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Biomedical subjects

A Serafini

Publications and source records attributed to A Serafini.

At least 19 recordsLinked to original sources

Octreotide scintigraphy in the head and neck.

OBJECTIVES/HYPOTHESIS: Octreotide is a somatostatin analogue that, when coupled to a radioisotope, produces a scintigraphic image of neuroendocrine tumors (NET) expressing somatostatin type 2 receptors (SSR 2). Octreotide scintigraphy (OS) may be useful in confirming the preoperative diagnosis of certain head and neck NET. Paragangliomas (PG), like many NET, have been found to have a high density of SSR 2 on the cell surfaces. Other NET of the head and neck include merkel cell carcinomas (MCC), medullary thyroid carcinomas (MTC), and esthesioneuroblastomas. STUDY DESIGN: A retrospective study that compared the results of OS with the histopathologic diagnosis in 74 patients with head and neck NET. RESULTS: Of the 60 patients undergoing evaluation for suspected paraganglioma, OS was correctly positive in 36 of the 37 patients with PG. OS was correctly negative in 19 of the 23 patients that did not exhibit PG. For PG, this yielded a sensitivity of 97% and a specificity of 82%. There were 14 patients in the nonparaganglioma group. OS detected or diagnosed all metastases in three patients with MTC, locoregional recurrences in two patients with esthesioneuroblastoma, an extrapituitary adenoma in one patient, and metastasis in two patients with MCC. It failed to detect a paraspinal metastasis in the third patient with MCC. CONCLUSION: On the basis of this series of patients, OS appears to be a reliable test to detect PG and may be helpful in detecting primary and metastatic disease for NET.

Carcinoma, Medullary↗

Effect of chitosan on in vitro release and ocular delivery of ofloxacin from erodible inserts based on poly(ethylene oxide).

The effects of chitosan hydrochloride (CH-HCl) on in vitro release of ofloxacin (OFX) from mucoadhesive erodible ocular inserts and on the relevant ocular pharmacokinetics have been studied both to contribute evidence of the ability of CH-HCl to enhance transcorneal penetration of drugs and to increase the therapeutic efficacy of topically applied OFX. Circular inserts of 6 mm in diameter, 0.8-0.9 mm in thickness and 20 mg in weight, medicated with 0.3 mg drug, were prepared by powder compression. The addition of 10, 20 or 30% medicated CH-HCl microparticles, obtained by spray-drying, to formulations based on poly(ethylene oxide) of MW 900 kDa (PEO 900) or 2000 kDa (PEO 2000) produced changes in the insert microstructure which accelerated both insert erosion and OFX release from inserts. The effect was stronger with higher CH-HCl fractions. Of the CH-HCl-containing formulations based on either PEO 900 or PEO 2000, PEO 900-CH-HCl (9:1 w/w) was more suitable for a prolonged OFX release. Following insertion in the lower conjunctival sac of the rabbit's eye, such an insert produced no substantial increase of AUC(eff) (AUC in the aqueous humour for concentrations >MIC(90%)) with respect to inserts based on plain PEO; however, it produced a concentration peak in the aqueous significantly higher than that produced by any of the CH-HCl-free PEO inserts, and well higher than the MIC(90%) for the more resistant ocular pathogens (7 microg/ml vs. 4 microg/ml). It has been argued that the increase was due to the ability of CH-HCl to enhance the transcorneal permeability of the drug.

Animals↗

Carcinoembryonic antigen immunoscintigraphy complements mammography in the diagnosis of breast carcinoma.

