Spatial stratification of host-seeking Diptera in boreal forests of northern Europe.

The stratification of haematophagous Diptera was assessed in two boreal forests in northern Sweden by placing traps baited with carbon dioxide at 1.5 m, 5.0 m and 10.0 m above the ground. More than 40 000 specimens were captured, including 617 biting midges (Ceratopogonidae), 4029 mosquitoes (Culicidae) and 36 092 black flies (Simuliidae). Catches at the various trap heights reflected the general vertical distribution of the preferred hosts, with mammalophilic flies predominating (68.6%) in catches at 1.5 m and ornithophilic flies (42.4%) in catches at 10.0 m; however, most flies that use host birds at ground level were caught in the lowest traps (e.g. 85.1% of Simulium annulus were collected at 1.5 m). Within-species variation in vertical patterns between forests suggests plasticity in responses to environmental factors such as vegetative structure.

Vertical distribution of haematophagous Diptera in temperate forests of the southeastern U.S.A.

The vertical distribution of blood-feeding flies in two temperate forests in the southeastern U.S.A. was determined by placing 15 Centers for Disease Control and Prevention miniature light traps (12 CO(2)-baited, three unbaited controls), without lights, at three heights (1.5 m, 5.0 m, 10.0 m). More than 6550 haematophagous flies, representing 49 species in four families, were collected. Eighteen species were taken almost exclusively (90-100%) at 1.5 m or 10.0 m, and the mean number of flies per trap differed significantly with height for another six species. Five species exhibited shifts in vertical distribution between the two forests, indicating that forest structure could influence the height of host searching. Most (52.5%) mammalophilic flies were collected at 1.5 m, whereas most (56.4%) ornithophilic flies were taken at 10.0 m, suggesting that host associations influence vertical distributions. The significant differences in the composition of haematophagous fly populations among forest strata emphasize the importance of trap placement in vector surveillance and of understanding the ecological relationships of blood-feeding flies.

Magma supply rate at kilauea volcano, 1952-1971.

The three longest Kilauea eruptions since 1952 produced lava at an overall constant rate of about 9 x 10(6) cubic meters per month (vesicle-free). This is considered to represent the rate of magma supply from a deep source, probably the mantle, because little or no summit deformation indicating high-level storage accompanied any of the three eruptions.

Predicting eruptions at mount st. Helens, june 1980 through december 1982.

Thirteen eruptions of Mount St. Helens between June 1980 and December 1982 were predicted tens of minutes to, more generally, a few hours in advance. The last seven of these eruptions, starting with that of mid-April 1981, were predicted between 3 days and 3 weeks in advance. Precursory seismicity, deformation of the crater floor and the lava dome, and, to a lesser extent, gas emissions provided telltale evidence of forthcoming eruptions. The newly developed capability for prediction reduced risk to life and property and influenced land-use decisions.

Deformation monitoring at mount st. Helens in 1981 and 1982.

For several weeks before each eruption of Mount St. Helens in 1981 and 1982, viscous magma rising in the feeder conduit inflated the lava dome and shoved the crater floor laterally against the immobile crater walls, producing ground cracks and thrust faults. The rates of deformation accelerated before eruptions, and thus it was possible to predict eruptions 3 to 19 days in advance. Lack of deformation outside the crater showed that intrusion of magma during 1981 and 1982 was not voluminous.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

Targeted disruption of the methionine synthase gene in mice.

Alterations in homocysteine, methionine, folate, and/or B12 homeostasis have been associated with neural tube defects, cardiovascular disease, and cancer. Methionine synthase, one of only two mammalian enzymes known to require vitamin B12 as a cofactor, lies at the intersection of these metabolic pathways. This enzyme catalyzes the transfer of a methyl group from 5-methyl-tetrahydrofolate to homocysteine, generating tetrahydrofolate and methionine. Human patients with methionine synthase deficiency exhibit homocysteinemia, homocysteinuria, and hypomethioninemia. They suffer from megaloblastic anemia with or without some degree of neural dysfunction and mental retardation. To better study the pathophysiology of methionine synthase deficiency, we utilized gene-targeting technology to inactivate the methionine synthase gene in mice. On average, heterozygous knockout mice from an outbred background have slightly elevated plasma homocysteine and methionine compared to wild-type mice but seem to be otherwise indistinguishable. Homozygous knockout embryos survive through implantation but die soon thereafter. Nutritional supplementation during pregnancy was unable to rescue embryos that were completely deficient in methionine synthase. Whether any human patients with methionine synthase deficiency have a complete absence of enzyme activity is unclear. These results demonstrate the importance of this enzyme for early development in mice and suggest either that methionine synthase-deficient patients have residual methionine synthase activity or that humans have a compensatory mechanism that is absent in mice.

