Selective retransplant after graft loss to nonadherence: success with a second chance.

Nonadherence (NA) is a difficult posttransplant problem that can lead to graft loss. A retransplant is controversial because of a fear of recurrent NA. We reviewed our center's data base and identified 114 kidney recipients who lost their graft to overt NA; of this group, 35 (31%) underwent a retransplant after a thorough reevaluation. We compared this NA retransplant group to a control group of second transplant recipients who did not lose their first graft to overt NA (non-NA) (n = 552). After 8 years of follow-up, we found no significant differences between the groups in actuarial graft or patient survival rates, renal function, or the incidence of biopsy-proven chronic rejection. However, 5 of 35 (14%) NA recipients versus 10 of 552 (2%) non-NA recipients lost their retransplant to NA (p = 0.0001). Twenty of 35 (57%) of the NA group exhibited repeat NA behavior after retransplant. We conclude that prior graft loss to NA is associated with increased graft loss to NA after retransplant. However, the majority of NA retransplant recipients did well-with overall long-term outcomes similar to those of the non-NA group. With careful patient selection and aggressive intervention, prior overt NA should not be an absolute contraindication to retransplantation.

Clinical significance of eosinophils in suspicious or borderline renal allograft biopsies.

AIMS: Renal allograft biopsies play a critical role in renal transplantation. Acute rejection characterized by tubulitis and intimitis is of primary concern. There is an association between eosinophilic infiltrates and irreversible acute rejection; however, the significance of eosinophils in biopsies that fall short of the diagnostic threshold for acute rejection has not been well studied. This report describes clinical course, treatment and long-term outcome of 5 transplant recipients with biopsy histology that showed borderline changes associated with eosinophilic infiltrates. METHODS: Clinical records were selected for review on the basis of biopsy histology satisfying the following criteria: presence of interstitial infiltrates with eosinophils, absence of definitive criteria for acute rejection and absence of findings suggestive of infection or cyclosporine toxicity. RESULTS: All identified biopsies occurred within the first month of transplantation, and histology showed varying degrees of patchy mononuclear cell infiltrates composed of lymphocytes, with eosinophilic infiltrates, but no evidence of acute rejection based on Banff criteria. These patients were taking trimethoprim-sulfamethoxazole and ranitidine at the time of biopsy. Serum creatinine returned to baseline levels in each case after stopping both drugs, and remained stable during the duration of follow-up without any documented episode of acute rejection. No patient received specific therapy for acute rejection. CONCLUSION: This report suggests that independent of decisions on treatment with high-dose steroids or anti-lymphocyte antibody preparations, the management algorithm should include stopping drugs associated with acute interstitial nephritis when non-diagnostic biopsies show eosinophilic infiltrates.

Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.

Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.

Use of plain radiography to screen for cervical spine injuries.

STUDY OBJECTIVE: Standard radiographic screening may fail to reveal any evidence of injury in some patients with spinal injury. The purposes of this investigation were to document the efficacy of standard radiographic views and to categorize the frequencies and types of injuries missed on plain radiographic screening of the cervical spine. METHODS: All patients with blunt trauma selected for radiographic cervical spine imaging at 21 participating institutions underwent a standard 3-view series (cross-table lateral, anteroposterior, and odontoid views), as well as any other imaging deemed necessary by their physicians. Injuries detected with screening radiography were then compared with final injury status for each patient, as determined by review of all radiographic studies. RESULTS: The study enrolled 34,069 patients with blunt trauma, including 818 patients (2.40% of all patients; 95% confidence interval [CI] 2.40% to 2.40%) having a total of 1,496 distinct cervical spine injuries. Plain radiographs revealed 932 injuries in 498 patients (1.46% of all patients; 95% CI 1.46% to 1.46%) but missed 564 injuries in 320 patients (0.94% of all patients; 95% CI 0.94% to 0.94%). The majority of missed injuries (436 injuries in 237 patients [representing 0.80% of all patients]; 95% CI 0.80% to 0.80%) occurred in cases in which plain radiographs were interpreted as abnormal (but not diagnostic of injury) or inadequate. However, 23 patients (0.07% of all patients; 95% CI 0.05% to 0.09%) had 35 injuries (including 3 potentially unstable injuries) that were not visualized on adequate plain film imaging. These patients represent 2.81% (95% CI 1.89% to 3.63%) of all injured patients with blunt trauma undergoing radiographic evaluation. CONCLUSION: Standard 3-view imaging provides reliable screening for most patients with blunt trauma. However, on rare occasions, such imaging may fail to detect significant unstable injuries. In addition, it is difficult to obtain adequate plain radiographic imaging in a substantial minority of patients.

