Leading indicators of community-based violent events among adults with mental illness.

BACKGROUND: The public health, public safety and clinical implications of violent events among adults with mental illness are significant; however, the causes and consequences of violence and victimization among adults with mental illness are complex and not well understood, which limits the effectiveness of clinical interventions and risk management strategies. This study examined interrelationships between violence, victimization, psychiatric symptoms, substance use, homelessness and in-patient treatment over time. METHOD: Available data were integrated from four longitudinal studies of adults with mental illness. Assessments took place at baseline, and at 1, 3, 6, 9, 12, 15, 18, 24, 30 and 36 months, depending on the parent studies' protocol. Data were analysed with the autoregressive cross-lag model. RESULTS: Violence and victimization were leading indicators of each other and affective symptoms were a leading indicator of both. Drug and alcohol use were leading indicators of violence and victimization, respectively. All psychiatric symptom clusters - affective, positive, negative, disorganized cognitive processing - increased the likelihood of experiencing at least one subsequent symptom cluster. Sensitivity analyses identified few group-based differences in the magnitude of effects in this heterogeneous sample. CONCLUSIONS: Violent events demonstrated unique and shared indicators and consequences over time. Findings indicate mechanisms for reducing violent events, including trauma-informed therapy, targeting internalizing and externalizing affective symptoms with cognitive-behavioral and psychopharmacological interventions, and integrating substance use and psychiatric care. Finally, mental illness and violence and victimization research should move beyond demonstrating concomitant relationships and instead focus on lagged effects with improved spatio-temporal contiguity.

Validation of sentinel lymph node dissection in prostate cancer: experience in more than 2,000 patients.

PURPOSE: Sentinel lymph node dissection (SLND) has replaced extended lymphadenectomy for nodal staging in several solid tumours. We present our results of SLND in prostate cancer in regard to detection and false-negative rate. METHODS: In a 2-day protocol about 300 MBq (99m)Tc-nanocolloid are injected into the prostate. Two hours later static scans of the pelvis are performed to get information about the number and location of radioactive lymph nodes. During surgery the radioactive nodes are excised with the help of a gamma probe and sent separately to the pathologist. The histological procedure includes haematoxylin and eosin staining, serial sections and immunohistochemistry. RESULTS: Since 1999, a total of 2,020 men underwent SLND alone or in combination with either standard or extended lymphadenectomy after radical retropubic prostatectomy. Lymph nodes positive for metastases were found in 16.7% of patients. The scintigraphic detection rate was 97.6% and the intraoperative detection rate 98%. For 187 lymph node-positive men who had either standard or extended lymphadenectomy in addition to SLND the false-negative rate could be calculated, resulting in false-negative findings in 11 of 187 patients (6%). CONCLUSION: Our results demonstrate that SLND in prostate cancer is a reliable procedure for nodal staging.

Microbial origin of desert varnish.

Scanning electron microscopy and energy dispersive x-ray analyses of desert varnish reveal that microorganisms concentrate ambient manganese that becomes greatly enhanced in brown to black varnish. Specific characteristics of desert varnish and of varnish bacteria support a microbial origin for manganese-rich films. Varnish microbes can be cultured and produce laboratory manganese films. Accordingly, natural desert varnish and also manganese-rich rock varnishes in nondesert environments appear to be a product of microbial activity.

Stable carbon isotope ratios of rock varnish organic matter: a new paleoenvironmental indicator.

Stable carbon isotope ratios of organic matter in rock varnishes of Holocene age from western North America and the Middle East show a strong association with the environment. This isotopic variability reflects the abundance of plants with different photosynthetic pathways in adjacent vegetation. Analyses of different layers of varnish on late Pleistocene desert landforms indicate that the carbon isotopic composition of varnish organic matter is a paleoenvironmental indicator.

Cation-ratio and accelerator radiocarbon dating of rock varnish on mojave artifacts and landforms.

The first accelerator radiocarbon dates of rock varnishes are reported along with potassium/argon ages of lava flows and conventional radiocarbon dates of pluvial lake shorelines, in an empirical calibration of rock varnish K(+) + Ca(2+)/Ti(4+) ratios with age in the Mojave Desert, eastern California. This calibration was used to determine the cation-ratio dates of 167 artifacts. Although cation-ratio dating is an experimental method, some dates suggest human occupation of the Mojave Desert in the late Pleistocene.

