gum hyperplasia, hirsutism, and cushingoid appearance. One child in group I (4.5%) and four children in group II (7.8%) developed posttransplant lymphoproliferative disorder after conversion. There was an improvement in growth in children who were less than the age of 12 years at the time of conversion and who were weaned off steroids; more significantly girls responded more favorably than boys. CONCLUSION: The benefit of transplantation is maintained long-term after conversion to tacrolimus for acute or chronic rejection. The response rate was significantly better in group I as compared with group 11. Marked improvement in growth, hypertension, and reversal of the brutalizing effects of CyA was noted after conversion to tacrolimus. The results suggest that early conversion of pediatric liver transplant patients is warranted for the treatment of acute and chronic rejection, and for improvements in quality of life.

Adolescent↗

Dimerization-dependent block of the proapoptotic effect of p75(NTR).

The biochemical mechanism by which neurons become dependent on neurotrophins for survival is unknown. We found previously that the common neurotrophin receptor, p75(NTR), is a mediator of neurotrophin dependence and that this effect requires a novel type of domain dubbed a neurotrophin dependence domain. We report here that, in contrast to other proapoptotic receptors such as Fas, apoptosis induction by p75(NTR) requires monomerization, with dimerization inhibiting the effect. Blocking the proapoptotic effect of the monomer by dimerization requires a distinct domain that lies at the carboxyterminus of p75(NTR). These results define a novel type of domain required for inhibiting apoptosis induction by p75(NTR).

Apoptosis↗

Post-transplantation lymphoproliferative disorders: advances in diagnosis, prevention and management in children.

With improving operative and postoperative survival after pediatric thoracic transplantation, attention has appropriately begun to focus on complications of long-term immunosuppression. One important complication is post-transplantation lymphoproliferative disorders. Much has been learnt about this spectrum of disorders over the last 15 years, including the pivotal role of primary Epstein-Barr virus infection in the etiology of most cases. Despite these advances, nomenclature remains confusing for the clinician, prediction of outcome is imprecise and treatment strategies are poorly defined. Indeed, no treatments have been subjected to comparative prospective clinical trials. Only recently has attention focussed on strategies for prevention. This article will review the current state of knowledge of post-transplantation lymphoproliferative disorders, with emphasis on recent advances in diagnosis, prevention and management.

Journal Article↗

Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.

Aged↗

Apoptosis, proliferation, and angiogenesis in oral tissues. Possible relevance to tumour progression.

Experimental animal models have demonstrated that angiogenesis is essential for tumour progression, whilst sustained tumour growth requires a positive balance between tumour cell proliferation and cell death (apoptosis). The aim of this study was to determine the relative contribution of apoptosis, proliferation, and angiogenesis to disease progression in the oral mucosa. Histological sections of 47 archival specimens were examined; these included four groups of oral tissues: normal mucosa (n=12), moderate dysplasia (n=11) severe dysplasia (n=6), and squamous cell carcinoma (n=18). Apoptotic cells were visualized by in-situ end-labelling of DNA, proliferative cells by staining with Ki-67 antibody, and blood vessels with von Willebrand factor (vWF) antibody. One-way analysis of variance showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis (vascularity) increased significantly with disease progression from normal oral mucosa, through dysplasia, to carcinoma (p<0.0001 for every index). The increase from normal mucosa to moderate dysplasia was significant for PI and vascularity, but not for AI. In contrast, the increase from dysplasia to carcinoma was significant for AI and vascularity, but not for PI. These data suggest that disease progression in the oral mucosa is accompanied by angiogenesis and increases in both epithelial proliferation and apoptosis. Net epithelial growth results from proliferation starting earlier and proceeding at a higher rate than apoptosis.

Adolescent↗

Joint symmetry in early and late rheumatoid and psoriatic arthritis: comparison with a mathematical model.

