Methotrexate osteopathy: five cases and systematic literature review.

INTRODUCTION: Methotrexate (MTX)-related osteopathy is rare, defined by the triad of pain, osteoporosis, and "atypical fractures" when it was first described in the 1970s in children treated with high doses MTX for acute leukemia. Since then, several cases have been reported in patients treated with low-dose MTX for inflammatory diseases. METHODS: A systematic research of cases of MTX-related osteopathy was performed in records of Rheumatology Department of Rennes University Hospital. Data collection focused on demographic data, corticosteroid doses, MTX doses and intake method, cumulative doses, year of diagnosis, fracture location, bone densitometry value, and osteoporosis treatment if necessary. A literature review was also conducted to identify other cases in literature and try to understand the pathophysiological mechanisms of this rare entity. RESULTS: We report 5 cases identified between 2011 and 2019, which represents the largest cohort described excluding oncology cases. Fracture locations were atypical for osteoporotic fractures. All patients improved in the following months with MTX withdrawal. All patients except one were treated with antiresorptives (bisphosphonates, denosumab). Two patients, treated with bisphosphonates, had a recurrence of fracture, once again of atypical location. Twenty-five cases were collected in literature with similar clinical presentation. The cellular studies that investigated the bone toxicity of MTX mainly showed a decrease in the number of osteoblasts, osteocytes, and chondrocytes in the growth plate and an increase in the number and activity of osteoclasts. In vitro, consequences of mechanical stimulation on human trabecular bone cells in the presence of MTX showed an alteration in mechano-transduction, with membrane hyperpolarization, acting on the integrin pathway. In contrast with our report, the cases described in the literature were not consistently associated with a decrease in bone mineral density (BMD). CONCLUSION: MTX osteopathy while rare must be known by the rheumatologist, especially when using this treatment for inflammatory conditions. The mechanisms are still poorly understood, raising the question of a possible remnant effect of MTX on osteo-forming bone cells, potentially dose-dependent. Methotrexate (MTX) osteopathy, described as a clinical triad, pain, osteoporosis, and atypical stress fractures, while rare, must be known by the rheumatologist. Our cohort of 5 cases represent the largest series of the literature. Pathophysiological studies raised the question of a dose-dependent remnant effect of MTX on osteo-forming bone cells.

Etiology of avascular osteonecrosis of the femoral head.

Avascular osteonecrosis of the femoral head (ONFH) is one of the causes of hip pain that clinicians need to know about. In many cases, it is a fortuitous discovery when pelvic X-rays is performed for another reason. In the other cases, pain reveals the disease. For the rheumatologist, a major part of the job is to look for a cause. An etiology can be found to ONFH in about 70% of the cases. Some of them are evident and the context give the diagnosis (corticosteroids, alcohol abuse…). However, in many cases, additional tests to imaging are required to make the causal diagnosis. In some cases, the treatment of the cause can prevent the recurrence of the disease.

External validation of Gout-calculator performance on a cohort of acute arthritis (SYNOLACTATE) sparing distal joints such as hallux and midfoot. A cross-sectional study of 170 patients.

