Increased risk of type 2 diabetes in antidepressant users: evidence from a 6-year longitudinal study in the E3N cohort.

AIM: To examine the association between antidepressant medication use and the risk of type 2 diabetes. METHODS: Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. RESULTS: Of the 63 999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. CONCLUSION: Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).

Comparison between disease onset patterns of Egyptian juvenile and adult systemic lupus erythematosus (single centre experience).

Background Systemic lupus erythematosus (SLE) is a complex autoimmune disease that occurs worldwide in both children and adults, with different disease manifestations, activity and severity between them. Objectives To analyse the difference in disease onset patterns and activity in Egyptian children and adults with SLE. Methods A retrospective cohort study conducted on 298 Egyptian SLE patients, 215 adults (a-SLE) (>18 years) and 83 children (j-SLE) (≤18 years). Disease onset, clinical manifestations and laboratory investigations were recorded. The systemic lupus erythematosus disease activity index (SLEDAI) was used to assess disease onset activity; renal biopsy was performed for all cases affected with renal symptoms. Results A total of 215 a-SLE (F/M: 14.4/1), mean age 29.65 ± 10.235 years, and 83 j-SLE (F/M: 5.4/1), mean age at diagnosis 12.63 ± 3.112 years. The most frequent initial a-SLE symptoms were constitutional (88.8%), mucocutaneous (71.2%), haematological (64.2%), articular (62.3%), renal (43.7%), vascular (15.3%), serositis (14.4%) and finally central nervous system (11.6%). There were no significant differences between a-SLE and j-SLE with regard to constitutional, mucocutaneous, renal, vascular and serositis manifestations, which were 92.8%, 74.7%, 53%, 16.9% and 10.8%, respectively, but the j-SLE haematological (88%) and central nervous system (30.1%) manifestations were significantly higher than a-SLE and articular manifestations were significantly lower in j-SLE (14.5%) than a-SLE. Antinuclear antibodies were positive for 95.3% of a-SLE and 97.6% of j-SLE. Anti-dsDNA was positive for 84.7% a-SLE and was significantly higher in j-SLE (92.8%). The SLEDAI score was 12.23 ± 4.966 in a-SLE and was significantly higher in j-SLE (27.13 ± 19.968). International Society of Nephrology lupus nephritis classes III and IV (42.4%) were the commonest findings in a-SLE; however, classes I and III (57.9%) were the commonest in j-SLE. Conclusions SLE had a wide variety of clinical and immunological manifestations, with some similarity and differences between a-SLE and j-SLE; juvenile onset lupus had a higher SLEDAI with more aggressive initial manifestations than a-SLE.

Molecular epidemiology of bovine anaplasmosis in Khyber Pakhtunkhwa, Pakistan.

Bovine anaplasmosis is endemic in Pakistan where it reduces livestock productivity and leads to high mortality, especially in young animals. This study was aimed to identify the potential risk factors responsible for the occurrence and spread of anaplasmosis in cattle and buffaloes for the first time in Pakistan. A total of 900 (cattle = 479, buffalo = 421) blood samples were collected irrespective of age and sex from three distinct zones of Khyber Pakhtunkhhwa (KP) province of Pakistan. Polymerase chain reaction (PCR) technique was used for the molecular detection of anaplasmosis. Data collected on a piloted questionnaire including 11 predicting variables which were analyzed using R-statistical software, and association between the dependent and independent variables was assessed using univariable analysis. Automated and manual approaches were exercised, producing comparable models. Key risk factors identified in all the approaches included species of the animal, breed of animal, sex of animal, tick infestation status, previous tick history, tick control status, and acaricides used (odds ratio > 1). The 611 bp DNA fragment specific for 16S rRNA gene of Anaplasma spp. was produced from 165 samples. The samples were confirmed for anaplasmosis through sequencing and BLAST queries. The findings of the current study conclude that by enhancing the protective measures to control the identified risk factors can reduce the spread of anaplasmosis in Pakistan.

Seroprevalence of Toxoplasma gondii in South Asian countries.

