TCC in Transplant Ureter--When and When Not to Preserve the Transplant Kidney.

We present four cases of transitional cell carcinoma of the transplant ureter (TCCtu). In three cases, localized tumor resection and a variety of reconstructive techniques were possible. Transplant nephrectomy with cystectomy was performed as a secondary treatment in one locally excised case. Transplant nephroureterectomy was performed as primary treatment in one case. The role of oncogenic viruses and genetic fingerprinting to determine the origin of TCCtu are described. Our cases and a systematic literature review illustrate the surgical, nephrological, and oncological challenges of this uncommon but important condition.

Accurate measurement of the through-plane water content of proton-exchange membranes using neutron radiography.

The water sorption of proton-exchange membranes (PEMs) was measured in situ using high-resolution neutron imaging in small-scale fuel cell test sections. A detailed characterization of the measurement uncertainties and corrections associated with the technique is presented. An image-processing procedure resolved a previously reported discrepancy between the measured and predicted membrane water content. With high-resolution neutron-imaging detectors, the water distributions across N1140 and N117 Nafion membranes are resolved in vapor-sorption experiments and during fuel cell and hydrogen-pump operation. The measured in situ water content of a restricted membrane at 80 °C is shown to agree with ex situ gravimetric measurements of free-swelling membranes over a water activity range of 0.5 to 1.0 including at liquid equilibration. Schroeder's paradox was verified by in situ water-content measurements which go from a high value at supersaturated or liquid conditions to a lower one with fully saturated vapor. At open circuit and during fuel cell operation, the measured water content indicates that the membrane is operating between the vapor- and liquid-equilibrated states.

Probing liquid distribution in partially saturated porous materials with hydraulic admittance.

The distribution of two immiscible fluids in a complex porous material during displacement is often central to understanding its function. Characterization of this distribution is traditionally determined via optically transparent flow cells. However, for opaque or thin porous materials of the order of hundreds of microns, optical visualization proves to be difficult and requires sophisticated imaging techniques that are expensive and difficult to come by. We describe here a bench-top tool that dynamically probes the hydraulic pathways leading to each free-interface within a single capillary and a bundle of seven capillaries at various saturations (i.e., hydraulic path lengths). A small volumetric displacement was applied to each interface such that the interfaces remained pinned at the capillary walls and the resultant oscillatory pressure drop was measured to determine the hydraulic admittance at each applied oscillation frequency. When the magnitude of the hydraulic admittance was plotted vs. applied oscillation frequency, a resonance peak was found for each degenerately filled capillary. The corresponding peaks were represented by a half-loop (100% filled) and full loops (partially filled) in a Nyquist plot. We compared the theoretical and measured admittance curves and found good agreement for both capillary systems at high filled states. The theoretical predictions became worse when the hydraulic path length was comparable to the capillary radius. The analysis for the hydraulic admittance of a bundle of capillaries is developed here and experimentally validated for the first time.

Oligosaccharide synthesis by coupled endo-glycosynthases of different specificity: a straightforward preparation of two mixed-linkage hexasaccharide substrates of 1,3/1,4-beta-glucanases.

Glycosynthases are engineered glycosidases which are hydrolytically inactive yet efficiently catalyse transglycosylation reactions of glycosyl fluoride donors, and are thus promising tools for the enzymatic synthesis of oligosaccharides. Two endo-glycosynthases, the E134A mutant of 1,3/1,4-beta-glucanase from Bacillus licheniformis and the E197A mutant of cellulase Cel7B from Humicola insolens, were used in coupled reactions for the stepwise synthesis of hexasaccharide substrates of 1,3/1,4-beta-glucanases. Because the two endo-glycosynthases show different specificity, towards laminaribiosyl and cellobiosyl donors, respectively, the target hexasaccharides were prepared by condensation of the corresponding disaccharide building blocks through sequential addition of the glycosynthases in a "one-pot" process. Different strategies were used to achieve the desired transglycosylation between donor and acceptor in each step, and to prevent unwanted elongation of the first condensation product and polymerization (self-condensation) of the donor: 1) selection of disaccharide donors differing in the configuration of the hydroxyl substituent normally acting as acceptor, 2) temporary protection of the polymerizable hydroxyl group of the donor, or 3) addition of an excess of acceptor to decrease the probability that the donor can act as an acceptor. The best procedure involved the condensation of alpha-lactosyl or 4II-O-tetrahydropyranyl-alpha-cellobiosyl fluorides with alpha-laminaribiosyl fluoride, catalyzed by E197A Cel7B, to give tetrasaccharide fluorides, which were then the donors for in situ condensation with methyl beta-cellobioside catalyzed by E134A 1,3/1,4-beta-glucanase. After isolation, the final hexasaccharides Gal/beta4Glcbeta4Glcbeta3Glcbeta4Glcbeta4Glcbeta-OMe and Glcbeta4Glcbeta4Glcbeta3Glcbeta4Glcbeta4-Glcbeta-OMe were obtained in 70-80% overall yields.

