A retrospective evaluation of doxorubicin-based chemotherapy for dogs with right atrial masses and pericardial effusion.

OBJECTIVE: To report the outcome of doxorubicin-based chemotherapy as the sole treatment for dogs with echocardiographically identified right atrial masses and pericardial effusion. METHODS: A retrospective study of case records of dogs with right atrial masses treated with doxorubicin. Dogs were excluded from the study if they had any type of surgery performed such as pericardiectomy or right atrial mass resection, or if their chemotherapy protocol did not include doxorubicin. The data collected included signalment, history, physical examination findings, diagnostic test results and long-term survival. RESULTS: Dogs with right atrial masses and pericardial effusion that received doxorubicin-based chemotherapy alone had a median survival of 139 · 5 days (range 2 to 302 days). Chemotherapy side effects were frequent but mild. CLINICAL SIGNIFICANCE: Doxorubicin-based chemotherapy alone appears to be a viable treatment option for dogs with echocardiographically identified right atrial masses and pericardial effusion.

Serum serotonin concentrations in dogs with degenerative mitral valve disease.

BACKGROUND: Increased serotonin (5HT) signaling has been implicated in valvular disease of humans and animals, including canine degenerative mitral valve disease (DMVD). High circulating 5HT concentration is a potential source of increased signaling, and serum 5HT concentrations have not been previously reported in dogs with DMVD. HYPOTHESIS: Dogs with DMVD and small breed dogs predisposed to DMVD have higher serum 5HT concentrations than large breed controls. ANIMALS: Fifty dogs affected with DMVD, 34 dogs predisposed to DMVD but without cardiac murmur or echocardiographic evidence of DMVD, and 36 healthy large breed control dogs. METHODS: Prospective analysis. Serum 5HT concentration was measured by an ELISA test. RESULTS: Median serum 5HT concentration was significantly higher in dogs with DMVD and in dogs predisposed to DMVD as compared with controls (DMVD, 765.5 ng/mL [interquartile range, 561.3-944.4]; predisposed, 774.9 ng/mL [528.3-1,026]; control, 509.8 ng/mL [320.8-708.8]; P= .0001). Subgroup analysis of predisposed dogs indicated significantly higher serum 5HT concentrations in Cavalier King Charles Spaniel (CKCS) dogs than in other breeds (CKCS, 855.0 ng/mL [635.8-1,088]; non-CKCS, 554.2 ng/mL [380.6-648.4]; P= .0023). Age, platelet count, and platelet morphology were not correlated with 5HT concentration in any group. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with DMVD had significantly higher serum 5HT concentrations when compared with large breed control dogs. Healthy CKCS dogs had significantly higher serum 5HT concentrations than other healthy dogs predisposed to DMVD. Additional investigation into a possible role of 5HT in the pathogenesis of DMVD is warranted.

Intraoperative detection of carcinoid tumor of the ovary by gamma probe.

PURPOSE: To demonstrate the detection of carcinoid tumor of the ovary by gamma probe during surgery in a patient in whom the exact location of a metastatic tumor was uncertain. METHODS: Twenty-four hours after injection of 350 MBq (9.5 mCi) I-123, an anterior image of the abdomen was acquired before surgery to demonstrate MIBG accumulation. Holding the ovary in the hand during the operation, a surgical gamma probe indicated the exact location of highest radioactivity. RESULTS/CONCLUSIONS: Intraoperative MIBG scanning is a useful noninvasive detection method to localize metastases of carcinoid in the ovary. This method should be used only when it is not clear where the area of increased activity is located in the body because there are certain costs involved.

Insight into the catalytic mechanism of DNA polymerase beta: structures of intermediate complexes.

