Neon heavy charged particle radiotherapy of glioblastoma of the brain.

PURPOSE: High-linear energy transfer (LET) radiation beams have potential applications in the treatment of glioblastoma, but have not yet demonstrated significant improvement in results. However, some patients have had local control of glioblastoma with high-LET irradiations such as neutrons and heavy charged particles. METHODS AND MATERIALS: In this collaborative study, 15 patients were entered into a randomized protocol comparing two dose levels of 20 and 25 Gy in 4 weeks of neon ion irradiation. This trial was intended to determine the optimal neon dose in terms of survival and effects of radiation. RESULTS: Fourteen patients were evaluable with no significant differences in median survival (13 and 14 months; p = NS) or median time to failure (7 and 9 months; p = NS) between the two dose arms. Three patients died of nontumor-related causes, of whom one (who died 19 months posttreatment) had autopsy confirmation of no tumor on pathological exam. The other two patients had stable magnetic resonance imaging scans at 6 and 22 months posttreatment. CONCLUSION: Although the results did not demonstrate the optimal high-LET dose level, there is an intriguing effect in that two patients had control of glioblastoma until death at 19 and 22 months. This suggests that better conformation of the high-LET dose to the tumor with neutron capture therapy or dynamic conformal heavy charged particle therapy might control glioblastoma while minimizing brain damage from radiation.

Pineoblastoma in adults.

This is the first report of a series of adults (> 16 years of age) with pineoblastomas who had their entire neuraxis staged at the time of diagnosis. Between 1975 and 1992, seven men and four women with histologically proven pineoblastomas were evaluated at the University of California, San Francisco. The median age at diagnosis was 36 years (range, 17-59 yr). All patients presented with symptomatic hydrocephalus. One patient had a complete surgical resection, eight had subtotal resections, and two had biopsies only. One patient refused any treatment or follow-up review and died 6 months after diagnosis. The five patients with positively staged disease had progression either focally or in the spine 8 to 49 months (median, 10 mo) after initial diagnosis and died 1 to 20 months after recurrence; the median overall survival time from the date of surgery was 30 months. In contrast, all five patients with negatively staged disease were alive without disease progression after a median of 26 months of follow-up. Our retrospective review shows that the extent of disease at diagnosis seems to be an important prognostic factor for pineoblastomas, as is true for medulloblastomas and other primitive neuroectodermal tumors. Initial staging should include examination of the cerebrospinal fluid and magnetic resonance imaging of the spine. Although patients with pineoblastomas are often treated with adjuvant systemic chemotherapy after craniospinal irradiation, the benefits of this approach are unclear.

Morphological and electrophysiological features of F76 and D1 neurones of the sub-oesophageal ganglia of Helix aspersa in vitro and in culture.

Identified neurones F76 and D1 of the suboesophageal ganglia of Helix aspersa were studied in the isolated ganglia in vitro and in culture. The neurones were examined electrophysiologically with current clamp and morphologically either with intracellular injections of Lucifer Yellow or biocytin. These nerve cells had very similar resting membrane potentials and responses to injected current. The projections of D1 and F76 have been characterised, with both neurones having two main axons. The F76 neurones project to the left pallial, right pallial, anal, and visceral nerves as well as to the left and right pleural ganglia. The D1 neurones have similar projections except that they do not project to the anal and visceral nerves. The bilateral symmetry to the pallial nerves and pleural ganglia is discussed. These cells were also studied electrophysiologically after mechanical isolation and culture. F76 and D1 neurones were separated by dissection (no enzymes) and cultured in three ways. In normal snail Ringer they remained viable for up to two weeks with no development. In Ringer preincubated with a ganglia or containing endothelial growth factor, neurite outgrowths were seen. Membrane potentials were significantly lower in cultured neurones than in vitro and the after hyperpolarization never went below resting in cultured cells but it did in vitro.

Effects of ozone on normal and potentially sensitive human subjects. Part I: Airway inflammation and responsiveness to ozone in normal and asthmatic subjects.