BACKGROUND: An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false-positive rate of mammography in certain patients. METHODS: This prospective, multicenter study evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen (CEA) antibody imaging in women with known or suspected breast carcinoma. Scintigraphic breast images were obtained approximately 3-8 hours after the administration of technetium 99m ((99)Tc) labeled anti-CEA Fab' and correlated with histopathology. RESULTS: The (99)Tc labeled anti-CEA Fab' detected tumor CEA expression in 46 of 49 women (94%) initially entered with known primary breast carcinoma regardless of histology or serum CEA levels. In women scheduled for biopsy confirmation of mammographic and physical examination findings, 104 (99)Tc labeled anti-CEA Fab' studies had a sensitivity of 61% (17 of 28 cases) and a specificity of 91% (69 of 76 cases). In total, (99)Tc labeled anti-CEA Fab' detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas, and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041), with 11 of 14 missed lesions </= T1, and proliferative histology significantly affected specificity (P = 0.012), with 5 of 7 false-positive tumors being premalignant. In 50 breast carcinoma patients, (99)Tc labeled anti-CEA Fab' also demonstrated axillary lymph node involvement regardless of serum CEA levels, with a sensitivity of 80% when more than three lymph nodes were positive. No immune response or other meaningful side effects occurred. CONCLUSIONS: (99)Tc labeled anti-CEA Fab' had high specificity and positive predictive values for breast carcinoma and the majority of false-positive studies were associated with an increased risk of malignancy. Improved imaging techniques, including dedicated gamma cameras for breast and axillary lymph node imaging, will likely improve the test's sensitivity for smaller lesions.

Adult↗

The effects of topical transforming growth factor-beta2 and anti-transforming growth factor-beta2,3 on scarring in pigs.

BACKGROUND: Transforming growth factor-b2 (TGF-b2) has been implicated in the inflammatory response and subsequent scarring during wound healing. OBJECTIVE: The experiment was designed to study the effects of a topical application of TGF-b2 and mouse monoclonal anti-TGF-b2,3 neutralizing antibody (anti TGF-b2,3) on the development of fibrosis during healing. METHODS: Sixteen full-thickness excision wounds were made in the paravertebral and thoracic area of four domestic pigs. On day 0, three wounds each were treated with: a) 5 mg of TGF-b2, b) 5 mg of 2% methylcellulose (mc), or c) 1.2 mg of anti-TGF-b2,3. As a vehicle for treatment of each wound methylcellulose 2% was used. Four wounds served as the untreated air-exposed control. Wounds were biopsied and the tissue sectioned and stained with hematoxylin and eosin on days 7, 14, and 45. Three blinded observers evaluated the wound specimens. RESULTS: Using computer-aided point count stereology on days 7, 14, and 45, we found a statistically significant increase (p <.05) in the number of nucleated cells in the TGF-b2-treated wounds as compared to the other control wounds. Wounds treated with anti-TGF-b2,3 had significantly (p <.05) fewer nucleated cells on days 7,14, and 45. Microscopically, the TGF-b2-treated wounds had a larger scar area as compared to anti-TGF-b2,3 and controls. CONCLUSION: Treating wounds with an antibody directed against TGF-b2 might be a useful clinical approach to reduce fibrosis.

Administration, Topical↗

Safety and efficacy of arcitumomab imaging in colorectal cancer after repeated administration.

UNLABELLED: In pivotal phase III clinical trials for detecting recurrent or metastatic colorectal cancer, most patients received a single arcitumomab injection. However, the early detection of postsurgical recurrence or metastases with arcitumomab will necessitate serial studies for surveillance. We present immunogenicity, safety, and imaging data supporting the use of multiple administrations of arcitumomab. METHODS: Human antimouse antibody (HAMA) response, adverse events, clinical laboratory values, and diagnostic imaging results were evaluated in 44 patients (24 men, 20 women; age range, 2878 y) after repeated arcitumomab administration (44 second and 3 third injections). Most patients initially had Dukes' class B or C colorectal cancer and had known or occult disease recurrence and elevated serum carcinoembryonic antigen levels at the time of the repeated injection. RESULTS: At the repeated injection, in no patient did elevated HAMA titers develop, hematology and serum chemistry changes were clinically insignificant, and only 1 adverse event (eosinophilia) was judged at least possibly related to arcitumomab. Arcitumomab imaging results at the second injection were comparable with those obtained in phase III trials after a single injection of arcitumomab, having a 78% per-lesion concordance with CT in the abdomen and pelvis and a 73% sensitivity and 94% specificity based on 9 patients with cancer confirmed surgically at 11 anatomic sites and excluded at 16 sites. CONCLUSION: These data indicate that at least 2 injections of arcitumomab can be given safely to patients with colorectal cancer, without increased immunogenicity and with imaging efficacy equivalent to the first administration.

