99mTc-MIBI SPET in non-small cell lung cancer in relationship with Pgp and prognosis

Higher technetium-99m methoxyisobutylisonitrile (MIBI) uptake in non-small cell lung cancer (NSCLC) has been reported to be associated with a positive response to chemotherapy. It has previously been found that in tumour cells, P-glycoprotein (Pgp) expression is of importance for tracer uptake. However, some studies have indicated that Pgp expression does not play an important role in (99m)Tc-MIBI uptake in NSCLC; indeed, a negative correlation between (99m)Tc-MIBI uptake and Pgp expression has been reported. Against the background of conflicting results, our aim was to evaluate the relationship between (99m)Tc-MIBI uptake, prognosis and Pgp expression in NSCLC. A total of 37 patients with NSCLC underwent (99m)Tc-MIBI single-photon emission tomography (SPET) before chemotherapy. In 19 patients both Pgp and p53 expression, and in two patients only p53 expression (due to the limited biopsy material), were measured with immunohistochemical staining. (99m)Tc-MIBI uptake was significantly higher in responders than in non-responders: 3.09+/-1.14 vs 2.24+/-0.88 ( P<0.03) and 3.09+/-1.08 vs 2.37+/-1.06 ( P<0.05) for the early ratio (ER) and the delayed ratio (DR), respectively. The wash-out rate (WR) of responders was not significantly different from that of non-responders. We found no significant differences in ER, DR and WR among the groups positive or negative for Pgp and p53 status. There was a significant positive correlation between the survival rate and both ER and DR: r=0.49 ( P=0.003) and r=0.40 ( P=0.018), respectively. Patients with ER and DR values above 3 showed significantly longer survival than those with values below 3: 14.7+/-8.5 months vs 7.3+/-5.1 months ( P<0.009) and 13.2+/-8.4 months vs 7.4+/-5.3 months ( P<0.04) for ER and DR, respectively. However, interestingly, and in contrast to expectations, patients with a Pgp score of +2 showed significantly longer survival (12.9+/-6.7 months) than those with Pgp scores of +1 (4.4+/-3.0 months) or - (negative) (3.8+/-2.2 months) ( P<0.009 and P<0.02, respectively). Our results suggest that in NSCLC, patients with higher (99m)Tc-MIBI uptake tend to show a positive response to chemotherapy, and patients with ER and DR values above 3 have a significantly better prognosis. We also found that Pgp expression seems to play only a minor role in (99m)Tc-MIBI uptake. Our finding that patients with ER and DR values above 3 have a better prognosis needs to be confirmed in larger series of patients.     

Salivary function in patients with chronic renal failure undergoing hemodialysis

PURPOSE: The aim of this study was to evaluate the changes in salivary gland function in patients with chronic renal failure (CRF) undergoing hemodialysis. METHODS: The group consisted of 23 patients with CRF (13 female, 10 male; mean age: 40 +/- 13 yr) and 14 healthy control subjects (mean age: 40 +/- 13 yr). All underwent dynamic salivary gland scintigraphy with gustatory stimulation. After intravenous administration of 99mTc pertechnetate, first, perfusion images at 2 seconds per frame were acquired for 1 minute, then dynamic images at 1 minute per frame were acquired for 45 minutes. At 30 minutes after injection, 10 ml lemon juice was given for 15 minutes as a gustatory stimulus. We obtained time-activity curves derived from regions of interest centered over the four major salivary glands. The following functional indices were calculated for each gland: the time of maximum radioactivity (Tmax) for the prestimulated period, the time of minimum radioactivity (Tmin), as an indicator of velocity of secretion after stimulation, and the Lem E5% value as an indicator of the secretion function. RESULTS: When the patients with CRF undergoing hemodialysis were compared to the controls, there were statistically significant differences in Tmax, Tmin and Lem E5% values for bilateral parotid glands, and Tmin values for bilateral submandibular glands (p < 0.05), there were no statistically significant differences in Tmax and Lem E5% values for bilateral submandibular glands. There were also significant differences in Tmax and Lem E5% values for bilateral parotid glands between mild oral problems and severe oral problems in patients with CRF (undergoing hemodialysis). CONCLUSION: In this study, prolonged Tmax and Tmin values, and decreased Lem E5% values for parotid glands and prolonged Tmin values for submandibular glands on salivary scintigraphy pointed out decreased parenchymatous and excretory function in patients with CRF undergoing hemodialysis.     

Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin

Neutrophil gelatinase associated lipocalin (NGAL) is a protein identified in human neutrophil granules. The aim of the study was to assess whether urine level of NGAL (uNGAL) could represent a novel, reliable marker of urinary tract infection (UTI) and to determine the optimal cutoff level for uNGAL to predict UTI in children. Sixty patients with symptomatic UTI and 29 healthy controls were enrolled the study. Urine NGAL was measured by enzyme-linked immunosorbent assay. A dimercaptosuccinic acid (DMSA) radionuclide scan was performed within 7 days in the patients with UTI in an attempt to distinguish pyelonephritis from cystitis. Mean uNGAL level was significantly higher in the UTI group than in the controls (91.02 ng/ml vs 14.29 ng/ml, p = 0.0001) and using a cutoff 20 ng/ml for uNGAL for diagnosis of UTI, sensitivity, and specificity were 97% and 76%, respectively [area under the curve (AUC): 0.979]. Mean uNGAL/creatinine ratio (uNGAL/Cr) was also significantly higher in the UTI group [201.81 ng/mg creatinine (Cr) vs 18.08 ng/mg Cr; p = 0.0001], and using a cutoff 30 ng/mg Cr for uNGAL/Cr for diagnosis of UTI, sensitivity and specificity were 98% and 76%, respectively (AUC: 0.992). In conclusion, both uNGAL and uNGAL/Cr can be used as a novel, sensitive marker for early prediction of UTI in the absence of acute kidney injury and chronic kidney disease, and the optimal cutoff value for prediction of UTI is lower than the values determined for acute kidney injury. Further investigations with larger patient groups are required to confirm our results.     

Tc-99m MIBI scintigraphy in tall cell variant of papillary thyroid carcinoma with negative radioiodine scan

We report on a 45-year-old man who had a mass on the wall of the anterior right hemithorax. An excisional biopsy indicated carcinoma metastasis from thyroid malignancy. Tc-99m methoxyisobutyl isonitrile (MIBI) scintigraphy revealed markedly increased activity on the left side of the thyroid and the thoracic wall mass. Postoperative histology revealed a tall cell variant of papillary thyroid carcinoma. Whole body scintigraphy after radioiodine treatment was negative twice. However, Tc-99m MIBI and bone scintigraphy showed multiple soft tissue and bone metastases in the follow-up period. He died 3 years later because of complications of distant lung metastases.     

No effect of angiotensin-converting enzyme gene polymorphism on disease progression and left ventricular hypertrophy in autosomal dominant polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) shows a variable clinical course suggesting that genetic modifiers might play a role. There are conflicting results about the effect of angiotensin-converting enzyme (ACE) gene polymorphism on the progression of renal failure in ADPKD. Also, the association between ACE gene polymorphism and the occurrence of left ventricular hypertrophy (LVH) has not been investigated in patients with ADPKD. METHODS: ACE genotype analysis was performed in 409 Caucasian patients (137 male, 272 female) with ADPKD. Echocardiographic examination was done in 164 of these patients. RESULTS: There were no significant differences between different ACE genotypes regarding renal function, renal volume, urinary protein excretion, blood pressure, the rate of hypertension, the age at diagnosis of hypertension, the rate of LVH and the incidence of end-stage renal disease (ESRD). CONCLUSION: ACE gene polymorphism does not have a significant effect on the development of ESRD and the prevalence of LVH in patients with ADPKD.     

Third left pulmonary vein with abnormal return associated with arteriovenous fistula

Anomalies of pulmonary veins are uncommon and vary widely in their anatomic spectrum and clinical presentation. A 20-year-old woman with complaints of effort-induced dyspnea and easy fatigability was diagnosed with a third left pulmonary vein with abnormal return and arteriovenous fistula accompanied by a secundum atrial septal defect (ASD). Complete surgical repair was performed by ASD closure with a pericardial patch and triple ligation of the left vertical vein and associated third pulmonary vein. The patient was discharged on the seventh postoperative day in good health. Her last control examination was performed in the second postoperative year, revealing normal echocardiographic findings with an excellent clinical course.     

Assessment of the relationship between asymmetric dimethylarginine and severity of erectile dysfunction and coronary artery disease

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between plasma ADMA concentration and severity of erectile dysfunction (ED) and coronary artery disease (CAD). We measured plasma levels of ADMA in 92 male patients. Patients were divided into three groups: group 1 (n = 41), patients with ED and without CAD; group 2 (n = 29), patients with stable CAD; group 3 (n = 22), control group (patients without CAD or ED). Erectile function was evaluated by the erectile function domain of the international index of erectile function (IIEF-EFD) a validated 15-item self-administered questionnaire. Erectile function is specifically addressed by six questions that form the so-called erectile function domain of the questionnaire. Each question is scored 0–5. ED is defined as any value <26. Patients with CAD who have stable angina pectoris were selected after coronary angiography. ADMA was analyzed by ELISA method. Group 1 had significantly higher concentrations of plasma ADMA than groups 2 and 3 (respectively, 0.75 ± 0.40 vs. 0.50 ± 0.30, P = 0.013; 0.75 ± 0.40 vs. 0.50 ± 0.25, P = 0.021). There was negative correlation between ADMA and IIEF-EFD score in all groups (n = 92) (r = −0.322, P = 0.002). In a multiple logistic regression analysis adjusting for age, hyperlipidemia, ADMA remained independent predictor for severe ED. Odds ratio for plasma ADMA was 14.151 (1.101–181.940; P = 0.042). First of all, this study provides that ADMA concentrations are significantly higher in patients who have ED when compared to patients with CAD and controls. Second, there was a negative correlation between ADMA and severity of ED. Elevating levels of circulating ADMA is an independent risk factor for severe of ED, and ADMA may be a link between CAD and ED.     

