New technologies in the radiotherapy clinic.

What are the limitations to the accuracy of our current technologies in radiation oncology? The immobilization of the patient, definition of the target, motion of the target and localization of the target are the major concerns that must be addressed. Current approaches to meet these needs have brought new technical systems with greater precision and new clinical procedures with higher expectations of practice. This text offers discussions on these issues, including advances in intensity-modulated radiotherapy planning, clinical target definition for the major tumor sites, management of organ motion, target localization and image guidance systems, and the expanding applications of high-precision treatment with stereotactic body radiotherapy.

The psychosocial impact of serological herpes simplex type 2 testing in an urban HIV clinic.

BACKGROUND/OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is a common infection among HIV infected people. HSV type specific serologies permit the diagnosis of previously unrecognised HSV-2 infection. While substantial psychosocial morbidity has been associated with a clinical diagnosis of genital herpes, the burden associated with a serological diagnosis of HSV-2 is unclear. This study prospectively measured the psychosocial response to a new serological HSV-2 diagnosis in patients receiving care at an urban HIV clinic. METHODS: At entry, sera were tested for HSV-1 and HSV-2 antibodies by western blot. Participants completed a 90 item psychosocial and life quality questionnaire at enrollment, and at 2 weeks, 3 months, and 6 months after receiving test results. RESULTS: Of 248 HIV infected participants, 172 (69.4%) were HSV-2 seropositive and 116 (67.4%) seropositive people did not have a previous history of genital herpes. After correction for multiple comparisons, no statistically significant differences were detected on the psychosocial and life quality scales between those who received a new HSV-2 serological diagnosis compared with those who were HSV-2 seropositive with a history of genital herpes, or those who tested HSV-2 seronegative. Additionally, no significant changes in scores were observed during follow up. CONCLUSIONS: HSV-2 was a common but often unrecognised infection in this urban HIV clinic and participants coped well with a positive HSV-2 result. Concerns about psychosocial burden should not deter serological testing for HSV-2. Given the epidemiological and clinical interaction between HSV-2 and HIV, these data support routine HSV-2 testing of HIV infected people.

One year comparison between two add-back therapies in patients treated with a GnRH agonist for symptomatic endometriosis: a randomized double-blind trial.

BACKGROUND: It has been proposed that hormonal supplementation during prolonged GnRH agonist therapy prevents hypoestrogenic side effects, including bone loss. The optimal combination for long-term treatments with safe metabolic profile remains questionable. A norprogesterone derivative, promegestone, was assessed for the first time in a double-blind trial. METHODS: Seventy-eight patients with endometriosis with rAFS (Revised American Society for Reproductive Medicine) scores of III-IV were randomly assigned to monthly leuprorelin 3.75 mg (1 year) which, after the third injection was used in combination with promegestone 0.5 mg (P) plus either estradiol placebo (PL) or estradiol 2 mg (E) per day. Bone mineral density (BMD) was determined at baseline, 6 and 12 months, and biological and clinical quarterly assessments were performed. Analysis was by the intention to treat method. RESULTS: At month 12, BMD changes from baseline were -6.1 +/- 3.7 and -4.9 +/- 4.0% in the PL-P group, at the spine and hip, respectively. This bone loss was prevented in the E-P group: -1.9 +/- 3.1 and -1.4 +/- 2.3%, respectively (P < 0.0001 inter-group comparisons). The BMD decrease in the E-P group was explained by the changes occurring during the first 6 months of treatment. There was no deleterious change in lipid parameters. Clinical improvement was observed without an inter-group difference. CONCLUSIONS: Estradiol 2 mg and promegestone 0.5 mg per day is an effective and safe add-back therapy, which can be proposed for prolonged leuprorelin treatment over 6 months in severe endometriosis.

Gastroscopic removal of an adjustable gastric band after partial intragastric migration.