Toxoplasmosis, a cosmopolitan zoonosis, is caused by an apicomplexan, obligate, intracellular protozoan parasite, Toxoplasma gondii. Nearly all animals, including humans, are at risk owing to its broad geographical distribution. The authors searched published data related to T. gondii in databases, including Google Scholar, PubMed and Science Direct for South Asian countries, and retrieved a total of 113 articles fulfilling the criterion of seroprevalence investigation. Toxoplasma gondii infection in livestock and humans was investigated using various serological tests. In these studies, a total of 14,431 samples from domestic animals and 53,899 samples from humans were screened for anti-T. gondii antibodies in all South Asian countries. Among the animals, cattle (n = 1,981), goats (n = 3,285), buffaloes (n = 1,695), sheep (n = 1,747), cats (n = 1,480), camels (n = 435), elephants (n = 45), pigs (n = 920), dogs (n = 1,604) and poultry (n = 1,206) were tested. This comprehensive review will be useful to biologists, public health workers, physicians and veterinarians and provides a better understanding of the distribution of T. gondii in this region. Furthermore, this knowledge will support efforts to find and apply effective prevention measures to better manage this zoonosis in South Asian countries.

La toxoplasmose est une maladie cosmopolite causée par Toxoplasma gondii, un protozoaire unicellulaire obligatoire appartenant au phylum des Apicomplexa. Du fait de sa distribution géographique, pratiquement toutes les espèces animales sont exposées, ainsi que l'homme. Les auteurs ont fait une recherche dans plusieurs bases de données, dont Google Scholar, PubMed et Science Direct, sur les articles consacrés à T. gondii dans les pays d'Asie du Sud, qui a permis d'extraire un total de 113 articles présentant toutes les caractéristiques d'une enquête sérologique. L'infection par Toxoplasma gondii chez l'homme et chez les animaux d'élevage a fait l'objet de plusieurs enquêtes recourant à divers tests sérologiques. Ces études font état d'un total de 14 431 échantillons prélevés d'animaux domestiques et de 53 899 échantillons prélevés chez l'homme, qui ont été soumis à une épreuve de détection d'anticorps dirigés contre T. gondii dans les pays d'Asie du Sud. Les études ont couvert les espèces suivantes : bovins (n = 1 981), chèvres (n = 3 285), buffles (n = 1 695), moutons (n = 1 747), chats (n = 1 480), chameaux (n = 435), éléphants (n = 45), porcs (n = 920), chiens (n = 1 604) et volailles (n = 1 206). Ce panorama exhaustif sera utile aux biologistes, aux intervenants en santé publique, aux médecins et aux vétérinaires et permettra de mieux appréhender la distribution de T. gondii dans la région. Ces connaissances contribueront à concevoir et à appliquer des mesures de prévention efficaces afin de mieux gérer cette zoonose dans les pays d'Asie du Sud.

La toxoplasmosis es una zoonosis cosmopolita causada por un protozoo, parásito intracelular obligado, del grupo de los apicomplejos: Toxoplasma gondii. Por su amplia distribución geográfica, constituye una amenaza para casi todos los animales, incluido el ser humano. Tras indagar en bases de datos de publicaciones (Google Scholar, PubMed y Science Direct) en busca de información relacionada con la presencia de T. gondii en los países del meridión asiático, los autores encontraron un total de 113 artículos que cumplían el criterio de dar cuenta de investigaciones sobre la seroprevalencia. Para estudiar la infección por Toxoplasma gondii en el ganado y el ser humano se habían empleado diversas pruebas serológicas. En el conjunto de esos estudios, que cubrían todos los países de Asia meridional, se habían analizado un total de 14.431 muestras de animales domésticos y 53.899 muestras humanas para detectar anticuerpos contra T. gondii. Los animales analizados eran: ganado vacuno (n = 1.981), cabras (n = 3.285), búfalos (n = 1.695), ovejas (n = 1.747), gatos (n = 1.480), camellos (n = 435), elefantes (n = 45), cerdos (n = 920), perros (n = 1.604) y aves de corral (n = 1.206). Este repaso general, que resultará útil a biólogos, agentes de salud pública, médicos y veterinarios, permite conocer mejor la distribución de T. gondii en la región, lo que además será de ayuda a la hora de determinar y aplicar medidas eficaces de prevención con objeto de controlar más eficazmente esta zoonosis en los países de Asia meridional.

