Radial nerve palsy in humeral shaft fractures with internal fixation: analysis of management and outcome.

INTRODUCTION: The incidence of radial nerve injury after humeral shaft fractures is on average 11.8% (Shao et al., J Bone Jt Surg Br 87(12):1647-1652, 2005) representing the most common peripheral nerve injury associated with long bone fractures (Korompilias et al., Injury, 2013). The purpose of this study was to analyze our current policy and long-term outcome, regarding surgically treated humeral shaft fractures in combination with radial nerve palsy. MATERIALS AND METHODS: We retrospectively analyzed the data of patients with surgically treated humeral shaft fractures from 01/01/2003 to 28/02/2013. The analysis included fracture type, soft tissue injury regarding closed and open fractures, type of fixation, management, and outcome of radial nerve palsy. RESULTS: A total of 151 humeral shaft fractures were fixed in our hospital. In 20 (13%) cases, primary radial palsy was observed. Primary nerve exploration was performed in nine cases. Out of the 13 patients with follow-up, 10 showed a complete, 2 a partial, and 1 a minimal nerve recovery. Two of them underwent a revision procedure. Secondary radial nerve palsy occurred in 9 (6%) patients postoperatively. In five patients, the radial nerve was not exposed during the initial surgery and, therefore, underwent revision with nerve exploration. In all 5, a potential cause for the palsy was found and corrected as far as possible with full recovery in 3 and minimal recovery in one patient. In four patients with exposure of the nerve during the initial surgery, no revision was performed. All of these 4 showed a full recovery. CONCLUSION: Our study showed an overall rate of 19% radial nerve palsy in surgically treated humeral shaft fractures. Most of the primary palsies (13%) recovered spontaneously, and therefore, nerve exploration was only exceptionally needed. The incidence of secondary palsy after surgery (6%) was high and mainly seen after plate fixation. In these cases, we recommend early nerve exploration, to detect and treat potential curable neural lesions.

The outcome of patients with nephrogenic systemic fibrosis after successful kidney transplantation.

Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis.

Kidney transplant function and histological clearance of virus following diagnosis of polyomavirus-associated nephropathy (PVAN).

Polyomavirus-associated nephropathy (PVAN) is managed by reduced immunosuppression with or without antiviral therapy. Data from 55 patients with biopsy-proven PVAN were analyzed for adverse outcomes and influence of baseline variables and interventions. During 20+/-11 months follow-up, the frequencies of graft loss, major and any functional decline were 15%, 24% and 38%, respectively. Repeat biopsies were performed in 45 patients with persistent PVAN in 47%. Low-dose cidofovir, IVIG and cyclosporine conversion were used in 55%, 20% and 55% of patients. No single intervention was associated with improved outcome. Of the variables examined, only degree of interstitial fibrosis at diagnosis was associated with kidney function decline. In contrast, donor source, interstitial fibrosis, proportion of BKV positive tubules and plasma viral load at diagnosis were all associated with failure of histological viral clearance. This retrospective, nonrandomized analysis suggests that: (i) Graft loss within 2 years of PVAN diagnosis is now uncommon, but ongoing functional decline and persistent infection occur frequently. (ii) Low-dose cidofovir, IVIG and conversion to cyclosporine do not abrogate adverse outcomes following diagnosis. (iii) Fibrosis at the time of diagnosis predicts subsequent functional decline. Further elucidation of the natural history of PVAN and its response to individual interventions will require prospective clinical trials.

Complete avoidance of calcineurin inhibitors in renal transplantation: a randomized trial comparing sirolimus and tacrolimus.

Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMF-prednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 +/- 19 mL/min vs. 63 +/- 18 mL/min, p = 0.57) or 2 years (61 +/- 17 mL/min vs. 61 +/- 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone.

Thymoglobulin induction decreases rejection in solitary pancreas transplantation.