Albuminuria as a predictor of heart failure hospitalizations in patients with type 2 diabetes

BACKGROUND: Heart failure (HF) occurs more frequently and is a significant cause of mortality in diabetic patients. The purpose of the current study is to ascertain risk factors that are predictive of HF hospitalizations in type 2 diabetic patients. METHODS: Longitudinal observational study of type 2 diabetic patients with baseline diastolic blood pressures > or =80 mm Hg and no history of New York Heart Association class III-IV HF or a serum creatinine > or =2.5 mg/dL nested within a randomized clinical trial. The outcome measure of this study was the first occurrence of HF hospitalization over a 5-year follow-up period. RESULTS: Patients with overt albuminuria at baseline had a higher and earlier occurrence of HF hospitalizations than those with micro- or normoalbuminuria (13.6% versus 3.3%, odds ratio [OR]=3.1, 95% confidence interval [CI]=2.15-4.60, P<.0001). In the multiple logistic regression analyses, the presence of overt albuminuria (OR 5.4, 95% CI=2.3-12.5, P<.001), history of myocardial infarction (OR 4.6, 95% CI=1.6-13.1, P=.004) and a history of New York Heart Association Class I or II HF (OR 8.0, 95% CI=2.2-28.6, P=.0014) at baseline were independently associated with HF hospitalizations. CONCLUSIONS: Overt albuminuria predicts the occurrence of HF hospitalizations in type 2 diabetic patients. Thus early aggressive treatment of diabetic nephropathy should be investigated as a means of preventing of HF.     

Enzymatic Debridement in Necrotizing Pancreatitis

Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge following necrotizing pancreatitis. Group IV was the intraperitoneal collagenase group following necrotizing pancreatitis. The progress of the groups was compared hematologically and histopathologically. There was no difference among the groups regarding the levels of leukocyte, hemogram, and urea. The differences in AST levels between Group I and II; and differences in glucose, calcium, LDH, AST, and amylase between Group II and III; between Group II and IV; between Group I and III; and between Group I and IV were statistically significant (P < 0.05). There were statistically significant differences between Group II and III, and Group II and IV regarding edema, acinar necrosis, inflammatory cell infiltration, hemorrhage, and fat necrosis (P < 0.05). In conclusion, the collagenase preparation used in this experimental pancreatitis model was found to be effective in the debridement of pancreatic necrosis.Key words: Acute pancreatitis, Necrose, Collagenase, DebridementAcute pancreatitis (AP) is a nonbacterial inflammatory disease of the pancreas that can range from interstitial edema to pancreatic necrosis in its severest form. In about 20% of AP attacks necrosis can develop in the pancreas while the disease limits itself and regresses in a couple of days in many patients (80%).¹The definitions that are still widely in effect today regarding the classification of acute pancreatitis were determined in 1992 at the Atlanta Conference.² The conference aimed at achieving a common classification for AP and its complications. Within severe acute pancreatitis, of which necrotizing pancreatitis is a part, organ failure and local complications can be seen (necrosis, pseudocyst, and abscess). Multiple organ failure and pancreatic necrosis are the factors that determine the prognosis. Half of the mortalities are observed within a period of 1 or 2 weeks. Necrotizing pancreatitis makes up for the 10–20% of AP cases. Severe pancreatitis has a high mortality rate and functional diseases like diabetes are seen in one-third to one-fifth of the recovered patients.³While the mortality rates are about 10% in the presence of sterile pancreatic necrosis, they go up over 30% in the existence of infected necrosis.¹ Regarding acute necrotizing pancreatitis, there is still no consensus on surgical indications and the time of surgical intervention, the surgical method to be used, and which patients need conservative treatment and which ones need surgical treatment. The goal in the surgical treatment of acute necrotizing pancreatitis is to isolate the necrotic tissue that might cause sepsis and multiple organ failure and to reduce the risk of mortality. The timing of necrosectomy as well as the way in which necrosectomy is performed is significant in necrotizing pancreatitis. The issue of the possibility that necrosectomy can be performed through minimally-invasive interventions instead of open surgery is still being discussed.³We planned to investigate the activity of collagenase clostridiopeptidase A (EC 3.424.3), which has never been attempted before in the debridement of experimental pancreatic necrosis (but which has been used for enzymatic debridement), and the enzyme preparation containing the accompanying proteases (Sterile Novuxol^®, Abbott, Uetersen, Germany). We aimed to evaluate the response of the disease to treatment through laboratory and histopathologic data, by using the enzyme preparation to treat necrotizing pancreatitis.