The catalytic reaction mediated by DNA polymerases is known to require two Mg(II) ions, one associated with dNTP binding and the other involved in metal ion catalysis of the chemical step. Here we report a functional intermediate structure of a DNA polymerase with only one metal ion bound, the DNA polymerase beta-DNA template-primer-chromium(III).2'-deoxythymidine 5'-beta,gamma-methylenetriphosphate [Cr(III).dTMPPCP] complex, at 2.6 A resolution. The complex is distinct from the structures of other polymerase-DNA-ddNTP complexes in that the 3'-terminus of the primer has a free hydroxyl group. Hence, this structure represents a fully functional intermediate state. Support for this contention is provided by the observation of turnover in biochemical assays of crystallized protein as well as from the determination that soaking Pol beta crystals with Mn(II) ions leads to formation of the product complex, Pol beta-DNA-Cr(III).PCP, whose structure is also reported. An important feature of both structures is that the fingers subdomain is closed, similar to structures of other ternary complexes in which both metal ion sites are occupied. These results suggest that closing of the fingers subdomain is induced specifically by binding of the metal-dNTP complex prior to binding of the catalytic Mg(2+) ion. This has led us to reevaluate our previous evidence regarding the existence of a rate-limiting conformational change in Pol beta's reaction pathway. The results of stopped-flow studies suggest that there is no detectable rate-limiting conformational change step.

Prospective study of the effect of laparoscopic hemifundoplication on motor and sensory function of the proximal stomach.

BACKGROUND: Some 30 per cent of patients develop dyspeptic symptoms following antireflux surgery. These symptoms may result from alterations in the motor and sensory function of the proximal stomach. METHODS: Proximal gastric motor and sensory function was studied with an electronic barostat in 12 patients with reflux who underwent laparoscopic hemifundoplication. In addition, 24-h pHmetry, gastric emptying (scintigraphy) and vagus nerve integrity (pancreatic polypeptide response to hypo-glycaemia) were assessed. Fifteen healthy volunteers served as controls. RESULTS: Laparoscopic hemifundoplication significantly decreased total acid exposure time (P < 0.05). Vagus nerve function remained intact in all but one patient. The mean(s.e.m.) lag phase for emptying of solids was significantly shorter after operation than before (15(3) versus 21(3) min; P < 0.05). Proximal gastric compliance was not significantly different before and after fundoplication. However, mean(s.e.m.) postprandial relaxation was significantly reduced (P < 0.05) after hemifundoplication compared with the value before operation (3341(1105) versus 12 763(3616) ml over 90 min) and in controls (14 567(2358) ml over 90 min). Postprandial fullness was significantly increased after hemi-fundoplication (P < 0.05). Postprandial gastric relaxation correlated with the lag phase for emptying of solids (r = 0.55, P < 0.02). CONCLUSION: After hemifundoplication, proximal gastric compliance is not altered but postprandial relaxation is impaired and associated with sensations of fullness and shorter duration of the lag phase for emptying of solids.

Motor and sensory function of the proximal stomach in reflux disease and after laparoscopic Nissen fundoplication.

OBJECTIVE: After Nissen fundoplication, dyspeptic symptoms such as fullness and early satiety develop in >30% of patients. These symptoms may result from alterations in proximal gastric motor and sensory function. METHODS: We have evaluated proximal gastric motor and sensory function using an electronic barostat in 12 patients after successful laparoscopic Nissen fundoplications (median follow-up; 12 months). Twelve age- and gender-matched patients with severe gastroesophageal reflux disease (GERD) and 12 healthy volunteers served as controls. Studies were performed in the fasting state and after meal ingestion. Gastric emptying tests were performed in all patients. Vagus nerve integrity was measured by the response of pancreatic polypeptide (PP) to insulin hypoglycemia. RESULTS: Minimal distending pressure and proximal gastric compliance were not significantly different between post-Nissen patients, GERD patients, and healthy controls. Postprandial relaxation of the stomach, however, was significantly (p < 0.05) reduced post-Nissen (267 +/- 34 ml), compared with controls (400 +/- 30 ml) and GERD (448 +/- 30 ml). Postprandial relaxation was significantly (p < 0.01) prolonged in GERD patients. Postprandial relaxation of the stomach correlated with gastric emptying of solids (r = 0.62; p = 0.01). Gastric emptying of solids became significantly (p < 0.05) faster after fundoplication. Postprandial fullness was significantly (p < 0.05) increased in the operated patients. CONCLUSIONS: Post-Nissen patients have a significantly reduced postprandial gastric relaxation and significantly accelerated gastric emptying, which may explain postoperative dyspeptic symptoms. The abnormalities result from fundoplication and not from vagus nerve injury or reflux per se, because in reflux patients gastric relaxation and gastric emptying are prolonged.