BACKGROUND: Solitary pancreas transplants, both pancreas transplant alone (PTA) and pancreas after kidney (PAK), have higher rejection rates and lower graft survivals than simultaneous pancreas-kidney transplants (SPK). The aim of this study is to compare three different antibody induction regimens in solitary pancreas transplant recipients and to assess the role of surveillance pancreas biopsies in the management of these patients. METHODS: Solitary pancreas transplant recipients between 01/98 to 02/00 (n=29) received induction with either daclizumab (1 mg/kg on day 0, 7, 14), OKT 3 (5 mg/day x0-7), or thymoglobulin (1.5 mg/kg/day x0-10). Maintenance immunosuppression was similar for the three groups. All rejections were biopsy-proven either by surveillance/protocol or when clinically indicated. RESULTS: The 1-year graft survival was 89.3% overall and 91.7% in the thymoglobulin group. Thymoglobulin significantly decreased rejection in the first 6 months when compared with OKT3 or daclizumab (7.7 vs. 60 vs. 50%). Acute rejections were seen on surveillance biopsies in the absence of biochemical abnormalities in 40% of patients. CONCLUSIONS: Thymoglobulin induction regimen led to a low incidence of acute rejection and a high rate of graft survival in solitary pancreas transplants. In addition, surveillance biopsies were useful in the detection of early acute rejection in the absence of biochemical abnormalities.

Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients.

The impact of cytomegalovirus (CMV) infection post-transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p = 0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p = 0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti-CMV preventive regimens while patients are treated with MMF.

Recurrent Goodpasture's disease due to a monoclonal IgA-kappa circulating antibody.

We describe the case of a 54-year-old man who first presented with a clinical syndrome manifested by recurrent pulmonary hemorrhage, hematuria, and mild renal insufficiency. Direct immunofluorescence of renal biopsy sections showed linear deposition of IgA-kappa in the glomerular (GBM) and tubular basement membranes. Serum protein immunoelectrophoresis was positive for a monoclonal immunoglobulin A (IgA)-kappa protein. Serum analysis showed circulating IgA anti-GBM antibodies. Treatment with high-dose steroids, cyclophosphamide, and plasma exchange resulted in resolution of the clinical picture. To the best of our knowledge, this is the first report of Goodpasture's disease associated with the presence of a circulating monoclonal IgA-kappa antibody.

Unrecognized severe postoperative hypercapnia: a case of apneic oxygenation.

Transcutaneous pulse oximetry is increasingly being used to supplant arterial blood gas measurement as a means to monitor oxygenation. Previous studies have demonstrated that, despite inadequate ventilation, oxygenation can be maintained during delivery of supplemental oxygen by a process known as diffusion respiration. In this setting, severe hypercapnia and acidosis rapidly develop. This case report demonstrates that pulse oximetry is an unreliable means to monitor adequacy of ventilation. A 75-year-old woman in good health suffered a fracture of the right hip that necessitated arthroplasty. During postoperative recovery, she remained unresponsive while receiving 100% oxygen through an endotracheal tube; mechanical ventilation was not used. Pulse oximetry indicated a blood oxygen saturation of 94 to 96%; however, results of blood gas studies 3 1/2 hours postoperatively revealed profound hypercapnia (arterial carbon dioxide tension, 265 mm Hg) and acidosis (pH, 6.65) but confirmed normal oxygen levels (arterial oxygen tension, 213 mm Hg). Assisted ventilation resulted in normalization of the blood gases and an improved level of consciousness. The patient was then transferred to Mayo Clinic Rochester and had an uneventful recovery.

Management and prevention of cytomegalovirus infection after renal transplantation.

We reviewed the epidemiologic characteristics, diagnosis, clinical features, and management of cytomegalovirus (CMV) infection after renal transplantation. CMV, the major viral pathogen after renal transplantation, increases patient morbidity and mortality. The spectrum of CMV infection ranges from latent infection to asymptomatic viral shedding to life-threatening multisystem disease. The two major risk factors for the development of CMV infection in renal transplant recipients are (1) preexisting CMV antibody seropositivity of either the organ donor or the recipient and (2) host immunosuppression. Blood cultures (but not urine cultures) positive for CMV predict the progression of asymptomatic infection to CMV disease, characterized by fever, malaise, myalgia, leukopenia, abnormal transaminase levels, and often involvement of the lung and gut. New genomic methods of viral detection now offer diagnostic advantages, including methods of detecting only actively replicating CMV. No evidence shows that CMV directly causes allograft rejection or glomerulonephritis, but patients with tissue-invasive CMV disease have higher rates of allograft loss and mortality than do those without the disease. Therapy for established CMV disease includes decreasing the immunosuppressive therapy and administering the antiviral agent ganciclovir sodium. Proven prophylactic strategies include limitation of exposure to the virus from CMV seropositive blood or organ donors, administration of CMV-specific immune globulin, and use of high-dose acyclovir therapy. Preemptive therapy with ganciclovir is a promising alternative to prophylaxis for patients at highest risk for progression to symptomatic CMV disease, such as those with CMV viremia and seropositive recipients receiving antilymphocyte therapy.

