Biomedical subjects
Publications and source records attributed to P Close.
Different factors can have deleterious effect the inspiratory muscles: increased intrinsic mechanical loading of the inspiratory muscles, functional inspiratory muscle weakness, increased ventilatory demand related to capacity... These muscle changes influence exercise tolerance and contribute to dyspnea.
This is a case report of a 71-year-old man who presented with an incidental finding of a mass in a solitary right testis. A scrotal ultrasound scan showed the typical features of a testicular epidermoid cyst. Tumour markers were not elevated and the patient was managed non-operatively. On reviewing the literature, we found no previous report on the non-operative management of testicular epidermoid cysts
As for other skeletal muscles, ventilatory muscle performance can be described in terms of strength and endurance. Ventilatory muscle strength is measured, for example, as the maximum inspiratory and expiratory mouth pressures. It is now a routine procedure in many pulmonary function laboratories. Measurements of ventilatory muscle endurance are more difficult but two general types of tests are used: maximum voluntary ventilation and inspiratory threshold loading.
Familial (hereditary) haemochromatosis (HH) is an iron storage disorder characterized by an increased intestinal absorption of iron and its accumulation in numerous tissues. The disease generates an iron overload with tissue damages also seen in haematologic disturbances (with dyserythropoiesis and haemolysis) and hepatic disorders. Besides typical mutations linked to HH (C282 Y and H63D, HFE locus), three other mutations have been identified and more have to be defined. A complete genetic testing is important to assess the risk of morbidity. Indeed, the clinical picture of HH is dependent upon the specific mutations as well as the individual context (sex, environment, associated hepatic and/or haematologic disorders). Porphyria cutanea tarda (PCT) has for long been found significantly associated with HH. It is now considered that hepatic iron overload related to the combination of heterogeneous genetic traits and environmental factors, including alcoholism and viral hepatitis, precipitates the expression of PCT through the inhibition of uroporphyrinogen decarboxylase (Uro.D).
It is now generally accepted that strenuous exhausting exercise can increase susceptibility to viral infection during the following days or weeks. This review addresses the role of mucosal immunity in respiratory illness and associations with the intensity, volume and duration of exercise. Indeed habitual exercise at an intense level can cause suppression of mucosal immune parameters.
Cardiopulmonary exercise testing is a unique tool to assess the limits and mechanisms of exercise tolerance. It is also useful for establishing the profiles and adequacy of the responses of the systems at submaximal and maximal exercises. The measure of VO2 max (maximal oxygen uptake) has become the "benchmark" to quantify cardiovascular functional capacity and aerobic fitness.
AIM: To study the distribution of Hodgkin's lymphoma in South African children and report the incidence of Epstein-Barr virus (EBV) as regards age, race, sex, and histological subtype; to investigate whether EBV is relevant to survival. METHODS: Immunohistochemistry (IHC) and in situ hybridisation (ISH) to detect EBV were performed on 47 South African children with classical Hodgkin's lymphoma, ranging in age from 3 to 14 years and coming from different ethnic backgrounds. The correlation between the presence of the virus and clinical outcome was assessed. RESULTS: The nodular sclerosing subtype predominated, comprising 89% of cases; the remaining 11% were of the mixed cellularity subtype. EBV was present in 68%. Full clinical data were available for 36 cases; EBV positive patients presented with less aggressive symptoms at diagnosis and had a significantly longer median survival than EBV negative patients. CONCLUSIONS: The distribution of EBV in South African childhood Hodgkin's lymphoma follows a pattern intermediate to that of industrialised and non-industrialized countries. Furthermore, our data suggest that there is an association between poor prognosis and the non-detection of EBV products in South African childhood Hodgkin's lymphoma.
Explore the source record for details and available documents.
