The Resistance of Certain Tissues to Invasion: Penetrability of Explanted Tissues by Vascularized Mesenchyme

If puppy tissues are explanted onto the chick chorioallantoic membrane, those tissues which normally have a blood supply are rapidly invaded by vascularized mesenchyme of host origin. Hyaline cartilage, a tissue virtually devoid of blood vessels, is impenetrable by proliferating mesenchyme of the host, while calcified cartilage, which normally is vascularized, is penetrable. The stroma of the cornea, another normally avascular tissue, is readily penetrable, but Descemet's membrane forms a barrier to invasion by host tissues. The experimental system used permits the design of experiments in which the study of factors responsible for the resistance of tissues such as cartilage to invasion can be undertaken.     

18F-labeled fluorodeoxyglucose positron emission tomography-guided surgery for recurrent colorectal cancer: a feasibility study

OBJECTIVE: Positron emission tomography (PET) scanning is an accepted diagnostic tool for the detection of colorectal cancer (CRC). The purpose of this study was to determine whether diagnostic information offered by preoperative PET scan could be used to detect disease intraoperatively using beta and gamma handheld probes. METHODS: Two studies were carried out. First, tumor "phantoms" were created using 62 microCi fluorodeoxyglucose (FDG) in a saline-filled basin. Gamma and beta handheld probes were used to determine detection characteristics with respect to probe type, distance from source, and isotope half-life. In a second study, probes were used intraoperatively to detect tumor in 10 patients with recurrent colorectal cancer as determined by preoperative PET scan. Counts relative to background were determined for each probe as was histopathologic correlation with probe-positive tissue. RESULTS: Phantom studies documented that FDG detection by each probe was nonlinearly related to source proximity and half-life. In human subjects, abnormal findings on preoperative PET studies were detected by both probes with tumor:normal ratios of 1.6 (beta) and 1.5 (gamma). All probe-positive tissue was histologically confirmed to be recurrent colorectal cancer. CONCLUSIONS: Intraoperative detection of CRC using an FDG source and beta and gamma probes correlates with preoperative PET. With further improvements in probe technology, successful differentiation of normal and tumor tissue as shown here may allow for more precise localization and directed resection.     

Rotator cuff tear: clinical experience with sonographic detection

Between June 1986 and April 1988, 86 sonographic examinations of the shoulder were performed on patients suspected of having rotator cuff tears. Major sonographic diagnostic criteria included (a) a well-defined discontinuity usually visible as a hypoechoic focus within the cuff, (b) nonvisualization of the cuff and (c) an echogenic focus within the cuff. Seventy-five patients underwent both sonography and arthrography. Compared with arthrography alone, ultrasound examinations enabled detection of 92% of rotator cuff tears (24 of 26 tears), with a specificity of 84% and a negative predictive value of 95%. Correlation was obtained in 30 of these patients who underwent surgery for rotator cuff tear or other soft-tissue abnormality. In this group, the sensitivity of sonography for detection of a tear was 93%, with a specificity of 73%, while for arthrography sensitivity was 87% and specificity was 100%. These data indicate that sonography is a useful, noninvasive screening procedure for patients suspected of having rotator cuff injury.     

Radioimmunoguided breast surgery using radiolabeled antibody NR-LU-10 FAB: a pilot study

AIM AND BACKGROUND: Radioimmunoguided surgery using radiolabeled NR-LU-10 Fab was evaluated as a method of intraoperative breast cancer detection. METHODS: Breast cancer patients were injected intravenously with 125I (74 MBq) labeled NR-LU-10 Fab (5 mg) and then underwent tumor excision 2, 4 or 7 days later, during which time the gamma detector probe was used to evaluate the primary tumor for evidence of radioactive uptake. RESULTS: Intraoperative probing revealed tumor localization in 7 of 10 patients (70%). Gamma probe counts of the excised tumor were elevated in all patients, although high counts in surrounding non-malignant tissue obscured the ability to detect the tumor in vivo in 3 patients. One patient with bilateral breast cancer was found to have a separate focus of occult tumor in each breast using the gamma detector probe. CONCLUSIONS: Radiolabeled NR-LU-10 Fab possesses favorable pharmokinetics and tumor-binding ability as a targeting agent. However, binding to non-malignant tissue limits its role in the intraoperative evaluation of tumor margins in breast cancer patients. Its role in other malignancies should be explored.     