[Influence of the injection technique on the false negative rate of SLNE in multifocal breast cancer]. / Einfluss der Injektionstechnik auf die Falsch-negativ-Rate bei der SLNE des mehrherdigen Mammakarzinoms.

AIM: We investigated the influence of the injection technique on the false negative rate in identifying the sentinel lymph node in multifocal breast cancer. PATIENTS, METHODS: 958 consecutive patients were divided into unifocal and multifocal breast cancer patients. The scintigrafic and intraoperative detection rate as well as the false negatives were calculated in relation to peritumoral or subareolar injection. RESULTS: In all patients the scintigrafic and intraoperative detection rate exceeded 99%, except in patients with multifocal cancer, who were injected peritumorally. In this group the intraoperative detection rate declined to 96%. In patients with unifocal breast cancer the false negative rate was below 5%, independent of the injection technique. Multifocal breast cancer patients showed a significant dependence on the injection technique. The false negative rate was 26.3% in patients with peritumoral injection and 5.6% in those with subareolar injection. CONCLUSION: The results clearly demonstrate that in multifocal breast cancer a reliable detection of a SLN is impossible with the peritumoral injection technique. Subareolar injection seems to be a way to operate on multifocal breast cancer with SLNE, but the number of investigated patients is too low for statistic approval. So, prospective studies should be performed to validate these preliminary results before SLNE becomes routine in multifocal breast cancer.

[Radioiodine therapy for combined disseminated and nodular thyroid autonomy. Results after using a correction term for the disseminated part]. / Radioiodtherapie bei kombinierter Schilddrüsenautonomie: Ergebnisse nach Korrektur für disseminierte Anteile.

AIM: In combined focal and disseminated thyroid autonomy a variety of concepts in the treatment with radioiodine are used. The difference lies mainly in the calculation of the autonomous volume. This retrospective study shows a new method of calculating the autonomous volume. PATIENTS AND METHODS: In 398 patients with combined thyroid autonomy and good correlation of scintigraphically hot nodules and lesions defined by ultrasound the volume of the nodules is ascertained from scintigraphic and ultrasound parameters and the volume of the disseminated autonomous tissue is assessed with a weighting factor (VF). This factor is the ratio of impulse density in a ROI over the disseminated volume divided by the corresponding impulse density over the nodular volume of the thyroid scintigraphy. The sum of nodular volume and weighted perinodular volume gives the total autonomous volume. A standard radioiodine test gives the maximum iodine-131-uptake and effective half-life to calculate the activity to obtain a treatment dose of 400 Gy. RESULTS: The rate of success with and without thyrostatic medication was 97% with an 18.6% rate of hypothyroidism observed from 4 months post therapy onwards. CONCLUSION: The use of the weighting factor VF in the treatment of combined autonomy leads to an excellent rate of success in patients with good correlation of functional imaging and ultrasound findings.

[Sentinel lymph node dissection in prostate cancer. Experience after more than 800 interventions]. / Sentinel-Lymphadenektomie beim Prostatakarzinom. Erfahrungen nach über 800 Eingriffen.

There is no consensus on which prostate cancer patients should undergo lymph node removal and which lymph nodes should be included. Therefore, most clinicians rely on nomograms and dispense with lymph node dissection in patients with low-risk disease. Meanwhile, there are some studies which prove that there are also lymph node metastases in patients with low-risk prostate cancer and that lymph node metastases are predominantly localized outside the region of standard lymphadenectomy. In more than 800 men we could show that lymph node metastases were found more often than shown in the Partin tables. These lymph node metastases were detected by sentinel lymph node dissection outside the region of standard and extended lymphadenectomy. Because of insufficient preoperative diagnostics it is unclear which patients have positive lymph nodes. Therefore, it is useful to perform lymph node dissection in every patient. Men with positive nodes could have a better prognosis, when sentinel and extended lymph node dissection are performed.

Biodistribution of boron in dogs with spontaneous intracranial tumors following borocaptate sodium administration.

