Use of state-of-the-art ultrasound techniques in diagnosing sarcoidosis of the salivary glands (Heerfordt's syndrome)

AIM: The parotid gland is a rare site of sarcoidosis (6% of all cases). The role of state-of-the-art ultrasound techniques in the diagnostic assessment of parotid sarcoidosis (Heerfordt's syndrome) is presented. PATIENTS AND METHODS: Four patients (three male, one female; aged 31-42 years) with inconclusive parotid swelling associated with fever and uveitis were referred for diagnostic assessment by the ENT outpatient service over a 1 year period. High-resolution ultrasound (US) was performed using the SONOLINE Elegra system with a 7.5-MHz wide-band transducer and various, special US techniques (tissue harmonic imaging, photopic imaging, color-coded duplex US, and power Doppler). Diagnoses were confirmed in all cases by puncture and histology. RESULTS: Two patients with typical lung findings (stage I and II sarcoidosis) and two patients without known sarcoidosis showed an inhomogeneous nodular appearance of the clinically enlarged salivary glands at US. Duplex US demonstrated hypervascularization in three cases and moderate, inhomogeneous vascularization in one. In comparison to plain B-mode scanning, optimal visualization of the hypodense, nodular, structural changes was achieved using contrast-enhancing techniques. All patients underwent US-guided puncture for determining the etiology of parotitis. Histology demonstrated granulomatous epitheloid cell inflammation. CONCLUSION: An inhomogeneous nodular appearance of the parenchyma of enlarged parotid glands with areas of hypervascularization, which is optimally depicted by state-of-the-art US techniques, should suggest Heerfordt's syndrome as a possible differential diagnosis.     

Biochemical course after radical retropubic prostatectomy: preliminary results

OBJECTIVE: To investigate prognostic factors in localized and lymphatically spread prostate cancer. METHODS: The biochemical course after radical retropubic prostatectomy in 306 patients was subject to a retrospective analysis. RESULTS: Prostate-specific antigen (PSA), Gleason score (prostatectomy specimen) and pathological stage proved to be prognostically relevant (p < 0.0001). PSA, Gleason score and tumor stage also were to be considered as (independent) prognostic factors by means of a multivariate analysis (p < 0.001), whereas perineural invasion (prostatectomy specimen) and preoperative bone marrow findings (CK 2) had no impact on the course of the disease. After a median follow-up of 1,307 days (3.6 years), a biochemical relapse occurred in 41.8%. CONCLUSION: High preoperative PSA values and the resulting high portion of advanced tumor stages are a possible basis for the high biochemical relapse rate in our collective. The learning curves of several surgeons and the previously more restrictive pelvic lymphadenectomy (surgical understaging) may also be considered causes.     

Unenhanced spiral computerized tomography in acute diagnosis of flank pain. Examination in contraindications for contrast medium administration

The diagnostic value of unenhanced helical computed tomography was investigated in a prospective study. In 53 patients (aged 35 to 82 years) with acute flank pain tomography was performed in addition to abdominal plain film and ultrasound examination. All 53 patients had a contraindication for intravenous administration of contrast medium. Ureteral calculi were either confirmed or excluded by retrograde ureteropyelography in 44 cases, in 9 patients by asservation of calculi and clinical follow-up. Helical computed tomography was able to precisely identify all of the 34 ureteral calculi, whereas abdominal plain films led to 6 false positive and 17 false negative findings. In 1 patient with retroperitoneal lymphoma (diagnosed by CT) false positive findings occurred. Unenhanced helical computed tomography reaches a distinctively increased diagnostic value (sensitivity 100%, specificity 95%, accuracy 97%) in the evaluation of acute flank pain as compared to conventional radiologic imaging and ultrasound. This non-invasive procedure is to be considered method of choice for patients with contraindications for the application of radiopaque material.     