OBJECTIVE: To evaluate the performance of the Gout-calculator in a cohort of consecutive acute arthritis affecting large and intermediate joints (without an attack on hallux or midfoot joints). METHODS: A retrospective study. Gout-calculator data were collected in medical records of patients included in the prospective consecutive cohort of acute arthritis called SYNOLACTATE. The diagnosis of gout was defined by the presence of sodium urate crystals in synovial fluid. The diagnostic performance of the Gout-calculator was studied by performing an ROC curve with the calculation of its AUC (95% CI) as well as the calculation of Sensitivity (Se), Specificity (Sp), and positive likelihood ratio (LR+). RESULTS: 170 patients with acute arthritis were included. Variables associated with the diagnosis of gout were as follows: serum uric acid > 350 µmol/L (OR 5.52 (2.52-12.1), p < 0.001), joint redness (OR 5.08 (1.85-14.0), p = 0.001), previous patient-reported arthritis attack (OR 4.04 (1.92-8.49), p < 0.001), male (OR 3.00 (1.17-7.69), p = 0.02), hypertension or cardiovascular disease (OR 2.33 (1.07-5.06), p = 0.03). The median (IQR) of Gout-calculator was significantly higher in gouty arthritis (7.0 [5.5-8.1]) than in associated-CPP acute arthritis (4.0 [2.0-5.8]), septic arthritis (3.0 [2.0-5.1]), or others arthritis (3.5 [2.0-5.5]). The AUC was 0.833 (0.768-0.897) with for the threshold ≥ 8, a Se at 27.5% (0.161-0.428), Sp 97.7% (0.934-0.992), and LR+ 11.9 (3.5-40). CONCLUSION: Despite diagnostic performances close to those published, the use of the Gout-calculator is not sufficient for the diagnosis of gout or to exclude the differential diagnosis of septic arthritis in the SYNOLACTATE cohort. KEY POINTS: • For a Gout-calculator threshold of ≤ 4, Sensitivity is 92.5%, Specificity 50.8% and LR- 0.15 to the gout diagnosis. • For a Gout-calculator threshold of > = 8, Sensitivity is 27.5%, Specificity 97.7% and LR+ 11.9 to the gout diagnosis. • In a population of acute arthritis affecting large joints, Gout-calculator is not sufficient to discriminate between gouty arthritis and septic arthritis.

Performance of Basic Life Support by Lifeboat Crewmembers While Wearing a Survival Suit and Life Vest: A Randomized Controlled Trial.

Introduction: Crewmembers of the "Royal Netherlands Sea Rescue Institution" (KNRM) lifeboats must wear heavy survival suits with integrated lifejackets. This and the challenging environment onboard (boat movements, limited space) might influence Basic Life Support (BLS) performance. The primary objective of this study was to assess the impact of the protective gear on single-rescuer BLS-quality. Material and Methods: Sixty-five active KNRM crewmembers who had recently undergone a BLS-refresher course were randomized to wear either their protective gear (n = 32) or their civilian clothes (n = 33; control group) and performed five 2-min sessions of single rescuer BLS on a mannequin on dry land. BLS-quality was assessed according to Dutch and European Resuscitation guidelines. A between group analysis (Mann-Whitney U) and a repeated within group analysis of both groups (Friedman test) were performed. Results: There were no major demographic differences between the groups. The protective gear did not significant impair BLS-quality. It was also not associated with a significant increase in the perceived exertion of BLS (Borg's Rating scale). Compression depth, compression frequency, the percentage of correct compression depth and of not leaning on the thorax, and ventilation volumes in both groups were suboptimal when evaluated according to the BLS-guidelines. Conclusions: The protective gear worn by KNRM lifeboat-crewmembers does not have a significant influence on BLS-quality under controlled study conditions. The impact and significance on outcome in real life situations needs to be studied further. This study provides valuable input for optimizing the BLS-skills of lifeboat crewmembers.

Cachectin/tumor necrosis factor mediates changes of skeletal muscle plasma membrane potential.

Lethal infections are associated with cellular dysfunction as evidenced by a decrease in the resting transmembrane potential difference (Em) of skeletal muscle fibers. Endotoxin stimulation of macrophages evokes production of cachectin, a protein that has been implicated as a mediator of the lethal effects of endotoxemia. In the present study, rat skeletal muscle fiber Em decreased when incubated with recombinant human cachectin. The reduction of Em induced by cachectin occurred in a dose-related fashion and was inhibited by mAb against the monokine. Infusion of cachectin induced a decline of skeletal muscle Em in vivo, and suggests that cachectin may acutely mediate alterations of skeletal muscle membrane function after infection.

Shock and tissue injury induced by recombinant human cachectin.

Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.

Broad-range 16 s rDNA PCR in synovial fluid does not improve the diagnostic performance of septic arthritis in native joints in adults: cross-sectional single-center study in 95 patients.