Adenocarcinoma↗

Current applications and perspectives of diagnostic nuclear medicine in oncology. Task Group of Oncology.

The characteristic of nuclear medicine is that it gives images of organs, structures and physiological or pathological processes, detecting the distribution of several radio-pharmaceuticals according to their uptake and metabolism. Its imaging can provide morphological information while at the same time containing data on cellular activity and functions. Such molecular imaging fulfils the modern orientations of oncology, where there is a need to define the presence of a malignancy in the earliest and most effective way, to characterise the neoplasm in terms of biological characteristics (e. g., proliferation, aggressiveness, differentiation, receptor status) and to obtain fundamental issues in patient management such as evaluation of disease extent, monitoring of therapies and study of treatment-induced side effects. The aim of this position paper is to discuss the main indications of nuclear medicine in diagnostic oncology reporting the most recent developments in nuclear medicine, and an extensive list of the major indications for nuclear medicine procedures. The techniques have been labelled as when considered essential in the diagnostic process, when they can give useful additional or information in combination with other instrumental diagnostic approaches, and alternative when they may be performed instead of other tests. These indications were derived by a general consensus within the Task Group of Oncology of the World Federation of Nuclear Medicine and Biology, and it should be stressed that only the current role of nuclear medicine was considered. The Task Group does not claim to have covered the entire range of nuclear medicine indications; in fact it was agreed to include only the most widely used techniques. The highly specific or very exceptionally used applications, or those still in development or under evaluation in clinical trials were not taken into consideration. The conclusion is that the current relationship between nuclear medicine and oncology can be defined not only as satisfactory but also as extremely promising, as nuclear medicine has the potential to compete with the most advanced radiological techniques of imaging, perhaps not so much in terms of sensitivity but more so in terms of specificity and biological characterisation. Several novel diagnostic procedures are able to solve clinical problems for which traditional radiology has shown clear limitations. Nuclear medicine remains today a dynamic medical specialty because it includes a combination of advances in basic science research, technology, cell biology and medical practice and it cannot be excluded that the new lines of research both towards new radiopharmaceuticals and advanced instrumentation will offer in the future new stimulating opportunities.

Forecasting↗

Breast cyst simulating metastases on iodine-131 imaging in thyroid carcinoma.

False-positive radioiodine uptake has been reported in many organ systems. We describe a female patient who had mixed papillary and follicular thyroid carcinoma, and on radioiodine total-body imaging demonstrated focal, lower-right chest uptake. Special prone imaging with the right breast dependent proved that the uptake was inside the right breast. Review of a recent breast ultrasound and mammograms showed this uptake to correspond to a large breast cyst. It is known that 131I breast uptake may be functional within the mammary gland. In this patient, it was due to retention within the cyst after the background activity decreased. Knowledge of this phenomenon may improve the interpretation of total-body 131INa studies.

Breast Neoplasms↗

Efficient parathyroidectomy guided by SPECT-MIBI and hormonal measurements.

UNLABELLED: Parathyroidectomy is a difficult and lengthy operation which is noncurative in 6% to 10% of cases. To improve the efficiency of this operation, a new dual diagnostic approach was prospectively applied. METHODS: Preoperative tomographic 99mTc-sestamibi (MIBI) scintography and intraoperative measurements of circulating parathyroid hormone (PTH) levels by a quick assay (QPTH) were used. Scintigraphy comprised immediate and delayed planar and SPECT of the neck and chest, following 20 mCi MIBI. The presence and location of persistent foci of abnormal activity found within the neck mediastinum on volume-rendered reprojection (RPJ) of the SPECT data were reported. The surgion, guided by the three-dimensional MIBI-SPECT/RPJ images, identified and excised the single or most prominent scintigraphic focus and applied the QPTH. If PTH levels fell from baseline by at least 50%, the operation was concluded. RESULTS: The operative time of primary parathyroidectomy was reduced from an average of 90 min (before the introduction of scintigraphy and intraoperative PTH measurements) to 57 min. All but two patients became normocalcemic. In 58 consecutive patients with hyperparathyroidism, MIBI-SPECT/RPJ correctly and precisely identified 51 of 53 (96%) primary parathyroid adenomas, 14 to 15 secondary hyperplasias and 2 of 3 hyperplastic glands in MEN (sensitivity 94%, specificity 92%). QPTH verified the excision of the primary parathyroid adenomas and predicted normocalcemia in 50 of 52 patients. In 6 patients with misleading scintigraphy, QPTH was especially useful and guided the surgeon to continue the operation until the abnormal parathyroid tissue was found and excised. CONCLUSION: MIBI-SPEC/RPJ and QPTH sequentially applied improved the efficiency of parathyroidectomy.

