Pharmacokinetics of indium-111-labeled B72.3 monoclonal antibody in colorectal cancer patients.

Mean time parameters provide a new approach to plasma pharmacokinetics of radiolabeled Mabs that may show important patient differences affecting diagnosis or treatment. We determined mean time pharmacokinetic parameters for 11 patients entered in a Phase I/II clinical trial for detection of colorectal cancer. Patients were administered 0.5-2 mg of B72.3 anti-TAG-72 radiolabeled with 3.5-5 mCi of 111In, plasma activity was measured over time. Mean time pharmacokinetic parameters were (mean +/- s.e.m.): mean residence time; body (MRTB) 88.9 +/- 7.2 hr, central (MRTC) 73.8 +/- 6.0 hr; mean transit time, central (MTTC) 41.1 +/- 9.0 hr; mean residence time, periphery (MRTP) 15.1 +/- 3.4 hr; intrinsic mean residence time, periphery (IMPTP) 39.0 +/- 7.6 hr; mean transit time, periphery (MTTP) 24.0 +/- 6.7 hr; probability of distribution (PRD) 50% +/- 10%; and n compartmental cycles of 4.54 +/- 2.3 times. In patients with increased circulating specific TAG-72 antigen, MRTC greater than MTTC and n much greater than 1. In patients without specific antigen, MRTC approximately equal to MTTC and n much less than 1. Pharmacokinetic studies may identify patients who do not have the tumor produced target antigen for the specific Mab and may provide an opportunity to select another specific Mab with an increased chance for successful diagnosis or treatment.     

Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid glands in patients with renal failure

Background. Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as thallium-technetium subtraction imaging in the preoperative localization of hyperplastic parathyroid glands in patients with renal failure. Reports have suggested that 50% of glands can be identified correctly by this method. The aim of this study was to improve on previous results and demonstrate that Tc-99m MIBI imaging has an important place in the preoperative work-up of these patients. Methods. Eighteen patients on renal replacement therapy were studied. All had tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method was employed. The imaging results were compared to the subsequent surgical and histological findings. Results. In the 12 patients in whom serum parathyroid hormone levels fell postoperatively to within or below the normal range, 38 of 46 glands (82.6%) were correctly identified and located in the correct quadrant of the thyroid gland. There were two false positive results where the imaging predicted glands not subsequently found by the surgeon. In the patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate accurately the site of the residual parathyroid tissue. Conclusion. Tc-99m MIBI imaging is able to identify more than 80% of hyperplastic parathyroid glands in renal failure patients if this reporting process is used, and locate them in the correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value when re-exploration of the neck is required for post-parathyroidectomy hyperparathyroidism. These results represent a significant improvement on the sensitivity of this imaging technique when compared to previous published data.     

Risk factors for spinal surgical-site infections in a community hospital: a case-control study.

OBJECTIVE: To characterize risk factors for surgical-site infection after spinal surgery. DESIGN: A case-control study. SETTING: A 113-bed community hospital. METHOD: From January 1998 through June 2000, the incidence of surgical-site infection in patients undergoing laminectomy, spinal fusion surgery, or both increased at community hospital A. We compared 13 patients who acquired surgical-site infections after laminectomy, spinal fusion surgery, or both with 47 patients who were operated on during the same time period but did not acquire a surgical-site infection. Information collected included demographics, risk factors, personnel involved in the operations, length of hospital stay, and hospital costs. RESULTS: Of 13 case-patients, 9 (69%) were obese, 9 (69%) had spinal compression, 5 (38.5%) had a history of tobacco use, and 4 (31%) had diabetes. Oxacillin-sensitive Staphylococcus aureus (6 of 13; 46%) was the most common organism isolated. Significant risk factors for postoperative spinal surgical-site infection were dural tear during the surgical procedure and the use of glue to cement the dural patch (3 of 13 [23%] vs 1 of 47 [2.1%]; P = .02) and American Society of Anesthesiologists risk class of 3 or more (6 of 13 [46.2%] vs 7 of 47 [15%]; P = .02). Case-patients were more likely to have prolonged length of stay (median, 16 vs 4 days; P< .001). The average excess length of stay was 11 days and the excess cost per case was $12,477. CONCLUSION: Dural tear and the use of glue should be evaluated as potential risk factors for spinal surgical-site infection. Systematic observation for potential lapses in sterile technique and surgical processes that may increase the risk of infection may help prevent spinal surgical-site infection.     

