Clinic‐based study of plexiform neurofibromas in neurofibromatosis 1

Individuals with neurofibromatosis 1 (NF1) develop both benign and malignant tumors at an increased frequency. One of the most common benign tumors in NF1 is the plexiform neurofibroma. These tumors cause significant morbidity and mortality on account of their propensity to grow and affect adjacent normal tissues. To determine the clinical profile of plexiform neurofibromas in NF1, we conducted a retrospective review of 68 NF1 patients with plexiform neurofibroma. In our series, 44% of tumors were detected by 5 years of age and most were located in the trunk and extremities. Only two patients developed malignant peripheral nerve sheath tumors in their preexisting plexiform neurofibromas. Lastly, we demonstrate that there were no specific clinical features of NF1 associated with the presence of plexiform neurofibroma. These results underscore the importance of careful serial examinations in the evaluation of patients with NF1. Am. J. Med. Genet. 92:132–135, 2000. © 2000 Wiley‐Liss, Inc.     

Histologic features of mycophenolate mofetil-related colitis: a graft-versus-host disease-like pattern

Mycophenolate mofetil (MMF) is widely used for maintenance immunosuppression in solid organ transplantation. Gastrointestinal toxicity, usually manifested as diarrhea, is the most common side effect of MMF. We evaluated colonic biopsies from 20 renal transplant patients with MMF-related diarrhea. The latter was defined by the absence of any other demonstrable etiology and improvement or resolution of symptoms by the discontinuation or reduction of the dose of MMF alone. These biopsies were compared with colon biopsies from patients with the following: acute graft-versus-host disease (GVHD, n=10), inflammatory bowel disease (IBD) or infectious colitis (n=10), and colon biopsies from renal transplant patients not receiving MMF (n=8). Normal colonic segments from surgical specimens served as normal controls (n=5). Colonic biopsies from patients with MMF-related diarrhea showed prominent crypt cell apoptosis and reactive/reparative changes including enterocyte cytologic atypia, increased neuroendocrine cells, and glandular architectural distortion. The changes were similar, although of milder degree to the ones seen in patients with acute intestinal GVHD. This pattern of injury was not seen in controls or in biopsies from transplant patients not receiving MMF, and it was markedly different from the one seen in idiopathic inflammatory or infectious colitis. The severity of histologic changes correlated significantly with the endoscopic degree of "colitis." There was no statistically significant correlation between histologic damage and the dose of MMF (corrected for body weight and renal function). MMF-related colitis is a distinct entity that displays histologic features remarkably similar to the ones associated with intestinal GVHD. This form of injury could be related to either direct toxicity or an "innocent by-stander" phenomenon secondary to the alteration of the immunologic microenvironment of the colon caused by the MMF.     

Comparison of anterior and posterior approaches in cervical spinal cord injuries

This study reports the results of 52 patients with unstable cervical spine injuries and associated spinal cord injuries randomized to either anterior or posterior stabilization and fusion. All patients had achieved reduction and had unstable injuries that were thought to require surgical stabilization. Patients requiring a specific approach for either reduction or decompression were not included. Frankel grades and ASIA motor index scores were followed in each patient as well as fusion status, changes in alignment, and pain at final follow-up. Neurologic improvement was noted in each group with no significant differences. In the anterior group, 70% improved at least 1 Frankel grade and 57% improved 1 Frankel grade in the posterior group. There were two nonunions in the anterior group (90% fusion) and none in the posterior group (100% fusion), although this was not statistically different. Seven patients in each group complained of pain at the final follow-up. There were no significant differences in fusion rates, alignment, neurologic recovery, or long-term complaints of pain in patients treated with either anterior or posterior fusion and instrumentation.     

Isolated visceral leishmaniasis presenting as an adrenal cystic mass

A 69-year-old woman presented with a large left retroperitoneal suprarenal mass. Radical resection of the left kidney and the mass revealed a cystic adrenal tumor with a weight of 1500 g. Histologic examination showed that the cyst was composed mostly of partially organized clotted blood. The periphery of the mass consisted of a thin rim of cortical and medullary adrenal tissue with superimposed granulomatous chronic inflammation. The infectious nature of the process was manifested by the scattered intracellular and extracellular Leishmania amastigotes that were found throughout the lesion. The differential diagnosis of cystic adrenal masses and the unusual presentation of visceral leishmaniasis are discussed in this context.     

Spinal cage retrieval and assessment of biologic response

Implant retrieval programs have been effective in understanding implant failure and biomaterial compatibility in joint arthroplasty; however, its application has not been extended extensively to the assessment of spinal constructs and implants. The objective of this study is to determine the efficacy of implant retrieval analysis as a standard for the assessment of explanted spinal implants. The limitations of clinical radiographic assessment of fusion through metal interbody devices are also identified. The implant analysis protocol is shown through a case report of a titanium mesh spinal fusion cage retrieved from a 54-year-old woman who had a pseudoarthrosis at the T12 cage interface. The implant analysis techniques include backscattered electron imaging, high-resolution contact radiography, histology, and fluorochrome analysis. An implant retrieval analysis program similar to the one discussed in the presented case study will enable an accurate assessment of outcomes of these commonly used implants and will guide future development.     

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.     

Concomitant pharmacotherapy among youths treated in routine psychiatric practice

OBJECTIVES: The aim of this study was to assess rates and correlates of concomitant pharmacotherapy in children and adolescents treated by psychiatrists in a broad range of clinical settings. METHODS: Cross-sectional data on 392 child and adolescent patients aged 2-17 years from the 1997 and 1999 American Psychiatric Practice Research Network Study of Psychiatric Patients and Treatments were used, and weighted estimates are provided. RESULTS: Findings indicate that 84% of child and adolescent patients received one or more psychopharmacologic medications; 52% of patients treated with medications received concomitant pharmacotherapy (i.e., two or more medications). Patients who were treated with psychopharmacologic treatments received a median of 2 medications (range, 1-6). Highest rates of concomitant pharmacotherapy were among patients with bipolar disorder (87%). Correlates of concomitant pharmacotherapy included: (1) having a diagnosis of bipolar disorder, (2) having co-occurring Axis I or II disorders or general medical conditions, and (3) currently receiving treatment in an inpatient setting. CONCLUSIONS: Over 40% of child and adolescent patients of psychiatrists were prescribed two or more psychopharmacologic medications. Patients with chronic and clinically complex conditions were more likely to receive concomitant pharmacotherapy. Most often, efficacy of U.S. Food and Drug Administration (FDA)-approved medications has been examined as monotherapy, and cautions on drug interactions and off-label use derived from multiple sources accompany each product. With high rates of concomitant pharmacotherapy among children and adolescents in psychiatric care, additional research on efficacy and safety of this treatment strategy is necessary.