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Aim: In therapy response monitoring by [¹⁸F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), different tumor delineations are used, resulting in different values for change in glucose metabolic rate (ΔMR(glu)). We propose a technique to compare metabolic rates in a region of interest (ROI) based on fixed volumes rather than on fixed thresholds. This method involves change in lesion size., Methods: In 49 patients with colorectal carcinoma (CRC) and 50 patients with non-small cell lung carcinoma (NSCLC) scheduled for chemotherapy, FDG-PET was performed at baseline and during chemotherapy. A ROI(fixed thresholds) was determined by using a 50% threshold on both baseline and follow-up FDG-PET. A ROI(fixed volumes) was determined by using a 50% threshold, determined on the series with the largest tumor volume. This ROI(fixed volumes) is used on consecutive scans. Predictive effects of both methods were investigated by survival analysis for overall and progression free survival., Results: In CRC, only ROI(fixed volumes) based ΔMR(glu) showed significant predictive ability. In NSCLC, both techniques showed significant predictive ability. During multivariate analysis, ROI(fixed volumes) determined ΔMR(glu) was an independent predictor for both overall and progression free survival in NSCLC whereas ROI(fixed thresholds) determined MRglu was not. After dichotomization at the median ΔMR(glu), median survival ratio was higher in ROI(fixed volumes) than ROI(fixed thresholds) for CRC (overall survival: 1.78 vs 1.25, progression free survival: 1.57 vs 1.21) and NSCLC (overall survival: 2.01 vs 2.01, progression free survival: 2.93 vs 2.13)., Conclusion: ROI(fixed volumes) based ΔMR(glu) shows better correlation with survival than ΔMR(glu) determined from a ROI(fixed thresholds).

Positron emission tomography (PET) using [(18)F]-fluoro-2'-deoxy-D-glucose (FDG) has an added value in the clinical management of patients with colorectal carcinoma (CRC). This includes restaging patients before surgical resection or local recurrence of liver metastases, assessment whether residual lesions are scar or recurrence and in pinpointing recurrence in case of unexplained increase in serum levels of carcinoembryonic antigen. At present, there is an increasing interest in new roles for FDG-PET, especially for characterization of lesions, for prognosis and response prediction and for early evaluation of treatment response to commenced therapy. FDG-PET may lead to better selection of patients for different therapeutic options or to early individual adjustment of current treatment. This systematic review aims to provide an up-to-date overview of literature on the current and potential value of FDG-PET in CRC patients by addressing staging and recurrence detection, prognosis and response prediction and evaluation of preoperative (chemo)radiotherapy for primary rectal carcinoma, ablative treatment for unresectable liver metastases and chemotherapy for advanced CRC.

A correct histological diagnosis, careful staging and detection of tumour response to treatment are all crucial in the management of sarcomas. Imaging is important in all of these stages. Sarcomas have distinct biological and treatment-related features posing challenges for imaging. For example, size measurements may not adequately reflect response rates. Techniques which can measure tissue function rather than generate merely anatomical data such as positron emission tomography (PET) are rapidly gaining interest. We discuss the importance of imaging in different stages of patient management, emphasising the unique characteristics of sarcoma. Furthermore, we discuss the potential of PET for the various indications, focussing on therapy evaluation.

Background: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer., Methods: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates., Results: There was an increase in the rates of death (P = 0.049 for DeltaMRGlu PET1-2; P = 0.017 for DeltaSUV PET1-2; P = 0.032 for DeltaMRGlu PET1-3; P = 0.048 for DeltaSUV PET1-3) and progression (P = 0.026 for DeltaMRGlu PET1-2; P = 0.035 for DeltaSUV PET1-2; P = 0.041 for DeltaMRGlu PET1-3; P = 0.081 for DeltaSUV PET1-3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of DeltaMRGlu and DeltaSUV cut-off levels., Conclusion: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG-PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.

Three patients, two women aged 66 and 43 years, respectively, and a man aged 76 years, presented with sudden, painful, blue areas in the toes with intact peripheral pulsations. One patient had a myeloproliferative syndrome due to essential thrombocytosis, the second patient had thromboangiitis obliterans, and the third patient had a cholesterol embolism, possibly due to the use of oral anticoagulants. After treatment, one patient recovered fully and the other two improved significantly. The blue toe syndrome is the pathophysiological consequence of end-arterial occlusion and frequently the first manifestation of a systemic disorder, such as atheroembolism or vasculitis. Adequate treatment is possible in most cases. Therefore, it is very important to recognise this disorder and its possible causes so as to prevent further episodes of local symptoms and especially systemic complications.