Cimetidine enhances cisplatin toxicity in mice

Summary The combination of the histamine H₂ antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P-388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls. However, when adult CD-1 mice were given higher but nonlethal CDDP doses of 10, 15, or 18 mg/kg, the addition of CMT significantly increased CDDP lethality (P<0.05 by Wilcoxon analysis). For the 3 groups, CMT-inhanced lethality occurred in 10% of mice given 10 mg/kg CDDP, 80% of mice given 15 mg/kg, and 100% of mice given 18 mg/kg CDDP. Thus, CMT can acutely alter CDDP toxicity without affecting antitumor efficacy in mice.     

The effect of glutathione (GSH) depletion in vivo by buthionine sulfoximine (BSO) on the radiosensitization of SR 2508

The effect of glutathione depletion (GSH) on the efficacy of SR 2508 was evaluated in two murine tumor models with single large doses of radiation or with low doses administered in an accelerated fractionated schedule. To deplete tumor GSH, buthionine sulfoximine (BSO) was administered in the animals drinking water (10 mM) following two i.p. injections of 450 mg/kg. This treatment decreased RIF and MCA tumor GSH concentrations by 95% and 80%, respectively. Mice (C3H/Sed) received BSO for 48-72 hr before the first dose of radiation, and were maintained on BSO drinking water for the duration of the fractionated course of therapy. SR 2508 (200-1000 mg/kg) was injected 45 min prior to each fraction of radiation. Radiation was administered as a single dose of 15 Gy or 20 Gy, for RIF and MCA tumors, respectively. Alternatively, animals received a fractionated course of radiotherapy which consisted of 2.5 Gy/fraction for the RIF, and 3 Gy/fraction for the MCA tumors, b.i.d. for five days (total of 10 fractions). Tumor response with and without BSO, and with and without SR 2508, was determined by regrowth delay. BSO pretreatment increased the efficacy of SR 2508 with single dose radiation in the MCA but not RIF tumor. SR 2508 administered with fractionated radiation produced lower enhancement ratios (SER) than with a single radiation dose. However, BSO significantly enhanced the efficacy of SR 2508 with fractionated radiation. BSO increased the maximum SER for SR 2508 (3 mM/fraction) from 1.2 to 1.4 in the RIF tumor, and from 1.4 to 1.8 in the MCA tumor. BSO also increased the toxicity of SR 2508 by a factor of 2. However, the ability of BSO to increase the efficacy of low doses of sensitizer at clinically relevant doses of radiation suggests that this combined modifier treatment may be of clinical benefit.     

A review of legal and policy issues in legislating compensation for victims of toxic substance pollution

Despite the actual and potential effects of toxic substance pollution upon human health, the United States Congress has never enacted a comprehensive victim compensation system. The approach of the Congress, to date, has been limited by a concern about legislating on a topic fraught with scientific uncertainty--the actual causation of injury or death by toxic substance pollution. Individuals who believe they have been injured by toxic substances often bring their claims in state courts, where they face the difficult task of proving causation. Industry is principally concerned with the high cost of a compensation system, not the public health issue of scientific causation. From a policy standpoint, legislation is needed that produces information and standards on causation which assist both victims and industry. Congress has the opportunity to craft legislation that will deal rationally with an epic problem. To do so, however, the Congress must recognize scientific uncertainty as an omnipresent element of causation in cases of toxic substance pollution. This starting point, a comprehensive system of compensating victims of toxic substance pollution, can be drafted to address the values of data collection, data interpretation, prevention, conservation of economic resources, and fairness.