Borocaptate sodium (Na2B12H11SH) is a potentially useful compound for boron neutron capture therapy of intracranial tumors. Tumor and normal tissue boron concentrations were evaluated in 30 dogs with naturally occurring intracranial tumors after i.v. borocaptate sodium infusion (55 mg boron/kg). Postmortem tissue boron concentrations were measured for three postinfusion time periods (2, 6, and 12 h) by inductively coupled plasma atomic emission spectroscopy. Mean boron concentrations for extracerebral tumors were 40.6 +/- 16.9 (2 h; n = 8), 25.9 +/- 11.7 (6 h; n = 5), and 8.6 +/- 4.5 micrograms boron/g (12 h; n = 6). Mean boron concentrations for intracerebral tumors were 30.6 +/- 17.5 (2 h; n = 7) and 2.9 +/- 1.8 micrograms boron/g (6 h; n = 4). Mean tumor boron concentrations were lower at longer postinfusion times. The tumor:normal brain boron concentration ranged from 0.8 to 19.8. Tumor:blood boron concentrations were less than one for all but three dogs and ranged from 0.04 to 1.4. Mean peritumor boron concentrations were highly variable but exceeded that of normal brain in 10 of 20 dogs. In some dogs, the mean peritumor boron concentration was similar to or exceeded the tumor boron concentration. Distant or contralateral normal brain had consistently low boron concentrations. Some cranial and systemic tissues had high boron concentrations, indicating substantial extravascular boron. The spontaneous animal tumors provided a realistic spectrum of data and enabled extensive sampling of diseased and normal tissues. The biodistribution of boron from borocaptate sodium administration was partially favorable because of high tumor boron concentrations. Empirical radiation dose tolerance studies should be used to determine the impact of the unfavorably high boron concentration of blood and some cranial tissues.

Hostility in schizophrenia: An integrated analysis of the combined Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the European First Episode Schizophrenia Trial (EUFEST) studies.

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.

Genetic and molecular complexity of the position effect variegation modifier mod(mdg4) in Drosophila.

mod(mdg4), also known as E(var)3-93D, is involved in a variety of processes, such as gene silencing in position effect variegation (PEV), the control of gypsy insulator sequences, regulation of homeotic gene expression, and programmed cell death. We have isolated a large number of mod(mdg4) cDNAs, representing 21 different isoforms generated by alternative splicing. The deduced proteins are characterized by a common N terminus of 402 amino acids, including the BTB/POZ-domain. Most of the variable C termini contain a new consensus sequence, including four positioned hydrophobic amino acids and a Cys(2)His(2) motif. Using specific antibodies for two protein isoforms, we demonstrate different distributions of the corresponding proteins on polytene chromosomes. Mutations in the genomic region encoding exons 1-4 show enhancement of PEV and homeotic transformation and affect viability and fertility. Homeotic and PEV phenotypes are enhanced by mutations in other trx-group genes. A transgene containing the common 5' region of mod(mdg4) that is present in all splice variants known so far partially rescues the recessive lethality of mod(mdg4) mutant alleles. Our data provide evidence that the molecular and genetic complexity of mod(mdg4) is caused by a large set of individual protein isoforms with specific functions in regulating the chromatin structure of different sets of genes throughout development.

P transposon-induced dominant enhancer mutations of position-effect variegation in Drosophila melanogaster.

P transposon induced modifier mutations of position-effect variegation (PEV) were isolated with the help of hybrid dysgenic crosses (pi 2 strain) and after transposition of the mutator elements pUChsneory+ and P[lArB]. Enhancer mutations were found with a ten times higher frequency than suppressors. The 19 pUChsneory(+)- and 15 P[lArB]-induced enhancer mutations can be used for cloning of genomic sequences at the insertion sites of the mutator elements via plasmid rescue. Together with a large sample of X-ray-induced (48) and spontaneous (93) enhancer mutations a basic genetic analysis of this group of modifier genes was performed. On the basis of complementation and mapping data we estimate the number of enhancer genes at about 30 in the third chromosome and between 50 and 60 for the whole autosome complement. Therefore, enhancer of PEV loci are found in the Drosophila genome as frequently as suppressor genes. Many of the enhancer mutations display paternal effects consistent with the hypothesis that some of these mutations can induce genomic imprinting. First studies on the developmentally regulated gene expression of PEV enhancer genes were performed by beta-galactosidase staining in P[lArB] induced mutations.

Nosocomial Salmonella epidemic.