BACKGROUND: Laparoscopic implantation of an adjustable gastric band is being performed widely. One potential complication is the transgastric migration of the band, that should be extracted. METHODS: The authors report a series of 182 patients, followed prospectively, October 1996 - April 2002, who had undergone insertion of the Swedish adjustable gastric band. All implantations had been completed by laparoscopy alone. RESULTS: There were no deaths. 15 complications were detected, of which 7 were intragastric migrations of the band (3.8%) at an average follow-up of 40 months. 6 were treated successfully by gastroscopy only, with a new cutter device and without complications. CONCLUSION: The endoscopic technique is beneficial even when the intraluminal migration is partial.

Carbon and nitrogen transfer from a desert stream to riparian predators.

Adult aquatic insects emerging from streams may be a significant source of energy for terrestrial predators inhabiting riparian zones. In this study, we use natural abundance delta(13)C and delta(15)N values and an isotopic (15)N tracer addition to quantify the flow of carbon and nitrogen from aquatic to terrestrial food webs via emerging aquatic insects. We continuously dripped labeled (15)N-NH(4) for 6 weeks into Sycamore Creek, a Sonoran desert stream in the Tonto National Forest (central Arizona) and traced the flow of tracer (15)N from the stream into spiders living in the riparian zone. After correcting for natural abundance delta(15)N, we used isotopic mixing models to calculate the proportion of (15)N from emerging aquatic insects incorporated into spider biomass. Natural abundance delta(13)C values indicate that orb-web weaving spiders inhabiting riparian vegetation along the stream channel obtain almost 100% of their carbon from instream sources, whereas ground-dwelling hunting spiders obtain on average 68% of their carbon from instream sources. During the 6-week period of the (15)N tracer addition, orb-web weaving spiders obtained on average 39% of their nitrogen from emerging aquatic insects, whereas spider species hunting on the ground obtained on average 25% of their nitrogen from emerging aquatic insects. To determine if stream subsidies might be influencing the spatial distribution of terrestrial predators, we measured the biomass, abundance and diversity of spiders along a gradient from the active stream channel to a distance of 50 m into the upland using pitfall traps and timed sweep net samples. Spider abundance, biomass and richness were highest within the active stream channel but decreased more than three-fold 25 m from the wetted stream margin. Changes in structural complexity of vegetation, ground cover or terrestrial prey abundance could not account for patterns in spider distributions, however nutrient and energy subsidies from the stream could explain elevated spider numbers and richness within the active stream channel and riparian zone of Sycamore Creek.

Identification of the target of monoclonal antibody A6H as dipeptidyl peptidase IV/CD26 by LC MS\MS.

The monoclonal antibody (MAb) A6H, originally developed to fetal renal tissues, was found to be highly reactive to renal cell carcinoma and was subsequently demonstrated to co-stimulate a subpopulation of T cells. The A6H antigen had not been identified heretofore. Antigen from detergent extracts of renal cell carcinoma cells (7860) was immunoabsorbed with A6H-agarose, and the resin-bound proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The antigen had a molecular weight of approximately 120 kDa as determined by Western blots. The 120-kDa protein band was excised and subjected to in-gel tryptic digestion, and the resulting peptides were separated and analyzed by liquid chromatography tandem mass spectrometry (LC MS\MS). The tandem mass spectra of the eluting peptides were used in combination with the SEQUEST computer program to search a human National Cancer Institute (NCI) protein database for the identity of the protein. The target antigen was shown to be dipeptidyl peptidase IV (DPP IV), which is also known as the cluster differentiation antigen CD26. Flow analysis of the expression of the A6H antigen and of CD26 on 7860 cells and on peripheral blood lymphocytes supported the identification of the A6H antigen as DPP IV. Recognition that the A6H antigen is DPP IV/CD26 afforded the opportunity to compare previous studies on A6H with those on other anti-CD26 antibodies in terms of expression in cancer cell lines and various tissues and as co-stimulators of T-cell activation.

Control of nitrogen export from watersheds by headwater streams.