The effect of neuroleptic medication on prepulse inhibition in schizophrenia patients: current status and future issues

RATIONALE: Prepulse inhibition (PPI) of the startle reflex is a powerful tool for investigating sensorimotor gating in both animals and humans. Evidence of impaired PPI in patients with schizophrenia suggests that PPI performance might serve as a promising model to investigate the neurobiological mechanisms of this disorder. Animal data show that experimentally induced PPI deficits can be removed by the administration of antipsychotic agents. Recent clinical studies suggest that neuroleptic medication is capable of improving deficient PPI performance in schizophrenia patients as well. OBJECTIVES: The present paper reviews the published data on PPI performance in schizophrenia patients, focussing on medication effects. Using a modified meta-analytic approach, the consistency of PPI deficits in schizophrenia patients across studies is explored. In particular, methodological issues of defining PPI deficits and assessing PPI improvements are considered. METHOD: Literature search produced 12 original studies that investigated PPI performance in schizophrenia patients using comparable experimental conditions. Percentage change scores were calculated to compare the actual amount of PPI observed in schizophrenia patients and healthy controls across studies. RESULTS: Results revealed that the amount of PPI in medicated schizophrenia patients was fairly consistent across all studies. For medicated schizophrenia patients, the amount of PPI varied between 30% and 65% for the critical lead intervals. Moreover, medicated patients showed around 20% less PPI than healthy controls. Whether these group differences were statistically significant depended on the composition of the control group that showed large variability across studies. CONCLUSIONS: To delineate the effects of neuroleptic medication on PPI performance more precisely, future research should not further rely on between-group comparisons. Rather, future clinical research should take advantage of longitudinal designs to disentangle state-dependent medication effects from more stable, trait-linked factors that contribute to PPI deficits in schizophrenia.     

Nefiracetam improves Morris water maze performance following traumatic brain injury in rats

Nefiracetam, a pyrrolidone derivative, is a nootropic agent that has facilitated cognitive function in a wide variety of animal models of cognitive dysfunction. The purpose of this study was to investigate the efficacy of the chronic postinjury administration of nefiracetam (DM-9384) in improving cognitive performance following central fluid percussion brain injury in rats. Twenty-four hours following surgical preparation, a sham injury or a moderate fluid percussive injury (2.1 atm) was delivered. Nefiracetam was administered chronically (0 or 9 mg/kg, po, for sham animals and 0, 3, or 9 mg/kg for injured animals) on postinjury days 1-15. Cognitive performance was assessed using the Morris water maze (MWM) on postinjury days 11-15. Chronic administration of 3 and 9 mg/kg nefiracetam attenuated MWM deficits produced by central fluid percussive brain injury. Importantly, the MWM performance of the injured animals treated with 9 mg/kg did not significantly differ from uninjured, sham animals. The 9-mg/kg dose of nefiracetam did not have a positive or negative effect on MWM performance of uninjured animals. The results of the present experiment suggest that a nootropic such as nefiracetam may be an appropriate treatment for trauma-induced cognitive dysfunction.     

Acute coronary syndromes. The diagnostic role of troponins

Acute coronary syndromes (ACSs) represent the acute life-threatening phases of coronary heart disease. Clinical symptoms, EKG, and CK-MB measurements are frequently insufficient to evaluate patients without persisting ST elevations. Serial determinations of troponin T or troponin I after arrival in hospital disclose minor myocardial injury in patients presenting as unstable angina. This finding allows the currently best risk stratification and may contribute to cost-effectiveness. Without elevated troponins the risk for death or myocardial infarction during 30 days follow-up is not more than 1%. The lack of elevated troponins does not implicate that these patients do not have coronary artery disease. Patients with positive evidence of troponins represent a high-risk group who should be hospitalized and further evaluated, because the risk for myocardial infarction and death in 30 days is approximately 20%. Current studies indicate that early revascularization under glycoprotein IIb/IIIa antagonists represent the optimal treatment.     

Cost effectiveness of human immunodeficiency virus postexposure prophylaxis for healthcare workers