Renal cell carcinoma: antitumor effects of leukocyte interferon.

Partially purified human leukocyte (alpha) interferon was administered i.m. at a dose of 3 x 10(6) units/day to 19 patients with metastatic renal cell carcinoma. Five patients (26%) showed partial responses; two patients (10.5%), objective minor responses; three patients (16%), mixed effects (evidence of biological effect with regression of some lesions but concomitant progression); two patients (10.5%), disease stabilization; and seven patients (37%), progressive disease. All tumor responses were seen in lung or mediastinal metastases. Tumor response significantly correlated with interferon-induced leukopenia and granulocytopenia and with pretreatment performance status. Antibodies to interferon were found in one patient prior to treatment. We concluded that interferon is a potential active antitumor agent in patients with renal cell carcinoma.

Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report.

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.

Adjuvant cyclophosphamide, doxorubicin, and cisplatin chemotherapy for bladder cancer: an update.

Seventy-one patients received adjuvant Cytoxan (cyclophosphamide; Bristol-Myers Co, Evansville, IN), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (CISCA) chemotherapy between March 1981 and March 1986. Patients received adjuvant CISCA chemotherapy if they had pathological findings that were thought to predict for high likelihood of relapse. These included the presence of resected nodal metastases, extravesicular involvement of tumor, lymphatic/vascular permeation of the primary tumor, or pelvic visceral invasion. Sixty-two patients at a similar high risk for recurrence did not receive adjuvant CISCA chemotherapy because they refused, had medical contraindications to therapy, or were not referred for chemotherapy. Two-hundred six patients had a cystectomy performed during the same study period but had none of the poor prognostic features suggesting a high risk for relapse. Sixty-two percent of the patients receiving adjuvant chemotherapy are alive and disease-free for a mean follow-up of 118 weeks (range, 28 to 310 weeks). A survival advantage exists for the adjuvant-treated patients when compared with those with unfavorable pathological findings who did not receive adjuvant chemotherapy (70% v 37%) (P = .00012): no difference exists in long-term disease-free survival for those with favorable pathological findings (long-term disease-free survival 76%) v those who received adjuvant chemotherapy (70%) (P = .33). Adjuvant CISCA chemotherapy prolongs the disease-free survival of some patients following a cystectomy. Patients who benefitted from adjuvant CISCA chemotherapy included those with resected nodal metastases, extra-vesicular involvement of tumor, and direct invasion of the pelvic viscera. Patients not benefitting from adjuvant CISCA chemotherapy in this analysis included those with lymphatic/vascular invasion in their primary tumor as the sole manifestation of high risk for relapse.

Primary chemotherapy for clinical stage II nonseminomatous germ cell tumors of the testis: a follow-up of 50 patients.

Fifty patients with clinical stage II nonseminomatous germ cell tumor of the testis (NSGCTT) were treated with primary chemotherapy followed by a retroperitoneal lymph node dissection (RPLND) in selected patients. The study population included 34 patients with retroperitoneal masses and elevated levels of serum biomarkers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [BHCG] ), five with needle aspiration biopsy-proven retroperitoneal metastases but normal levels of biomarkers, and 11 in whom there were rising levels of serum biomarkers but no radiographic evidence of retroperitoneal metastases. Forty-eight patients (96%) achieved a complete response (CR), with a mean disease-free survival of 132 weeks (range, 55 to 273 weeks). Two patients developed recurrent disease. One died and one achieved a second CR with further therapy (48 + weeks). Postchemotherapy RPLND was required in 11 patients (22%). Patients with embryonal carcinoma had a lower frequency of RPLND (8%) than patients with teratomatous elements in their primary tumor [36%, P = .014]. To reduce the frequency of double therapy (surgery +/- chemotherapy), we propose individualized therapy. Patients presenting with clinical stage II embryonal carcinoma of the testis should receive primary chemotherapy. Patients with clinical stage II NSGCTT and teratomatous elements in their primary tumor continue to require an RPLND. Those patients with intermediate volume disease (greater than 2 cm less than or equal to 5 cm in maximum diameter) may be treated with an RPLND only. Patients with higher volume teratomatous elements (greater than 5 cm less than or equal to 10 cm in maximum diameter) are likely to require the combination of chemotherapy and surgery.

Chemotherapy of extragonadal germ cell tumors.