OBJECTIVE: To evaluate the diagnostic performance of bacterial identification by broad-range polymerase chain reaction (PCR) of ribosomal DNA (rDNA) 16 s (16S rDNA PCR) for the diagnosis of septic arthritis on native joints. METHODS: Patients with acute mono or oligoarthritis who underwent synovial fluid puncture and prospective follow-up allowing definitive diagnosis (septic arthritis, crystal related disease, chronic inflammatory arthritis, undifferentiated arthritis) were recruited in this single-center study. Systematic analysis of synovial fluid included leukocytes count, search for urate and pyrophosphate crystals with polarized light microscopy, direct bacteriological examination (gram staining), bacteriological culture, and 16S rDNA PCR. RESULTS: Ninety-five patients were included, 34 of which (35.8%) had septic arthritis. Nineteen (20.0%) patients had received probabilistic antibiotic therapy prior to joint puncture. Gram + cocci infection accounted for 79.4% of septic arthritis, of which nearly half (47.1%) was caused by Staphylococcus aureus. Eight (23.5%) septic arthritis patients had a 16S rDNA PCR positive in the synovial fluid with an AUC of 0.618 (95% CI, 0.493-0.742), a sensitivity of 0.24 (95% CI, 0.12-0.40), and a specificity of 1.00 (95% CI 0.94-1.00). The diagnostic performance of 16S rDNA PCR was lower than that of direct examination (AUC at 0.691, CI 95%, 0.570-0.812), blood cultures (AUC at 0.727, CI 95%, 0.610-0.844), and culture (0.925, CI 95%, 0.856-0.994) for the diagnosis of septic arthritis. There was no difference in the positivity of 16S rDNA PCR according to previous exposure to antibiotics. CONCLUSIONS: 16 s rDNA PCR in the synovial fluid does not improve the diagnostic performance of septic arthritis on native adult joints, particularly for Gram-positive cocci infections.

Low prevalence of osteoporosis treatment in patients with recurrent major osteoporotic fracture.

The majority of patients do not receive anti-osteoporotic treatment following a major osteoporotic fracture, despite the guidelines and the availability of effective anti-osteoporotic treatments. The fight against factors limiting the diagnosis and treatment of osteoporosis should become a priority to improve secondary prevention after an initial osteoporotic fracture. PURPOSE: Despite the availability of effective anti-osteoporotic treatments, osteoporosis management is currently insufficient. The main objective of this study was to assess the prevalence of anti-osteoporotic treatments introduced after an initial prior major osteoporotic fracture during hospitalization for recurring fractures. METHODS: We conducted an observational, cross-sectional, bicentric study that included all patients aged over 50 years who were hospitalized or seen in consultation for major osteoporotic fracture. RESULTS: One hundred twenty-eight out of two hundred four (62.7%) patients had a past history of major osteoporotic fracture and therefore had an indication of treatment based on guidelines. Among these patients, only 43/128 (33.5%) had received anti-osteoporotic treatment as secondary prevention after the initial fracture. The main causes of non-prescription identified were the attending physicians' ignorance of the indication of treatment (n = 30; 35.3%), ignorance of the fracture (n = 17; 20%), and comorbidities (n = 12; 14.1%). The failure to introduce treatment was associated with the presence of comorbidities with a Charlson Comorbidity Index ≥6 (OR = 0.34 [0.16-0.73], p < 0.05), dementia (OR = 0.23 [0.08-0.72], p < 0.05), and past history of proximal femur fracture (OR = 0.20 [0.04-0.91], p < 0.05). CONCLUSIONS: Two thirds of patients with a past history of major osteoporotic fracture presenting with a new fracture were not treated. The main reason for lack of treatment seems to stem from the incorrect assessment of the patient's fracture risk. Although major osteoporotic fracture leads to an increased risk of mortality and requires treatment, the significance of patient comorbidities was an independent risk factor leading to non-treatment.