Inflammatory bowel disease activity assessment using technetium-99m-HMPAO leukocytes.

Aim of the study was to evaluate [99mTc]hexamethyl-propylamine-oxime (HMPAO) leukocyte scintigraphy for the assessment of disease activity and extent in inflammatory bowel disease patients. Results and scores of scintigraphy using [99mTc]HMPAO-labeled leukocytes were retrospectively compared with the activity index of van Hees, laboratory parameters, and gastroenterologists' assessment of disease using endoscopy, radiology, and histology plus clinical parameters in 136 patients with Crohn's disease (115) and ulcerative colitis (21) and in 29 controls. There were 114 positive and 22 negative [99mTc]HMPAO leukocyte scintigrams. Sensitivities for active disease at 1 and 3 hr were 98% and 98% and specificities were 100% and 83%, respectively. [99mTC]HMPAO leukocyte scintigraphy is superior to the activity index and the gastroenterologists' clinical assessment of active inflammation in IBD patients. Scintigraphy allows assessment of the existence, extent, and intensity of active inflammation in IBD patients in one examination with high accuracy.

Pulmonary embolism: validation of spiral CT angiography in 149 patients.

PURPOSE: To assess the reliability of spiral computed tomographic (CT) angiography of the pulmonary arteries in the diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: One hundred forty-nine patients clinically suspected of having PE underwent spiral CT angiography and ventilation-perfusion (V-P) scintigraphy. Pulmonary angiography was also performed when the results of the V-P scan were indeterminate. Imaging results of spiral CT angiography were compared and validated against a normal perfusion scan in 40 patients, a high-probability scintigram in 53 patients, and a pulmonary angiogram in 56 patients. RESULTS: Spiral CT angiograms were of satisfactory diagnostic quality in all 149 patients. The sensitivity of spiral CT angiography for the detection of PE was 94% (64 of 68 patients) (observer 1) and 82% (56 of 68 patients) (observer 2), and the specificity was 96% (78 of 81 patients) (observer 2). Good interobserver agreement was obtained for spiral CT angiographic results (kappa = .774). Spiral CT angiography proved to be effective in the detection of PE in pulmonary arteries up to the segmental level but not in the smaller subsegmental branches. Isolated subsegmental PE accounted for three false-negative spiral CT angiographic results for both observers. CONCLUSION: Spiral CT angiography is an accurate method for the detection and exclusion of PE, with the exception of isolated subsegmental PE.

Dietary fish oil in renal transplant recipients treated with cyclosporin-A: no beneficial effects shown.

This study aimed to determine whether dietary supplementation with fish oil has a beneficial effect on graft function and the incidence of rejection in renal allograft recipients treated with cyclosporin A (CsA). Renal function, blood pressure, the incidence of acute rejection episodes, graft survival, and renal histology and immunochemistry were investigated. In a randomized, placebo-controlled, double-blind trial, groups of 25 recipients of primary cadaveric renal allografts who had been treated with CsA took fish oil (30% C20:5 omega-3 and 20% C22:6 omega-3) or coconut oil (63% C8:0 and 36% C10:0) at 6 g/day for 3 months. There were no differences between the two patient groups with regard to HLA matching, panel-reactive antibody titers, or the demographic characteristics of donors or recipients. The GFR and effective RPF were determined at 1, 3, and 12 months after transplantation by simultaneous measurement of (125I-)iothalamate and (131I-)hippuran clearances. At 1 yr after transplantation, patients treated with fish oil showed better renal function than did the control patients, but this difference was not statistically significant. Blood pressure and antihypertensive drug use were similar in both groups. The number of rejection episodes was also similar, and renal histopathological and immunohistochemical studies showed no significant differences between the fish-oil group and the control patients. It is concluded that fish oil, at a dose of 6 g/day, has no beneficial effect after renal transplantation within the time scale of the study.

Is it possible to assess disease activity of inflammatory bowel disease with scintigraphy?

