A new tool to assess the mechanical properties of bone due to collagen degradation.

Current clinical tools for evaluating fracture risk focus only on the mineral phase of bone. However, changes in the collagen matrix may affect bone mechanical properties, increasing fracture risk while remaining undetected by conventional screening methods such as dual energy x-ray absorptiometry (DXA) and quantitative ultrasound (QUS). The mechanical response tissue analyzer (MRTA) is a non-invasive, radiation-free potential clinical tool for evaluating fracture risk. The objectives of this study were two-fold: to investigate the ability of the MRTA to detect changes in mechanical properties of bone as a result of treatment with 1 M potassium hydroxide (KOH) and to evaluate the differences between male and female bone in an emu model. DXA, QUS, MRTA and three-point bending measurements were performed on ex vivo emu tibiae before and after KOH treatment. Male and female emu tibiae were endocortically treated with 1 M KOH solution for 1-14 days, resulting in negligible collagen loss (0.05%; by hydroxyproline assay) and overall mass loss (0.5%). Three-point bending and MRTA detected significant changes in modulus between days 1 and 14 of KOH treatment (-18%) while all values measured by DXA and QUS varied by less than 2%. This close correlation between MRTA and three-point bending results support the utility of the MRTA as a clinical tool to predict fracture risk. In addition, the significant reduction in modulus contrasted with the negligible amount of collagen removal from the bone after KOH exposure. As such, the significant changes in bone mechanical properties may be due to partial debonding between the mineral and organic matrix or in situ collagen degradation rather than collagen removal. In terms of sex differences, male emu tibiae had significantly decreased failure stress and increased failure strain and toughness compared to female tibiae with increasing KOH treatment time.

Postchemotherapy ejaculatory azoospermia: fatherhood with sperm from testis tissue with intracytoplasmic sperm injection.

PURPOSE: To define the success of testis sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in azoospermic men with a history of chemotherapy. PATIENTS AND METHODS: In a retrospective study, 23 men with ejaculatory azoospermia and a history of chemotherapy underwent TESE in a search for usable spermatozoa. In six patients cryopreserved tissue and in nine patients fresh tissue provided sperm for an ICSI cycle. Histologic analysis of the testis was performed in all patients. The presence or absence of sperm, fertilization rates with ICSI, and final outcomes of pregnancy were recorded. RESULTS: Spermatozoa were found on TESE in 15 (65.2%) of 23 men. On histopathology, the predominant pattern observed was Sertoli cell only (47.8%), followed by hypospermatogenesis (30.4%), mixed (17.4%), and late maturation arrest (4.3%). The fertilization rate was 65.2%, and ongoing/delivered pregnancies occurred in 30.8% of cycles. Six healthy boys and four healthy girls have been born to date. CONCLUSION: Men who are azoospermic and have had prior cytotoxic therapy make up a small subgroup of males with nonobstructive azoospermia. It is important to define and characterize this subgroup and better define their true fertility potential. Approximately two thirds of these men have retrievable testis sperm, which may be used with ICSI to have healthy offspring. This exciting avenue for paternity has heretofore not been available to such patients.

Testicular tissue extraction in a young male with 47,XXY Klinefelter's syndrome: potential strategy for preservation of fertility.

OBJECTIVE: To describe a case involving the cryopreservation of testis tissue retrieved from a 15-year-old male teenager with Klinefelter's syndrome. DESIGN: Case report. SETTING: An academic medical center. PATIENT(S): A 15-year-old boy with Klinefelter's syndrome. INTERVENTION(S): Microsurgical testis sperm extraction with cryopreservation of harvested tissue. MAIN OUTCOME MEASURE(S): Spermatozoa within testis tissue. RESULT(S): Successful extraction and cryopreservation of three vials of sperm-containing testis tissue. No effect on subsequent testosterone levels. CONCLUSION(S): Testis tissue extraction in the adequately virilized but azoospermic young male with 47, XXY Klinefelter's syndrome may be a strategy to preserve future biological paternity.

Intra-abdominal pulmonary sequestration: a benign suprarenal mass.