We report here the results of a multiphase project to assess the significance of airway responsiveness and airway injury in ozone (O3)* sensitivity. In Phase I, we measured the preexposure methacholine responsiveness of 66 normal subjects and then exposed these subjects to 0.2 ppm O3 for 4 hours with moderate exercise. Preexposure methacholine responsiveness was weakly correlated with O3-induced increases in specific airway resistance (sRaw) but not O3-induced declines in forced expiratory volume in one second (FEV1) or forced vital capacity (FVC). In addition, O3-induced lower respiratory symptoms were not well correlated with O3-induced changes in lung function. In Phase II, we exposed 23 normal subjects to O3, following an identical protocol to that of Phase I, and then performed bronchoscopy with proximal airway lavage (PAL), bronchoalveolar lavage (BAL), and bronchial biopsy at 18 hours after exposure. Ozone-induced increases in percentage of neutrophils and total protein concentration were observed in both bronchial fraction and BAL fluids; increased percentage of neutrophils also was observed in PAL fluid. These increases were correlated with O3-induced increases in sRaw, but not with O3-induced declines in FEV1 or FVC. Ozone also appeared to increase expression of intercellular adhesion molecule-1, an important mediator of neutrophil recruitment, in bronchial mucosa. In Phase III, we exposed a group of 19 asthmatic subjects to O3, following a protocol identical to that of Phase II. We then compared the lower respiratory symptom and lung function responses of the asthmatic subjects to those of the 81 normal subjects who participated in Phase I, Phase II, or both. The changes in the PAL and BAL fluids of the asthmatic subjects were compared with those of the normal subjects who participated in Phase II. Although both the asthmatic and nonasthmatic subjects showed significant O3-induced changes in lower respiratory symptoms, FEV1, FVC, and sRaw, no significant differences were found between the groups. For sRaw, however, a nonsignificant trend toward a greater O3-induced increase was noted for the asthmatic subjects. In contrast, the O3-induced increases in percentage of neutrophils and total protein concentration in BAL fluid were significantly greater for the asthmatic subjects than for the nonasthmatic subjects. These data suggest that although the lower respiratory symptom and lung function responses to O3 are not markedly greater in asthmatic subjects than in healthy subjects, the inflammatory response of the asthmatic lung may be more intense.

Spread of bloodborne viruses among Australian prison entrants.

OBJECTIVES: To assess spread of bloodborne viruses among prison entrants in Victoria, Australia. DESIGN: Voluntary confidential testing of all prison entrants for markers of exposure to bloodborne viruses with collection of minimal data on demography and risk factors over 12 months. SETTING: Her Majesty's Prisons, Pentridge and Fairlea, Victoria, Australia. SUBJECTS: 3429 male and 198 female prison entrants (> 99% of all prison entrants); 344 entered prison and were tested more than once. MAIN OUTCOME MEASURES: Prevalence and incidence of antibodies to HIV, hepatitis B, and hepatitis C viruses, and minimal data on risk factors. RESULTS: 1562 (46%) gave a history of use of injected drugs, 1171 (33%) had antibody to hepatitis B core antigen, 1418 (39%) were anti-hepatitis C positive including 914 (64%) of the men who injected drugs, 91 (2.5%) were positive for hepatitis B surface antigen, and 17 (0.47%) were positive for antibody to HIV. Incidence rates for infection with hepatitis B and C virus were 12.6 and 18.3 per 100 person years, respectively; in men who injected drugs and were aged less than 30 years (29% of all prison entrants) these were 21 and 41 per 100 person years. Seroconversion to hepatitis B or C was associated with young age and shorter stay in prison. Only 5% of those who were not immune to hepatitis B reported hepatitis B immunisation. CONCLUSIONS: Hepatitis B and C are spreading rapidly through some populations of injecting drug users in Victoria, particularly among men aged less than 30 years at risk of imprisonment in whom rates of spread are extreme; this group constitutes a sizeable at risk population for spread of HIV. This spread is occurring in a context of integrated harm reduction measures outside prisons for prevention of viral spread but few programmes within or on transition from prisons; it poses an urgent challenge to these programmes.

Organization of tomato bushy stunt virus genome: characterization of the coat protein gene and the 3' terminus.

We have synthesized cDNA clones of the genome of the cherry strain of tomato bushy stunt virus (TBSV-cherry) and have used them as hybridization probes to identify and position two 3' coterminal subgenomic RNAs of approximately 2.2 and 0.9 kilobases (kb) in length. The 5' termini of the two subgenomic RNAs have been mapped to positions located 2156 and 936 nucleotides respectively from the 3' terminus of the viral genome. The nucleotide sequence of cDNA clones encompassing the region of the genome containing both of the subgenomic RNAs has been determined. The sequence data indicate that two nested open reading frames (ORFs) occur in the most 3' proximal location on the genome suggesting that the 0.9-kb subgenomic RNA potentially encodes two polypeptides of 19,397 and 21,610 Da. Comparison of the amino acid sequence of a potential translation product of 41,024 Da encoded by the first ORF of the 2.2-kb subgenomic RNA with the published capsid protein amino acid sequence of the BS-3 strain of TBSV indicates that the 2.2-kb subgenomic RNA encodes the capsid protein. The TBSV coat protein cistron is located internally on the genome and thus its genetic organization differs from that reported for most other small, spherical viruses with monopartite genomes. Amino acid sequence comparisons of analogous regions of the cucumber necrosis virus (CNV) genome confirms a close relationship between the viruses.