A programme of individualized and self-administration of medicines in a hospice.

Hospice care is changing. Statistics show that people are surviving longer with cancer and many more are choosing to be cared for in the community. The hospice is no longer an institution solely for the care of people in the terminal phase of their illness but is involved in the palliation of symptoms, so allowing patients to return home to independent living. It was with this in mind that we recognized the need for the introduction of a programme of individualized and self-administration of medication at the hospice where we work. Although self-administration of medication was our first aim, the individuality of care brought about by its introduction, the adaptations required to include all palliative care patients and the resulting enhancement of holistic patient care, has become the main thrust of the project. This article will explore the term 'self-administration of medication'; the evidence of its use in other areas of health care; the rationale for change within the hospice movement; consequences to practice; and the staged implementation of a programme of individualized and self-administration of medication.

Irinotecan and cisplatin in advanced gastric or gastroesophageal junction carcinoma.

Chemotherapy for advanced gastric and gastroesophageal junction carcinomas remains suboptimal. Both irinotecan (Camptosar) and cisplatin (Platinol) are active against this group of malignancies. This article focuses on the results of an ongoing phase II trial with this combination in patients with advanced gastric or gastroesophageal junction carcinoma. Data from this trial suggest that the combination of irinotecan and cisplatin is active in untreated as well as previously treated patients with gastric or gastroesophageal junction carcinoma.

Phase I study of irinotecan and concurrent radiation therapy for upper GI tumors.

Irinotecan (Camptosar) is an active chemotherapeutic agent for lung, gastric, esophageal, and colorectal cancers and a potent radiosensitizer. This phase I study was designed to assess the maximum tolerated dose of weekly irinotecan combined with concurrent radiotherapy for patients with locally advanced, unresectable gastric, gastroesophageal junction, or esophageal cancer. Patients who received previous chemotherapy (excluding irinotecan) or who experienced recurrent cancer after surgery were eligible for this protocol. The total dose of radiation did not exceed 50.4 Gy (28 fractions of 1.8 Gy each). The starting dose level of irinotecan was 30 mg/m2 infused over 90 minutes given weekly for 5 weeks. Subsequent dose levels were increased in 10 mg/m2 increments to 40, 50, 60, and 70 mg/m2. Of 15 patients who have been enrolled to date, all are evaluable for toxicities and 12 for response. Major hematologic toxicities (grade 3/4) were neutropenia, chills, hemorrhage, and anemia. Grade 3/4 gastrointestinal toxicities included nausea, vomiting, dehydration, anorexia, and constipation. Other severe nonhematologic toxicities included fatigue, hypotension, and hypothermia, as well as cardiovascular toxicities. There was no severe diarrhea and no treatment-related deaths. Of the 12 evaluable patients, 7 (58%) responded, including 2 complete responses; 4 (30%) had no change and 1 had progressive disease. Survival ranged from 1 month to 15 months, with a median survival of 8 months. When the total dose of irinotecan given concurrently with radiotherapy was higher than 250 mg/m2, patients experienced significantly more severe grade 3/4 toxicities than with lower doses (P = .04), with no improvement in response rate. It was concluded that weekly doses of irinotecan of up to 60 mg/m2 with concurrent radiotherapy given over 5 weeks was feasible and demonstrated good response. This regimen did not cause severe diarrhea or pneumonitis, but neutropenia and fatigue were major toxicities. The study continues to accrue.

