Combination of immunosuppressive agents in treatment of steroid-resistant minimal change disease and primary focal segmental glomerulosclerosis

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. METHODS: Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. RESULTS: With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. CONCLUSION: Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.     

Topacheous gout as a rare cause of spinal stenosis in the lumbar region. Case report

Despite the fact that gout is a common metabolic disorder, because its involvement of the axial skeleton is rare the diagnosis is often delayed, even in patients with long-standing gout who present with neurological deficits. The authors report the case of a woman with a history of extensive gout, emphasizing the clinical, radiological, and pathological features of a lumbar spinal stenosis.     

Retinal degeneration and other eye disorders in wives of farmer pesticide applicators enrolled in the agricultural health study

Retinal degeneration is the leading cause of visual impairment in older adults. An association between retinal degeneration and fungicide use was observed previously among farmer pesticide applicators in the Agricultural Health Study, a large study of farm families from Iowa and North Carolina. The objective of this investigation was to determine whether wives of these farmer pesticide applicators were at increased risk of retinal degeneration. Self-reported cross-sectional data obtained via questionnaire between 1993 and 1997 from 31,173 wives were used. Associations of specific pesticides and groups of pesticides based on function (fungicides, herbicides, insecticides, and fumigants) or chemical structure (organophosphates, organochlorines, and carbamates) with eye disorders were evaluated using logistic and hierarchical logistic regression analyses. Self-reported retinal degeneration was associated with the wife's fungicide use (odds ratio = 1.9, 95% confidence interval: 1.2, 3.1) after adjustment for age and state of residence. Specific fungicides that appeared to drive this association were maneb or mancozeb and ziram. No associations between pesticide use and other eye disorders were found. Although these findings for retinal degeneration are based solely on self-reported disease, they are consistent with those reported for farmer pesticide applicators. These findings suggest that exposure to some fungicides and other pesticides may increase the risk of retinal degeneration and warrant further investigation.     

Preparation of 125iodine-labelled methotrexate and its use in a magnetisable particle solid-phase radioimmunoassay

Two techniques for the iodination of methotrexate are described, involving covalent linkage to the drug of ¹²⁵I-labelled N-succinimidyl-3-(4-hydroxyphenyl)propionate (Bolton and Hunter reagent), or to ¹²⁵I-labelled histamine. A rapid highly specific radioimmunoassay for methotrexate was developed, employing a specific antiserum covalently linked to magnetisable particles, and ¹²⁵I-labelled methotrexate as tracer. Incubation times for the assays were 60 and 10 min for the Bolton and Hunter reagent-linked methotrexate and ¹²⁵I-labelled histamine-linked methotrexate respectively. Separation of bound from free antigen was achieved by a rapid magnetic separation system. Results obtained for serum samples correlated closely with those using an enzymatic (dihydrofolate reductase) competitive protein binding assay for methotrexate. A major advantage of the assay is its potential for processing large numbers of samples rapidly, making it highly suitable for routine clinical use.     

Distinction of long bone stress fractures from pathologic fractures on cross-sectional imaging: how successful are we?