Objective: To investigate the role of 18fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in the initial staging of clinical stage I and II nonseminomatous germ cell tumours (NSGCTs) and in re-staging (non)seminomatous GCTs after chemotherapy., Patients and Methods: FDG-PET studies were undertaken in 50 patients. FDG uptake was interpreted visually and when possible the standardized uptake value was determined. A FDG-PET scan was taken in five patients with clinical stage I and in seven with stage II NSGCT. The scans were validated by histology. Stage I patients underwent a retroperitoneal lymph node dissection because of vascular invasion in the primary tumour. Thirty-eight scans were taken after completing chemotherapy (28 NSGCTs and 10 seminomatous GCTs), and validated by histology or clinical follow-up., Results: In stage I NSGCT, FDG-PET staging was equivalent to computed tomography (CT) staging. One small lesion, consisting of mature teratoma, was missed by both FDG-PET and CT. In stage II NSGCT, FDG-PET missed two lesions (mature teratoma and retroperitoneal mass with a small component of embryonal cell carcinoma) whereas CT correctly classified all. In 20 of 28 patients with NSGCT, histology was obtained after chemotherapy. In one of three patients with viable tumorous residual mass the FDG-PET scan was clearly positive; in four of 12 with mature teratoma and inflammation components retroperitoneally, the FDG-PET was also positive. In contrast, eight patients with solitary mature teratoma had a negative PET result. In four of five patients with necrosis after chemotherapy the PET result was correctly negative. All eight patients on surveillance had a negative PET scan and were free of disease at median (range) of 14 (8-18) months. Interestingly, of the 12 patients with a correct negative PET result, 11 had no mature teratoma in their primary tumour. Nine of 10 patients with SGCT were correctly staged. Two FDG-PET studies showed increased uptake; in one, a viable seminomatous mass was found and in the other there was inflammation in the residual mass. In all other patients the FDG-PET scan correctly predicted absence of viability in the residual mass., Conclusions: In primary staging, FDG-PET has no benefit over CT. In re-staging, a negative FDG-PET result predicts fibrotic residual mass in seminomatous GCT. Moreover, it could be useful to predict fibrotic residual mass in NSGCT in those patients with no teratoma component in their primary tumour.

Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of (68)Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to (68)Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 (+/-0.3) min and 48 (+/-7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70+/-20 min post injection. Kidney uptake averaged <50% compared with spleen uptake. Of 40 lesions predefined by computed tomography and/or magnetic resonance imaging, (68)Ga-DOTATOC PET identified 100%, whereas (111)In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ((111)In-octreotide: 1.5:1) to 100:1 for CNS ((111)In-octreotide: 10:1). With (68)Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using (68)Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with (111)In-octreotide scintigraphy.

Background: Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available., Methods: We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies., Results: At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02)., Conclusions: Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.

Objective: To ascertain to what extent the dramatic decrease in coronary heart disease (CHD) mortality from 1972 to the present can be attributed to a change in risk factors., Design: Descriptive study based on literature data., Setting: The Netherlands., Methods: Changes in four risk factors were assessed: a survey on trends in average systolic and diastolic blood pressure and serum cholesterol from three national screening projects, conducted 1974-1980, among 30,000 men and women aged 37-43 years, 1981-1986 among 80,000 men aged 33-37 years, and 1987-1992 among 42,000 men and women aged 20-59 years, and the percentage of smokers observed by the Foundation on Public Health and Smoking in yearly surveys among 20,000 people from the age of 15. Using a preventable proportion calculation, the effect on mortality was estimated of the observed changes in these risk factors, applying published relative risks and regression coefficients for these risk factors for men. The estimated curves were compared with the coronary mortality curves observed by the Netherlands Central Bureau of Statistics., Results: From 1974 to 1992 a substantial decrease in the percentage of smokers and in men a moderate decrease in average serum cholesterol level were observed. Serum cholesterol decreased little in women. Changes in blood pressure were not consistent. The calculations predicted a 33% decrease in CHD mortality; the decrease actually observed was 48% for men aged 20-69 and 42% for women., Conclusion: It appears that by far the largest proportion of the decrease in CHD mortality can be explained by a decrease in the values of relevant risk factors (cholesterol and smoking) and only a small part by improved therapy.