[Cryptococcal infections in non-HIV infected patients. Study of four cases and review of literature]. / Infections à cryptocoque chez des patients non VIH. A propos de quatre cas et revue de la littérature.

BACKGROUND: Cryptococcal infections are frequent in HIV-infected patients and are regularly looked after. This infection may occur in others immunosuppressives situations and, in those cases, diagnosis is often delayed. METHODS: We report four cases of cryptococcal infections in patients whose immunosuppression isn't related with HIV infection but due to chronic lymphocytic leukemia, giant cell temporal arteritis, gastric neoplasm and lupus. Diagnosis, prognostic and treatment are detailed. RESULTS: Four patients aged from 25 to 76 presented a cryptococcal infection (three meningitis). A woman died at the admission. Another died seven years later. The two others are still alive under treatment. When infected, all patients were immunodeficiency. CONCLUSION: Cryptococcal infection may occur in patients non-HIV-infected patients. Early detection is needed to improve prognostic.

[Synovial biopsy under US guidance: technical considerations and results]. / Technique et évaluation du guidage échographique pour la réalisation de biopsies synoviales.

PURPOSE: To describe and assess ultrasound (US) guided biopsy of peripheral joint synovial membrane. METHOD: Between January 2002 and January 2005, 83 patients have undergone biopsies of synovial membrane performed under ultrasonographic guidance, as a diagnostic procedure for monoarthritis of unknown etiology. After synovial thickening was confirmed by US examination, the optimal approach to the joint was decided in accordance with maximal synovial thickening localization and adjacent anatomic structures. The absence of complications related to the biopsy was verified by continuous ultrasonographic scanning during and immediately after the procedure. The procedure was rated as successful if synovial tissue was identified by histologic examination of the biopsy specimen. Success rate of the procedure was compared to the fluoroscopic guided biopsy success rate that was formely published in medical literature. RESULTS: Synovial tissue was obtained in 78 cases (94%) (shoulder (100%), elbow (75%), wrist (85.7%), hip (88.2%), knee (97%), ankle (100%). No complication occurred. CONCLUSION: US guided biopsy of peripheral joint synovial membrane is a safe and effective technique that has multiple advantages compared to fluoroscopic guided procedure.

Effect of tamoxifen on stromal protein synthesis in the human prostate.

To test the hypothesis that estrogen may have significant biological effects on the human prostate, we studied the effects of in vivo administration of tamoxifen, an antiestrogen, on human prostatic stromal protein synthesis in vitro. This was done by measuring [3H]proline incorporation in vitro in stromal cells separated enzymatically with 0.5% collagenase and trypsin from hypertrophic prostatic tissue removed at surgery. A mechanical method for separation of epithelium and stroma was attempted, but cell damage resulted in very low incorporation of [3H]proline into protein. Twelve patients were given 20 mg tamoxifen twice daily for 10 days before surgery. The serum levels of tamoxifen at the time of surgery ranged from 200-500 pmol/ml. Control tissues (14) were obtained from untreated patients. Tamoxifen decreased stromal protein synthesis, as measured by counts per min/mg protein, to approximately one third of that found in control patients (control mean, 102,428; tamoxifen-treated mean, 34,111; P less than 0.01). These results support the concept that estrogen has a significant role in the regulation of stromal protein synthesis and the pathophysiology of benign prostatic hypertrophy.

Tissue dihydrotestosterone levels and clinical response to hormonal therapy in patients with advanced prostate cancer.

