Mapping dynamic epithelial cell proliferative activity within the oral cavity of man: a new insight into carcinogenesis?

Our aim was to characterize epithelial cell proliferative activity within the oral cavity and to find out if there were differences between sites with high and low incidence of cancer. A total of 105 samples of clinically normal mucosa were harvested from various intra-oral sites. Excised specimens were incubated in vitro with tritiated thymidine and bromodeoxyuridine to 'double label' cells undergoing DNA synthesis, and enable calculation of the duration of S phase and estimation of variables of cell flux to and from S. Mean labelling indices (percentage of cells within the S phase of the cell cycle) were highest in the floor of mouth (12.3%) and ventral tongue (10.1%), while activity was lowest in the dorsum of tongue (4.3%) and the palate (7.2%), P<0.001. In general, both cell influx and the duration of S increased proportionally to the labelling index. Sites with a high incidence of cancer were characterized by high labelling indices, increased cell influx and a prolonged S phase.     

Interventional catheter magnetic resonance angiography with a conventional 1.5-T magnet: work in progress

Magnetic resonance contrast enhancement depends on the relative timing of image acquisition. Limited human trials have demonstrated efficacy of intra-arterial gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) in delineating vascular anatomy with X-rays. The present study assessed the ability of dynamic MR during intra-arterial Gd-DTPA administration to demonstrate vascular anatomy compared to conventional angiography as the gold standard. As interventional MR techniques using dedicated magnets proliferate, the ability to perform invasive MR angiography with a conventional magnet would be of great utility at established sites. Four subjects referred for different types of angiography underwent dynamic MR studies, including one with iliac artery stenting (Palmaz P204, Johnson and Johnson). All were examined with conventional angiography, and again after dynamic intra-arterial (IA) Gd-DTPA infusion. Coronal MRI images of the body were acquired using a 1.5-T superconducting magnet (three with a GE Signa, one with Philips NT), fast spoiled gradient echo (FSPGR); echo time (TE) = 4.2 msec, repetition time (TR) = 68-150 msec, flip = 75 degrees, 0-600 s after dilute Gd-DTPA IA bolus injection during sequential breath-hold acquisitions of 13-32 s each. All arteries were detected with dynamic MR. The FSPGR MRI with IA Gd-DTPA administration can provide adequate time and spatial resolution to demonstrate arterial anatomy and arterial stent patency.     

Treatment of infrarenal aortic stenosis by stent placement: a 6-year experience

There is a significant re-stenosis rate with percutaneous treatment of stenoses of the infrarenal abdominal aorta with balloon angioplasty. Since 1990 the authors have primarily treated local infrarenal aortic stenoses with metallic endoluminal stents. The authors' experience with 12 consecutive patients (nine women and three men, aged from 30 to 72 years (mean age = 57 years)) is presented. Follow-up is available in 11 cases over 7-78 months (mean 32 months). The procedure was technically successful in all patients. Of the 11 patients with follow-up available, claudication was cured (n = 7) or significantly improved (n = 4). Those with persisting claudication had concurrent distal arterial disease. Periprocedural complications occurred in five cases, with two significant complications. One case required iliac angioplasty for embolized aortic atherosclerotic plaque, and one case required surgical thrombectomy and vein patch for iliac thrombosis complicating iliac dissection, without long-term sequelae in either case. One patient has had recurrent symptomatic aortic stenosis occurring 6 years after initial stenting, which responded to further stent insertion. Primary patency of 91% and secondary assisted patency of 100% has been achieved. Primary treatment of infrarenal aortic stenosis with endoluminal stenting results in high patency rates, with low morbidity and relatively low complication rates.     

Radiation exposure of the families of outpatients treated with radioiodine (iodine-131) for hyperthyroidism.

Patients who receive radioiodine (iodine-131) treatment for hyperthyroidism (195-800 MBq) emit radiation and represent a potential hazard to other individuals. Critical groups amongst the public are fellow travellers on the patient's journey home from hospital and members of the patient's family, particularly young children. The dose which members of the public are allowed to receive as a result of a patient's treatment has been reduced in Europe following recently revised recommendations from ICRP. The annual public dose limit is 1 mSv, though adult members of the patient's family are allowed to receive higher doses, with the proviso that a limit of 5 mSv should not be exceeded over 5 years. Unless the doses received during out-patient administration of radioiodine can be demonstrated to comply with these new limits, hospitalisation of patients will be necessary. The radiation doses received by family members (35 adults and 87 children) of patients treated with radioiodine at five UK hospitals were measured using thermoluminescent dosimeters mounted in wrist bands. Families were given advice (according to current practice) from their treatment centre about limiting close contact with the patient for a period of time after treatment. Doses measured over 3-6 weeks were adjusted to give an estimate of values which might have been expected if the dosimeters had been worn indefinitely. Thirty-five passengers accompanying patients home after treatment also recorded the dose received during the journey using electronic (digital) personal dosimeters. For the "adjusted" doses to infinity, 97% of adults complied with a 5-mSv dose limit (range:0.2-5.8 mSv) and 89% of children with a 1-mSv limit (range: 0.2-7.2 mSv). However 6 of 17 children aged 3 years or less had an adjusted dose which exceeded this 1 mSv limit. The dose received by adults during travel was small in comparison with the total dose received. The median travel dose was 0.03 mSv for 1 h travel (range: 2 microSv-0.52 mSv for 1 h of travel time). These data suggest that hyperthyroid patients can continue to be treated with radioiodine on an out-patient basis, if given appropriate radiation protection advice. However, particular consideration needs to be given to children aged 3 years or younger. Admission to hospital is not warranted on radiation protection grounds.     

Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft. Received for publication on March 8, 1999; accepted on April 30, 1999     

Increased apoptosis of immunoreactive host cells and augmented donor leukocyte chimerism, not sustained inhibition of B7 molecule expression are associated with prolonged cardiac allograft survival in mice preconditioned with immature donor dendritic cells plus anti-CD40L mAb.

BACKGROUND: We previously reported the association among donor leukocyte chimerism, apoptosis of presumedly IL-2-deficient graft-infiltrating host cells, and the spontaneous donor-specific tolerance induced by liver but not heart allografts in mice. Survival of the rejection-prone heart allografts in the same strain combination is modestly prolonged by the pretransplant infusion of immature, costimulatory molecule-(CM) deficient donor dendritic cells (DC), an effect that is markedly potentiated by concomitant CM blockade with anti-CD40L (CD154) monoclonal antibody (mAb). We investigated whether the long survival of the heart allografts in the pretreated mice was associated with donor leukocyte chimerism and apoptosis of graft-infiltrating cells, if these end points were similar to those in the spontaneously tolerant liver transplant model, and whether the pretreatment effect was dependent on sustained inhibition of CM expression of the infused immature donor DC. In addition, apoptosis was assessed in the host spleen and lymph nodes, a critical determination not reported in previous studies of either spontaneous or "treatment-aided" organ tolerance models. METHODS: Seven days before transplantation of hearts from B10 (H-2b) donors, 2x10(6) donor-derived immature DC were infused i.v. into C3H (H-2k) recipient mice with or without a concomitant i.p. injection of anti-CD40L mAb. Donor cells were detected posttransplantation by immunohistochemical staining for major histocompatibility complex class II (I-Ab) in the cells of recipient lymphoid tissue. CM expression was determined by two-color labeling. Host responses to donor alloantigen were quantified by mixed leukocyte reaction, and cytotoxic T lymphocyte (CTL) assays. Apoptotic death in graft-infiltrating cells and in areas of T-dependent lymphoid tissue was visualized by terminal deoxynucleotidyltransferase-catalyzed dUTP-digoxigenin nick-end labeling and quantitative spectrofluorometry. Interleukin-2 production and localization were estimated by immunohistochemistry. RESULTS: Compared with control heart transplantation or heart transplantation after only DC administration, concomitant pretreatment with immature donor DC and anti-CD40L mAb caused sustained elevation of donor (I-Ab+) cells (microchimerism) in the spleen including T cell areas. More than 80% of the I-Ab+ cells in combined treatment animals also were CD86+, reflecting failure of the mAb to inhibit CD40/ CD80/CD86 up-regulation on immature DC in vitro after their interaction with host T cells. Donor-specific CTL activity in graft-infiltrating cells and spleen cell populations of these animals was present on day 8, but decreased strikingly to normal control levels by day 14. The decrease was associated with enhanced apoptosis of graft-infiltrating cells and of cells in the spleen where interleukin-2 production was inhibited. The highest levels of splenic microchimerism were found in mice with long surviving grafts (>100 days). In contrast, CTL activity was persistently elevated in control heart graft recipients with comparatively low levels of apoptotic activity and high levels of interleukin-2. CONCLUSION: The donor-specific acceptance of rejection-prone heart allografts by recipients pretreated with immature donor DC and anti-CD40L mAb is not dependent on sustained inhibition of donor DC CM (CD86) expression. Instead, the pretreatment facilitates a tolerogenic cascade similar to that in spontaneously tolerant liver recipients that involves: (1) chimerism-driven immune activation, succeeded by deletion of host immune responder cells by apoptosis in the spleen and allograft that is linked to interleukin-2 deficiency in both locations and (2) persistence of comparatively large numbers of donor-derived leukocytes. These tolerogenic mechanisms are thought to be generic, explaining the tolerance induced by allografts spontaneously, or with the aid of various kinds of immunosuppression.