A 34-year-old white woman presented with an 8.5-cm left suprarenal mass. Evaluation revealed normal adrenal hormone function. Pathologic examination after surgical removal revealed a rare benign condition, intra-abdominal extralobar pulmonary sequestration (accessory lung).

Pre-operative assessment of axillary lymph node status in patients with breast adenocarcinoma using intravenous 99mtechnetium mAb-170H.82 (Tru-Scint AD).

Immunoscintigraphy of the axilla has potential utility for the diagnostic and prognostic assessment of patients with breast adenocarcinoma. mAb-170H.82 is a murine monoclonal antibody (mAb) derived against synthetic Thomsen-Friedenreich (TF) antigen. Tru-Scint AD, a 99mTc-mAb-170H.82 immunoconjugate, has previously been shown to localize in various human adenocarcinomas. The purpose of this study was to evaluate the accuracy of this immunoconjugate in the pre-operative assessment of axillary lymph nodes in patients with known breast adenocarcinoma. Sixteen patients with documented primary breast cancer were injected intravenously with 1 mg of immunoconjugate (radioactivity 1.8 GBq) and imaged 22-24 hrs post-injection. Both planar and single photon emission computed tomographic (SPECT) images were obtained and reviewed in a blinded fashion. Imaging results were compared with surgical and pathological findings. Seven of 16 patients were found to have histologically positive axillary nodes: 5 of these sites were detected by immunoscintigraphy (sensitivity = 71%). Nine patients had pathologically disease-free axillary nodes: only 1 of these was misidentified as positive by immunoscintigraphy (specificity = 89%). These results suggest that immunoscintigraphy with 99mTc-mAb-170H.82 has promise in the detection of axillary lymph node involvement in patients with breast cancer. Further studies are warranted to define the role of immunoscintigraphy in axillary staging.

Compartmental analysis of the pharmacokinetics of radioiodinated monoclonal antibody B72.3 in colon cancer patients.

Sixteen patients with colorectal cancer were administered 37-74 MBq (1 mg) of radioiodinated B72.3 monoclonal antibody. Pharmacokinetic analysis was carried out on plasma and urine samples. Elimination from the plasma was biexponential with a mean T1/2 alpha of 3.7 h and T1/2 beta of 62.4 h. The plasma clearance was fit to a two-compartmental model. This was combined with a previously reported model for radioiodine to construct a composite model. There was a good correlation (r = 0.952) between the model-predicted and observed excretion of radioiodine suggesting that the composite model is compatible with the pharmacokinetics of the radiolabelled antibody.

Comparative dual label study of first and second generation antitumor-associated glycoprotein-72 monoclonal antibodies in colorectal cancer patients.

Radiolabeled first-generation anti-tumor-associated glycoprotein-72 (TAG-72) monoclonal antibody (MAb), B72.3, has proven useful in detecting primary and secondary colorectal carcinoma. It has been anticipated that the development of second-generation, higher affinity, anti-TAG-72 MAbs, CC49 and CC83, would be of greater use in cancer detection and of value in radioimmunotherapy of human cancer. We compared the pharmacokinetics, biodistribution, and immune responses of 131I-labeled CC49 and CC83 to 125I-labeled B72.3 by preoperatively coninjecting dual-labeled MAbs into 16 colorectal cancer patients. The imaging properties of radiolabeled CC49 and CC83 were also assessed. Pharmacokinetics of all three MAbs were identical, and there were no differences in the uptake of any of three MAbs in tumor and normal tissues. Maximum tumor uptake was 0.0041% of the injected dose/g for 125I-B72.3, 0.0024% for 131I-CC49, and 0.0029% for 131I-CC83. Radiolabeled CC49 and CC83 detected most known tumor sites on scintigrams without any clear advantage for either MAb. Nonspecific splenic and testicular uptake was frequently observed. Anti-idiotypic human anti-mouse antibody responses were seen more frequently with B72.3 than with CC49 or CC83. We conclude that higher affinity, radiolabeled anti-TAG-72 MAbs can detect colorectal cancer but do not penetrate these tumors more effectively than B72.3. Improvements in tumor detection and radioimmunotherapeutic strategies will likely require the administration of smaller fragments of MAb molecules or novel delivery systems rather than the continued development of higher affinity MAbs.