Glucocorticoid inhibition of urokinase-like plasminogen activators in cultured human lymphoblasts

Two human lymphoblast cell lines, LICR-LON-HMy2 (HMy2 cells) and GM4672A cells, are moderately growth inhibited by dexamethasone (1,4-pregnadien-9-fluoro-16 alpha-methyl-11 beta, 17 alpha, 21-triol-3,20-dione) (Dex). Both cell types secrete a urokinase (UK)-like plasminogen activator (PA). Treatment of both HMy2 and GM4672A cells with Dex for 1-4 days inhibits extracellular PA activity in a concentration-dependent manner, being half-maximal at approximately 1 X 10(-9)M. Inhibition of PA in both cell types is specific for active glucocorticoids, and this specificity parallels the ability of various steroids to bind to glucocorticoid receptors. HMy2 cell PA is fully suppressible by Dex, whereas up to one third of the activator expressed by GM4672A cells is resistant to glucocorticoid inhibition. Mixing experiments using a UK standard and conditioned media from Dex-treated cells suggest an absence of glucocorticoid-inducible inhibitors to UK or plasmin in both cell types. However, conditioned media from Dex-treated GM4672A cells inhibits a portion of the homologous cellular activator in conditioned media from control GM4672A cells. Thus, low levels of glucocorticoid-inducible inhibitors may contribute to, but cannot fully account for, Dex inhibition of GM4672A PA activity. Glucocorticoid-inducible inhibitors in HMy2 cells are either totally absent or are present at undetectable levels. Thus, regulation of UK-like PAs in HMy2 and GM4672A cells differs with respect to the extent to which glucocorticoids inhibit constitutively expressed activator levels, as well as the possible contribution of glucocorticoid-inducible inhibitors to the regulatory process in GM4672A cells.     

Electrophoretic analysis of red blood cells in polycythaemia

In contrast with previously published observations, this study has found no increase in the net negative surface charge of the red blood cells (RBC) from patients with various forms of polycythaemia when compared with normal subjects. Two sub-populations of RBCs with different electrophoretic mobilities (EPM), termed fast and slow, were present in samples from both patients and normal individuals. Frequently, the slow cell population in RBCs from patients with polycythaemia, particularly the apparent polycythaemia sub-group, was of a lower EPM and contained more cells than the corresponding population in normal subjects. The membrane-bound sialic acid content of RBCs from patients with primary proliferative polycythaemia, associated with iron deficient RBC changes, was increased if the results were expressed per unit volume of RBCs and decreased if the sialic acid concentration was presented per number of RBCs. These results imply that differences in surface charge of RBCs are of no value in discriminating between primary and secondary polycythaemia.     

Mixed meningeal and brain plasma-cell granuloma: an example of an unusual evolution

Summary We report a study of a 22-year-old woman with a plasma-cell granuloma (PCG), a rare intracranial lesion characterized by a non-neoplastic polyclonal proliferation of plasma cells and other mononuclear cells. She presented after a generalized seizure and CT-scan and magnetic resonance images demonstrated a left temporo-basal tumour mass involving both the meningeal layers and the brain parenchyma. Histopathological examination of a biopsy led to the diagnosis of a typical PCG. After a short course of steroid administration, the clinical and radiological features improved and complete regression of the lesion was shown after one year and persisted at four-year follow-up. This dramatic regression of an intracranial PCG shows that neither surgical removal nor radiation therapy is required to treat a broad skull base PCG.     

Acute Polymyositis Following Renal Transplantation

Myositis is a rare complication following renal transplantation and is most commonly the result of drug-mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60-year-old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle-fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high-dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease.     

Surgical removal of unilateral vestibular schwannomas after failed Gamma Knife radiosurgery

One of the primary criticismes of vestibular schwannoma (VS) radiosurgery is that the risk of surgical morbidity is increased for patients whose tumor progresses after the procedures. We reviewed the French experience of operated patients after failed Gamma Knife radiosurgery. From July 1992 to January 2002, 25 out of the 1000 treated patients underwent another treatment procedure for a gamma knife failure. Excluding the NF2 patients, 21 patients have been operated and the present study shows the data collected for 20 of them. In order to analyze the difficulties observed during the surgery, a questionnaire was filled by the surgeons. The mean interval between radiosurgery and removal was 36 Months, from 10 to 83 Months. The mean increase in Volume was 559% (37 to 3036%, median 160%). Evolution of the Koos grading was found from 8 grade II, 10 grade III et 2 grade IV to 10 grade III and 10 grade IV. Patients have been operated for radiological tumor growth in 7 cases and for clinico-radiological evolution in 13 cases. In 9 cases, the surgeon considered that he had to face unusual difficulties mainly because of adhesion of the tumor to neurovascular structures. Tumor removal was total in 14 cases, near total in 4 cases and subtotal in 2 cases. One case of venous infarction was noticed at the second day following surgery responsible of hemiparesis and aphasia that gradually recovered. At last follow-up examination, facial nerve was normal (House and Brackmann grade I and II) in 10 cases while it was a grade III in 7 cases and grade IV and V in 3 cases. We recommend that the decision for surgical removal of growing vestibular schwannoma after Gamma Knife treatment should be done after a sufficiently long follow-up period. Our results show that the quality of removal and of facial nerve preservation might be impaired by radiosurgery in half of cases. However these results do not support a change in our policy of radiosurgical treatment of small to medium size vestibular schwannoma.     

