Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients.

BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is an Epstein-Barr virus-associated malignancy that occurs in the setting of pharmacologic immunosuppression after organ transplantation. With the increased use of organ transplantation and intensive immunosuppression, this disease is becoming more common. We explore reduction in immunosuppression as an initial therapy for PTLD. METHODS: We analyzed our organ transplant patient database to identify patients with biopsy-proven PTLD who were initially treated with reduction of their immunosuppressive medications with or without surgical resection of all known disease. RESULTS: Forty-two adult patients were included in this study. Thirty patients were treated with reduction in immunosuppression alone. Twelve patients were treated with both reduction in immunosuppression and surgical resection of all known disease. Thirty-one of 42 patients (73.8%) achieved a complete remission. Of those patients who were treated with reduction in immunosuppression alone, 19 of 30 (63%) responded with a median time to documentation of response of 3.6 weeks. Multivariable analysis showed that elevated lactate dehydrogenase (LDH) ratio, organ dysfunction, and multi-organ involvement by PTLD were independent prognostic factors for lack of response to reduction in immunosuppression. In patients with none of these poor prognostic factors, 16 of 18 (89%) responded to reduction in immunosuppression in contrast to three of five (60%) with one risk factor and zero of seven (0%) with two to three factors present. The analysis also showed that increased age, elevated LDH ratio, severe organ dysfunction, presence of B symptoms (fever, night sweats, and weight loss), and multi-organ involvement by PTLD at the time of diagnosis are independent prognostic indicators for poor survival. With median follow-up of 147 weeks, 55% of patients are alive with 50% in complete remission. CONCLUSIONS: Reduction in immunosuppression is an effective initial therapy for PTLD. Clinical prognostic factors may allow clinicians to identify which patients are likely to respond to reduction in immunosuppression.

Natriuretic peptides and their therapeutic potential.

Natriuretic peptides are a group of naturally occurring substances that act in the body to oppose the activity of the renin-angiotensin system. There are three major natriuretic peptides: atrial natriuretic peptide (ANP), which is synthesized in the atria; brain natriuretic peptide (BNP), which is synthesized in the ventricles; and C-type natriuretic peptide (CNP), which is synthesized in the brain. Both ANP and BNP are released in response to atrial and ventricular stretch, respectively, and will cause vasorelaxation, inhibition of aldosterone secretion in the adrenal cortex, and inhibition of renin secretion in the kidney. Both ANP and BNP will cause natriuresis and a reduction in intravascular volume, effects amplified by antagonism of antidiuretic hormone (ADH). The physiologic effects of CNP are different from those of ANP and BNP. CNP has a hypotensive effect, but no significant diuretic or natriuretic actions. Three natriuretic peptide receptors (NPRs) have been described that have different binding capacities for ANP, BNP, and CNP. Removal of the natriuretic peptides from the circulation is affected mainly by binding to clearance receptors and enzymatic degradation in the circulation. Increased blood levels of natriuretic peptides have been found in certain disease states, suggesting a role in the pathophysiology of those diseases, including congestive heart failure (CHF), systemic hypertension, and acute myocardial infarction. The natriuretic peptides also serve as disease markers and indicators of prognosis in various cardiovascular conditions. The natriuretic peptides have been used in the treatment of disease, with the most experience with intravenous BNP in the treatment of CHF. Another pharmacologic approach being used is the inhibition of natriuretic peptide metabolism by neutral endopeptidase (NEP) inhibitor drugs. The NEP inhibitors are currently being investigated as treatments for CHF and systemic hypertension.

Serum creatinine and blood urea nitrogen over a six-year period in the very old. Creatinine and BUN in the very old.

In a population of 141 very elderly subjects, there was a small but significant decline in BUN and creatinine at 3 years, which persisted at 6 years although partially attenuated. A similar pattern of falling BUN and creatinine was seen in the 31 subjects who began the study with mild azotemia. There was no significant change in the subjects' mean Body Mass Index during the 6-year period of observation. The azotemic subjects had a rate of death or dropout from the study similar to that of the entire cohort. Mean systolic blood pressure fell by 5.4 mm Hg (p < 0.05) and diastolic blood pressure by 2.1 mm Hg (p = NS) by 6 years. Users of diuretics or NSAID had a mean BUN and creatinine comparable to those not taking these medications. We conclude that BUN and serum creatinine do not necessarily increase with time in the old old, even in those with mild azotemia, hence, several determinations of these parameters may be needed to ensure accuracy. While renal function in the elderly probably does not improve with time, it may stabilize due to improvement in blood pressure. Use of diuretics and NSAID by functioning elderly individuals is not necessarily associated with worsening azotemia.

