Riedel's thyroiditis and retroperitoneal fibrosis in multifocal fibrosclerosis: positron emission tomographic findings

PURPOSE: The authors describe F-18 fluorodeoxyglucose positron emission tomographic (FDG PET) imaging features of Riedel's thyroiditis and retroperitoneal fibrosis in a patient with multifocal fibrosclerosis. MATERIALS AND METHODS: A 41-year-old woman in whom Riedel's thyroiditis had been diagnosed 7 months earlier was examined for fatigue, anorexia, and lower back pain, irradiating to the abdomen. Abdominal sonography and computed tomography showed a retroperitoneal mass. A biopsy of this mass showed histopathologic findings of retroperitoneal fibrosis. FDG PET was performed to evaluate the activity of the retroperitoneal fibrosis and to screen for other areas of fibrosclerosis. RESULTS: The FDG-PET images showed an intense hypermetabolic abdominal mass surrounding the aorta and increased glucose metabolism in the thyroid. No other sites of abnormal FDG metabolism were noted. These abnormalities disappeared after 4 months of steroid therapy. CONCLUSIONS: Sites of multifocal fibrosclerosis can be demonstrated by FDG PET, probably as a result of active inflammation involving lymphocytes, plasma cells, and fibroblast proliferation. FDG PET can help to establish the diagnosis of multifocal fibrosclerosis and evaluate the activity and patient response to corticosteroid therapy.     

Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery

We conducted this double-blinded, randomized study to assess the analgesic effect of repeated administrations of paracetamol, administered as propacetamol, an injectable prodrug formulation of paracetamol, and to compare this with the analgesic effects of morphine. Patients experiencing moderate to severe pain after elective surgical removal of bone-impacted third-molar teeth under general anesthesia were randomly assigned to receive IV propacetamol 2 g (n = 31), IM morphine 10 mg (n = 30), or placebo (n = 34). Five hours later, the treatments were readministered at half of the previous dosages. Standard measures of analgesia were collected repeatedly for 10 h. Propacetamol and morphine were significantly more effective than placebo in all primary measures of analgesia over 5 h after the first administration and globally over 10 h (first and second administrations). After the first dose, 21 of the 34 patients in the placebo group required rescue medication, compared with 6 of the 31 in the propacetamol group (P < 0.0009) and 4 of the 30 in the morphine group (P < 0.0001). No statistically or clinically significant differences were found between propacetamol and morphine for any sum or peak measures of analgesia. No serious adverse events were reported; adverse events were significantly less frequent in the propacetamol group than in the morphine group (P < 0.027). Propacetamol administered IV in repeated doses (2 g followed by 1 g) has a significant analgesic effect that is indistinguishable from that of morphine administered IM (10 mg followed by 5 mg) after dental surgery, with better tolerability. IMPLICATIONS: After moderately painful surgical procedures, IV paracetamol, administered as propacetamol, may be an asset in the control of acute postoperative pain.     

Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft-versus-host disease after liver transplantation

BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.     

Influence of obesity on in-hospital and early mortality and morbidity after myocardial revascularization.

OBJECTIVE: Obese patients are thought to have an increased risk for complications in coronary artery bypass surgery. Several risk stratification systems do not identify obesity as a variable for risk adjustment. The aim of this study is to evaluate the in-hospital and early (one year) mortality and morbidity in obese and non-obese patients after a CABG in the UMC St Radboud. METHODS: The data of 1130 patients undergoing a myocardial revascularization from January 2000 to August 2002 were analyzed. Obesity was measured by the body mass index (BMI). A BMI>or=30 kg/m2 was defined as obese. We compared 206 obese patients with 924 non-obese patients. Uni- and multivariate analysis were used to analyze the results. The 1-year survival was analyzed using Kaplan-Meier methods. RESULTS: There were no significant differences between obese and non-obese patients according to postoperative myocardial infarction, re-operation for bleeding, in-hospital mortality, renal complications, neurological complications, pulmonary complications, gastrointestinal complications, re-intubation, re-admission on intensive care, ventilation time, days on intensive care, days in hospital and late mortality. Only the incidence of postoperative wound infections was increased in obese patients, 8.3% in the obese versus 4.4% in the non-obese (P=0.02). Multivariate analysis identified obesity only as risk factor for postoperative for wound infections (P=0.04, odds ratio: 1.97). CONCLUSIONS: Obese patients do not have an increased risk of in-hospital and early (1 year) mortality after CABG. However, obese patients have an increased risk of postoperative wound infections compared to non-obese patients.     

Pneumothorax after left pneumonectomy: implantation of an intrapleural prosthesis

Postpneumonectomy syndrome is defined as an airway obstruction due to mediastinal shift and rotation after pneumonectomy. A patient who had undergone a left pneumonectomy for bronchial carcinoma 13 years before presented with tension pneumothorax of her remaining lung. Although all factors relevant to the development of postpneumonectomy syndrome were ascertained, the patient had a pneumothorax rather than an airway obstruction. This pneumothorax was treated surgically. The goal of this operation was to reduce the right pleural cavity volume by implanting an intrapleural prosthesis in the pneumonectomy cavity. This treatment is identical to that used for postpneumonectomy syndrome, which allows the right lung to be rejoined with the thoracic wall.     