99mTc-HMPAO-leukocyte scintigrams were compared with the activity index (AI) of Van Hees in 145 inflammatory bowel disease (IBD) patients. Labelling of leukocytes with 99mTc-HMPAO was less time-consuming and less laborious than 111In-labelling of granulocytes; in addition, the radiation dose for the patient is lower and the shorter acquisition time allows multiple views. In a previous comparative study 99mTc-leukocytes proved superior to 111In-granulocytes in detecting active IBD. The present study shows that a positive AI (> 125) is associated with a positive 99mTc-leukocyte scintigram (40 pts); a negative 99mTc-leukocyte scintigram is only found in patients with a negative AI (27 pts). In 30 out of 78 patients with an AI < or = 125 and a positive scintigram these positive results were confirmed by radiological and/or endoscopic examinations, but in the remaining 48 patients verification of the scintigraphic result was prohibited due to the absence of other confirmative examinations within 1 month of scintigraphy. In our view 99mTc-leukocyte scintigraphy may well be the gold standard for functional assessment of inflammation intensity and localization in IBD patients.

Technetium-99m labelled human immunoglobulin scintigraphy predicts rheumatoid arthritis in patients with arthralgia.

The ability of 99mTc-IgG scintigraphy to predict the development of rheumatoid arthritis (RA) in 47 patients with arthralgia was investigated. 99mTc-IgG scintigraphy and the serum test for rheumatoid factor (RF), measured at the beginning of a year long study, were compared for their ability to predict RA. During the study 8 patients developed RA. The specificity and positive predictive values of RF in predicting RA were 79% and 50% respectively; and for 99mTc-IgG scintigraphy 97% and 88%. The sensitivity and negative predictive values of RF were 100% and of 99mTc-IgG-scintigraphy 88% and 97% respectively. In conclusion, 99mTc-IgG scintigraphy has additional value to RF with respect to the prediction of the development of RA in patients with arthralgia.

Technetium-99m labelled polyclonal human IgG scintigraphy before and 26 weeks after initiation of parenteral gold treatment in patients with rheumatoid arthritis.

OBJECTIVE: To determine effectiveness of technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to monitor variation in arthritis activity in patients with rheumatoid arthritis (RA). METHODS: The results of semiquantitative 99mTc-IgG scintigraphy were compared with those of examination before and 26 weeks after initiation of parenteral gold treatment in 19 patients with RA. RESULTS: Clinical and laboratory variables of arthritis activity as well as the scores of 99mTc-IgG scintigraphy were significantly lower after gold treatment compared to the scores before treatment. However, the difference between the mean scores of 99mTc-IgG scintigraphy before and after treatment was statistically significant for more joints than such difference in scores for joint pain and joint swelling. CONCLUSION: 99mTc-IgG scintigraphy is able to reflect variations in arthritis activity in patients with RA.

Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to histological examination.

OBJECTIVE: This study addressed the following questions: How does 99mTc-IgG scintigraphy compare to physical examination in the detection of synovitis as determined histologically, and is 99mTc-IgG scintigraphy a sensitive detector of histologically documented synovitis activity in the absence of clinically detectable knee joint swelling? METHODS: The results of measuring synovitis activity by physical examination and by scintigraphy with technetium-99m labelled polyclonal human immunoglobulin G (99mTc-IgG) were compared with the results of histological examination of synovial biopsies taken from the knee joints of patients with rheumatoid arthritis (n = 21), osteoarthritis (n = 9) and various other rheumatic diseases (n = 10). RESULTS: The sensitivity of 99mTc-IgG scintigraphy in detecting synovitis activity, as determined histologically (85%), was higher than the sensitivity of joint swelling (65%). In the absence of clinically detectable knee joint swelling the sensitivity of 99mTc-IgG scintigraphy was 83%. CONCLUSION: This study shows that 99mTc-IgG scintigraphy is a more sensitive method than physical examination in detecting histologically documented synovitis activity.

Cerebral blood flow during migraine attacks without aura and effect of sumatriptan.