The complete genome structure and synthesis of infectious RNA from clones of tomato bushy stunt virus.

The complete sequence of the genome of the cherry strain of tomato bushy stunt virus (TBSV), a member of the tombusvirus group, was determined. A full-length clone of the genome containing a bacteriophage T7 RNA polymerase promoter was assembled from partial cDNA clones. In vitro transcripts of the genome, either with or without a 5' cap structure, were highly infectious. In addition, a genomic clone modified to contain an EcoRI restriction site as a signature mutation was infectious. Five genes are encoded by the TBSV genome. The first ORF from the 5' terminus encodes a p33 protein as well as a p92 product translated by read-through of the amber terminator for p33. The capsid protein gene resides internally, and two ORFs for proteins of 19 and 22 kDa reside at the 3' terminus. These last three genes are expressed from two subgenomic RNAs. The genomic organization of TBSV agrees with previous models for tombusviruses. Computer alignments of TBSV proteins with those of two other tombusviruses suggest greater relatedness among the members of this group than previously reported.

Exposure to hepatitis A virus among blood donors, injecting drug users and prison entrants in Victoria.

To assess prevalence of exposure to hepatitis A virus (HAV) among injecting drug users (IDUs) and prison entrants in Victoria, and to compare this with prevalence of HAV among a reference population of blood donors, sera stored from two previous studies and from randomly selected blood donors were tested for total antibody to HAV. The first study was a longitudinal study of field-recruited IDUs from 1990 to 1992 and the second was a study of all prison entrants in 1991-92 (both studies were carried out in Victoria); blood donors were from the Australian Red Cross Blood Bank Victoria in 1995. Forty-five per cent of 2175 prison entrants and 51% of 293 IDUs were seropositive for HAV, compared with 30% of 2995 blood donors. When standardized for age against the blood donors, HAV seropositivity in IDUs was 44% and in prison entrants 60%. The strongest association of HAV seropositivity among the IDUs on multivariate analysis was a history of imprisonment. There are high rates of exposure to HAV among prison entrants, whether with a history of IDU or not, and among IDUs who have a prison history. The role of sharing contaminated injecting equipment in transmission of HAV seems to be less important than institutionalization per se. With adequate resourcing, both populations are appropriate targets for HAV vaccination, especially in a context of continuing decline of transmission of HAV in the general community.

De novo generation of defective interfering RNAs of tomato bushy stunt virus by high multiplicity passage.

Defective interfering (DI) RNAs were generated de novo in each of 12 independent isolates of tomato bushy stunt virus (TBSV) upon serial passage at high multiplicities of infection (m.o.i.) in plants, but not in any of 4 additional isolates after 11 serial passages at low m.o.i. The DI RNAs were detected in RNA isolated from virus particles and in 2.3 M LiCl-soluble RNA fractions isolated from inoculated leaves. Symptom attenuation leading to persistent infections was closely correlated with the passage in which DIs first developed. Comparisons of nucleotide sequences of 10 cDNA clones from 2 DI RNA populations and with a previously characterized TBSV DI RNA revealed the same four regions of sequence from the TBSV genome were strictly conserved in each of the DI RNAs: the virus 5' leader sequence of 168 bases; a region of approximately 200-250 bases from the viral polymerase gene; approximately 70 bases from the 3' terminus of the viral p19 and p22 genes; and approximately 130 bases from the 3' terminal noncoding region. Conservation of the sequence motif present in all of the DIs suggests that there might be a common mechanism of DI formation as well as selection pressure to maintain sequences essential for replication and encapsidation.

Ozone-induced airway inflammation in human subjects as determined by airway lavage and biopsy.