Epidemiology of cervical spine injury victims.

STUDY OBJECTIVE: We sought to characterize demographics and injury patterns among patients undergoing emergency department cervical spine radiography for blunt traumatic injury. METHODS: All patients with blunt trauma undergoing cervical spine radiography at 21 centers were enrolled in this prospective, observational study. Patients' date of birth, age, sex, and ethnicity were noted before cervical spine radiography. RESULTS: Demographic factors associated with cervical spine injury, present in 818 of 33,922 patients, included the following: age of 65 years or older (relative risk [RR] 2.09; 95% confidence interval [CI] 1.77 to 2.59); "other" ethnicity (RR 1.79, 95% CI 1.46 to 2.19); male sex (RR 1.72, 95% CI 1.48 to 2.00); and white ethnicity (RR 1.50, 95% CI 1.31 to 1.72). Hispanic ethnicity (RR 0.64, 95% CI 0.51 to 0.79), female sex (RR 0.58, 95% CI 0.50 to 0.67), black ethnicity (RR 0.55, 95% CI 0.45 to 0.66), and age of less than 18 years (RR 0.39, 95% CI 0.27 to 0.55) were associated with reduced risk of cervical spine injury. CONCLUSION: Among patients undergoing ED cervical spine radiography, cervical spine injury is more common among the elderly, male subjects, and patients of white or "other" ethnicity. Because cervical spine injury occurs in patients in all demographic categories, however, this information cannot be used to select individual patients who should or should not undergo imaging.

Diurnal cyclosporine dosing optimizes exposure and reduces the risk of acute rejection after kidney transplantation.

Acute rejection (AR) following transplantation may be due to episodic subtherapeutic cyclosporine (CsA) levels related to diurnal variation of hepatic drug metabolism. We postulated that asymmetrical dosing of CsA based on individualized pharmacokinetic profiles would optimize drug exposure and decrease the risk of AR. We prospectively treated all patients undergoing kidney transplantation with a diurnally split dose of CsA microemulsion given q 12 hours (3.5 mg/kg q a.m., 3.0 mg/kg qPM). Morning doses were adjusted to reach a day-time area under the concentration curve (AUC) of 7,800 ng hour/ml (utilizing 2 hour and 6 hour levels) and evening doses were adjusted to a morning trough of 300 ng/ml. Patients received high-dose steroids tapered to 20 mg prednisone by day 6. CsA was started within 36 hours and mycophenolate mofetil (1000 mg q 12 hour) was added on day 3 in most patients and continued for 3 months. Only one patient received antibody induction. Thirty kidneys (67% cadaveric) were transplanted into 28 adult patients (50% African American, 57% men). Therapeutic targets were reached in all patients prior to discharge and maintained during the study period. At 3 months follow-up, there was not a single episode of documented AR and mean creatinine was 1.5 +/- 0.1 mg/ml. Twelve patients required biopsy for allograft dysfunction; however no histological evidence of AR or CsA-toxicity was identified and the creatinine normalized in each case without altering immunosuppression. Patients continued to require increased CsA doses in the AM compared to the PM (P<0.05) throughout the study to maintain target levels. Diurnal dosing of CsA based on individual pharmacokinetic profiles optimizes CsA exposure and reduces the risk of AR during the first 3 months after transplantation.

Cerebral ventricular shunts.

Cerebral ventricular shunts are siphoning devices used to treat hydrocephalus. They are placed within cerebral ventricles and peripheral cavities such as the ventricular atrium or peritoneal cavity. Complications include obstruction of cerebral spinal fluid (malfunction) and infection. Morbidity and mortality rates are high when shunt malfunction and infection are not treated emergently. This report summarizes the physical examination of patients with ventricular shunts, reviews the type of shunts commonly used, discusses shunt malfunctions (causing overshunting or undershunting of cerebrospinal fluid) and infections, and makes recommendations concerning empiric antibiotic therapy for shunt infection. The technique of tapping a shunt is presented for management of patients with elevated intracranial pressure that does not respond to non-invasive maneuvers to lower the pressure.

The role of gender in heart transplantation.