OBJECTIVE: To study regional cerebral blood flow (rCBF) during migraine attacks without aura and after treatment with sumatriptan. DESIGN AND INTERVENTION: We performed three technetium Tc99m hexemethyl-propyleneamineoxime single photon emission computed tomography scanning procedures in patients with migraine who participated in a double-blind, placebo-controlled, randomized clinical trial (1) outside an attack, (2) during an attack, and (3) after treatment of the attack with 6 mg of subcutaneous sumatriptan. SETTING: University hospital. PATIENTS: We studied 20 patients with migraine without aura, 15 of whom were evaluated under all three conditions and five of whom were evaluated under only two conditions. OUTCOME MEASURES: The single photon emission computed tomographic images were evaluated semiquantitatively with regard to (1) the degree of asymmetry of the rCBF between the headache side and the nonheadache side and (2) the ratio of the rCBF in regions of interest to the rCBF in two reference areas (cerebellum or frontal cortex). RESULTS: We found no significant rCBF asymmetries outside or during the attack or after treatment with sumatriptan, and there were no significant changes of the rCBF ratios during the attack (compared with outside the attack) or after treatment of the attack (compared with during the attack). CONCLUSION: Migraine attacks without aura and treatment of the attacks with 6 mg of subcutaneous sumatriptan are not associated with detectable focal changes of the rCBF.

Value of 99mTc-IgG scintigraphy in the prediction of joint destruction in patients with rheumatoid arthritis of recent onset.

The ability of technetium-99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) scintigraphy to predict joint destruction in patients with rheumatoid arthritis (RA) was investigated in this study. The progression of radiographically determined joint destruction in wrists, hands and feet was compared with the results of physical and laboratory examination, as well as 99mTc-IgG scintigraphy, measured at the beginning of a year-long study on 30 patients with RA of recent onset. The sensitivity of joint swelling in predicting the progression of radiographically determined joint destruction ranged between 57% and 74%. The sensitivity of 99mTc-IgG scintigraphy ranged between 71% and 100%. The specificity and positive predictive value both of joint swelling and 99mTc-IgG scintigraphy were low. Multiple regression analysis showed that for the total joint score, and for the metacarpophalangeal and forefeet joints, progression of radiographically determined joint destruction was primarily predicted by 99mTc-IgG scintigraphy. Joint swelling, ESR and IgM rheumatoid factor did not contribute to this prediction. We concluded that 99mTc-IgG scintigraphy is superior to conventional clinical and laboratory measurements in RA with respect to prediction of joint destruction.

Extraskeletal localization of 99mTc-labeled bone-seeking tracers in bone scintigraphy.

In this article clinical examples of extraskeletal localization of technetium-99m (99mTc)-labeled diphosphonate are described. In several of these cases this finding was relevant for clinical decision-making. 99mTc-labeled diphosphonates have been used for skeletal imaging since 1971, and from 1973 on many reports of extraskeletal localizations of these agents have been published. This visualization can be due to (1) an abnormality of the excretory route of 99mTc-labeled diphosphonate or (2) increased uptake in pathologically altered tissues and organs. The latter has been recorded in a multitude of disease processes, such as ischaemic injury, inflammatory processes, benign or malignant neoplasms, non-skeletal metastases, malignant pleuritis, scars, radiation injury and amyloidosis. Although the precise mechanism of extraskeletal uptake of 99mTc-labeled diphosphonate remains uncertain, binding of this radiopharmaceutical to calcium-containing compounds is thought to play a critical role.

Joint scintigraphy for quantification of synovitis with 99mTc-labelled human immunoglobulin G compared to late phase scintigraphy with 99mTc-labelled diphosphonate.

The ability of scintigraphy with technetium 99m-labelled polyclonal human immunoglobulin G (99mTc-IgG) to detect and quantify arthritis activity was studied in 24 patients with RA and in 10 patients with OA. The results of 99mTc-IgG scintigraphy were compared with those of scintigraphy with 99mTc-labelled hydroxymethylene-diphosphonate (HDP). The mean joint scores of 99mTc-IgG scintigraphy in RA patients with active disease were significantly higher (P < 0.001) than the mean scores in patients with inactive disease. The mean joint scores were also higher in patients with erosions compared to those in patients without erosions (P < 0.05). For 99mTc-HDP scintigraphy no significant differences were found between the mean joint scores of these patient groups. Comparison of scintigraphic results between patients with RA and OA revealed that the mean joint score of 99mTc-IgG scintigraphy was significantly (P < 0.001) higher in the patients with RA than in patients with OA, whereas for 99mTc-HDP scintigraphy this difference was not significant. These results show that 99mTc-IgG scintigraphy, when compared to 99mTc-HDP scintigraphy, is a more specific method of detecting synovitis and, also, shows differentiation between different degrees of arthritis activity in RA.