A comparative (15)N-tracer study of nitrogen dynamics in headwater streams from biomes throughout North America demonstrates that streams exert control over nutrient exports to rivers, lakes, and estuaries. The most rapid uptake and transformation of inorganic nitrogen occurred in the smallest streams. Ammonium entering these streams was removed from the water within a few tens to hundreds of meters. Nitrate was also removed from stream water but traveled a distance 5 to 10 times as long, on average, as ammonium. Despite low ammonium concentration in stream water, nitrification rates were high, indicating that small streams are potentially important sources of atmospheric nitrous oxide. During seasons of high biological activity, the reaches of headwater streams typically export downstream less than half of the input of dissolved inorganic nitrogen from their watersheds.

Choledochocele demonstrated by computed tomographic cholangiography: report of a case.

Choledochocele is a rare cystic congenital malformation of the distal common bile duct, the precise pathogenesis of which remains unclear. It is usually diagnosed in adulthood after many examinations for unclear digestive symptoms, as in the patient whose case is described herein. Of all the diagnostic techniques available, endoscopic retrograde cholangiography (ERCP) seems to be the best; however, it is an invasive procedure associated with some morbidity. Spiral computed tomographic cholangiography with three-dimensional reconstruction is also an interesting screening technique. Malignant transformation of a choledochocele occurs very rarely, compared with other cystic malformations of the biliary tract. If a choledochocele is small and symptomatic, the lesion can be treated by endoscopic sphincterotomy, but larger cysts are more effectively removed by a surgical cystoduodenostomy. We present herein the case of a 25-year-old woman admitted to our hospital in March 1998 with upper right quadrant abdominal pain caused by a choledochocele, who was successfully treated by a cystoduodenostomy.

Preclinical feasibility study of NMP179, a nuclear matrix protein marker for cervical dysplasia.

OBJECTIVE: To evaluate, in a preclinical feasibility study, the efficacy of NMP179, a monoclonal antibody recognizing a cervical tumor-associated nuclear matrix antigen, for the early detection of high and low grade cervical intraepithelial neoplasia. STUDY DESIGN: In a blind study involving two clinical sites, NMP179 immunocytochemical staining data from 261 cervicovaginal Thin-Prep specimens were evaluated. Assay sensitivity and specificity were calculated based upon a positive threshold of > 10 immunostained cells per case, using cytologic diagnosis as an end point. RESULTS: Based upon the examination of squamous epithelial cells, NMP179 detected 96.7% of cases with cytologically diagnosed high grade squamous intraepithelial lesions (HSIL) and 70.5% of low grade squamous intraepithelial lesions. The antibody also reacted with 29.6% of normal (within normal limits or benign cellular changes) smears. CONCLUSION: The NMP179 assay detected HSIL with very high accuracy (96.7%). The assay was 79.3% sensitive for the detection of low and high grade cervical intraepithelial neoplasia (grades 1-3), with a specificity of 70.4%. NMP179 may be an effective marker for the early detection of preneoplastic squamous intraepithelial lesions of the cervix and may be useful as an adjunctive tool for better management of cervical intraepithelial neoplasia.

Histamine phase shifts the hamster circadian pacemaker via an NMDA dependent mechanism.

The SCN acts as the central pacemaker for circadian rhythms in mammals. Histamine has been shown to affect circadian rhythms both in vivo and in vitro. We investigated the mechanism by which histamine phase shifts circadian rhythms in vitro. Hypothalamic slices containing the SCN were prepared from golden hamsters, and spontaneous firing rates of individual cells were recorded on the second day in vitro. Application of histamine (1 microM-10 mM) at the extrapolated time of 2 h after lights off (ZT 14) on day 1 in vitro delayed the time of peak firing in a dose-dependent manner. Pre-exposure to the N-methyl-D-aspartate (NMDA) receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (AP-5; 100 microM-1 mM) 5 min before histamine (1 microM) was applied to the slice blocked the phase-delaying effects of histamine. Application of the H1 blocker mepryamine (100 nM) or the H2 blocker cimetidine (10 microM) followed by histamine had no effect on the phase delay induced by histamine. In whole cell recordings from acutely dissociated neurons of hamster SCN, histamine (50 microM) was shown to potentiate NMDA-evoked currents by 52 +/- 12%. These experiments demonstrate that histamine phase shifts of the circadian clock are dependent on NMDA receptor activation and that histamine can directly potentiate NMDA currents in SCN neurons. Histamine may alter circadian clock function by acting directly on NMDA receptors, possibly via binding to the polyamine site.