Juvenile systemic lupus erythematosus: onset patterns and short-term outcome in Egyptian children, a single-center experience.

OBJECTIVE: The objective of this article is to define disease onset pattern and understand the response to therapy in children with systemic lupus erythematosus (SLE) in Egypt. METHODS: A prospective cohort of 41 Egyptian children diagnosed with SLE was analyzed. SLE Disease Activity Index (SLEDAI) score was used to record disease activity at onset, and renal biopsy was performed to define the stage of lupus nephritis. Response to therapy over a follow-up period ranging from 10 to 50 months was evaluated. RESULTS: The mean age at diagnosis was 12.12 ± 3.45 years. Thirty-six (87.8%) patients were females. Most patients had multiple manifestations at onset. The most common presenting symptoms were pallor and fever (51.2% and 43.9%, respectively). Lupus nephritis was found in 27 (65.9%) children. International Society of Nephrology (ISN) classes I and III were the most common findings on renal biopsy. Neuropsychiatric manifestations were present at disease onset in 19 patients (46.3%) with a bad prognostic course. At diagnosis, high SLEDAI scores were recorded (mean: 29.95 ± 2.06). The mean renal SLEDAI score was 10.2 ± 4. At follow-up 16 (39.02%) patients were in complete remission, 10 (24.39%) were in partial remission, two (4.87%) had active disease, five (12.9%) had relapsed, four (9.75%) had died and four (9.75%) patients were lost to follow-up. CONCLUSIONS: Egyptian children with SLE appear to have severe disease on presentation with high SLEDAI scores and high prevalence of lupus nephritis, but respond well to therapy with a favorable short-term prognosis.

Excess non-psychiatric hospitalizations among employees with mental disorders: a 10-year prospective study of the GAZEL cohort.

OBJECTIVE: To examine whether non-psychiatric hospitalizations rates were higher in those with mental disorders. METHOD: In a cohort of 15,811 employees, aged 35-50 years in 1989, mental disorder status was defined from 1989 to 2000. Hospitalizations for all-causes, myocardial infarction (MI), stroke, and cancer, were recorded yearly from 2001 to 2011. Negative binomial regression models were used to estimate hospitalization rates over the follow-up. RESULTS: After controlling for baseline sociodemographic factors, health-related behaviors, self-rated health, and self-reported medical conditions, participants with a mental disorder had significantly higher rates of all-cause hospitalization [incidence rate ratio, IRR=1.20 (95%, 1.14-1.26)], as well as hospitalization due to MI [IRR=1.44 (95%, 1.12-1.85)]. For stroke, the IRR did not reach statistical significance [IRR=1.37 (95%, 0.95-1.99)] and there was no association with cancer [IRR=1.01 (95%, 0.86-1.19)]. A similar trend was observed when mental disorders groups were considered (no mental disorder, depressive disorder, mental disorders due to psychoactive substance use, other mental disorders, mixed mental disorders, and severe mental disorder). CONCLUSION: In this prospective cohort of employees with stable employment as well as universal access to healthcare, we found participants with mental disorders to have higher rates of non-psychiatric hospitalizations.

Socioeconomic position predicts long-term depression trajectory: a 13-year follow-up of the GAZEL cohort study.