Forty-nine patients with histologically proven germ cell tumors arising in extragonadal sites were retrospectively reviewed. Included in the review were an additional seven patients with undifferentiated tumors with a pathologic appearance compatible with that of a germ cell tumor and elevated levels of serum biomarkers (beta subunit of human chorionic gonadotropin [beta-HCG] +/- alpha-fetoprotein [AFP]. Nineteen patients had a pure seminoma arising in an extragonadal site, whereas 30 patients had nonseminomatous germ cell tumors. Seven patients had primary undifferentiated tumors with elevated levels of serum biomarkers. Sixteen (84%) of the 19 patients with pure extragonadal seminomas with normal levels of serum AFP are alive and free of disease. Eighteen of these 19 patients received platinum-containing regimens and four had received prior chemotherapy that failed. Of the patients with nonseminomatous germ cell tumors, 12 (40%) of the 30 are alive and free of disease with vinblastine/bleomycin +/- cisplatin (13 patients) or CISCAII (cisplatin, cyclophosphamide, and doxorubicin) (nine patients) alternating CISCAII/VBIV (eight patients) chemotherapy. None of the seven patients with undifferentiated germ cell tumors are alive and free of disease. Three of the five patients with pure anterior mediastinal endodermal sinus tumors treated with chemotherapy remain alive and free of disease. Of the seven patients with choriocarcinomas arising in extragonadal sites, three are alive and free of disease. A classification for patients with extragonadal germ cell tumors incorporating site of origin, histology, and likelihood of being truly extragonadal is proposed. The implications of this classification are discussed.

Muscle-invasive bladder cancer treated with external beam radiotherapy: prognostic factors.

PURPOSE: To determine the relationship of several potential prognostic factors to the outcome measures of pelvic control, freedom from metastases, and overall survival for bladder cancer patients treated with definitive external beam radiotherapy. METHODS AND MATERIALS: The records of 135 patients treated with high-dose, planned continuous-course, external beam radiotherapy for muscle-invasive transitional cell bladder cancer were reviewed. These patients were treated to an average total dose of 6588 +/- 475 cGy with an average fractional dose of 207 +/- 18 cGy using megavoltage. Median potential follow-up for all patients, including those who died, was 249 months. RESULTS: The actuarial results at 5 year were 31% pelvic control, 58% freedom from metastases, and 26% overall survival. In the univariate analyses, several factors were correlated with disease outcome including clinical stage, tumor morphology, gross total transurethral resection (TURBT), findings at bimanual exam after TURBT, clinical perivesical extension, age, and clinical complete response at first follow-up cystoscopy (Clinical-CR). A Cox proportional hazards model revealed that only Clinical-CR was independently predictive of pelvic control. In terms of freedom from metastases, only Clinical-CR and clinical stage were significantly associated with outcome in the multivariate analysis. When the multivariate analysis was restricted to T2 and T3 tumors only, then clinical perivesical extension replaced stage as being associated with freedom from metastases. The only factors significantly related to overall survival in the Cox proportional hazards model were Clinical-CR, age, and complete TURBT; stage was of borderline significance when only pretreatment factors were considered. CONCLUSIONS: Clearly, the most important prognostic factor was Clinical-CR. The pretreatment factors of stage, clinical perivesical extension, and gross total TURBT also correlated with outcome, but, to a lesser degree. For patients medically unfit for radical cystectomy radiotherapy is a viable option, particularly for selected patients. Patients with T4 tumors are poor candidates for definitive radiotherapy and should be treated palliatively if they cannot tolerate systemic therapy.

Significance of downstaging in muscle-invasive bladder cancer treated with preoperative radiotherapy.

PURPOSE: The relationship between clinical-to-pathologic downstaging and patient outcome following preoperative radiotherapy was examined, focusing on the mechanism (selection vs. treatment effect) responsible for the benefit seen from such downstaging. METHODS AND MATERIALS: Three hundred and one patients were treated with preoperative radiotherapy plus cystectomy (PREOP) to a median dose of 50 Gy in 25 fractions between 1960-1983. These patients were compared to 225 patients treated with radical cystectomy, with or without chemotherapy (CYST), between 1984-1990. Multiagent chemotherapy was given to 68% of those in the CYST group and was not given to any in the PREOP group. Lymph node involvement was not formally evaluated in the PREOP group, while 20% had pathologic involvement in the CYST group. RESULTS: Clinical-to-pathologic downstaging (P < T stage) was found in 73% treated with PREOP and 29% treated with CYST (p < 0.0001, chi-square). The only factors that correlated with P < T staging for the PREOP and CYST groups when each was considered separately were clinical stage, blood urea nitrogen level, and creatinine level (p < 0.05, chi-square). Multivariate logistic regression revealed that treatment (PREOP vs. CYST) correlated independently with P < T staging (p < 0.0001). The relationship of actuarial local control to distant metastasis at 5 years in patients that were downstaged, as stratified by clinical stage and treatment, was then examined. Local control rates for P < T staged T2/T3a patients were independent of treatment (PREOP vs. CYST), while distant metastasis rates were significantly greater for those in the PREOP group. In contrast, P < T staged T3b patients in the PREOP group had significantly better local control and distant metastasis rates. CONCLUSIONS: Significantly higher P < T staging rates were observed with PREOP as compared to CYST, and this was a consequence of the radiotherapy given. The relationship of downstaging from radiotherapy to local control and distant metastasis was contingent on clinical stage. The results of Stage T2/T3a and T3b patients were divergent and supported treatment effect, rather than selection, as the mechanism consistent with the patient outcomes observed.