Phase II study of prolonged infusion of Taxol in patients with metastatic colorectal carcinoma.

PURPOSE: Taxol represents a new class of anticancer agents with activity against a wide variety of solid tumors. In preclinical systems, its cytotoxicity is schedule dependent with prolonged exposure being more effective. We studied a 120-hour infusion schedule of Taxol in patients with metastatic measurable colorectal carcinoma who had had one prior 5-FU-based chemotherapy. METHODS: Patients with measurable metastatic colorectal carcinoma were eligible. Patients had to have normal liver, renal, and bone marrow functions. Written informed consent was obtained from all patients. The starting dose of Taxol was 150 mg/m2 infused over 120-hours in the outpatient setting. Taxol was repeated every 21 days. RESULTS: Fifteen patients were registered. Among 14 evaluable patients, we did not observe any complete or partial response. Major toxicity included myelosuppression and mucositis. There was no treatment-related death. CONCLUSION: Taxol administered by this schedule was found ineffective in patients with metastatic colorectal carcinoma who had previously received one 5-FU-based chemotherapy.

Phase II study of Taxol in patients with advanced gastric carcinoma.

PURPOSE: Taxol (paclitaxel) represents a new class of anticancer agent with activity against a wide variety of solid tumors. It has been found to be active in patients with adenocarcinoma and squamous cell carcinoma of the esophagus. To determine its activity against gastric adenocarcinoma, we conducted a phase II trial of Taxol in chemotherapy-naive patients with advanced disease. PATIENTS AND METHODS: Patients with measurable, unresectable, metastatic gastric carcinoma with performance status < or = 2 by Zubrod scale were eligible. Patients had to have normal liver, renal, and bone marrow functions. Written informed consent was obtained from all patients. The starting dose of Taxol was 200 mg/m2 infused over either 3 hours (in the first 15 patients) or 24 hours (in the subsequent 18 patients). Taxol was repeated every 21 days. Response was evaluated after two courses. RESULTS: Thirty-three patients were registered. The median number of courses was two (range, 1 to 12; total, 112 courses). Thirty patients were evaluable for response and toxicity. Among the first 15 patients (two inevaluable) receiving Taxol over 3 hours, there were one partial response (PR) (one of 13 patients, or 8%; 95% confidence interval, 0% to 36%) and three minor responses (MRs). However, among the 18 patients (one inevaluable) receiving Taxol over 24 hours, there were four PRs (four of 17 patients or 23%; 95% confidence interval, 7% to 50%) and three MRs. The overall PR rate was 17% (five of 30 patients; 95% confidence interval, 6% to 35%). The median duration of PR was 6.5 months (range, 2.3 months to 11.3+ months. There were no treatment-related deaths. Myelosuppression was more severe with the 24-hour schedule than with the 3-hour schedule. CONCLUSIONS: Taxol has a modest degree of activity against gastric carcinoma. It is well tolerated by the patients. Further studies of Taxol in combination with other active agents against gastric carcinoma should be considered.

Morbidity following pelvic inflammatory disease.

OBJECTIVE: To examine patterns of morbidity following hospitalisation for pelvic inflammatory disease (PID). DESIGN: Cohort study using Oxford Record Linkage Study data. SETTING: Oxfordshire and West Berkshire. SUBJECTS: One thousand three hundred fifty-five women discharged from hospital for the first time with a diagnosis of pelvic inflammatory disease during the interval 1970-1985, together with 10,507 control women discharged with various other diagnoses. MAIN OUTCOME MEASURES: Hospital admission for abdominal pain, gynaecological pain, endometriosis, hysterectomy, and ectopic pregnancy. Data were not available in this analysis on pregnancies other than ectopic pregnancy. RESULTS: In comparison with the controls, women with a diagnosis of PID were ten times more likely to be admitted for abdominal pain, four times more likely to be admitted for gynaecological pain, six times more likely to be admitted for endometriosis, eight times more likely to be admitted for hysterectomy and ten times more likely to be admitted for ectopic pregnancy. CONCLUSIONS: Serious sequelae of PID are common, even in a study unable to examine the effects of the disease on fertility. The data on hysterectomy are particularly interesting; the operation in women with pelvic inflammatory disease is most often a consequence of the inflammatory process itself.