A clinicopathologic study of thrombotic microangiopathy in IgA nephropathy

Thrombotic microangiopathy (TMA) occurs in IgA nephropathy, but its clinical significance is not well described. We retrospectively examined a series of 128 patients diagnosed with IgA nephropathy between 2002 and 2008 who had a mean follow-up of 44±27 months. In our series, 53% presented with lesions of TMA, acute or organized, in arteries and/or arterioles. Among patients with TMA, 4% were normotensive, 25% had controlled hypertension, and 71% had uncontrolled hypertension. Of those with uncontrolled hypertension, 26% had malignant hypertension. Histologically, the group with TMA had a significantly greater percentage of sclerotic glomeruli and worse tubulointerstitial fibrosis than those of the group without TMA. However, a significant minority of patients had near-normal histology, with minimal tubular atrophy (20%) and/or <20% interstitial fibrosis (24%). TMA rarely occurred in the absence of significant proteinuria. During follow-up, a doubling of serum creatinine or ESRD occurred in all patients with laboratory evidence of TMA, in 42% of those with morphologic evidence but no laboratory evidence of TMA, and in 11% of those without TMA. In summary, lesions of TMA are frequent in IgA nephropathy and may occur in normotensive patients with near-normal renal histology. Although the pathophysiologic mechanisms involved remain undetermined, the current study rules out severe hypertension or advanced renal disease as sole causes.     

Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity

Null mutations in the PCSK1 gene, encoding the proprotein convertase 1/3 (PC1/3), cause recessive monogenic early onset obesity. Frequent coding variants that modestly impair PC1/3 function mildly increase the risk for common obesity. The aim of this study was to determine the contribution of rare functional PCSK1 mutations to obesity. PCSK1 exons were sequenced in 845 nonconsanguineous extremely obese Europeans. Eight novel nonsynonymous PCSK1 mutations were identified, all heterozygous. Seven mutations had a deleterious effect on either the maturation or the enzymatic activity of PC1/3 in cell lines. Of interest, five of these novel mutations, one of the previously described frequent variants (N221D), and the mutation found in an obese mouse model (N222D), affect residues at or near the structural calcium binding site Ca-1. The prevalence of the newly identified mutations was assessed in 6,233 obese and 6,274 lean European adults and children, which showed that carriers of any of these mutations causing partial PCSK1 deficiency had an 8.7-fold higher risk to be obese than wild-type carriers. These results provide the first evidence of an increased risk of obesity in heterozygous carriers of mutations in the PCSK1 gene. Furthermore, mutations causing partial PCSK1 deficiency are present in 0.83% of extreme obesity phenotypes.     

Range of motion in femoroacetabular impingement

Recent epidemiological studies have demonstrated that radiographic features specific to femoroacetabular impingement appear far more frequently in healthy and asymptomatic cohorts than previously anticipated. It remains unclear how incidental findings should be interpreted clinically. In addition, several authors have suggested that a decreased range of motion is part of the clinical presentation of femoroacetabular impingement. The purpose of the present study was to describe and analyze differences in range of motion between femoroacetabular impingement patients, asymptomatic individuals with incidental radiographic findings and healthy controls, using a validated electromagnetic tracking system. Furthermore, it was evaluated which motions were clinically relevant and could be used to differentiate between these three groups. We found all evaluated motions to differ significantly between patients and controls. The anterior impingement test showed a significant difference between patients and asymptomatic cases. In conclusion, functional evaluation of the range of motion appeared in this study as a useful tool in the diagnostic work-up of femoracetabular impingement.     

Expression of minichromosome maintenance MCM6 protein in meningiomas is strongly correlated with histologic grade and clinical outcome

The 2007 World Health Organization histologic grading of meningiomas is associated with recurrence and clinical outcome. However, distinction of grade I from grade II (atypical) meningiomas can be challenging. In the World Health Organization classification, there are 4 parameters on the basis of which grade II status can be determined: mitotic rate, cytoarchitectural features, brain invasion, and/or histologic subtype. Furthermore, this classification fails to detect grade I recurrent meningiomas, for which other prognostic criteria would be needed. The aim of this study was to evaluate the respective value of several markers involved in cell cycle as effective tools to predict recurrence. This retrospective study was based on a series of 59 meningiomas (grade I: 32 of 59, grade II: 27 of 59, all harboring ≥4 mitoses/1.6 mm), analyzed with the following immunohistochemical markers: MCM6, Ki-67, PHH3, cyclin D1, and p53. We found a significant correlation between histologic grade and mean labeling index for MCM6 (grade I: 21.8% vs. grade II: 65.8%; P<0.001), Ki-67 (3.2% vs. 16.9%; P<0.001), PHH3 (0.7‰ vs. 2.8‰; P<0.001), cyclin D1 (50.4% vs. 70.0%; P=0.005), and p53 (17.3% vs. 32.4%; P=0.017). Histologic grading and mitotic index were correlated with progression-free survival (P=0.010 and P=0.020, respectively). A nearly linear correlation was found between progression-free survival and staining for MCM6 (P<0.001), Ki-67 (P=0.003), and PHH3 (P=0.037) but not for cyclin D1 (P=0.400) and p53 (P=0.758). The interobserver agreement coefficients for MCM6, Ki-67, PHH3, cyclin D1, and p53 were, respectively, 0.97 (95% confidence interval, 0.95-0.98), 0.93 (0.89-0.96), 0.81 (0.70-0.88), 0.90 (0.83-0.94), and 0.84 (0.73-0.90). In conclusion, because of its strong level of expression and sharp difference in labeling index between indolent and recurrent tumors, MCM6 is the most efficient marker to identify tumors with a high risk of recurrence.