OBJECTIVE: The United States Public Health Service (USPHS) published recommendations for human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) of healthcare workers in May 1998. The aim of this study was to analyse the cost effectiveness of the USPHS PEP guidelines. DESIGN AND SETTING: This was a modelling study in the setting of the US healthcare system in 1989. The analysis was performed from the societal perspective; however, only HIV healthcare costs were considered and health-related losses of productivity were not included. METHODS: A decision tree incorporating a Markov model was created for 4 PEP strategies: the current USPHS recommendations, triple drug therapy, zidovudine monotherapy or no prophylaxis. A probabilistic sensitivity analysis using a Monte Carlo simulation was performed. Confidence intervals (CIs) around cost-effectiveness estimates were estimated by a bootstrapping method. RESULTS: The costs (in 1997 US dollars) per quality-adjusted life-year (QALY) save by each strategy were as follows: monotherapy $US688 (95% CI: $US624 to $US750); USPHS recommendations $US5211 (95% CI: $US5126 to $US5293); and triple drug therapy $US8827 (95% CI: $US8715 to $US8940). The marginal cost per year of life saved was: USPHS recommendations $US81 987 (95% CI: $US80 437 to $US83 689); triple drug therapy $US970 451 (95% CI: $US924 786 to $US 1 014 429). Sensitivity testing showed that estimates of the probability of seroconversion for each category of exposure were most influential, but did not change the order of strategies in the baseline analysis. With the prolonged HIV stage durations and increased costs associated with recent innovations in HIV therapy, the marginal cost effectiveness of the USPHS PEP strategy was decreased to $US62 497/QALY saved. All 3 intervention strategies were cost effective compared with no postexposure prophylaxis. CONCLUSIONS: Current USPHS PEP recommendations are marginally cost effective compared with monotherapy, but the additional efficacy of triple drug therapy for all risk categories is rewarded by only a small reduction in HIV infections at great expense. For the foreseeable future, assuming innovations in therapy that employ expensive drug combinations earlier in the HIV disease course to extend life expectancy and the increasing prevalence of HIV drug resistance, our model supports the use of the USPHS PEP guidelines.     

Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles

Experimental data show accumulation of superparamagnetic iron oxide (SPIO) particles in atherosclerotic plaques. SPIO uptake occurred in plaques, suggesting an increased endothelial permeability and macrophage infiltrates as signs of inflammatory plaque activity. We incidentally observed SPIO uptake in aortic and arterial wall segments in patients who had originally received the magnetic resonance (MR) contrast agent for staging lymph node metastases. Twenty patients (19 male, 1 female; mean age, 64; range, 41-78 years) with bladder or prostate cancer underwent MR imaging (MRI) using a T2*-weighted high-resolution gradient-echo sequence prior to and 24-36 hours after intravenous injection of 2.6 mg of Fe/kg of SPIO (Sinerem). The aorta, both common external and internal iliac, as well as both superficial femoral arteries, were retrospectively analyzed for atherosclerotic wall changes. One patient was excluded. A positive finding was defined as an area of pronounced signal loss on postcontrast images clearly confined to the arterial wall, which was absent in the precontrast examination or increased in size. Such a finding was observed in one to three arteries in 7 of the 19 patients. The pronounced signal loss in the wall of the aorta and pelvic arteries seen in part of an elderly patient population after intravenous SPIO administration strongly suggests that this contrast agent accumulates in human atherosclerotic plaques.     

Biochemotherapy for the treatment of metastatic malignant melanoma: a systematic review

BACKGROUND: The incidence of malignant melanoma has increased in recent years. Current therapies for metastatic melanoma include chemotherapy and a variety of immunotherapeutic choices. With no established standard treatment option, the evaluation of biochemotherapy is warranted. METHODS: A systematic review of the literature was conducted to locate randomized controlled trials, meta-analyses, systematic reviews, and evidence-based practice guidelines published up to April 2007. RESULTS: Nine eligible randomized controlled trials were identified, including six comparing chemotherapy alone to biochemotherapy (chemotherapy combined with interleukin-2 and interferon). Response rates were significantly higher with biochemotherapy in only two trials, although when data were pooled, biochemotherapy was superior to chemotherapy on response (relative risk, 1.52; 95% confidence interval, 1.24-1.87; p<0.0001) but did not delay time to progression (Hazard ratio, 0.80; 95% confidence interval, 0.63-1.01; p=0.06). Biochemotherapy was not associated with a statistically significant survival benefit in any of the individual trials or in a pooled analysis (Hazard ratio, 0.95; 95% confidence interval, 0.78-1.17; p=0.64). Biochemotherapy is a toxic therapy, and patients are likely to experience serious hematologic, gastrointestinal, cutaneous, and constitutional toxicities, although when conducted in the correct setting, grade 3 and 4 effects appear to be manageable, and treatment-related death can be minimized. CONCLUSION: The results of available studies are inconsistent with regard to benefit (response, time-to-progression, and survival) and show consistently high toxicity rates. Therefore, biochemotherapy is not recommended for the treatment of metastatic malignant melanoma in adults.