Nasopharyngeal carcinoma. A study examining Asian patients treated in the United States.

From 1972 to 1991, 126 Asian patients with nasopharyngeal carcinoma underwent definitive radiation therapy for locoregional disease: 86 men, 40 women. Median age was 50. All patients received external-beam irradiation with cobalt 60 or 4-18 MV x-rays. Local recurrence, regional recurrence, and distant metastases were 22%, 11%, and 23%, respectively. Local recurrence progressively increased with increasing T stage, but doses in those who recurred did not differ from the group as a whole. Regional recurrence was not associated with T or N stage or dose. Patients with N2 disease had the highest distant metastatic rate. The 5- and 10-year overall survival rates were 54% and 38%, respectively. Of age, gender, and histology, only age less than 50 was found to be favorably prognostic. No severe long-term complications were observed, and acute reactions were acceptable. Our survival results are comparable with results found both in Asia and North America. Nonetheless, altered fractionation techniques and/or other radiation modalities should be further explored to improve locoregional control.

The microbial loop in flowing waters.

The microbial loop in flowing waters is dependent on allochthonous sources of carbon, which vary in quality. The proportion of dissolved organic carbon (DOC) that can be degraded ranges from <1 to over 50%, and the bioavailability of DOC (micrograms bacterial biomass produced per milligram DOC present) ranges over two orders of magnitude. Bioavailability of DOC is predictable from the ratio of H/C and O/C of the DOC, but further work is needed to develop simple predictors of bioavailability of DOC in a range of environments. Consumers of bacteria in streams range in size from protists to insect larvae, with highest rates of bacterial consumption found among the meiofauna and certain filter feeders and grazers. Because there appear to be fewer trophic transfers in the lotic microbial loop, it functions more as a link in flowing waters than it appears to do in the marine plankton.

Whole-lung irradiation for Kaposi's sarcoma.

Twenty-five patients were treated with whole-lung irradiation for symptomatic pulmonary KS. Treatment was most often given four days per week, 150 cGy per fraction, to 1050-1500 cGy (mean 1224 cGy). No acute toxicity was observed. 89% of patients completing therapy reported improvement in dyspnea. All patients responding symptomatically could reduce (and 78% could eliminate) oxygen use. Chest x-rays showed concurrent improvement in 78% of cases, although this was > or = 50% clearance of infiltrate in only 28%. Symptomatic improvement was prompt, always occurring during the 2-2 1/2 week therapy course. Clinical response was transient in some patients, but 12 weeks after therapy 56% remained symptomatically improved. Pulmonary KS indicated an advanced stage of AIDS and survival was short (mean: 15.7 weeks after completion of therapy). Patients with poor performance status (Karnovsky: < or = 30%) and progression of disease despite chemotherapy had very short survival (mean: 3.2 weeks). For such patients, a supportive care only approach without radiotherapy is suggested. For others, whole-lung irradiation provides prompt symptomatic improvement for most patients, and offers a simple treatment approach with little toxicity for often debilitated patients.

[History of the research on differentiating Hepatitis A and B]. / Historique des recherches sur la différenciation des Hépatites A & B.

The numerous researches devoted to 'jaundice' during the Second World War have brought to light the existence of an infectious type of hepatic jaundice or 'homologous serum jaundice' following parenteral injection of vaccines containing human serum and blood transfusions, which were carried out on a large scale at the time. This type of serum jaundice was then gradually differentiated from 'catarrhal', contagious or epidemic jaundice by clinical trials along with large series of animal studies. Finally, the epidemiological, clinical and biological data obtained made it possible to establish, between 1944 and 1954, the viral etiology of these two types of jaundice: the A virus, present in the patients' blood and stools, was considered to be the agent responsible for epidemic hepatitis; the B virus, present primarily in the blood, was held to be responsible for serum hepatitis.