Adenoma↗

Cardiovascular magnetic resonance imaging goes beyond anatomy.

Magnetic resonance imaging (MRI) provides noninvasive functional information as well as a three-dimensional anatomic display of the cardiovascular system. MRI of protons, phosphorus, or sodium nuclei is currently being investigated to characterize cardiovascular pathology, and the potential benefits of paramagnetic contrast agents are becoming apparent. Finally, techniques to quantitate blood flow, vascular pressures, chamber volumes, ventricular ejection fractions, and cardiac output are being developed.

Contrast Media↗

Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting abdominal and pelvic tumors: 68% versus 40% (P < .05). The combination of antibody scan and CT scan was superior to CT scan alone: 80% versus 40% (P < .01). Lesions as small as 0.5 cm in diameter were detected by antibody scan. The CT scan appears superior to the antibody scan for liver metastases. Patients with a high serum titer of HAMA from previous exposure to murine antibodies were successfully imaged. Antibody scans obtained with 99mTc-88BV59 have imaging characteristics similar to murine antibody scans obtained with radiolabeled IgGs. The absence or weak immunogenicity of the human monoclonal antibodies makes them good candidates for radioimmunodetection and radioimmunotherapy.

Breast Neoplasms↗

Bone mineral density after bicycle ergometry training.

The effect of functional electrical stimulation (FES) cycle ergometry on bone mineral density (BMD) was investigated in six spinal cord injury (SCI) quadriplegic men. Each subject trained three days a week for six months on an FES cycle ergometer. Pretraining and posttraining BMD measurements of the proximal femur were performed using dual photon absorptiometry. Mean pretraining BMD (percent norm) for the femoral neck, Ward triangle, and trochanter were 66.65, 57.43, and 57.67, respectively. After six months of FES cycle ergometry, mean BMD measurements were 66.15, 57.07, and 55.13, respectively. There was no statistically significant difference between the pretraining and posttraining BMD measurements. All subjects were found to have osteoporotic proximal femurs when BMD was expressed as a percent of their age-matched controls. Bone mineral density measurements were subsequently performed on three additional men with SCI who had exercised for three years with the FES cycle ergometry modality. Their mean BMDs were not significantly different from the experimental group. This study demonstrated that six months of FES cycle ergometry did not produce an increase in BMD.

Absorptiometry, Photon↗

Experimental increase in brain HIPDM uptake by hypercapnia.

The 30-min brain uptake of [125I]HIPDM was measured in conscious rats--normocapnic (n = 8), hypercapnic (n = 12), and hyperoxic (n = 6). A mean 41.2% higher uptake was found in the brains of hypercapnic animals (p less than 0.01). In the three groups of rats, brain HIPDM uptake had a negative correlation with body weight (p less than 0.001) and a positive correlation with arterial pCO2 (p less than 0.01), when adjusted for body weight. These results indicate that HIPDM uptake with hypercapnia may be used as a provocative test to measure cerebral blood flow reserves.

Animals↗

Osteomyelitis of the base of the skull.