Individuals with low socioeconomic position have high rates of depression; however, it is not clear whether this reflects higher incidence or longer persistence of disorder. Past research focused on high-risk samples, and risk factors of long-term depression in the population are less well known. Our aim was to test the hypothesis that socioeconomic position predicts depression trajectory over 13 years of follow-up in a community sample. We studied 12 650 individuals participating in the French GAZEL study. Depression was assessed by the Center for Epidemiological Studies-Depression scale in 1996, 1999, 2002, 2005 and 2008. These five assessments served to estimate longitudinal depression trajectories (no depression, decreasing depression, intermediate/increasing depression, persistent depression). Socioeconomic position was measured by occupational grade. Covariates included year of birth, marital status, tobacco smoking, alcohol consumption, body mass index, negative life events and preexisting psychological and non-psychological health problems. Data were analyzed using multinomial regression, separately in men and women. Overall, participants in intermediate and low occupational grades were significantly more likely than those in high grades to have an unfavorable depression trajectory and to experience persistent depression (age-adjusted ORs: respectively 1.40, 95% confidence interval (CI) 1.16-1.70 and 2.65, 95% CI 2.04-3.45 in men, 2.48, 95% CI 1.36-4.54 and 4.53, 95% CI 2.38-8.63 in women). In multivariate models, the socioeconomic gradient in long-term depression decreased by 21-59% in men and women. Long-term depression trajectories appear to follow a socioeconomic gradient; therefore, efforts aiming to reduce the burden of depression should address the needs of the whole population rather than exclusively focus on high-risk groups.

Cognitive hostility and suicide.

OBJECTIVE: To determine whether a specific component of hostility (i.e. cognitive or behavioural) may predict suicide in a prospective design, controlling for depressive mood. METHOD: In 1993, 14,752 members of the 'GAZ et ELectricité' (GAZEL) cohort (10,819 men, mean age=49.0 years; 3933 women, mean age=46.2 years) completed the Center for Epidemiologic Studies Depression Scale and at least one subscale (i.e. cognitive or behavioural hostility) of the Buss and Durkee Hostility Inventory. Dates and causes of death were obtained annually. RESULTS: During a mean follow-up of 15.7 years, 28 participants completed suicide (24 men, four women). Suicide was predicted by depressive mood [relative index of inequality (RII) (95% CI)=8.16 (1.97-33.85)] and cognitive hostility [RII (95% CI)=10.76 (2.50-46.42)], but not behavioural hostility [RII (95% CI)=1.37 (0.38-4.97)]. These associations remained significant after adjustment for potential confounders. After mutual adjustment, however, suicide remained significantly associated with cognitive hostility [RII (95% CI)=8.87 (1.52-51.71)] (RII reduction: 34.6%), but no longer with depressive mood [RII (95% CI)=2.03 (0.41-10.07)] (RII reduction: 79.1%). CONCLUSION: Cognitive rather than behavioural hostility is associated with an increased risk of suicide, independently of baseline depressive mood.

Hostility and depressive mood: results from the Whitehall II prospective cohort study.

BACKGROUND: The psychosocial vulnerability model of hostility posits that hostile individuals, given their oppositional attitudes and behaviours, are more likely to have increased interpersonal conflicts, lower social support, more stressful life events (SL-E) and higher likelihood of depression. However, little research has tested this hypothesis using large-scale prospective samples. The present study aims to assess the predictive value of hostility for depressive mood. METHOD: Data are from 3399 participants in the Whitehall II cohort study, aged 35-55 years at baseline (phase 1 1985-1988). Cynical hostility was measured at phase 1. Depressive mood was assessed at phase 7 (2002-2004). Sociodemographic characteristics, health-related behaviours, common mental disorders and antidepressant medication intake were assessed at phase 1. SL-E and confiding/emotional support were measured at phases 1, 2 (1989-1990) and 5 (1997-1999). RESULTS: Compared with participants in the lowest quartile of cynical hostility, those in the highest quartiles were more likely to have depressive mood [second quartile: odds ratio (OR) 1.58, 95% confidence interval (CI) 1.14-2.20; third quartile: OR 2.78, 95% CI 2.03-3.77; fourth quartile: OR 4.66, 95% CI 3.41-6.36] in analysis adjusted for sociodemographic characteristics. This graded association was somewhat attenuated (18%) but remained robust to adjustments for the covariates measured at baseline and follow-up. The association was also evident in participants free of mental health difficulties at baseline. CONCLUSIONS: Cynical hostility is a strong and robust predictor of depressive mood. Consideration of personality characteristics may be crucial to the understanding and management of depression.

Metabolic imaging of rat brain during pharmacologically-induced tinnitus.