Effects of compression stockings on sympathetic activity and heart rate variability in individuals with spinal cord injury

Objective

To investigate whether wearing graduated compression stockings (GCS) could affect the sympatho-adrenergic and heart rate variability (HRV) responses at rest and after a strenuous wheelchair exercise in individuals with spinal cord injury (SCI).

Design

Crossover trial.

Setting

Department of Physical Medicine and Rehabilitation, Saint Etienne, France.

Participants

Nine men with SCI (five with low paraplegia: LP, four with high paraplegia: HP).

Interventions

Two maximal wheelchair exercise tests: with and without GCS (21 mmHg).

Main outcome measures

HRV measurements: high frequency (HF), low frequency (LF), and LF/HF ratio. Norepinephrine (NOR) and epinephrine (EPI), at rest and post-exercise. Secondary measures were: blood pressure, heart rate, maximal power output, oxygen uptake, stroke volume, cardiac output, at rest, during and after exercise.

Results

When wearing GCS: LFnu_wavelet-post significantly increased and HFnu_wavelet-post significantly decreased (P < 0.05) in SCI subjects, leading to an enhance ratio of LF_wavelet/HF_wavelet and a significantly increased in NOR_rest (P < 0.05).

Conclusions

GCS induces an enhanced sympathetic activity in individuals with paraplegia, regardless of the level of the injury. Enhanced post-exercise sympathetic activity with GCS may help prevent orthostatic hypotension or post-exercise hypotension.     

Liver-kidney recipients with chronic viral hepatitis C treated with interferon-alpha

Antiviral therapy with interferon-alpha (IFN-alpha) and pegylated IFN-alpha (PEG-IFN-alpha) for chronic hepatitis C (HCV)-infected kidney recipients remains controversial. IFN-alpha is not recommended in most cases because it induces severe acute graft rejection. However, IFN-alpha, as PEG-IFN-alpha, is associated with a more pronounced immune response, and is well tolerated in HCV-infected liver recipients without causing graft rejection. In combined liver-kidney transplant (LKT) recipients, IFN-alpha has been occasionally used and appears to be well tolerated. All LKT recipients with a functioning kidney and liver having a HCV replication and who needed IFN-alpha therapy have been included in the study. The occurrence of liver and/or renal acute rejection as well as the HCV replication has been collected. A total of 12 LKT patients treated with PEG-IFN-alpha plus ribavirin have been studied. No acute rejection was observed. Renal function remained stable during and after discontinuing treatment, without any graft dysfunction. Two patients had a partial viral response and four had a sustained viral response. All patients, whatever their viral response, had decreased liver-enzyme levels. Response to PEG-IFN-alpha therapy was correlated with steroid dose and transaminase level when PEG-IFN-alpha was started. These data suggest that the combination therapy of PEG-IFN-alpha plus ribavirin did not have a higher risk of acute kidney-graft rejection after liver-kidney transplantation.     

Prospective, Multicenter, 3-Year Trial of Laparoscopic Adjustable Gastric Banding with the MIDBAND?

Background

Although laparoscopic adjustable gastric banding (LAGB) is a popular metabolic/bariatric procedure, few prospective studies have assessed its outcomes. This study aimed to prospectively assess LAGB safety and effectiveness outcomes using the MIDBAND? (MID, Dardilly, France).

Methods

Between May 2005 and September 2006, 262 morbidly obese patients underwent primary gastric banding with pars flaccida technique in 13 French medical centers. Excess weight loss and change in body mass index (BMI, kilogram per square meter), percentage of patients with comorbidities, and obesity-related complications were recorded. Patients were followed at 6-month intervals for 3?years. A multivariable individual growth model was used to analyze weight change over time and determine potential predictors of weight loss.

Results

The majority of patients were female (n?=?233, 89%), with mean age of 36.4?±?9.7?years. At 3?years, LAGB with MIDBAND resulted in significant decrease in mean BMI from 41.8?±?4.2 to 30.7?±?5.8 (p?p?Conclusion Prospective outcomes demonstrate the safety and efficacy of gastric banding over time using the MIDBAND. Individual growth modeling demonstrated that postoperative weight loss is strongly related to the frequency and consistency of follow-up visits.