Infection in the marrow of the temporal, occipital, and sphenoid bones is an uncommon, but increasing occurrence. It is usually secondary to infections beginning in the external auditory canal and is caused almost uniformly by the gram negative Pseudomonas aeruginosa bacteria. Technetium and gallium scintigraphy help in the early detection of such infections while CT scans demonstrate dissolution of bone in well-developed cases. Headache is the predominant symptom. Dysphagia, hoarseness, and aspiration herald the inevitable march of cranial nerves. We have diagnosed and treated 17 cases of osteomyelitis of the skull base. Although the total mortality rate is 53%, it is now a curable disease. Six of our last 8 patients remain alive, although 1 is still under treatment. Treatment is medical and requires the long-term concomitant intravenous administration of an aminoglycoside and a broad spectrum semisynthetic penicillin effective against the causative organism.

Aminoglycosides↗

Improving the technique of nuclear cystography: the manometric approach.

A simple technique of manometric scintigraphic retrograde cystography was applied prospectively to 125 patients (85 per cent children) with 142 studies. 99mTechnetium sulfur colloid (0.5 to 1 mCi.) was instilled in the bladder followed by increments of normal saline under manometric control. The sensitivity of the test was increased when the filling phase was concluded at 25 cm. water pressure rather than when the patient complained of fullness (usually at 15 cm.). The studies had a voiding phase that was essential for patients in whom pressures greater than 15 cm. could not be achieved. Reflux was not detected on the voiding phase alone in 5 patients and the voiding phase could not be performed in 5 of 34 positive studies. It was not possible to predict volumes of fluid instilled to achieve satisfactory pressures. Monitoring during the entire study was necessary to diagnose reflux, which may occur at low or high pressure, or while voiding only.

Adolescent↗

The role of hepatobiliary scintigraphy in differentiating acute cholecystitis from acute nonbiliary pancreatitis.

Thirty-five patients with acute nonbiliary pancreatitis were studied with 99m-Technetium para isoproply iminodiacetic acid in order to determine its ability to differentiate acute nonbiliary pancreatitis from acute cholecystitis. Of acute nonbiliary pancreatitis patients 90.3% (28/31) visualized their gallbladder in 1 h, 9.7% (3/31) had delayed visualization of gallbladder, and no patient in this category failed to visualize their gallbladder. Two of four patients with acute episodes of pancreatitis superimposed on chronic pancreatitis visualized their gallbladder. Biliary scintigraphy remains to be a valuable tool in differentiating acute nonbiliary pancreatitis from acute cholecystitis.

Acute Disease↗

Comparisons of scintigraphy with In-111 leukocytes and Ga-67 in the diagnosis of occult sepsis.

In a prospective study involving 32 patients with clinical suspicion of focal infection, the sensitivity and specificity of In-111-labeled leukocyte (In-WBC) scintigraphy were compared with those of Ga-67 scintigraphy performed 24-48 hr later. Of a total of 192 body sites studied, 26 foci of infection were diagnosed by aspiration, cultures, or chest radiographs. Indium-WBC indicated 19 (73%) true-positive (TP) and four (2.5%) false-positive (FP) foci of abnormal accretion; Ga-67 had 21 (81%) TP and 15 (9%) FP. The 7/26 (27%) false-negative (FN) In-WBC scintigrams involved infection foci of more than 2-wk duration; the 5/26 (19%) FN Ga-67 studies were in patients with infections manifested for less than 1 wk. The results of this study are useful in considering the indications of the two tracers.

Abscess↗

The role of H.I.D.A./P.I.P.I.D.A. scanning in diagnosing cystic duct obstruction.

A newer approach to the early diagnosis of acute biliary tract disease is review. Ninety-two patients were evaluated with a new hepatobiliary agent (H.I.D.A/P.I.P.D.A.) for the presence of cystic duct obstruction. Seven patients with suspected acute gall bladder disease were dropped from the study for the lack of pathologic confirmation of the diagnosis. Forty-four of the remaining 85 patients were subsequently operated on and found to have acute cholecystitis. Forty-three of the 44 had cystic duct obstruction demonstrated on H.I.D.A. Scan (one false negative). An additional 23 patients underwent cholecystectomy for chronic disease. In this group, the gallbladder scan was only 43% (10/23) accurate in correctly identifying disease. Eighteen patients with nonbiliary disease had normal scans. The accuracy of ultrasonography and the scan are also compared in a smaller subgroup of 53 patients who had both studies.

Acute Disease↗