Ozone (O3) is a major constituent of urban air pollution. The acute effects of the inhalation of O3 at ambient or near-ambient concentrations on bronchoalveolar lavage (BAL) end points consistent with a distal lung inflammatory response have been well documented in human subjects. Animal toxicologic studies have shown that the airway is also a major site of O3-induced injury and inflammation. To date, no studies have confirmed this finding in human subjects. Effects of O3 on the proximal airways are not adequately studied by BAL, which is primarily influenced by events occurring in the terminal bronchioles and alveoli. We hypothesized that O3 causes injury and inflammation in the airways in addition to that previously documented to occur in the distal lung. We performed isolated lavage of the left mainstem bronchus and forceps biopsy of the bronchial mucosa in a group of 14 healthy, athletic subjects 18 h after exposure to 0.20 ppm O3 for 4 h during moderate exercise in order to assess this possibility. We followed an identical protocol in a similar group of 12 subjects exposed to filtered air. The mean (SD) total cell count and the lactate dehydrogenase (LDH) concentration in the isolated airway lavage were significantly greater after O3 than after air, 13.9 (20.5) versus 4.9 (5.4) cells/ml x 10(4) and 18.9 (11.2) versus 9.6 (9.0) U/L, respectively. Morphometry (2,070 neutrophils/cm2 of tissue for O3 and 330 neutrophils/cm2 of tissue for air) demonstrated that O3 exposure induced an acute inflammatory cell influx into the airway.(ABSTRACT TRUNCATED AT 250 WORDS)

Ozone-induced decrements in FEV1 and FVC do not correlate with measures of inflammation.

In order to test the hypothesis that changes in lung function induced by ozone (O3) are correlated with cellular and biochemical indices of respiratory tract injury/inflammation, we exposed 20 healthy subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and SRaw) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with isolated left main bronchus proximal airway lavage (PAL) and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following end points: total and differential cell counts, and total protein, fibronectin, interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) concentrations. The study population was divided into two groups, least-sensitive (n = 12; mean O3-induced change in FEV1 = -7.0%) and most-sensitive (n = 8; mean O3-induced change in FEV1 = -36.0%). We found a significant O3 effect on SRaw (p<0.001) and lower respiratory symptoms (p<0.001) for all subjects combined, but no significant differences between the least- and most-sensitive groups. Ozone exposure increased significantly percent neutrophils in PAL (p=0.01); percent neutrophils, total protein, and IL-8 in bronchial fraction (p<0.001, p<0.001, and p<0.01, respectively); and percent neutrophils, total protein, fibronectin, and GM-CSF in BAL (p<0.001, p<0.001, p<0.01, p=0.05, respectively) for all subjects combined; there were no significant differences, however, between least- and most-sensitive groups. Our results indicate that levels of O3-induced symptoms and respiratory tract injury/inflammation were not correlated with the magnitude of decrements in FEV1 and FVC.

HIV prevalence at reception into Australian prisons, 1991-1997.

OBJECTIVE: To measure the extent and outcome of HIV antibody testing at reception into Australian prisons. DESIGN: Cross-sectional survey at reception into prison. PARTICIPANTS AND SETTING: People received into Australian prisons from 1991 to 1997. MAIN OUTCOME MEASURES: Number of people tested for HIV infection and prevalence of diagnosed HIV infection. RESULTS: In 1991-1997, HIV antibody testing was carried out for 72% of prison entrants in Australia; the percentage tested declined significantly from 76% in 1991 to 67% in 1997 (P < 0.001). In New South Wales, the percentage of entrants tested at reception into prison dropped from almost 100% in 1991-1994 to 45% in 1997, whereas in the Northern Territory, South Australia and Western Australia the extent of testing increased significantly (P < 0.001). HIV prevalence was 0.2% among people received into Australian prisons in 1991-1997, and did not differ by sex. Most people with HIV infection (242/378; 64%) received into prison in 1991-1997 had been diagnosed at a previous entry; 136 people (36% of the total number of diagnoses) were newly diagnosed at reception into prison. CONCLUSIONS: A national monitoring system in place from 1991 indicates generally high rates of HIV antibody testing and a low prevalence of HIV infection among people entering Australian prisons. In each year, people not previously known to the prison health service to have HIV infection were received into prison, indicating continuing HIV infection in the population entering Australian prisons.

Chondrosarcoma of the larynx after radiation treatment for vocal cord cancer.

The case of a 57-year-old man with chondrosarcoma of the laryngeal cartilage is presented, occurring 16 years after radiation treatment for squamous cell carcinoma of the right true vocal cord. Chondrosarcoma of the larynx is an uncommon tumor. The location, grade, and time elapsed from initial treatment make it probably that this patient's chondrosarcoma is associated with his prior radiation treatment. However, it is a rare occurrence, this being the second case reported in the literature.