The interstitial cells of Cajal complex within the gut wall function as a pacemaker to direct peristalsis. Their neoplastic counterpart is the gastrointestinal pacemaker cell tumor, a spindle and/or epithelioid cell mesenchymal tumor previously known as gastrointestinal stromal tumor or incorrectly called leiomyosarcoma in some cases of older reports. Although numerous cases of gastrointestinal leiomyosarcomas have been documented in the English-language literature, no pediatric case of gastrointestinal stromal tumor or gastrointestinal pacemaker cell tumor has, to our knowledge, been recorded. Herein, we report a case of congenital gastrointestinal pacemaker cell tumor confirmed by immunohistochemistry and electron microscopy in a full-term male newborn.
Background: The polymerase chain reaction (PCR) has become a useful method to determine monoclonality in T-cell lymphomas. The authors investigated a number of T-cell lymphoma cases to determine (1) the monoclonality detection rate in South African T-cell lymphoma cases and (2) whether variation in detection of monoclonality exists in T-cell lymphoma subtypes. Methods and Results: Thirty T-cell lymphoma cases, including pleomorphic peripheral T-cell lymphomas, precursor T-lymphoblastic lymphomas, large-cell anaplastic lymphomas, and one cutaneous lymphoma, were assessed. DNA was purified from paraffin-embedded tissue and amplified with consensus oligonucleotide primers directed at the rearranged T-cell receptor-gamma genes. Monoclonality was found in 73% of cases, similar to previous reports. Pleomorphic peripheral T-cell lymphomas (89%) were detected most successfully; lymphoblastic (73%) and large-cell anaplastic lymphomas (58%) had lower detection efficiencies. Conclusions: Some T-cell lymphoma subtypes are less successfully detected; additional primer sets should be used to improve detection.
Translocations of the MLL gene at chromosome band 11q23 are the most common cytogenetic alterations in de novo leukemia in infants and in leukemia related to chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice suggest that additional mutational events may by required for full leukemogenesis. Therefore, we used single-strand conformation polymorphism analysis and an allele-specific restriction enzyme assay to investigate the frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL), 10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary leukemias were AML, 1 was biphenotypic, 1 was ALL, and 2 were diagnosed as myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both mutations occurred in infant monoblastic variants. RAS mutations were otherwise absent in this series. This is the first report of congenital leukemias where translocation of the MLL gene and RAS mutation coexist. The frequency of RAS mutations in de novo AMLs with MLL gene translocations is similar to that in other forms of AML, but RAS mutations play a limited role in lymphoid and treatment-related leukemias with similar translocations.
BACKGROUND: Patients who undergo total hip replacement have a high risk of thromboembolic complications. Recombinant hirudin (desirudin), a specific inhibitor of thrombin, represents a new development in antithrombotic therapy. We compared the efficacy and safety of desirudin with those of a low-molecular-weight heparin (enoxaparin) for the prevention of thromboembolic complications in patients undergoing primary total hip replacement. METHODS: Both treatments, which were assigned in a randomized, double-blind manner, were started preoperatively: enoxaparin on the evening before surgery, and desirudin within 30 minutes before the start of surgery. The dose of desirudin was 15 mg subcutaneously twice daily, and the dose of enoxaparin was 40 mg subcutaneously once daily. The duration of treatment was 8 to 12 days. Deep-vein thrombosis was verified by bilateral venography performed at the end of the treatment period or earlier, if there were clinical signs of deep-vein thrombosis. RESULTS: At 31 centers in 10 European countries, 2079 eligible patients were randomly assigned to receive desirudin or enoxaparin. A total of 1587 patients were included in the primary analysis of efficacy. In the desirudin group, as compared with the enoxaparin group, there was a significantly lower rate of proximal deep-vein thrombosis (4.5 vs. 7.5 percent, P=0.01; relative reduction in risk, 40.3 percent) and a lower overall rate of deep-vein thrombosis (18.4 vs. 25.5 percent, P=0.001; relative reduction in risk, 28.0 percent). The safety profiles were similar in the two treatment groups. CONCLUSIONS: When administered 30 minutes before total hip replacement surgery, desirudin is more effective than enoxaparin in preventing deep-vein thrombosis.
OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of desirudin in subjects with various degrees of renal impairment in comparison with subjects with normal renal function. METHODS: Eight subjects with normal renal function (creatinine clearance > 90 ml/min) received 0.5 mg/kg desirudin intravenously over 30 minutes. Four subjects with mild renal failure (creatinine clearance between 61 and 90 ml/min) received 0.5 mg/kg. Five subjects with moderate renal failure (creatinine clearance between 31 and 60 ml/min) received 0.25 mg/kg. Six subjects with severe renal failure (creatinine clearance < 31 ml/min) received 0.125 mg/kg. RESULTS: Specific maximum concentration values (maximum concentrations corrected to a dose of 1 mg/kg) increased slightly with decreasing creatinine clearance. Mean specific area under the plasma concentration-time curve increased by a factor of 1.15, 2.83, and 7.0 for subjects with mild, moderate, and severe renal failure, respectively, compared with healthy subjects. Total urinary excretion of desirudin was about 55% to 60% of the dose in all four groups; elimination was delayed for subjects with moderate and severe renal failure. Total and renal clearance of desirudin were proportional to creatinine clearance. Total plasma clearance of desirudin was proportional to renal clearance of the drug. Prolongation of activated partial thromboplastin time was increased among subjects with moderate and severe renal failure despite a dose reduction. Area under the dynamic activated partial thromboplastin time curve for subjects with moderate renal failure remained the same as that for healthy subjects despite a dose reduction by a factor of two. Area under the dynamic curve increased by a factor of about 1.5 for subjects with severe renal failure despite a dose reduction by a factor of four. CONCLUSION: A dose reduction by a factor of six is recommended for persons with severe renal failure.
Specific inhibition of thrombin is a new method for the prevention of postoperative deep-vein thrombosis. The objective of this multicenter, randomized, double-blind study was to compare the efficacy and safety of desirudin (Revasc, CGP 39393; fifteen milligrams two times a day) with that of unfractionated heparin (5000 international units three times a day) in patients having a primary elective total hip replacement. The medications were administered subcutaneously, starting preoperatively and continuing for eight to eleven days. The primary end point was a confirmed thromboembolic event during the treatment period. The presence of deep-vein thrombosis was evaluated with bilateral venograms, which were centrally assessed by two independent radiologists. A total of 445 eligible patients were randomized: 220, to management with heparin, and 225, to management with desirudin. A per-protocol analysis of efficacy was performed for the 351 patients (79 per cent) for whom an adequate bilateral venogram had been made within eight to eleven days after the operation or who had had a proved thromboembolic event. The prevalence of confirmed deep-vein thrombosis was thirteen (7 per cent) of 174 patients who had received desirudin and forty-one (23 per cent) of 177 patients who had received heparin, a significant difference (p < 0.0001). The prevalence of proximal deep-vein thrombosis was also significantly reduced (p < 0.0001), by 79 per cent, in the group that had received desirudin (six [3 per cent] of 174 patients) compared with in the group that had received heparin (twenty-nine [16 per cent] of 177). There were no confirmed pulmonary embolisms or deaths during the period of prophylaxis. During a six-week follow-up period, pulmonary embolism was confirmed in four patients, all of whom had received heparin. There was no significant difference between the treatment groups with respect to bleeding variables or bleeding complications. These data demonstrate that a fixed dose of fifteen milligrams of desirudin, started preoperatively and administered subcutaneously twice daily for at least eight days, provided effective, safe prevention of thromboembolic complications, with no specific requirements for laboratory monitoring, in patients who had a total hip replacement.
The roles of the bcl-2 and p53 proteins in Hodgkin's disease (HD) are poorly understood. We therefore compared their detected presence in Hodgkin and Reed-Sternberg/large atypical (H-RS/LA) cells immunohistochemically with the percentages of these cells double-labeled for CD30 and DNA strand breaks (DNA fragmentation index, DFI); mitotic indices (MI); and the EBV infection status. We found a highly significant inverse correlation between the fractions per case of H-RS/LA cells expressing bcl-2/p53 proteins and the DFI of CD30+ elements. No marked effect of these two oncoproteins on MI was noticed, although these parameters and DFI of CD30+ cells were linearly related. EBV infection of H-RS/LA cells exerted only a limited effect on the parameters tested. The results of this study suggest that overexpressed bcl-2 and, to some extent, p53 proteins in H-RS/LA cells of HD primarily counteract deletion of these cells.