Although much is known about the perceptual characteristics of tinnitus, its neural origins remain poorly understood. We investigated the pattern of neural activation in central auditory structures using positron emission tomography (PET) imaging in a rat model of salicylate-induced tinnitus. Awake rats were injected with the metabolic tracer, fluorine-18 fluorodeoxyglucose (FDG), once in a quiet state (baseline) and once during salicylate-induced tinnitus. Tinnitus was verified using a behavioral technique. Brain imaging was performed using a high-resolution microPET scanner. Rats underwent magnetic resonance imaging (MRI) and reconstructed MRI and microPET images were fused to identify brain structures. FDG activity in brain regions of interest were quantified and compared. MicroPET imaging showed that FDG activity in the frontal pole was stable between baseline and tinnitus conditions, suggesting it was metabolically inert during tinnitus. Inferior colliculi (p=0.03) and temporal cortices (p=0.003) showed significantly increased FDG activity during tinnitus relative to baseline; activity in the colliculi and temporal cortices increased by 17%+/-21% and 29%+/-20%, respectively. FDG activity in the thalami also increased during tinnitus, but the increase did not reach statistical significance (p=0.07). Our results show increased metabolic activity consistent with neuronal activation in inferior colliculi and auditory cortices of rats during salicylate-induced tinnitus. These results are the first to show that microPET imaging can be used to identify central auditory structures involved in tinnitus and suggest that microPET imaging might be used to evaluate the therapeutic potential of drugs to treat tinnitus.

What characterizes cancer family history collection tools? A critical literature review.

Background: Many tools have been developed for the standardized collection of cancer family history (fh). However, it remains unclear which tools have the potential to help health professionals overcome traditional barriers to collecting such histories. In this review, we describe the characteristics, validation process, and performance of existing tools and appraise the extent to which those tools can support health professionals in identifying and managing at-risk individuals. Methods: Studies were identified through searches of the medline, embase, and Cochrane central databases from October 2015 to September 2016. Articles were included if they described a cancer fh collection tool, its use, and its validation process. Results: Based on seventy-nine articles published between February 1978 and September 2016, 62 tools were identified. Most of the tools were paper-based and designed to be self-administered by lay individuals. One quarter of the tools could automatically produce pedigrees, provide cancer-risk assessment, and deliver evidence-based recommendations. One third of the tools were validated against a standard reference for collected fh quality and cancer-risk assessment. Only 3 tools were integrated into an electronic health records system. Conclusions: In the present review, we found no tool with characteristics that might make it an efficient clinical support for health care providers in cancer-risk identification and management. Adequately validated tools that are connected to electronic health records are needed to encourage the systematic identification of individuals at increased risk of cancer.

Optimization of 124I production via 124Te(p,n)124I reaction.

(124)I was produced, via (124)Te(p,n)(124)I reaction, in greater than 3.7GBq (100 mCi, EOB) amount by bombarding (124)TeO(2) targets at 24 microA current for about 8h. This was achieved by keeping the target at 37 degrees relative to the beam during irradiation, by sweeping the beam across the target and by keeping the incident energy of the proton at 14.1MeV. The time-averaged yield of our 8h run was 21.1 MBq/microAh (0.57 mCi/microAh), which was 90% of the theoretical yield calculated using thick target yield data obtained from the reported excitation function for the reaction. At the end of bombardment, the level of (125)I and (126)I impurities, co-produced with (124)I, were 0.03% and 0.007%, respectively.

Association between current perceived stress and incident diabetes is dependent on occupational status: Evidence from the IPC cohort study.