A patient admitted to the hospital with diarrhea due to Salmonella heidelberg subsequently developed fatal disseminated salmonellosis, despite vigorous antimicrobial treatment. Beginning five weeks after the initial patient's death, nine patients developed hospital-acquired S heidelberg infections characterized by diarrhea (in seven) and bacteremia (in two). A careful search for salmonellosis among patients and hospital staff revealed two asymptomatic excretors. Extensive culturing of samples from the environment did not show any contaminated objects or reservoirs. The epidemic ended after initiation of an energetic handwashing campaign and isolation procedures. The strain of S heidelberg isolated was resistant to chloramphenicol, ampicillin, and gentamicin. Especially interesting in the epidemic were the prolonged time between death of the index case and the appearance of nosocomial cases, the high fatality rate, and the marked antibiotic resistance.

Boron neutron capture therapy (BNCT): a radiation oncology perspective.

Boron neutron capture therapy (BNCT) offers considerable promise in the search for the ideal cancer therapy, a therapy which selectively and maximally damages malignant cells while sparing normal tissue. This bimodal treatment modality selectively concentrates a boron compound in malignant cells, and then "activates" this compound with slow neutrons resulting in a highly lethal event within the cancer cell. This article will review this treatment modality from a radiation oncology, biology, and physics perspective. The remainder of the articles in this special issue of the Journal will provide a survey of the current "state-of-the-art" in this rapidly expanding field, including information with regard to boron compounds and their localization.

High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells.

Consecutive patients with non-Hodgkin's lymphoma (NHL, n = 133) or Hodgkin's disease (HD, n = 20) were treated with 12.0 Gy of fractionated total body irradiation, etoposide 60 mg/kg, and CY 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Seventy-nine patients received purged (n = 62) or unpurged BM (n = 17), and 74 received unpurged PBSCs alone (n = 56) or with BM (n = 18). The median day for achieving a sustained granulocyte count of 0.5 x 10(9)/I was 14 range (7-66) for BM recipients and 10 (7-30) for PBSC +/- BM recipients (P = 0.03). A platelet count of 20 x 10(9)/I was achieved at a median of day 24 (6-145) in BM recipients and day 11 (range, 7-56) in PBSC +/- BM recipients (P = 0.007). The median number of platelet units transfused was 86 (0-1432) for BM recipients and 30 (6-786) for PBSC +/- BM recipients (P = 0.001). The median number of hospital days was 36 (10-88) for BM recipients and 27 (14-76) for PBSC +/- BM recipients (P = 0.0001). The unadjusted Kaplan-Meier (KM) estimates of survival, event-free survival (EFS) and relapse at 2 years were 0.57, 0.45 and 0.43 for patients receiving BM and 0.55, 0.36 and 0.59 for patients receiving PBSC +/- BM. After adjusting for confounding variables, the estimated relative risk (RR) of death from any cause was 0.92 (P = 0.75), of relapse was 1.25 (P = 0.39), of non-relapse mortality was 0.71 (P = 0.42) and of mortality and/or relapse was 1.17 (P = 0.48) for patients receiving PBSC +/- BM as compared to BM. For 46 patients with NHL receiving unpurged PBSC alone, the unadjusted KM estimate of relapse was 0.61 compared with 0.48 for 52 comparable patients receiving purged BM, while the RR for relapse for patients receiving unpurged PBSCs was 1.37 (P = 0.33) after adjusting for other significant covariates. These data confirm previous observations that patients who receive PBSC +/- BM have faster engraftment, fewer transfusions and shorter hospital stays than patients who receive only BM. There were no statistically significant differences between the two groups in survival, relapse, death from causes other than relapse and event-free survival.

Effects of 12 months quinapril therapy in asymptomatic patients with chronic aortic regurgitation.