Local control of muscle-invasive bladder cancer: preoperative radiotherapy and cystectomy versus cystectomy alone.

PURPOSE: The role of preoperative radiotherapy for patients with muscle-invasive bladder cancer remains controversial. Since 1985, the primary modality for treatment of these patients at our institution has been radical cystectomy alone. Prior to that time, the use of preoperative and cystectomy had been the mainstay of treatment. In this retrospective review we compare the results of these treatments, focusing on local control. METHODS AND MATERIALS: The preoperative radiotherapy and radical cystectomy (PREOP) group was comprised of 338 patients with muscle-invasive (Stages T2-T4) transitional cell carcinoma of the bladder treated between 1960 and 1983. A mean total dose of 49.3 +/- 0.2 Gy (+/- SE) was administered at 2 Gy per fraction 4-6 weeks prior to cystectomy. The radical cystectomy alone (CYST) group was comprised of 232 patients treated between 1985 and 1990. The median follow-up for the PREOP group was 91 months and for the CYST group was 54 months. Only those patients who completed planned PREOP (n = 301) and CYST (n = 220) treatments were included in the analyses described below. RESULTS: The treatment groups were stratified by clinical stage and compared in terms of actuarial local control. There were no differences between the groups for Stage T2 or T3a patients, and there were not enough Stage T4 patients in the PREOP group with which to make a meaningful comparison. However, for those with T3b disease, actuarial 5 year local control for the PREOP group (n = 92) was 91%, compared to 72% for the CYST group (n = 43). This difference was significant at p = 0.003 (log rank). Patients with T3b disease who received PREOP also fared slightly better at 5 years in terms of freedom from distant metastasis (67% vs. 54%), disease freedom (59% vs. 47%), and overall survival (52% vs. 40%); although, these differences did not reach statistical significance. The distribution of prognostic factors in the groups was analyzed to determine if this could account for the differences in local control in Stage T3b patients. For patients with Stage T3b disease, the only significant difference was by grouped age (p < 0.05, chi-square), which was not a significant factor in the univariate analyses of local control. A multivariate analysis using Cox proportional hazards models revealed pretreatment hemoglobin, blood urea nitrogen (BUN) concentration, and treatment type (PREOP vs. CYST) to be independently predictive of local control. CONCLUSION: We document here in a large number of patients treated at a single institution that preoperative radiotherapy had a significant impact on local control for patients with clinical Stage T3b disease. Because the CYST patients were treated using modern-day surgical techniques and 80% of those with Stage T3b disease received multiagent chemotherapy, it is probable that any biases, if present, would favor the CYST group. Thus, the differences between PREOP and CYST described may be underestimated. Preoperative radiotherapy should be considered as an adjunct to chemotherapy and surgery for clinical Stage T3b patients.

Mammalian orthologs of C. elegans unc-119 highly expressed in photoreceptors.

PURPOSE: To characterize orthologous human and murine cDNAs isolated through separate screens designed to identify genes expressed preferentially in retina. METHODS: By screening bovine, murine, and human retinal cDNA libraries, human UNC-119 clones of two varieties and a murine cDNA clone corresponding to the most abundant human transcript were isolated. Northern blot and reverse transcription-polymerase chain reaction analyses were used to determine tissue distribution of UNC-119 expression; in situ hybridization localized it in retina to photoreceptors. Fluorescence in situ hybridization was used to map the human structural gene, and its intron- exon boundaries were elucidated by polymerase chain reaction amplification and sequencing genomic DNA. RESULTS: UNC-119 was expressed at high levels in photoreceptors and at low levels elsewhere. The most abundant transcript encoded a protein of 240 amino acids with homology to Caenorhabditis elegans UNC-119. Rat and human cDNAs of UNC-119 have been previously reported as human retinal gene 4 and rat retinal gene 4 (HRG4 and RRG4). An alternative splice form in humans arose from retention of the 3'-most intron, seemed to be retina-specific, and encoded a protein of 220 amino acids. The human structural gene mapped to 17q 1.2 and comprised at least five exons and four introns. A patient with neurofibromatosis type 1, which also maps to 17q11.2, and cone-rod dystrophy was examined for a deletion of UNC-119 but no abnormalities were found. CONCLUSIONS: Given its strong degree of evolutionary conservation and abundant and nearly exclusive expression in photoreceptors, it is likely that UNC-119 plays an important role in vision and is a strong candidate gene for retinal diseases that map to 17q11.2.