BACKGROUND: The effect of donor and recipient gender on the outcome of heart transplantation (HT) remains uncertain. METHODS: One hundred seventy-four patients who underwent HT were divided into four groups according to donor and recipient gender. Group A consisted of 81 men who received male donor hearts, group B of 18 women who received female donor hearts, group C of 21 women who received male donor hearts, and group D of 54 men who received female donor hearts. All patients were treated by the same group of surgeons according to standard HT protocols. Comparisons were made between groups with regard to short- and long-term outcomes. RESULTS: Donor gender and recipient gender did not affect outcomes significantly. Overall, donor-recipient gender mismatching significantly increased the number of rejection episodes and reduced creatinine clearance, survival, and censored survival in the first year after HT (p < 0.05). More specifically, among female recipients, donor-recipient gender mismatching significantly increased the number of rejection episodes and decreased creatinine clearance in the first year after HT (p < 0.05); among male recipients, donor-recipient gender mismatching significantly reduced 1-year survival and censored survival to date after HT (p < 0.05). CONCLUSIONS: Donor-recipient gender matching plays a significant role in determining HT outcomes.

Secondary acute angle closure glaucoma: a complication of AIDS.

A 58-year-old man with advanced AIDS presented to the emergency department complaining of headache and decreased vision bilaterally. On evaluation, he was found to have intraocular pressures of 69 and 65 mm Hg. After topical treatment with miotics and apraclonidine, he was given intravenous acetazolamide (Diamox) and peripheral iridotomy was performed. The pressures did not improve significantly. Secondary acute angle closure glaucoma was diagnosed. Emergency physicians should consider this diagnosis when evaluating AIDS patients with visual complaints.

Reengineering the emergency evaluation of chest pain.

This article presents strategies for enhancing the emergency department care delivered to patients with chest pain and suspected acute myocardial infarction. It also describes the planning and implementation of an emergency department reengineering project at a university medical center. The establishment of chest pain evaluation centers within emergency departments has been associated with improved clinical outcomes and cost control. Creating such a center requires careful revamping of diagnostic and treatment algorithms, a process that must be based on information from all departments affected by the changes.

Management of left ventricular assist device infection with heart transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to heart transplantation (HT). Infection of the LVAD in this patient population represents a serious complication, as simple LVAD removal or delaying HT may result in death. To improve outcomes in this group of patients, we performed HT in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD implantation followed by HT. Ten underwent HT in the absence of LVAD infection (group 1); and 8, in the presence of LVAD infection (group 2). All patients were treated similarly except for modification of immunosuppression in group 2 patients. RESULTS: Infectious and noninfectious complications were equivalent between the two groups. There was no difference between groups in regard to intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8), wound complications (three versus none), and mean length of hospital stay after HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too seriously ill to allow LVAD removal or delay of HT. Transplantation in the face of infection is an effective treatment option.

A multidisciplinary approach to chest pain evaluation and management.

Chest pain evaluation centers in emergency departments efficiently exclude acute myocardial infarctions but are limited in identifying patients with acute cardiac ischemia (ACI) without infarction. Short-term prognosis is similar for patients discharged with ACI and for those who had an infarction. Subsequently, for suspected ACI, cardiology or primary care is consulted, providing follow-up coronary angiography or stress testing, but often requiring repeat labwork and resulting in significant time delays. A coordinated approach to chest pain management--an early multidisciplinary effort--provides an efficient and cost-effective approach to chest pain evaluation and management, while reducing potentially dangerous delays in identifying ACI.

The impact of elevated serum IgA and race on primary recipient renal allograft survival.