Cardiac atrial natriuretic factor during evolution of congestive heart failure.

Congestive heart failure (CHF) is a pathophysiological condition associated with increased plasma levels of atrial natriuretic factor (ANF), a peptide hormone of cardiac origin that participates in the homeostatic control of intravascular volume and vascular tone. Atrial myocytes serve as the principal source of ANF under physiological conditions, although recent studies have demonstrated that ventricular myocardium may also synthesize ANF in models of CHF associated with ventricular hypertrophy. The current study was designed to investigate the roles of atrial and ventricular myocardium to synthesize, store, and release ANF during the evolution of tachycardia-induced CHF in the dog. The present study demonstrates a persistent elevation of plasma ANF during the evolution of CHF. In acute CHF (3 h), plasma ANF increased independent of cardiac ANF synthesis. In chronic CHF (15 and 30 days), plasma ANF is maintained by an increase in atrial synthesis and release of the peptide, without recruitment of ventricular ANF synthesis. The present study demonstrates that in acute CHF the increase in plasma ANF is regulated by release of stored peptide, and in chronic CHF the persistent elevation of plasma ANF is maintained by an increase in atrial synthesis of ANF.

Laboratory experience for understanding the physiological basis of diuretic therapy.

A combined lecture and laboratory experience was designed to enhance medical school students' understanding of the physiological basis of diuretic therapy. Studies are performed by students in anesthetized dogs to determine the effects of four clinically useful diuretics on renal function. The objective of the experience is to 1) learn the mechanisms of action, clinical indications, and adverse effects of diuretics; 2) review the renal physiology of glomerular filtration and sodium metabolism; and 3) complete analysis and interpretation of experimental data. These sessions provide an effective practical educational experience in applying the scientific method to begin to understand the physiology and pharmacology of diuretics.

Endothelin: a new cardiovascular regulatory peptide.

Endothelin, a recently discovered peptide produced by endothelial cells, contracts vascular strips in vitro with greater potency than any previously known vasoconstrictor. Infusions of pharmacologic doses of endothelin in vivo result in a prolonged pressor response and a preferential impairment of renal hemodynamic and excretory functions. Endothelin also directly stimulates the release of aldosterone from the adrenal gland and inhibits renin release in vitro. A highly sensitive and specific radioimmunoassay has confirmed that endothelin circulates in human plasma, and increased plasma endothelin levels have been associated with various cardiovascular disease states. This review summarizes the current knowledge about the molecular biologic features and physiologic actions of endothelin and also explores the role of endothelin, through its local and systemic function, as a regulator of vascular tone in normal and pathophysiologic states.

Acute interstitial nephritis: immunologic and clinical aspects.

Acute interstitial nephritis is a common renal syndrome that may be associated with a variety of infections and drug therapies or may develop without an identified cause. Three cases are presented to illustrate the three types of acute interstitial nephritis--drug related, infection related, and idiopathic. Cell-mediated immune mechanisms seem to be more important than humorally mediated mechanisms in the pathogenesis of acute interstitial nephritis. Frequently, eosinophils are identified as a component of the interstitial cellular infiltrate, and eosinophiluria and eosinophilia have been claimed to be helpful in the diagnosis of acute interstitial nephritis, especially the drug-induced type. Neither eosinophiluria nor the presence of increased urinary levels of eosinophil major basic protein, however, is specific for the diagnosis of acute interstitial nephritis. Patients with drug-induced interstitial nephritis frequently have symptoms and signs suggestive of a hypersensitivity syndrome and rarely have more dramatic anaphylactic manifestations. Systemic glucocorticoids have been shown to be beneficial in this type of acute interstitial nephritis.

Renal response to atrial natriuretic factor is modulated by intrarenal angiotensin II.