OBJECTIVE: To establish a mathematical model to predict the probability of symmetry of joint involvement as a function of the number of joints involved and to compare expected with actual probabilities in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and in early and late disease. METHODS: Random involvement of joints was assumed, and the binomial theorem was used to give the frequency distribution of involved joints as a function of each joint count. Ten joint pairs were included: shoulder, elbow, wrist, metacarpophalangeal joints, proximal interphalangeal (PIP) joints of the hands, hip, knee, ankle, metatarsophalangeal joints, and PIP joints of the feet. Observed probabilities were obtained from subjects with early (duration < or =12 months) and late PsA and RA. RESULTS: The number of subjects in each of the disease subgroups was as follows: early PsA n = 33, late PsA n = 77, early RA n = 61, late RA n = 93. Observed probabilities of symmetry exceeded predicted probabilities for all disease subgroups. The median number of involved joints in each group was as follows: early PsA 4, late PsA 8, early RA 8, late RA 15 (chi2 = 95.3, 3 degrees of freedom, P = 0.0001, by Kruskal-Wallis test). After correcting for the discrepancy in the number of involved joints, no difference in joint symmetry was found between the groups (chi2 = 1.77, P = 0.62 by Friedman two-way analysis of variance). Similar results were obtained when individual hand and foot joints were analyzed separately. CONCLUSION: The pattern of joint involvement is often used to distinguish between rheumatoid and psoriatic arthritis. This study confirms that symmetry is largely a function of the total number of joints involved and that, in terms of joint pattern, differences between these disorders are more quantitative than qualitative. Both disorders have high absolute values of symmetry, particularly in the joints of the wrist and hand.

Adolescent↗

Anterior magnetic phrenic nerve stimulation: laboratory and clinical evaluation.

OBJECTIVE: Anterior magnetic stimulation (aMS) of the phrenic nerves is a new method for the assessment of diaphragm contractility that might have particular applications for the clinical assessment of critically ill patients who are commonly supine. DESIGN: We compared aMS with existing techniques for measurement of diaphragm weakness and fatigue in 10 normal subjects, 27 ambulant patients with suspected diaphragm weakness and 10 critically ill patients. SETTING: Laboratory and intensive care unit of two university hospitals. RESULTS: Although aMS was not demonstrably supramaximal in normal subjects, the mean value of twitch transdiaphragmatic pressure (Tw Pdi) obtained at 100% of stimulator output, 23.7 cmH2O, did not differ significantly from that obtained with bilateral supramaximal electrical stimulation (ES), 24.9 cmH2O, or bilateral anterior magnetic phrenic nerve stimulation (BAMPS), 27.3 cmH2O. A fatiguing protocol produced a 20 % fall in aMS-Tw Pdi and a 19% fall in BAMPS-Tw Pdi; the fall in aMS-Tw Pdi correlated with the fall in BAMPS-Tw Pdi (r2 = 0.84, p = 0.03) indicating that aMS can detect diaphragm fatigue. In ambulant patients aMS agreed closely with existing measures of diaphragm strength. The maximal sniff Pdi correlated with both the aMS-Tw Pdi (r2 = 0.60, p < 0.0001) and the BAMPS-Tw Pdi (r2 = 0.65, p < 0.0001) and the aMS-Tw Pdi was a mean (SD) 2.2 (4.3) cmH2O less than BAMPS-Tw Pdi. In addition, aMS correctly identified diaphragm dysfunction in patients studied on the ICU. CONCLUSIONS: We conclude that aMS is of clinical value for the investigation of suspected diaphragm weakness.

Action Potentials↗

Randomized trial of the effects of cholesterol-lowering dietary treatment on psychological function.

PURPOSE: Epidemiological studies have suggested that cholesterol lowering could affect psychological functioning. This study was designed to test whether cholesterol-lowering diets adversely affect mood and cognitive function.5.2 mM [198 mg/dL]) to either a low-fat diet, a Mediterranean diet, or a waiting-list control. Cholesterol levels, psychological well-being (depression, anxiety, hostility), and cognitive function were assessed at baseline, 6 weeks, and 12 weeks. RESULTS: Total serum cholesterol levels fell significantly more in the intervention groups (8.2% reduction) than in the control group (P <0.001). All three groups showed a modest improvement in psychological well-being during the 12-week treatment period, but there were no differences among the groups. There were no between-group differences on three measures of cognitive function, but for a fourth measure, which involved the task with the greatest processing load, the two intervention groups did significantly worse (P <0.001) than the control group. The change in performance was correlated with the change in total serum cholesterol level (r = 0. 21, P = 0.01). CONCLUSIONS: Two dietary interventions that successfully lowered serum cholesterol levels had no adverse effect on mood. There was some evidence for a relative impairment in cognitive function in the treated groups in one of four cognitive tests, but additional studies will be required to determine the relevance of this finding.

Adult↗

Systemic amyloidosis presenting as a mass of the conjunctival semilunar fold.

PURPOSE: To report a case of systemic amyloidosis that presented as a mass of the plica semilunaris (semilunar fold) of the conjunctiva. METHODS: Case report. RESULTS: A healthy 56-year-old man developed a fleshy, hemorrhagic lesion of the semilunar fold of the left conjunctiva. Excisional biopsy revealed an acellular lesion of the conjunctival stroma that stained positively for Congo red and showed apple-green birefringence and dichroism with polarization microscopy. The diagnosis was amyloidosis of the semilunar fold of the conjunctiva. Subsequent evaluation disclosed systemic amyloidosis. The patient remains asymptomatic. CONCLUSIONS: Although conjunctival amyloidosis usually occurs as a localized lesion without systemic involvement, it can be the initial sign of systemic amyloidosis.