Dihydrotestosterone (DHT) levels were measured by RIA in tumor tissue from 32 men with advanced prostate cancer and correlated with their clinical responses to antiandrogen therapy. In 24 patients with tumor tissue DHT levels greater than 2.5 ng/g, 20 initially responded to therapy with partial objective regression or were objectively stable for 12 or more months, while 4 patients relapsed in less than 1 yr. The average disease-free interval in this group was 24 months, with 9 patients still continuing in partial objective regression or objective stability. Of 8 patients with DHT levels less than 2.0 ng/g, 5 had either objective progression or were objectively stable for 6 months or less; 2 other patients have completed remissions ranging from 16-24 months, while 1 patient remains objectively stable for 21 months to date. The average disease-free interval in patients with DHT levels less than 2.0 ng/g was 9.75 months, which is significantly less (P less than 0.001) than that of patients with DHT levels greater than 2.5 ng/g. There was no discernible relationship between the Gleason histological grade of prostate cancer and initial clinical response to therapy in these same patients. In summary, this study supports the thesis that tissue DHT levels may be a useful marker for predicting the clinical response of prostate cancer to antiandrogen therapy.

Thermogenic and nitrogen response to submaximal exercise in parenterally repleted normal man.

To determine whole-body energy and nitrogen responses to submaximal exercise during repletion levels of intravenous feeding (IVF), five normal male volunteers were hospitalized and underwent serial changes in nutritional intake consisting of weight-maintaining oral feeding (4 d), starvation (10 d), and weight-increasing parenteral feeding (10 d). Twelve-hour aliquots for urinary nitrogen, creatinine, and 3-methylhistidine were collected during the final 36 h of oral feeding and IVF. During these experimental periods, indirect calorimetry was utilized to determine resting oxygen consumption and that occurring during a 1-h period of submaximal (40% of maximal) upright, bicycle exercise. Despite differences in the route of nutrient delivery, oxygen uptake during a fixed rate of exercise (75 W) was similar during oral (16.7 +/- 0.4 mL X kg-1 X min-1) and IVF (14.7 +/- 1.0 mL X kg-1 X min-1). When compared with basal urinary losses, submaximal exercise resulted in diminished nitrogen (p less than 0.01, oral) and 3-methylhistidine (p less than 0.05, oral; p less than 0.01, IVF) excretion during a 12-h post-exercise recovery period.

Comparison of various hormonal therapies for prostatic carcinoma.

The goals of hormonal therapy for prostatic cancer are to decrease circulating plasma testosterone to castration levels; prevent a rise in or reduce circulating prolactin; and block residual androgen at the cell level. Orchiectomy is very effective but does not prevent residual adrenal androgens from being converted to dihydrotestosterone (DHT); also, it has no effect on plasma prolactin. Estrogen has no known effect on androgen-receptor concentration or DHT binding to receptor and raises plasma prolactin. It also has significant side effects. Megestrol acetate, the only antiandrogen currently available for use in the United States, has been shown to block androgen from all sources. It produces a transient reduction in plasma testosterone to levels somewhat higher than those in castrated men, and it has no effect on plasma prolactin. When used in a dose of 120 mg/day in combination with 0.5 to 1.5 mg of estradiol per day, it acts synergistically to suppress pituitary gonadotropins and maintain plasma testosterone at castration levels for periods of up to 1 year. Newer therapies being studied include flutamide, a nonsteroidal antiandrogen, and luteinizing hormone-releasing hormone (LHRH). Data on these agents are limited and comparisons with standard therapies are needed.

Conduit reconstruction of the right ventricular outflow tract. Lessons learned in a twelve-year experience.

From September 1979 to July 1991, a total of 163 patients have undergone valved conduit reconstruction of the right ventricular outflow tract when a right ventricle-pulmonary artery connection was absent or right ventricular outflow tract enlargement was required. From September 1979 through October 1984, 24 porcine valved conduits were implanted with an operative mortality of 38% (9/24). There were no early failures, but by 9 years after the operation 9 of 15 survivors (60%) had severe conduit obstruction, which resulted in death in 2 patients and reoperation in 6. From May 1985 to June 1991, 24 patients received cryopreserved aortic allografts to correct congenital anomalies. Operative mortality was 25% (6/24) and, again, early conduit function was good. There were 4 (22%) late deaths that were not related to the aortic allograft. At a mean follow-up of 3.4 years, 11 of the 13 survivors (85%) had allograft calcification and 8 of the 13 (62%) had mild to moderate conduit stenosis or regurgitation, or both; two of them required conduit replacement. Distal anastomotic problems that might have been avoided with bifurcated pulmonary allografts were apparent in 4 (36%) patients. Cryopreserved pulmonary allografts were placed in 115 patients between April 1985 and January 1991, with 18 (16%) operative deaths. Late deaths that were not allograft related occurred in 7 of 97 surviving patients (7%). Six patients (6%) underwent reoperation, 2 because of primary pulmonary allograft failure. The 84 remaining patients are free of symptoms with little or no allograft calcification or echocardiographic evidence of significant conduit stenosis or regurgitation. Experience with porcine valved conduits and aortic and pulmonary allografts suggests that pulmonary allografts are the conduit of choice for right ventricular outflow tract reconstruction.