Atrial natriuretic peptide and its potential role in pharmacotherapy.

Atrial natriuretic peptide (ANP) is a 28 amino-acid polypeptide secreted into the blood by atrial myocytes after atrial pressure and distension. Although its role in humans is not clear, it can produce a variety of physiologic effects including vasodilatation, natriuresis, and suppression of the renin-angiotensin-aldosterone axis. These actions are potentially useful in a variety of pathologic states such as hypertension and congestive heart failure, and diverse methods to augment the effects of ANP in these states have been devised. The results are exciting and, despite some problems, may lead to the pharmacologic use of enhancement of ANP actions in several clinical disorders.

[Bipolar endoprosthesis in fractures of the femoral neck. Apropos of 201 cases, 116 after a 6-year follow-up]. / La prothèse intermédiaire dans les fractures du col du fémur. A propos de 201 cas dont 116 avec un recul médian de 6 ans.

We report our experience with 201 SEM bipolar prostheses used to treat femoral neck fractures in patients with a mean age of 70 years and a mean follow-up of 57 months (median 75 months). Clinical outcome was favorable with 94 per cent satisfactory results (very good and good). Femoral complications requiring reoperation (conversion to total hip replacement) occurred in 2.2 per cent of cases. Among the 163 patients for whom roentgenographic data were available, 5 (3.6 per cent) developed evidence of acetabular wear but remained symptom-free and did not require reoperation. As compared with Moore's prosthesis, the SEM bipolar prosthesis seems to provide substantially better clinical and roentgenographic results. For the treatment of femoral neck fractures, total hip replacement seems to provide results comparable to those reported here but requires a more sophisticated operative technique and carries a greater risk of subsequent dislocation. Two factors prevent the widespread use of the bipolar prosthesis at present: the need for femoral grouting which carries a well-documented risk of hemodynamic complications, and the higher cost of the device.

[Lesions of the ligaments associated with distal fractures of the radius. 58 intraoperative arthrographies]. / Lésions ligamentaires associées aux fractures distales du radius. A propos de cinquante-huit arthrographies peropératoires.

Intracarpal ligamentous tears and fractures of the radius often have a similar mechanism. For instance, no prospective studies have defined the real incidence of such associations, which are not antagonistic. The authors performed a systematic operative wrist arthrogram during distal radius fractures in a group of 58 patients with a mean age less than 50 years. Such a population was at low risk of degenerative ligamentous tears. Triangular fibrocartilage complex was torn in two-thirds of all types fractures. Extra-articular radius fractures were associated with an intracarpal ligamentous tear in 25% and always a luno-triquetral lesion type. In contrast, intra-articular and radius styloid fractures were frequently associated with a scapho-lunate lesion.

[Severe multiple injuries. Strategy and results. Experience at the Hôpital de la Pitié in 1988 and 1989]. / Polytraumatisés graves. Stratégie et résultats. Expérience de l'Hôpital de la Pitié 1988 et 1989.

In our series of 97 patients with multiple in juries observed in 2 consecutive years (1988-1989), we have selected only the most severe injuries, of which the patients died within 48 hours, and those that required a long stay in the intensive care department. On admission, we recorded 49 cases of stage II or more severe coma, and 67% of patients under respiratory assistance with an instable hemodynamic state. Out of the 44 deaths recorded, 30 subjects were comatose from the beginning. The justifies the confrontation of 3 specialist teams in 2/3 of cases. The specific recruitment of the hospital and the selection of the most severe cases of these "people under a death sentence" for the study shows a heavy toll of mortality (45,4%), including 60% on the first day. The main cause of death is head injuries (81%). The multivisceral and infectious consequences of long-lasting, heavy intensive care and pulmonary or myocardial contusions account fort secondary deaths in 25% of the patients who had survived. Emergent neurosurgical operations are exceptional, but a neurosurgeon's opinion is always essential. Orthopedic surgical issues are not specific, but the frequency of spinal lesions must be emphasized (27,2%). In this series, 85% of the patients with multiple trauma presented with a lesion of the locomotive apparatus and underwent emergent surgery in every second case in satisfactory conditions. Severe thoracic and maxillofacial lesions requiring surgery are rare. Abdominal lesions are more frequent (17%) and must be dealt with in priority, but they rarely cause death. On the contrary, lesions to the major blood vessels and retroperitoneal compound lesions have a very poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)