Amyloidosis↗

Acoustic interaction of humpback whales and whale-watching boats.

The underwater acoustic noise of five representative whale-watching boats used in the waters of west Maui was measured in order to study the effects of boat noise on humpback whales. The first set of measurements were performed on 9 and 10 March, close to the peak of the whale season. The ambient noise was relatively high with the major contribution from many chorusing humpback whales. Measurements of boat sounds were contaminated by this high ambient background noise. A second set of measurements was performed on 28 and 29 April, towards the end of the humpback whale season. In both sets of measurements, two of the boats were inflatables with outboard engines, two were larger coastal boats with twin inboard diesel engines and the fifth was a small water plane area twin hull (SWATH) ship with inter-island cruise capabilities. The inflatable boats with outboard engines produced very complex sounds with many bands of tonal-like components. The boats with inboard engines produced less intense sounds with fewer tonal bands. One-third octave band measurements of ambient noise measured on 9 March indicated a maximum sound pressure level of about 123 dB re 1 microPa at 315 Hz. The maximum sound pressure level of 127 dB at 315 Hz was measured for the SWATH ship. One of the boats with outboard engines produced sounds between 2 and 4 kHz that were about 8-10 dB greater than the level of background humpback whale sounds at the peak of the whale season. We concluded that it is unlikely that the levels of sounds produced by the boats in our study would have any grave effects on the auditory system of humpback whales.

Acoustics↗

The influence of gemcitabine and cisplatin schedule on response and survival in advanced non-small cell lung cancer.

PURPOSE: Gemcitabine-cisplatin combinations are among the most active for the treatment of non-small cell lung cancer. Previous reports have suggested that the day of cisplatin administration affects both toxicity and drug delivery. We undertook this retrospective analysis to determine whether it also affects response and survival. PATIENTS AND METHODS: This was a retrospective analysis of six studies of gemcitabine and cisplatin. Gemcitabine, 1000-1500 mg/m(2) was administered on days 1, 8, and 15 of a 28 day cycle. In four studies cisplatin 100 mg/m(2) was administered with mannitol diuresis every four weeks on either day 1, day 2 or day 15. In two studies cisplatin 25-30 mg/m(2) was administered on day 1, 8 and 15. Standard prognostic factors including age, gender, stage, performance status, and histologic subtype were analyzed along with day of cisplatin administration. Single variable Cox proportional hazards regressions were performed. This was followed by multiple variable Cox proportional hazards regression, beginning with a full model containing terms for gender, age, performance status and stage. The least statistically significant terms were subsequently dropped from the model to reach a final model with only statistically significant variables. A similar approach was followed to fit a multiple variable logistic regression model to overall response data. RESULTS: Overall response rates were highest (36-46%) in the three studies that administered cisplatin on days 2 or 15, and these studies had the highest 1-year survival rates (52-58%). Survival was better for patients who received cisplatin on day 2 or 15 compared to those treated on either day 1 or weekly on days 1, 8, 15 (P=0.020). In the final model of the Cox regression analysis, survival was better for cisplatin on days 2 or 15 (hazard ratio=0.69, P=0.008) and female gender (hazard ratio=0.72, P=0.036). Only cisplatin delivery on day 2 or day 15 predicted for significantly better response (42 vs. 29%, P=0.036). CONCLUSION: In a 28 day cycle in which gemcitabine is administered day 1, 8 and 15, the best therapeutic index is achieved with cisplatin administration on day 2 or 15.

Adult↗

Public reform and the privatisation of poverty: some institutional determinants of health seeking behaviour in southern Tanzania.

This paper explores the changing institutional context of health service delivery in rural Tanzania through an anthropological analysis of the kinds of healing strategies pursued by men and women when they are ill. In some rural districts popular dissatisfaction with state medical provision is not manifested in a rejection of the allopathic medicine with which it is associated, but in increased reliance on an emerging informal sector of private medical provision. Although this sector provides a valued and accessible service to certain categories of clients it delivers poor quality treatment, serving to reinforce the cyclical relationship between poverty and ill health. Despite the best intentions of major public sector reforms neither government nor other agencies are able to meet rural demand for health services. Reliance on the parallel market for medical provision is likely to continue, at least in the short term, with negative consequences for health.