The present study in anesthetized dogs (n = 8) was designed to test the hypothesis that intrarenal angiotensin II (ANG II) attenuates the increase in sodium excretion in response to atrial natriuretic factor (ANF). To test this hypothesis, renal hemodynamic and excretory responses to systemically administered ANF (0.3 micrograms.kg-1.min-1) were assessed in the presence of ANG II infusion into the left kidney (ANG II K) at a nonpressor dose (1.5 ng.kg-1.min-1) and with an infusion of saline into the right kidney, the latter which served as control (CK). During ANF infusion, absolute increases in urinary sodium excretion (delta + 160.8 +/- 44.7 vs. delta + 369.4 +/- 56.9 mu eq/min, P less than 0.005) and fractional sodium excretion (delta + 2.55 +/- 0.62 vs. delta + 4.26 +/- 0.82%, P less than 0.03) were markedly attenuated in the ANG II K compared with CK. Glomerular filtration rate increased only in the CK. Urine osmolality decreased in both the ANG II K and CK. These studies demonstrate an attenuated natriuresis to ANF in the presence of intrarenally infused ANG II, which is associated with a blunted increase in glomerular filtration rate. These studies support the hypothesis that the renal hemodynamic and excretory responses to ANF are modulated by intrarenal ANG II.

Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor.

The current studies were designed to investigate the mechanisms in the intact anesthetized dog that control the release of atrial natriuretic factor (ANF). In vitro, mechanical stretch of atrial tissue produces an increased release of ANF. In vivo, changes in atrial pressure correlate positively with circulating ANF levels. The present investigations used 6 open-chest anesthetized dogs to evaluate the role of atrial pressure versus atrial stretch, the latter determined by atrial transmural pressure, in the release of ANF. In a paired design, animals underwent cardiac tamponade followed by constriction of the aorta and pulmonary artery. Tamponade produces a balanced increase in intra-atrial and pericardial pressures. Thus, despite an elevated atrial pressure, there is no increase in transmural pressure producing atrial stretch. Great artery constriction increases intra-atrial but not pericardial pressure, resulting in an increase in atrial transmural pressure and atrial stretch. Cardiac tamponade increased right atrial pressure (0.8 +/- 0.3 to G.6 +/- 0.6 mm Hg, p less than 0.001) and pulmonary capillary wedge pressure (3.7 +/- 0.6 to 8.8 +/- 0.6 mm Hg, P less than 0.001). Constriction of the aorta and pulmonary artery also increased right atrial pressure (1.5 +/- 0.8 to 6.3 +/- 0.8 mm Hg, p less than 0.05) and pulmonary capillary wedge pressure (4.6 +/- 0.3 to 7.8 +/- 1.0 mm Hg, p less than 0.05). Atrial transmural pressure increased only during great artery constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of atrial peptide system in renal and endocrine adaptation to hypotensive hemorrhage.

Hypotensive hemorrhage (HH) is characterized by intravascular volume depletion, avid renal sodium retention, and activation of the renin-angiotensin-aldosterone system (RAAS). The current studies were designed to investigate whether intravascular volume depletion would modulate circulating atrial natriuretic factor (ANF) and, further, to examine what contribution, if any, a decrease in ANF would have in mediating the antinatriuresis and RAAS stimulation associated with HH. Two groups of anesthetized dogs underwent controlled arterial hemorrhage to reduce mean arterial pressure by 15-20 mmHg. Data were collected before and immediately after HH. One group (n = 6) underwent hemorrhage alone, whereas a second group (n = 5) underwent HH with simultaneous administration of alpha-human ANF (2.5 ng.kg-1.min-1), a dose calculated to prevent a reduction in ANF. In the untreated group, circulating ANF was significantly reduced after hemorrhage (79.4 +/- 7.4 to 57.2 +/- 3.4 pg/ml, P less than 0.05), whereas in the treated group ANF increased significantly (73.5 +/- 12.2 to 147.4 +/- 17.2 pg/ml, P less than 0.05). Despite differences in circulating ANF, both groups had similar reductions in urinary sodium excretion and renal blood flow, and similar increases in plasma renin activity. These studies demonstrate that circulating ANF is significantly reduced in HH; however, the mechanism of antinatriuresis and activation of the RAAS is independent of the reduction in circulating ANF.

Atrial natriuretic peptide decreases cardiac output independent of coronary vasoconstriction.

Studies were performed in isolated, Langendorff-perfused rat hearts and anesthetized dogs to determine the effects of synthetic atrial natriuretic peptide (ANP 8-33) on the coronary circulation. In vitro studies in the rat examined coronary flow dynamics to ANP 8-33 over a defined range from physiologic to pharmacologic concentrations. No changes in coronary flow or chronotropic and inotropic function of the isolated Langendorff-perfused heart were observed in response to increasing concentrations of ANP 8-33 (10(2) to 10(6) pg/ml). In the dog, a low, nonhypotensive dose of ANP 8-33 (0.05 microgram/kg/min) decreased cardiac output with no change in coronary blood flow or coronary vascular resistance. At a high, hypotensive dose (0.3 microgram/kg/min) ANP 8-33 decreased cardiac output in association with transient coronary vasodilation. Continued infusion resulted in a decrease in coronary blood flow and arterial pressure with no change in coronary vascular resistance. Thus, in vitro physiologic and pharmacologic concentrations of ANP, or in vivo low concentrations of ANP, do not result in an alteration in coronary flow. In vivo ANP 8-33, at both nonhypotensive and hypotensive concentrations, decreased cardiac output in the absence of coronary vasoconstriction.