In this center, 3 major factors have favorably improved cadaver renal allograft survival rates. The good risk recipient has been associated with a better graft survival and lower mortality. This factor cannot easily be controlled because of an increasing percentage of poor risk recipients awaiting transplantation in most major centers. Recipient blood transfusions administered both before transplantation and at the operating table have led to a better allograft survival in our center. Cadaver donor genotyping with haplotype matching of donor-recipient pairs has resulted in an improved graft survival. As sharing of kidneys between centers becomes more common, it is encouraging to note that one method of preservation is not superior to the other.

The cerebrospinal fluid glutamine level was determined and an electro-encephalogram was made at roughly the same time in 41 patients on 55 occasions. A modified electro-encephalographic grading for practical use was introduced, because the classical electroencephalographic grading described by PARSONS-SMITH et al. (1957) does not apply to patients in deep coma. A significant correlation was found between the natural logarithms of cerebrospinal fluid glutamine levels and the electro-encephalic grade. In combination, these parameters provide valuable diagnostic and prognostic information in hepatic encephalopathy, and each can serve separately for follow-up purposes.

The effect of blood transfusion was analyzed in 194 first cadaver renal transplants and 86 living related renal transplants. The association of blood transfusion with HLA genotyping and poor risk recipients was analyzed. Exclusion of poor risk recipients improved graft survival among the transfused group of patients but not in the small subgroup of nontransfused recipients. No effect of blood transfusion was observed in the living related group. Improved graft survival was observed in both the haplotype-matched and nonhaplotype-matched transfused cadaver recipients. The haplotype-transfused recipients had grafts survival rates of 69 and 66% at 1 and 2 years, respectively. The greatest beneficial effect was seen in the double haplotype-transfused cadaver recipients with graft survival rates of 80 and 71% for the same period. The lack of beneficial effect of transfusion in the living related patients is felt to be a result of the fact that the maximum effect had already been achieved by a far superior donor-recipient histocompatibility than is able to be achieved in a large group of cadaver recipients.

The transient visual-evoked potentials (VEP), recorded in patients suffering from generalized epilepsy, can be characterized by a duplication of the negative peak with a latency of 70-100 ms, a strong increase in amplitude of the negative peak between 80 and 130 ms and the development of a high amplitude slow negative wave following the primary complex. In this study we have investigated to which degree these changes are influenced by the intravenous administration of clonazepam and sodium valproate. Therefore, VEPs were registered in 30 patients, suffering from generalized epilepsy, just before and immediately after the intravenous injection of 0.4-0.8 mg clonazepam and further at 15, 30 and 16 min thereafter. The same procedure was applied on 10 patients treated with an intravenous injection of 400 mg sodium valproate. In both groups we found more or less a reduction in number and degree of the mentioned VEP changes. The improvement was associated with a strong decrease in amplitude of the VEP components in the group treated with clonazepam but was not seen in the sodium valproate group.

The results of preservation of the two kidneys of the same animal by two different techniques and then reimplanted on the same femoral artery, have been compared. The two methods are the following: 1) Short starting perfusion by Collins solution and than cold storage a 4 degrees C in the same solution. 2) Continuous perfusion by machine supplied by pulsatile pump, oxigenator, cooling. The first more impressive result by using continuous perfusion is the possibility of nullifying the effects of warm ischemia up to 30'. Kidney preservation with continuous perfusion is like to give less problems in the postoperatory period. Some weeks after transplantation however, the problems seems to increase in comparison with kidneys stored in Collins solution and not rarely sudden GFR decreases or anurias without immunologic rejection has been observed. Cautious conclusion should advise to use Collins solution when there has not been a long warm ischemia.

A renal transplant recipient presented with bleeding esophageal varices. Needle biopsy, later confirmed by operative wedge biopsy, showed slight periportal fibrosis but no cirrhosis or hepatitis. No etiology for his liver disease could be determined and he could not be differentiated from other reported patients with idiopathic noncirrhotic portal hypertension (IPH). His liver biopsy did show massive hepatic iron deposition. He had received about 115 units of blood while on hemodialysis and had taken oral iron supplementation for 8 years. IPH has been associated with toxin exposure, especially arsenic and vinyl chloride. This case suggests that excessive iron deposition may also lead to IPH and the indiscriminate use of iron supplementation in hemodialysis or renal transplant patients should be avoided.