The influence of respiratory acid-base status on adult pulmonary vascular resistance before and after cardiopulmonary bypass.

Respiratory acid-base status has recently been shown to affect pulmonary vascular resistance (PVR) in adults following cardiac surgery. The purpose of this study was to examine what influence cardiopulmonary bypass has on the pulmonary vascular response to changes in respiratory acid-base status. Fifteen consecutive patients undergoing aortocoronary bypass were studied under general anesthesia both before and after cardiopulmonary bypass. Arterial PCO2 was manipulated by the addition of 5 percent carbon dioxide to the breathing circuit. Both before and after bypass, PVR increased significantly as PCO2 rose from 30 mm Hg to 50 mm Hg (p < 0.05). The PVR returned to baseline as PCO2 was returned to 30 mm Hg. These data suggest that increased PVR induced by hypercarbic acidemia is not simply a result of the effects of cardiopulmonary bypass on the pulmonary circulation. Instead, we conclude that respiratory acid-base status is an important determinant of adult PVR. We believe these data may be helpful in the treatment of mechanically ventilated patients, since patients are at particular risk of having abnormalities develop in respiratory acid-base status.

Influence of enterectomy on peripheral tissue glutamine efflux in critically ill patients.

Glutamine and alanine are dominant nitrogen carriers from skeletal muscle stores to splanchnic organs. In addition, these amino acids may also serve as a primary energy source for the gastrointestinal tract during injury. To investigate these contributions, we studied extremity amino acid efflux during hypocaloric dextrose feedings and during total parenteral nutrition in a population of normal volunteers (NL VOL) (n = 9), a group of patients with sepsis who had undergone laparotomy without bowel resection and were in the intensive care unit (ICU) (n = 7), and patients with sepsis after laparotomy (PT) (n = 2) who had recently undergone greater than 80% bowel resection. Circulating alanine and glutamine levels were significantly lower in the patients compared with NL VOL under both feeding conditions. The peripheral output of alanine was higher in the ICU group than in the NL VOL during hypocaloric feedings. Glutamine efflux, however, was independent of either the counterregulatory hormone or substrate background. By contrast, enterectomy was associated with a marked decrease of extremity glutamine efflux compared with NL VOL or the ICU patients who did not undergo enterectomy (-62 +/- 9 nmol/min/dl tissue in the PT vs -265 +/- 32 nmol/min/dl tissue in the NL VOL and -311 +/- 58 nmol/min/dl tissue in the ICU group) during the dextrose feedings; this difference persisted during subsequent total parenteral nutrition (+12 +/- 13 nmol/min/dl tissue in PT vs -178 +/- 56 nmol/min/dl tissue in the NL VOL and -287 +/- 81 nmol/min/dl tissue in the ICU group). These data suggest that distinct mechanisms regulate peripheral alanine and glutamine balance and that the gastrointestinal tract provides a feedback signal to peripheral tissues to maintain glutamine mobilization under both nonstressed and stressed conditions.

Effect of hormonal and substrate backgrounds on cell membrane function in normal males.