Adult↗

Open label, multi-centre phase II study of raltitrexed ('Tomudex') in patients with inoperable squamous-cell carcinoma of head and neck.

BACKGROUND: Raltitrexed ('Tomudex') is a folate based inhibitor of thymidylate synthase which has been registered in Europe and Australia for the treatment of advanced colorectal cancer. In a European phase I trial of raltitrexed anti-tumour activity was seen in two patients with head and neck cancer, prompting the current study. PATIENTS AND METHODS: From November 1996 to December 1998, 24 patients with metastatic or recurrent squamous-cell carcinoma of the head and neck from 7 Australian centres received raltitrexed, 3 mg/m2 given intravenously over 15 minutes every 3 weeks, for a maximum of 6 cycles. Patients were required to be chemotherapy naïve and have measurable disease, age > 18 years, WHO performance status initially < or = 2, no significant intercurrent illness or organ dysfunction and a life expectancy > 12 weeks. RESULTS: Twenty-two men and two women, median age 65 years, median performance status 1 were enrolled. Fifteen patients (63%) had received both prior surgery and radiotherapy. In 15 patients (63%) there was recurrent locoregional disease only. Twelve patients (50%) received one cycle of treatment with only four patients (17%) receiving four or more cycles of treatment. No patient achieved a complete or partial response, although 5 patients experienced stable disease which lasted a median of 188 days (range 61-436). The median survival for the whole group was 101 days (range 20436). Raltitrexed was generally well tolerated with minimal antiproliferative toxicity. CONCLUSIONS: Single-agent raltitrexed does not demonstrate significant anti-tumour response rates in patients with predominantly locally recurrent head and neck cancer.

Adult↗

Respiratory muscle activity in patients with COPD walking to exhaustion with and without pressure support.

The function of the diaphragm and other respiratory muscles during exercise in chronic obstructive pulmonary disease (COPD) remains controversial and few data exist regarding respiratory muscle pressure generation in this situation. The inspiratory pressure/time products of the oesophageal and transdiaphragmatic pressure, and the expiratory gastric pressure/time product during exhaustive treadmill walking in 12 patients with severe COPD are reported. The effect of noninvasive positive pressure ventilation during treadmill exercise was also examined in a subgroup of patients (n=6). During free walking, the inspiratory pressure/time products rose early in the walk and then remained level until the patients were forced to stop because of intolerable dyspnoea. In contrast, the expiratory gastric pressure/time product increased progressively throughout the walk. When patients walked the same distance assisted by noninvasive positive pressure ventilation, a substantial reduction was observed in the inspiratory and expiratory pressure/time products throughout the walk. When patients walked with positive pressure ventilation for as long as they could, the pressure/time products observed at exercise cessation were lower than those observed during exercise cessation after free walking. It is concluded that, in severe chronic obstructive pulmonary disease, inspiratory muscle pressure generation does not increase to meet the demands imposed by exhaustive exercise, whereas expiratory muscle pressure generation rises progressively. Inspiratory pressure support was shown to substantially unload all components of the respiratory muscle pump.

Aged↗

Cryptosporidial infections after solid organ transplantation in children.

The diagnosis and treatment of moderate-to-severe diarrhea in solid organ transplant recipients is often a challenge because of the variety of infectious and non-infectious causes. The morbidity associated with this clinical condition is of particular significance in the pediatric population where malnutrition may lead to poor growth and development. Rarely, Cryptosporidium has been identified as the cause of clinically significant diarrhea in pediatric solid organ transplant patients. A retrospective review identified cases of cryptosporidiosis among the 1160 non-renal, abdominal organ transplant recipients cared for at the Children's Hospital of Pittsburgh between 1981 and June 1998. Four cases of clinically significant diarrhea were identified in three liver transplant recipients and one small bowel transplant recipient. Endoscopy and biopsy with histologic confirmation diagnosed three cases; ova and parasitic examination of stool specimens identified the fourth case. Therapy varied among the patients depending on when they had been diagnosed as, over the years, different and newer agents have been indicated for the treatment of cryptosporidiosis. All four patients resolved their infections. Hence, endoscopy and biopsy is recommended for pediatric transplant patients who present with chronic diarrhea of unknown etiology. The patients who may be at a higher risk for cryptosporidial infections include those with an increased immunosuppressive state (i.e. pre-existing immunodeficiency, malignancy, re-transplantation, and those receiving higher doses of immunosuppressive therapy). While cryptosporidiosis is a non-lethal complication, it allows the clinician to gain further insight into the degree of immunosuppression of their patient.

Adolescent↗