Pseudosarcomatous fibromyxoid tumor of the urinary bladder.

The light-microscopic, immunohistochemical, and ultrastructural features of two examples of a pseudosarcomatous fibromyxoid tumor of the urinary bladder are reported. Both patients were women, 56 and 52 years old. Gross hematuria was the chief complaint and occurred for two days and two weeks, respectively, before presentation. Cystoscopy revealed a 2 X 1 X 1 cm mass located at the dome in case 1 and a 4 X 3 X 3 cm mass at the left posterior lateral wall in case 2. Microscopically, the lesions were composed of spindle, plump, or stellated fibroblast-like cells embedded in myxoid stroma with little collagen; mitotic figures were about 2 per 10 high-power fields, and both cases showed encroachment of the superficial muscle bundles. Because of bizarre spindle cell proliferation, occasional mitoses, and invasion to the underlying muscle, these lesions were initially diagnosed as embryonal rhabdomyosarcoma. However, follow-up examination disclosed the benign nature of these lesions. There was no previous instrumentation or surgery on the genitourinary tract. Immunohistochemical and ultrastructural studies revealed the fibroblastic-myofibroblastic nature of these lesions. These cases illustrate that clinicopathologic correlation is essential to define certain pseudosarcomatous lesions.

Cadaver kidney preservation with Viacell organ perfusion apparatus.

Sixty-five kidneys (63 homografts and two autografts) underwent ex vivo preservation for periods of up to 34 hours with the Viacell renal perfusion system. Eighty percent of the homografts and both of the autografts functioned immediately. A correlation existed between poor perfusion characteristics and poor immediate function. Prolonged perfusion with this apparatus (more than 20 hours) probably had no deleterious effect on ultimate than 20 hours) probably had no deleterious effect on ultimate graft function. The machine offers portability, rapid refitting, and the ability to perfuse each kidney separately.

Surgical management of renal cell carcinoma with inferior vena cava tumor thrombus.

BACKGROUND: The optimal management of patients with renal cell carcinoma with inferior vena cava tumor thrombus remains unresolved. Traditional approaches have included resection with or without the use of cardiopulmonary bypass. Chemotherapy has played a minor role except for biotherapeutic agents used for metastatic disease. METHODS: From January 1989 to January 1996, 37 patients with renal cell carcinoma and inferior vena cava tumor thrombus underwent surgical resection. The 27 men and 10 women had a median age of 57 years (range, 29 to 78 years). Thirty-six patients presented with symptoms; 21 had hematuria. Distant metastases were present in 12 patients. Tumor thrombi extended to the infrahepatic inferior vena cava (n = 16), the intrahepatic inferior vena cava (n = 16), the suprahepatic inferior vena cava (n = 3), and into the right atrium (n = 2). All tumors were resected by inferior vena cava isolation and, when necessary, extended hepatic mobilization and Pringle maneuver, with primary or patch closure of the vena cavotomy. Cardiopulmonary bypass was necessary in only 2 patients with intraatrial thrombus. RESULTS: Complications occurred in 11 patients, and 1 patient died 2 days postoperatively of a myocardial infarction (mortality, 2.7%). Twenty patients are alive; overall 2- and 5-year survival rates were 61.7% and 33.6%, respectively. For patients without lymph node or distant metastases (stage IIIa), 2- and 5-year survival rates were 74% and 45%, respectively. The presence of distant metastatic disease (stage IV) at the time of operation did not have a significant adverse effect on survival, as reflected by 2- and 5-year survival rates of 62.5% and 31.3%, respectively. Lymph node metastases (stage IIIc) adversely affected survival as there were no long-term survivors. CONCLUSIONS: Resection of an intracaval tumor thrombus arising from renal cell carcinoma can be performed safely and can result in prolonged survival even in the presence of metastatic disease. In our experience, extracorporeal circulatory support was required only when the tumor thrombus extended into the heart.