Positron emission tomography in the clinical staging of patients with Stage I and II testicular germ cell tumors

OBJECTIVES: To evaluate the accuracy of fluorodeoxyglucose positron emission tomography (PET) compared with computed tomography (CT) staging in patients with Stage I and II testicular germ cell tumors (GCTs). METHODS: From January 1995 to July 1997, in 37 patients with clinical Stage (CS) I (n = 25) and CS II (n = 12) GCT (24 nonseminomas, 13 seminomas), PET and CT were compared in the initial staging. After PET, the patients with nonseminomatous GCT were staged surgically by retroperitoneal lymph node dissection and the patients with seminomatous GCT were followed up clinically. RESULTS: Correct staging by PET was achieved in 34 of 37 patients compared with correct CT staging in 29 of 37 patients. Of 10 metastatic lesions, 7 and 4 were detected by PET and CT, respectively. PET did not show false-positive signals. PET was unable to detect vital cancer with a maximal diameter less than 0.5 cm or teratoma at any size. CONCLUSIONS: PET was useful for detecting viable tumor in lesions that are visible on CT scan and, thus, it may omit false-positive CS II lesions. However, PET was not able to identify mature teratoma. In this study, PET did not improve the staging in patients with CS I tumor.     

Quality and outcomes management in the primary care practice

In response to the trend away from thinking of health care as a commodity to one in which quality is a differentiating feature among providers, primary care practices must focus on outcomes management. This article reviews the various clinical and office-based processes that influence practice outcomes. These include patient management, chart management, practice guidelines, clinical pathways, case management, and patient information. The key to a quality program and successful outcomes management is a commitment on the part of physicians to managing these processes so that best outcomes are achievable.     

Role of blood-brain barrier P-glycoprotein in limiting brain accumulation and sedative side-effects of asimadoline, a peripherally acting analgaesic drug.

Studies with knockout mice lacking mdr1a P-glycoprotein (P-gp) have previously shown that blood-brain barrier P-gp is important in preventing the accumulation of several drugs in the brain. Asimadoline (EMD 61753) is a peripherally selective kappa-opioid receptor agonist which is under development as a therapeutic analgaesic. From the structural characteristics of this drug and its peripheral selectivity, we hypothesized that it is transported by P-gp. Using a pig-kidney polarized epithelial cell line transfected with mdr cDNAs, we demonstrate that asimadoline is transported by the mouse mdr1a P-gp and the human MDR1 P-gp. Furthermore, we show that in mdr1a/1b double knockout mice, the absence of P-gp leads to a 9 fold increased accumulation of asimadoline in the brain. In line with this accumulation difference, mdr1a/1b (-/-) mice are at least 8 fold more sensitive to the sedative effect of asimadoline than wild-type mice. Interestingly, the oral uptake of asimadoline was not substantially altered in mdr1a/1b (-/-) mice. Our results demonstrate that for some drugs, P-gp in the blood-brain barrier can have a therapeutically beneficial effect by limiting brain penetration, whereas at the same time intestinal P-gp is not a significant impediment to oral uptake of the drug.     

2,4-Diphenyl furan diamidines as novel anti-Pneumocystis carinii pneumonia agents.

Dicationic 2,4-bis(4-amidinophenyl)furans 5-10 and 2, 4-bis(4-amidinophenyl)-3,5-dimethylfurans 14 and 15 have been synthesized. Thermal melting studies revealed high binding affinity of the compounds to poly(dA-dT) and to the duplex oligomer d(CGCGAATTCGCG)2. All of the new compounds were effective against Pneumocystis carinii pneumonia in the immunosuppressed rat model with up to 200-fold increase in activity compared to the control compound pentamidine. No toxicity was noted for 5, 7-10 at the dose of 10 micromol/kg/d; however, the isopropyl analogue 7 showed toxicity comparable to pentamidine at the dosage of 20 micromol/kg/d. Dimethylation of the parent compound on the furan ring resulted in reduced activity and increased toxicity.     

Neurological soft signs in schizophrenia: Assessment and correlates

A German version of the Neurological Evaluation Scale (NES) was administered to 143 schizophrenic patients, 45 of them being severly chronic and disabled. Seventy-eight alcohol-dependent inpatients and 57 healthy volunteers were tested as control groups. Neurological soft signs (NSS) were rated with convincing agreement. Schizophrenic patients are more impaired on all scales than healthy controls. The chronic, severly disabled schizophrenic patients are more impaired compared with the main group of schizophrenic patients and both control groups. A significant patients and alcohol-dependent patients was only found for the subscale Motor Coordination. Compared with healthy controls the alcohol-dependent patients show a higher NES total score. The NES total score was related to the relative width of the third ventricle. Total score and subscales were correlated consistently with the level of cognitive functioning as measured by the Raven Standard Progressive Matrices and various neuropsychological tests presumably sensitive to dysfunctions of the prefrontal cortex. The NSS were related to positive as well as to negative symptoms, the correlations with negative symptoms being confined to items of Cognitive Disorganization. This close association of psychomotor and cognitive dysfunctions may be seen as related to the frequently discussed dysfunctions of the prefrontal cortex or the neurointegrative deficit postulated by Meehl.     

Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer

Whole-body fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed during the follow-up of 33 patients suffering from differentiated thyroid cancer. Among them there were 26 patients with papillary and seven with follicular tumours. Primary tumour stage (pT) was pT1 in six cases, pT2 in eight cases, pT3 in three cases and pT4 in 14 cases. FDG PET was normal in 18 patients. In three patients a slightly increased metabolism was observed in the thyroid bed, assumed to be related to remnant tissue. In one case local recurrence, in ten cases lymph node metastases (one false-positive, caused by sarcoidosis) and in three cases distant metastases were found with FDG PET. In comparison with whole-body scintigraphy using iodine-131 (WBS) there were a lot of discrepancies in imaging results. Whereas three patients had distant metastases (proven with¹³¹I) and a negative FDG PET, in four cases¹³¹I-negative lymph node metastases were detectable with PET. Even in the patients with concordant staging, differences between¹³¹I and FDG were observed as to the exact lesion localization. Therefore, a coexistence of¹³¹I-positive/FDG-negative,¹³¹I-negative/FDG-positive and¹³¹I-positive/FDG-positive malignant tissue can be assumed in these patients. A higher correlation of FDG PET was observed with hexakis (2-methoxyisobutylisonitrile) technetium-99m (I) (MIBI) scintigraphy (performed in 20 cases) than with WBS. In highly differentiated tumours¹³¹I scintigraphy had a high sensitivity, whereas in poorly differentiated carcinomas FDG PET was superior. The clinical use of FDG PET can be recommended in all cases of suspected or proven recurrence and/or metastases of differentiated thyroid cancer and is particularly useful in cases with elevated serum thyroglobulin levels and negative WBS.     

The P & T Committee Part 2: involvement by pharmacy, medical, and nursing personnel

An active and enthusiastic participation by all members of the P & T Committee greatly improves committee effectiveness and productivity. Specific responsibilities for the physician, pharmacist, and nursing members of the committee are presented and discussed. In addition, the importance of open communication among committee members is reviewed. Examples of problems that may develop and suggested solutions are also presented.     

Psychomotor disturbances in psychiatric patients as a possible basis for new attempts at differential diagnosis and therapy

Parts I-III of this series used psychometric assessment of motor performance in psychiatric patients and indicated a "psychotic-motor syndrome" (PMS) in schizophrenic and affective psychoses, which was not found in "neurotic"/reactive or healthy persons. Part IV yielded signs of concomitant brain dysfunction in these patients, demonstrated by EEG mapping as well as other (SPECT/PET) neuroimaging methods. Apart from this "basic science" interest into the pathophysiology of endogenous psychoses we engaged in the development of motor training programs using the PMS as "target" syndrome. We hypothesized, that motor training would not only improve disturbed motor behaviour, but ameliorate other symptoms of psychopathology also. These assumptions were supported in the first two independent studies involving n = 45 and n = 31 ICD-9 mono- and/or bipolar endogenous depressed patients, respectively (the studies on schizophrenic patients being reported finally as part VI of this series, along with the final version of our modified motor test battery). Examples of the motor training programs are provided in this paper, although the final version of the complete programs will be published separately for space reasons and for better availability for routine clinical use.     

Awareness of breast cancer incidence and risk factors among healthy women.

The efficacy of early breast cancer detection programmes seems to be mainly influenced by the awareness of breast cancer in general among healthy women. This study aimed to provide information about women's understanding of breast cancer incidence and risk of disease. Based on a newly developed questionnaire 2108 healthy women were asked about their knowledge and perceptions in relation to breast cancer incidence, risk factors, risk perception and level of concern. Of these women 78.8% were well aware of breast cancer in general terms. However, there were major aspects such as incidence or risk factors that were poorly understood. Only one-third correctly estimated the incidence of breast cancer; 95% understood breast cancer in the familial history as a risk factor, but only 57% understood the age risk; 37.1% of women perceived hormonal contraceptives and 35.9% hormonal replacement therapy as risk factors of breast cancer. The latter estimation was significantly higher in women above 40 years. Recommendations for the improvement of cancer prevention programmes include targeting understanding of lifetime risk of breast cancer, age as a risk factor, survival from breast cancer or hormonal factors. There is a need to separately address the perceptions of women depending on age, social status and educational levels.     

Membranes for endotoxin removal from dialysate: considerations on feasibility of commercial ceramic membranes

As the quality of water in dialysis fluid varies considerably, dialysate is often contaminated by large amounts of bacteria and endotoxins. Membrane properties and operating pressures are acknowledged to give high-flux dialysis with bicarbonate the bacteriological potential to favor passage of endotoxin fragments from the dialysate into the blood stream. Therefore, a sterile dialysate will have to become a standard. Ultrafiltration across hydrophobic synthetic membranes was shown to remove endotoxins (and their fragments) from dialysis water by the combined effect of filtration and adsorption. However, each module can be used for a limited time only. Ceramic membranes may represent an alternative to polymeric membranes for endotoxin removal. In this article, we tested the capacity of different commercial ceramic membranes with nominal molecular weight cut-off down to 1,000 to retain endotoxins from Ps. aeruginosa. The tested membranes did not generally produce dialysate meeting the Association for the Advancement of Medical Instrumentation standard. When using aluminum-containing membranes, we detected aluminum leaking into the dialysate that could possibly be transported into the blood stream.