Hormonal and substrate influences on in vivo cellular membrane function were evaluated in 15 healthy male volunteers. Each subject underwent serial evaluations of membrane function in the anterior tibialis muscle, as assessed by transcutaneous measurement of resting membrane potential (Em). Group A subjects (n = 9) underwent measurement of resting Em in the basal state and again during the 10th day of intravenous feeding (IVF). Group B subjects (n = 6) underwent measurement of resting Em in the basal state during epinephrine infusion and again during epinephrine infusion on the 7th day of IVF. Percutaneous needle biopsy of the vastus lateralis muscle permitted calculation of transmembrane electrolyte distribution from the Nernst equation, using the measured Em and the chloride space method. Hospitalization with intake of a defined-formula enteral diet for 3 days resulted in depolarization (P less than 0.05) of resting Em (-75.3 +/- 1.6 mV) compared with normal (-79.8 +/- 0.9 mV). Despite 10 days of subsequent IVF, further depolarization (P less than 0.05) of resting Em (-71.2 +/- 1.2 mV) was observed. In the dual presence of IVF and exogenous epinephrine infusion, there was an increase (P less than 0.05) in intracellular potassium concentration and repolarization of resting Em (-80.6 +/- 0.8 mV) to normal levels. These data indicate that hormonal background and substrate availability contribute to the in vivo modulation of cellular membrane function in human skeletal muscle, possibly through facilitation of sodium-dependent amino acid transport across the cell membrane.

Hemodynamic advantage of left atrial epinephrine administration after cardiac operations.

Cardiac surgical patients frequently require catecholamines, typically administered via the central venous circulation. Potential disadvantages of this route of administration include catecholamine metabolism by the pulmonary vascular bed before gaining access to the heart and pulmonary vasoconstriction producing increased pulmonary vascular resistance. We therefore prospectively compared administration of epinephrine via the left atrium versus central venous administration of epinephrine with particular interest in cardiac output, mean pulmonary artery pressure, and pulmonary vascular resistance. Fifteen consecutive aortocoronary bypass patients were studied after cardiopulmonary bypass. Epinephrine (mean dose, 0.07 +/- 0.02 micrograms.kg-1.min-1) was administered via the central venous route, then via the left atrium, then via the central venous route again. Hemodynamic data were collected 10 minutes after changing the route of administration. Left atrial administration of epinephrine produced a 35% greater cardiac output, 25% lower pulmonary artery pressure, and 32% lower pulmonary vascular resistance when compared with central venous administration (all significant; p < 0.05). Left atrial epinephrine administration may offer hemodynamic advantage in cardiac surgical patients in whom central venous administration does not produce an adequate cardiac output or in patients with pulmonary hypertension to avoid any further increase in pulmonary vascular resistance.

Use of pleural Tenckhoff catheter to palliate malignant pleural effusion.

Malignant pleural effusion and its treatment both cause substantial morbidity in patients with advanced neoplastic disease. We hypothesized that this morbidity might be ameliorated by placement of an indwelling Tenckhoff catheter into the involved pleural space. Catheters were placed in 9 patients under local anesthesia. Three patients underwent bilateral catheter placement, for a total of 12 catheters placed. Four of the 9 patients had undergone previous unsuccessful pleurodesis (using tetracycline or bleomycin). Whenever it became symptomatic, the malignant pleural effusion was simply drained into a calibrated container and the volume recorded. Patients were followed on a weekly basis until their death (mean, 16 weeks). The mean drainage was 477 mL per 24 hours (range, 200 to 1,100 mL). No pleural space infections occurred, although local cellulitis developed in 3 patients around the catheter exit site; all patients responded to oral antibiotics. There were no significant changes in either the serum albumin or total protein levels. No catheters malfunctioned and no patients required further treatment or hospitalization for symptoms of malignant pleural effusion. We conclude that this technique may reduce the morbidity stemming from malignant pleural effusion and its treatment by allowing patients to conveniently and painlessly drain the effusion at home when it becomes symptomatic. This technique may provide superior palliation in patients with malignant pleural effusion.