This report illustrates the improving trend in patient survival of recipients of cadaver and living-related kidneys. Mortality has been less than 3% for living-related recipients and less than 8% at one year for recipients of cadaver kidneys excluding diabetic patients. Although mortality of the diabetic recipient group receiving cadaver kidneys remains a problem, it has decreased in the last year such that overall mortality of the entire diabetic group is 20% at one year. The various factors leading to improved graft function rate are also emphasized.

An ischemic forearm test with simultaneous measurement of both lactate and ammonia can be used as a screening method for myoadenylate deaminase deficiency (MADD) and for various glyco(geno)lytic defects. A standardized and a nonstandardized test have been compared in a group of 186 patients with exertional myalgia. Standardization of the ischemic forearm test has led to greater yields of both lactate and ammonia in venous return blood of patients and controls. The sensitivity of the proposed test procedure in detecting MADD patients was 100%, whereas the specificity amounted to 98.8% among exertional myalgia patients.

In a study to determine the nature and frequency of cardiac side effects during long-term administration of tricyclic antidepressant drugs in usual dosages in the aged, 32 geriatric patients were followed for an average of 36.6 weeks. Ten of them received amitriptyline in a daily dosage of 20-75 mg for 53 weeks (average); in 2, electrocardiographic side effects developed, viz, inversion of the T waves or evidence of acute coronary insufficiency. Imipramine was administered to 21 patients in a daily dosage of 20-100 mg (average, 66 mg) over a period of 40 weeks; in 3 instances major side effects developed--intermittent left bundle-branch block, acute coronary insufficiency with node dysfunction, or T-wave inversion with sinus tachycardia; in 1 instance there was a minor side effect, viz, tachycardia only. In 1 patient, acute myocardial infarction developed after two 10-mg doses of nortriptyline. Five of the 7 patients with cardiac side effects had prior organic heart disease. It was concluded that the incidence of cardiac side effects in aged persons given tricyclic antidepressant drugs in the usual therapeutic dosages for a prolonged period is great enough to warrant frequent careful monitoring of cardiac status during therapy.

20 isolated dog kidneys were perfused in vitro at 37 degrees C during 6h in a closed circuit system with a Roller pump maintaining a pulsatile flow with a constant output. The perfusate electrolyte concentrations were kept constant. In 12 experiments where a hemodiluted standardized perfusion fluid was used, a significant (0.01 greater than p greater than 0.001) correlation (r = 0.798) was found in the beginning of the experiments between the mean arterial pressure expressed in mm Hg (y) and the renin level, expressed in log U/1 (x): y = 57.0+76.8x. In 4 other experiments, phenoxybenzamine added to the perfusion fluid decreased the arterial pressure but did not prevent the rise of the renin level. In 4 other experiments where the perfusion fluid did not contain blood, renin level and arterial pressure increased, whereas in the experiments using a circuit without a kidney, the renin level did not rise. The possible role of the renin-angiotensin system in causing increased renal vascular resistance during in vitro kidney perfusions is discussed.

To determine if the beneficial effect of blood transfusion on renal allograft survival can be obtained without risk of presensitization, we examined the effect of transfusions given on the day of transplant surgery in a series of 180 primary cadaveric renal allografts. Three-month graft survival of those transfused only on the day of transplant was significantly better than the graft survival of those never transfused, and was not significantly different from graft survival of those transfused during the dialysis waiting period. Maximal beneficial effect was achieved by administration of as few as two to three units. We conclude that the benefits of transfusion can be obtained while minimizing the risks of presensitization if transfusion is minimized during the dialysis waiting period and patients are electively transfused at the time of transplant.

Plasma adenosine, inosine and hypoxanthine concentrations were assayed in 7 controls, 5 MADD patients and 6 McArdle patients before and after ischaemic forearm exercise. The MADD patients showed a significantly lower increase in plasma inosine and hypoxanthine following exercise as compared to the controls. In the McArdle patients the increase in plasma inosine and hypoxanthine after exercise did not differ significantly from the control values. The plasma adenosine increase was very low in the three test groups and there were no significant differences.