Myocardial stiffness and reparative fibrosis following coronary embolisation in the rat

The structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardium, was undertaken to address these issues. Collagen volume fraction (trichrome), fibrillar collagens (picrosirius-polarisation technique), and the stress-strain relations of the intact myocardium (isolated hearts) were determined 30 d after the infusion of microspheres into the left ventricle. Significant differences from controls included: (a) the presence of hypertension secondary to renovascular embolisation; (b) a greater volume fraction of collagen that included not only a meshwork of short, taut appearing, thick and thin collagen fibres, interposed between muscle in areas of cell loss, but also a perivascular fibrosis involving intramyocardial coronary arteries; (c) elevated active stiffness, and (d) a more exponential diastolic stress-strain relation with increased stiffness at strains of 5% or more. These findings suggest that the replacement fibrosis accompanying myocyte necrosis has distinguishing morphological features involving fibrillar collagen and which because of its structure, alignment, and location relative to muscle leads to enhanced myocardial stiffness, including a more exponential rise in the diastolic stress-strain relation. The perivascular accumulation of collagen suggests that additional factors other than microsphere induced necrosis were responsible for this reactive fibrosis.     

Incidence of cervical dyskaryosis in Ireland: report of a five-year audit

The implementation of a national cervical screening programme in Ireland will require agreement on achievable standards in reporting cervical cytology similar to those published by the NHS cervical screening programme. Due to the opportunistic nature of screening in the Republic of Ireland, national incidence figures for uterine cervical disease are not available. An audit of our practice was performed to find the incidence of human papilloma virus related cervical disease in our population. Our laboratory reported 158,066 cases from 1996-2000. The overall rate of dyskaryosis increased from 3.6% to 7.9%, mostly due to increased low grade dyskaryosis (up from 2.3% to 6.0%). High grade dyskaryosis also increased (from 1.3% to 1.9%), particularly in the under-25 year age group who account for a growing proportion of high grade dyskaryosis (from 15.4% of all high grade diagnoses in 1996 to 23.0% in 2000). The positive predictive value of a diagnosis of high grade dyskaryosis remained stable between 76.0 and 79.5%. While opportunistic screening data may not be directly applicable to the entire screening population it is hoped that these data may form a foundation on which to estimate national incidence figures and define achievable standards for cervical screening cytology in Ireland.     

Hemin-binding surface protein from Bartonella quintana

Bartonella quintana, the agent of trench fever and a cause of endocarditis and bacillary angiomatosis in humans, has the highest reported in vitro hemin requirement for any bacterium. We determined that eight membrane-associated proteins from B. quintana bind hemin and that a approximately 25-kDa protein (HbpA) was the dominant hemin-binding protein. Like many outer membrane proteins, HbpA partitions to the detergent phase of a Triton X-114 extract of the cell and is heat modifiable, displaying an apparent molecular mass shift from approximately 25 to 30 kDa when solubilized at 100 degrees C. Immunoblots of purified outer and inner membranes and immunoelectron microscopy with whole cells show that HbpA is strictly located in the outer membrane and surface exposed, respectively. The N-terminal sequence of mature HbpA was determined and used to clone the HbpA-encoding gene (hbpA) from a lambda genomic library. The hbpA gene is 816 bp in length, encoding a predicted immature protein of approximately 29.3 kDa and a mature protein of 27.1 kDa. A Fur box homolog with 53% identity to the Escherichia coli Fur consensus is located upstream of hbpA and may be involved in regulating expression. BLAST searches indicate that the closest homologs to HbpA include the Bartonella henselae phage-associated membrane protein, Pap31 (58.4% identity), and the OMP31 porin from Brucella melitensis (31.7% identity). High-stringency Southern blots indicate that all five pathogenic Bartonella spp. possess hbpA homologs. Recombinant HbpA can bind hemin in vitro; however, it does not confer a hemin-binding phenotype upon E. coli. Intact B. quintana treated with purified anti-HbpA Fab fragments show a significant (P < 0.004) dose-dependent decrease in hemin binding relative to controls, suggesting that HbpA plays an active role in hemin acquisition and therefore pathogenesis. HbpA is the first potential virulence determinant characterized from B. quintana.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。