Time spent in hospital by children as a health care indicator: inter-district comparisons.

It has been widely recommended that children should be admitted to hospital only if treatment cannot be provided at home, and that durations of hospital stay should be minimized. We have used record linkage to calculate a statistic which is not yet commonly available, the total time spent in hospital by children per year, and have compared this between six districts in the Oxford Region. Hospitalization rates for children who stayed a total of two days or less per year in hospital increased over time; rates for children who stayed more than two days declined. Mean and median total days spent in hospital varied between districts but, in absolute terms, the differences were small at less than one day's difference between districts per year per child admitted. Inter-district variation decreased over time, although the variation in use of day case care which remained suggests that some districts could still do more work in this fashion.

Conditions accounting for substantial time spent in hospital in children aged 1-14 years.

To identify the clinical conditions associated with substantial time spent in hospital by children aged 1-14 years, records of children admitted to hospital in 1975, 1979, and 1984 were studied. Analysis was by linkage of abstracts of routine records of hospital inpatient care in six districts in southern England covered by the Oxford record linkage study. The total time spend in hospital in the acute specialties each year was calculated by summing the lengths of stay of all episodes of care for each child in each year. First, admissions with long median times in hospital per child admitted were identified. These included, notably, fracture of femur and, in the later years, leukaemia, other malignant neoplasms, and congenital disorders of metabolism. Second conditions were identified which accounted for large numbers of children with lengths of stay of five days or more. These included, in particular, congenital anomalies, asthma, and appendicitis. Third, conditions were identified which accounted for the largest numbers of bed days used. These included congenital anomalies, hypertrophy of tonsils and adenoids, asthma, otitis media, appendicitis, and head injury. Median time spent in hospital per child admitted declined for most conditions but increased for leukaemia, other malignant neoplasms, and congenital disorders of metabolism. Admission rates for children who spent five days or more in hospital each year declined for all common conditions except asthma which increased. Total numbers of beds used increased for asthma and otitis media but declined for all other common conditions.

Making the transition to postsecondary education and training.

A nationally representative sample of youth with disabilities who recently exited high school was studied to determine the participation of the youth in postsecondary educational programs. The results show that youth with disabilities participate in postsecondary programs at only one-quarter the rate attained by their counterparts without disabilities and at only one-third the rate attained by economically disadvantaged youth. The relationship of postsecondary education for youth with disabilities to long-term success in employment is yet to be determined.

Transition and other services for handicapped students in local education agencies.

A survey was conducted among special education administrators in 1,450 local education agencies (LEAs) nationwide, to determine the availability of vocational programs and transition-oriented services for handicapped youth. Results showed that most LEAs offer at least some vocational programs; transition-oriented services as not as frequently available, particularly in smaller LEAs. In addition to size of LEA, community employment opportunities and the availability of adult services were related to whether an LEA offered any transition-related services.

Quantitative studies of the fate of epidermal Langerhans cells after X-irradiation of guinea-pig and mouse footpad skin.

Langerhans cell numbers, morphology and distribution were observed in cross sections of footpad epidermis at intervals from 1 to 28 days after exposure of the hind feet of CBA/H mice or albino guinea-pigs to a single absorbed dose of 20 Gy (2000 rad) of X-rays. In mice, the number of Langerhans cells reactive with anti-macrophage F4/80 monoclonal antibody steadily declined by approximately 85% within 10 days after irradiation, consistent with previous studies, in which Langerhans cells were identified in epidermal sheets by ATPase activity or presence of Birbeck granules. Remaining Langerhans cells were exceptionally dendritic. Very few Birbeck granule-containing cells were found in murine popliteal lymph nodes before or after irradiation but damaged cells were present in superficial strata of irradiated epidermis. The morphology and number of epidermal F4/80-positive cells approached normal by 15 days after irradiation. In guinea-pigs, gradual suprabasal movement and loss of rounded, ATPase-positive Langerhans cells from the epidermis were detectable from 5 to 20 days after irradiation but the magnitude of the cell loss and redistribution was partially obscured by the simultaneous appearance of clusters of replacement Langerhans cells in the basal layer and by keratinocyte hyperplasia.