Cardio-renal-endocrine dynamics during stepwise infusion of physiologic and pharmacologic concentrations of atrial natriuretic factor in the dog.

Infusion of alpha-human atrial natriuretic factor (alpha-h-ANF) into pentobarbital anesthetized dogs (n = 10) at 0.0025, 0.005, 0.01, and 0.3 micrograms/kg/min was performed to differentiate the physiologic actions of atrial natriuretic factor from its pharmacologic actions. The lowest doses of atrial natriuretic factor infusion resulted in circulating levels that were previously produced by 0-10% saline volume expansion. At the lowest infusion rate, circulating ANF increased 31 +/- 3 pg/ml, resulting in a significant increase in absolute sodium excretion, fractional excretion of sodium, and fractional excretion of lithium, and a significant decrease in urine osmolality. A greater change in circulating atrial natriuretic factor (96 +/- 12 pg/ml) was required to significantly decrease right atrial pressure, cardiac output, and plasma renin activity, and to increase systemic vascular resistance and total and fractional excretion of potassium. The highest dose of atrial natriuretic factor infused was required to decrease arterial pressure and renal vascular resistance. The present study demonstrates that atrial natriuretic factor is natriuretic and diuretic at physiologic concentrations; at low concentrations, atrial natriuretic factor appears to decrease the whole kidney proximal tubular reabsorption of sodium and does not affect glomerular filtration rate; a greater (but physiologic) change in circulating atrial natriuretic factor is required to significantly decrease cardiac output, cardiac filling pressure, and plasma renin activity than is required to significantly increase sodium excretion; and a decrease in systemic arterial pressure and vascular resistance does not occur at physiologic concentrations of atrial natriuretic factor.

Atrial natriuretic peptide during mineralocorticoid escape in the human.

The relationship between plasma atrial natriuretic peptide (ANP) and mineralocorticoid escape was examined in six normal men (age, 20-32 yr) treated with 0.4 mg/day fludrocortisone acetate for 9-14 days. Urinary sodium excretion decreased from 162 +/- 15 (SEM) meq/24 h before to 97 +/- 10 meq/24 h during fludrocortisone acetate administration (P less than 0.05). Despite continued fludrocortisone acetate administration, sodium excretion subsequently returned to baseline (escape). Plasma ANP increased from 33 +/- 6 pg/ml (control) to 55 +/- 14 pg/ml on the first day of escape (P less than 0.05). Escape was associated with a decrease in PRA from 0.90 +/- 0.22 (control) to 0.26 +/- 0.08 ng/ml X h (escape, P less than 0.05). The escape phenomenon was not associated with a significant change in mean arterial pressure or glomerular filtration rate. This study demonstrates that mineralocorticoid escape is temporally related to a significant increase in circulating ANP.

Cardiorenal-endocrine dynamics during and following volume expansion.

The relationship between atrial pressure, atrial natriuretic peptide (ANP), the renin-angiotensin-aldosterone system, and renal hemodynamic and excretory function was examined during and following acute 10% body weight saline volume expansion and measurements were made at 3.3, 6.6, and 10% body weight volume expansion in pentobarbital anesthetized dogs (n = 10). Right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP), fractional excretion of Na (FENa), and ANP all increased in parallel during volume expansion. Plasma renin activity (PRA) and aldosterone decreased in parallel during 10% volume expansion. Following 10% volume expansion, saline was infused at the peak urine flow rate to maintain peak volume expansion. Despite continued saline infusion, RAP, PCWP, and ANP decreased in parallel. In contrast, FENa remained increased, and aldosterone and PRA remained depressed. These studies demonstrate that atrial pressures, ANP, and FENa increase in parallel during volume expansion; this suggests a role for ANP in modulating acute atrial volume overload. During stable volume expansion periods, however, despite a decrease in ANP levels, Na excretion remains elevated, suggesting that non-ANP mechanisms may be important in maintaining natriuresis during stable volume expansion.