This study correlated overall serum IgA levels in pretransplant (preTx) sera with graft survival. IgA levels, determined by nephelometry, were normally distributed, with a mean level of 255 +/- 139 mg/dl and a median of 234 mg/dl in 631 adult primary kidney allograft recipients and a mean level of 213 +/- 123 mg/dl with a median of 196 mg/dl for 100 retransplant recipients. Improved 3-year survival was associated with a high preTx IgA serum level in primary recipients (Kaplan-Meier analysis, P = 0.01), but not in retransplant patients. After stratifying by race, IgA correlated with graft survival in Caucasian, Hispanic, and "other" (Middle Eastern, Indian subcontinent, and Asian) primary recipients (P < or = 0.04), but not in African Americans. Higher survival rates were not associated with IgA in primary recipients stratified for rejection episodes, blood transfusions, or HLA-DR mismatches. Graft survival was improved in patients with > 2 HLA-AB mismatches and serum IgA above the median. PreTx IgA level and IgA alpha-HLA activity were significantly associated in preTx sera of primary renal allograft recipients (chi 2 = 7.145, P = 0.01), although only 9% (12/133) of sera tested displayed IgA anti-HLA class I reactivity. Thus, enhanced graft survival mediated by elevated serum IgA levels may due in part to competition for allograft HLA class I binding with deleterious Ig subclasses or immune effector cells. Elevated serum IgA may also reflect an altered immunoregulatory state. The results suggest that, depending on the racial group, preTx serum IgA levels are a prognostic indicator of graft survival in primary renal allograft recipients.

Raynaud's phenomenon in the emergency department.

Raynaud's phenomenon manifests as triphasic color changes of the digits, induced by exposure to low temperature or emotional stress. It is a relatively common disorder, estimated to affect 5% to 10% of the general population and 25% to 30% of otherwise healthy women. Although usually self-limiting, it can be severely painful and debilitating, and complicated by ulcerations and tissue necrosis. For the emergency physician treating a patient with an acute presentation of the phenomenon, the main challenges are to achieve adequate pain control, reverse vasospasm, and maintain viable tissue. Emergency treatment can also extend to patient education and arrangement of appropriate referrals and follow-up care.

Renal transplantation.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. The authors present a rational approach to the pre-, intra-, and postoperative care required for successful patient management.

Influence of sleep deprivation on learning among surgical house staff and medical students.

BACKGROUND: Sleep deprivation as a result of in-house night call may alter capacity to learn. Surgical residents and medical students, in both sleep-deprived and rested states, read surgical journal articles and later answered questions regarding their content as a measure of ability to learn while participating in scheduled night call. METHODS: Medical students (n = 35) and residents (n = 21) rotating on surgical services kept logs of hours slept during a 4-week study period. Subjects read six selected articles at separate early morning sittings during weeks 1 and 3. A multiple choice test was given 1 week after each session to assess short-term recall, and all tests were given again 3 months later to assess retention of information over the longer term. Scores were compared with the sleep data. Subjective measures of fatigue and motivation elicited from subjects also were evaluated. RESULTS: Sleep deprivation (4 hours or less uninterrupted sleep per night) resulted in increased fatigue and decreased motivation among medical students and residents (p < 0.05, t test). Objective scores on tests administered 1 week and 3 months after reading did not show an effect attributable to sleep deprivation (p > 0.05, t test). CONCLUSIONS: Sleep deprivation leads to subjective feelings of increased fatigue and decreased motivation. Residents and medical students, however, whether sleep deprived or not, obtain comparable scores on objective tests measuring both short-term and long-term retention of newly learned material. The ability to learn medically relevant information does not appear to be significantly altered by the degree of sleep deprivation associated with clinical rotations on surgical services.

Transplantation 1994: the year in review.

Progress during 1994 has yielded important positive effects on the clinical practice of transplantation. During the span of one generation, organ transplantation has moved from an experimental endeavor to an established therapeutic modality. Technical advances have improved the safety of the surgical enterprise, such that the major focus of research is now immunosuppressive therapy. Although tacrolimus has been approved for use in liver transplantation, ongoing trials seek to establish its role in the immunosuppressive arsenal. Undoubtedly, the introduction of mycophenolate mofetil and Neoral in the coming year, and probably sirolimus shortly thereafter, will broaden the spectrum of immunosuppressive agents, thereby improving transplant results. The recently completed multicenter studies not only demonstrated effective cooperative efforts by the transplant community, but also offered new insights into the more efficient design of future clinical trials. Although rejection remains the major barrier to transplant success, increasingly it is recognized that improved outcomes demand a decreased spectrum of iatrogenic side effects that markedly increase morbidity. Thus, strides in immunosuppressive management must be evaluated both by mitigation of rejection episodes and by quality of life measures. The ultimate goal of achieving transplant tolerance is now being addressed in clinical studies. There is no universal agreement concerning the role of chimerism as a strategy for tolerance induction; preclinical studies suggest that refined donor-type antigens or selectively enriched donor-cell infusions represent more likely tolerogenic stimuli. The challenge of inducing immunologic tolerance remains an elusive goal as we approach the new millennium.