AIM: The role of stress in the onset of type 2 diabetes is a widespread lay belief, yet observational studies have produced inconsistent results. This study aimed to test the hypothesis that the association between perceived stress and incident diabetes might depend on occupational status (OS). METHODS: The four-item Perceived Stress Scale (PSS-4) was completed at baseline by 22,567 participants in the labour force (16,193 men, 6374 women; mean age: 44.5±9.8 years) who had undergone two health checkups subsidized by the French national healthcare system. All subjects were free from diabetes at baseline, defined as a fasting blood glycaemia≥7mmol/L or the use of antidiabetic drugs. RESULTS: After a mean follow-up of 5.3±2.1 years, 527 participants (2.3%) had incident diabetes. After adjusting for sociodemographic, behavioural and biomedical risk factors as well as self-rated health, the association between baseline perceived stress and diabetes at follow-up was non-significant for the total study population. However, perceived stress was significantly associated with incident diabetes in participants of low OS [odds ratio (OR) for a five-point increment: 1.39; 95% confidence interval (CI): 1.02-1.90]. In contrast, there was a negative association between perceived stress and diabetes among those of high OS (OR: 0.60; 95% CI: 0.41-0.88) and no association within other occupational categories. The interaction between perceived stress and OS was significant (P<0.01). CONCLUSION: This study suggests that the association between perceived stress and diabetes onset is dependent on OS. Furthermore, this association does not appear to be explained by the classical risk factors for diabetes.

Road mobility and the risk of road traffic accident as a driver. The impact of medical conditions and life events.

STUDY OBJECTIVE: We conducted a longitudinal investigation of the impact of self-reported life events and medical conditions on changes in road mobility on the wheel between 2000 and 2002 in order to assess whether these changes would affect the risk of road traffic accident (RTA). METHODS: Data are from a cohort of workers and retirees from the French national gas and electricity companies (the Gazel cohort). In the present study, 10,483 participants were included (7843 men aged 51-61 years and 2640 women aged 46-61 years, in 2000). The link between mobility and the risk of RTA was approximated using data on RTA number during lifetime and reported mobility in 2000. We then compared changes in road mobility between 2000 and 2002 resulting from life events and medical conditions reported to have occurred in the year 2001 or changed when compared to year 2000. We also compared road mobilities in 2000 in order to assess any pre-existing differences before life events and medical conditions. This led to estimation of the effect of road mobility changes on the risk of RTA. RESULTS: Changes in road mobility associated with life events and medical conditions were only found among men. These changes in road mobility were minimal. Ensuing changes in the risk of RTA were estimated to be small (odds-ratios ranged from 0.94 to 1.01). The only life events found to be associated with increased road mobility was an important purchase. Hospitalization, serious RTA, and retiring were associated with reduced road mobility. Concerning medical conditions, men who reported cataract, angina pectoris, diabetes, anxiety and stress, sleep disorder, and depression decreased their road mobility. CONCLUSION: We found no or moderate changes in road mobility resulting from life events and medical conditions, suggesting that results from previous published studies that assessed the impact of life events or medical conditions on RTA were not jeopardized by improper adjustment for road mobility.

Gamma probe assisted ex vivo detection of small lymph node metastases following the administration of indium-111-labeled monoclonal antibodies to colorectal cancers.

This study evaluated the ability of ex vivo gamma-probe scanning to detect lymph node metastases in resected surgical specimens from primary colorectal carcinoma patients undergoing external scintigraphy following intravenous administration of 4.1-5.3 mCi of 111In-labeled anti CEA monoclonal antibodies. The ex vivo probe counting technique led to a twofold to fourfold increase in the number of detectable lymph nodes with the majority measuring 2-5 mm in diameter. Results indicate a potentially useful role for ex vivo probe counting in detection and mapping small (2-5 mm) lymph nodes metastases.

Indium-labeled anti-colorectal carcinoma monoclonal antibody accumulation in non-tumored tissue in patients with colorectal carcinoma.

Indium-111- (111In) labeled murine monoclonal antibodies ZCE 025 (against carcinoembryonic antigen) and CYT-103 MAb B72.3 (against tumor-associated glycoprotein - 72) have been used to image patients with colorectal cancers with encouraging results. The objectives of this study were to assess the frequency and causes of 111In MAb localization in tumor-free, benign tissues. Thus, scans of 75 patients who have undergone exploratory surgery following radioimmunoscintigraphy with 111In-ZCE 025 (n = 37) or 111In-CYT-103 (n = 38) were reviewed in conjunction with operative and histopathology reports. Localization in non-tumored tissues was seen in 10.8% and 13.1%, respectively, of patients receiving ZCE 025 and CYT-103. The most common sites involved were: degenerative joint disease, abdominal aneurysms, postoperative bowel adhesions, and local inflammatory changes secondary to surgery or external irradiation. Review of patients' medical history and results of concurrent diagnostic modalities is likely to lessen the false-positive rate of 111In-labeled MAb scan interpretation.