Plasma pharmacokinetics, effect on coagulation parameters, and safety and tolerability of an intravenous infusion of REVASC before, during and after a DDAVP infusion were investigated. Twelve healthy volunteers were given an intravenous bolus dose followed by a constant rate four-hour infusion of REVASC. Fifteen-minute infusions of 0.9% saline and DDAVP were started two and three hours respectively after the start of the REVASC infusion. Plasma REVASC concentrations were not affected by either the saline or DDAVP infusion. REVASC infusion produced an increase in APTT which plateaued between 0.5 and 3 hours. After the DDAVP infusion there was a tendency towards a new lower plateau whilst the REVASC infusion continued. There were no serious adverse events or bleeding episodes throughout the study. In conclusion, the co-administration of intravenous DDAVP has no effect on the plasma pharmacokinetics of REVASC and partially reverses the REVASC-induced increase in APTT. This may represent a role for DDAVP in the partial reversal of anticoagulation induced by REVASC.
We re-appraised the cell renewal pattern in Hodgkin's disease (HD), considering that most, though not all, Hodgkin/Reed-Sternberg (H-RS) cells exhibit abortive mitoses and that a substantial fraction of these exhibits DNA damage suggestive of imminent or actual cell death. Using combined immunohistochemistry and in situ end-labeling to detect strand breaks, the percentage per case of CD30+ (mainly H-RS) cells with DNA fragmentation (DNA fragmentation index [DFI]) was estimated. For each case, we registered the mitotic index (MI) of CD30+ cells and the percentage of Ki-67+ atypical large cells. To quantify the sum of our parameters for mitosis, whether successful or not, and DNA damage, we introduced the kinetic event index (KEI = MI + DFI). Only DFI and KEI distinguished significantly between mixed cellularity and nodular sclerosis HD. The values for MI and DFI, and therefore for KEI, CD30+ and CD30- small lymphoid cells were proportional. The percentages of Ki-67+ large atypical cells (median 50%) did not correlate significantly with either MIs or DFIs of CD30+ cells. Cluster analysis revealed the existence, independent of histological subtype, of 2 large groups of HD with different KEIs. Our findings suggest that cell deletion plays an important role in HD. Further, it appears that proliferation-associated antigens in H-RS cells do not reflect successful cell production in this disorder.
BACKGROUND: The frequency of thromboembolism after major orthopaedic surgery continues to be high despite prophylaxis. New agents such as CGP 39393, a recombinant form of hirudin, may be more effective than existing therapies. METHODS: In this double-blind, multicentre, European study the efficacy of three doses of CGP 39393, in comparison with unfractionated heparin, were examined in 1119 patients undergoing elective hip surgery. Patients were randomly allocated to receive by subcutaneous injection either 10, 15, or 20 mg of CGP 39393 twice daily or 5000 IU of heparin three times daily. All treatments were started just before surgery and continued for 8-11 days, until bilateral venography was performed. FINDINGS: The occurrence of thromboembolism was significantly reduced in patients treated with CGP 39393 compared to heparin. The frequency of deep-vein thrombosis was 34.2% in the heparin group as compared to 23.9% (p=0.0113), 18.4% (p=0.0003), and 17.7% (p=0.0001) in the 10 mg, 15 mg, and 20 mg CGP 39393 groups, respectively. At all dose levels, CGP 39393 was more effective than heparin in preventing proximal deep-vein thrombosis. The frequency of proximal thrombosis was 19.6% in the heparin group as compared to 8.5% (p<0.001), 3.1% (p<0.001), and 2.4% (p<0.001) in the 10 mg, 15 mg, and 20 mg CGP 39393 groups, respectively. All treatments were well tolerated. INTERPRETATION: This study indicates that specific inhibition of thrombin by prophylactic CGP 39393 significantly reduces thromboembolic complications in patients undergoing total hip replacement.