OBJECTIVE: The objectives of our study were to define CT and MRI features that distinguish pathologic fractures from stress fractures and to compare the performance of CT and MRI with radiography. MATERIALS AND METHODS: Two reviewers retrospectively reviewed 45 MR images, 37 CT scans, and 43 radiographs in 59 patients (30 biopsy-proven pathologic fractures and 29 stress fractures followed to resolution). The features observed on MRI were abnormal bone marrow (well-defined, ill-defined); intracortical, periosteal, or muscle T1 or T2 signal; endosteal scalloping; and a soft-tissue mass. The features seen on CT were marrow abnormality and character (well-defined, ill-defined, permeative, moth-eaten), endosteal scalloping, periosteal reaction (benign, aggressive), and a soft-tissue mass. Reviewers rated their confidence for diagnosing a pathologic fracture on a 1-3 scale (< 50%, 50-95%, > 95% sure, respectively) with each technique. Performance of each technique was defined by reviewer accuracy and area under the receiver operating characteristic curve (Az); the frequency with which the MRI and CT features were associated with pathologic and stress fractures was calculated. RESULTS: For both reviewers, accuracy for differentiating pathologic from stress fractures was highest on MRI (accuracy/Az: reviewer 1, 98%/0.97; reviewer 2, 93%/0.99); CT (reviewer 1, 88%/0.83; reviewer 2, 82%/0.90) was less accurate than radiography (reviewer 1, 94%/0.98; reviewer 2, 88%/0.96). On MRI, pathologic fractures compared with stress fractures exhibited well-defined T1 marrow signal (83% vs 7%, respectively; p < 0.001), endosteal scalloping (58% vs 0%, p < 0.001), muscle signal (83% vs 48%, p = 0.026), and a soft-tissue mass (67% vs 0%, p < 0.001). On CT, pathologic fractures compared with stress fractures exhibited marrow abnormality (84% vs 17%, respectively; p = 0.001), endosteal scalloping (44% vs 0%, p = 0.006), and aggressive periosteal reaction (36% vs 0%, p = 0.04). CONCLUSION: MRI is useful for distinguishing pathologic from stress fractures, especially after inconclusive radiographic findings. Specifically, pathologic fractures exhibit well-defined T1 marrow alterations, endosteal scalloping, and adjacent soft-tissue abnormalities.     

Hypogeusia as a complication of uvulopalatopharyngoplasty and use of taste strips as a practical tool for quantifying hypogeusia

Hypogeusia is an uncommon complication of uvulopalatopharyngoplasty (UPPP) and few reports in the literature have documented it. Excision of part of the soft palate and damage to the glossopharyngeal nerve or its lingual branch as a result of diathermy or surgery are the possible causes. The case of a 45-year-old male who suffered hypogeusia following UPPP is reported herein. He reported no improvement over a 6-month period. Quantitative assessment of his taste threshold for the 4 basic tastes using taste strips showed a score of 7/18, indicating hypogeusia. The possibility of taste disorder as a postoperative complication should be discussed before patients consent to UPPP Postoperative taste threshold assessment should be done using taste strips if the patient complains of taste disorders.     

Effect of radioiodine therapy on thyroid nodule size and function in patients with toxic adenomas

BACKGROUND: Autonomously functioning toxic adenomas are a common cause of hyperthyroidism. Although 131I seems to be a good therapeutic option with little postablative hypothyroidism for these patients, only a small number of recent studies have objectively evaluated changes in nodule size by ultrasonography following radioiodine therapy. METHODS: We prospectively followed 39 patients with a mean age of 51.2 (35-75) years for 12 months and the patients who remained toxic thereafter, until euthyroidism was provided. Thyroid function tests, sonographic volumes were determined initially and 3, 6 and 12 months after treatment. Radioiodine doses of 3.7 MBq.g(-1) thyroid tissue corrected to a 100% 24 h 131I uptake were given. Thirty patients received a single dose, two required two doses and three required three to five doses of 131I due to persistent thyrotoxicosis. Sonographic volumes of the diffuse parts of the glands decreased significantly by 18% from a mean+/-SD value of 50+/-27.6 ml to 41+/-27.4 ml by the end of the 12 months. A significant decrease (8.3%, P=0.002) was achieved in the first three months. Toxic adenomas decreased in size more efficiently (54%) from a mean of 26+/-24 ml to 12+/-10 ml during 12 months, but also most significantly (28.8%, P=0.003) in the first 3 months of the follow-up. Thirty of the patients (76.9%) became euthyroid at the end of 12 months of follow-up. Four patients (10.3%) became overtly hypothyroid during the follow-up. CONCLUSION: Single or multiple doses of radioiodine can successfully treat toxic adenomas with a low rate of hypothyroidism and considerable nodule-volume reduction.