Indium-111 white blood cell scan for infectious complications of polycystic renal disease.

This case report describes the localization of a unilateral renal abscess with [111In]oxine-labeled autologous leukocyte scanning in a febrile patient with polycystic renal disease, after other noninvasive imaging procedures failed to identify a source of infection. In polycystic renal disease, leukocyte scans have advantages over standard diagnostic modalities and are very helpful in planning appropriate therapy.

Safety and role of repeated administrations of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE 025 in the postoperative follow-up of colorectal carcinoma patients.

The safety and clinical utility of repeated administrations of 111In-ZCE 025 were evaluated in 25 patients who have undergone colorectal carcinoma resection. Fifteen patients were clinically and radiologically free of recurrences and asymptomatic while 10 had rising CEA and/or symptoms. We repeatedly imaged the patients following intravenous administrations of 40 mg ZCE 025, every 4 to 6 mo. Side effects occurred in 16% of patients who received two or more infusions. Sixteen lesions were detected by immunoscintigraphy in 11 patients who were free of disease by CT scans or other imaging modalities. Ten recurrences were surgically confirmed in seven patients. Radiographic and clinical follow-up confirmed the remaining 6 Mab-positive lesions. Elevated human anti-mouse antibody (HAMA) titers were detectable in the sera of 30% and 64% of patients following the 1st and 2nd Mab injection respectively, but did not interfere with successful immunoscintigraphy nor correlated with the occurrence of side effects. This study suggests that a negative Mab scan indicates that a patient will remain free of recurrence; conversely, a positive scan was associated with recurrences of disease.

Antibody imaging in breast cancer.

Radiolabeled antibodies have been studied by several investigators for their ability to detect and stage breast cancers. Studies with Technetium-99m labeled anti-CEA monoclonal antibodies, Iodine-123, Indium111 labeled anti-mucin antibodies such as HFMG, B72.3, anti-TF and Iodine-125 labeled B72-3 have demonstrated the ability of radioimmunoscintigraphy in detecting over 80% of breast cancer lesions, but lower sensitivity and specificity for accurate staging of the axillae. Non-specific localization of radiolabeled monoclonal antibodies in tumor negative nodes even following lymphoscintigraphy appear to be the major factor limiting the widespread clinical application of radioimmunoscintigraphy in staging newly diagnosed breast cancer patients. Preliminary studies with Tc-99m labeled CEA-Scan appear to indicate a useful role of this agent in distinguishing between benign and malignant breast lesions in patients with indeterminate mammographic findings.

Breast cancer imaging with radiolabeled antibodies.

Over the past 2 decades, numerous anticancer antibodies against different molecular targets and labeled with different gamma-emitting radionuclides have been studied in human tumor xenografts and in clinical trials. In breast cancer, these molecular targets have included principally tumor-associated antigens, such as carcinoembryonic antigen (CEA) and the polymorphic epithelial mucin antigen, MUC1, and more recently the growth factor receptors, EGF-R and HER-2/neu. No antibody-based agent has yet been approved for clinical use in the diagnosis of mammary carcinoma, because few trials have addressed the issue of clinical use of these imaging agents in the management of breast cancer patients. Recently, the CEA antibody Fab' fragment approved for colorectal cancer detection, Arcitumomab (CEA-Scan, [Immunomedics, Morris Plains, NJ]), has been found to image both palpable and nonpalpable breast lesions that were suspicious on screening mammograms. Results to date indicate that Arcitumomab can complement mammography by providing a high specificity and positive predictive value, thus indicating when a patient with an abnormal mammogram may proceed directly to definitive surgery without an intermediate diagnostic biopsy. Breast cancer immunoscintigraphy holds promise for advancing toward immunoPET, which should combine the specificity of antibodies with the high sensitivity and resolution of PET. It is also the foundation of breast cancer radioimmunotherapy with humanized antibodies against CEA and MUC1, as well as other immunotherapy strategies.