This study was performed to assess the effects of one year of ACE inhibition with quinapril on left ventricular performance and morphology in asymptomatic patients with chronic aortic regurgitation. Pre- and afterload reduction is known to have beneficial effects in patients with chronic aortic regurgitation. To date, no controlled study has been reported analyzing long term influence of ACE inhibitor treatment on asymptomatic patients with chronic aortic regurgitation. Twelve asymptomatic patients with isolated moderate to severe chronic aortic regurgitation, no coronary disease on coronary angiography and no previous vasodilator treatment were studied under control conditions and after three and 12 months of quinapril therapy (10-20 mg/day) using echocardiography and simultaneous right heart catheterization and radionuclide ventriculography at rest and during supine bicycle exercise. After one year quinapril therapy regurgitant fraction fell by 17% compared to control before therapy (p = 0.001), left ventricular enddiastolic volume at rest was reduced from 150 +/- 33 to 128 +/- 30 ml/m2 (p = 0.0003) and endsystolic volume decreased from 55 +/- 27 to 44 +/- 28 ml/m2 (p = 0.0005). Left ventricular ejection fraction at rest averaged 0.64 +/- 0.11 at control and increased after one year therapy to 0.67 +/- 0.11 (p = 0.05). With maximum exercise (100 W), ejection fraction failed to rise at control; after one year therapy with quinapril it increased to 0.70 +/- 0.15 (p = 0.019). Moreover, after one year quinapril therapy there was a significant reduction of 35% in left ventricular mass compared to control.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sentinel lymph node detection by preoperative lymphoscintigraphy and intraoperative gamma probe guidance in malignant melanoma]. / Nachweis des Sentinel-Lymphknotens mittels präoperativer Lymphszintigraphie und intraoperativer Gammasondenmessung bei malignem Melanom.

AIM: The purpose of this work was to prove the clinical significance of nuclear medical procedures in pre- and intraoperative detection of the SLN. METHODS: In the past 4 years, we did preoperative lymphoscintigraphy in 214 patients (pts.). Intraoperative localisation of the SLN with a hand-held gamma probe followed in 150 pts. RESULTS: In 214 pts. 247 lymphatic draining regions were found by preoperative scintigraphy. In 3 pts. with melanoma of the cheek no lymphatics/lymph nodes could be detected. 14 pts. showed interval lymph nodes. In 150 pts. gamma probe guided SLNE was done. In 2 pts. with supraclavicular primary tumor 4 SLN had been defined by preoperative scintigraphy but only 2 could be found intraoperatively. In all other cases (98.7%) the sentinel node was detected correctly by the gamma probe and then removed. In 19 of 150 pts. (12.7%) metastases were detected in the pathologic specimen. The incidence of lymph node metastases showed a continuous increase from 0% at tumor stage pT1 to 44% at stage pT4. CONCLUSION: SLNE is an accurate method to determine nodal involvement in melanoma and minimizes operative invasiveness in melanoma surgery.

[Sentinel lymph node diagnosis in prostatic carcinoma: II. Biokinetics and dosimetry of 99mTc-Nanocolloid after intraprostatic injection]. / Sentinel-Lymphknoten-Diagnostik beim Prostatakarzinom: Teil II: Biokinetik und Dosimetrie von 99mTc-Nanokolloid nach intraprostatischer Injektion.

AIM: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the radiotracer into the parenchyma of the prostate. The activity was deposited in liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The aim of this work is to determine biokinetical data and to estimate radiation doses to the patient. METHODS: The patients with prostate cancer received a sonographically controlled, transrectal administration of 99mTc-Nanocoll, injected directly into both prostate lobes. In 10 randomly selected patients radionuclide distribution and its time course was determined via regions of interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph nodes. The uptake in the SLNs was estimated from gamma probe measurements at the surgically removed nodes. To compare tumour positive with tumour free lymph nodes according to SLN-uptake and SLN-localisation we evaluated 108 lymph nodes out of 24 patients with tumour positive SLN. For calculating the effective dose according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1 software. RESULTS: The average uptake of separate organs was: bladder content 24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied activity remained in the prostate. The residual activity was mainly accumulated in bone marrow and blood. Occasionally a weak activity enrichment in intestinal tract and kidneys could be recognized. The effective dose to the patient was estimated to 7.6 microSv/MBq. The radioactivity uptake of the SLN varied in several orders of magnitude between 0.006% and 0.6%. The probability of SLN-metastasis was found to be independent from tracer uptake in the lymph node. The radioactivity uptake of the SLNs in distinct lymph node regions showed no significant differences. CONCLUSION: The radiotracer is transferred out of the prostate via blood flow, by direct transfer via the urethra into the bladder and by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in lymph nodes as the only criterion to characterize SLNs.

[Sentinel lymph node diagnosis in prostatic carcinoma: I: Method and clinical evaluation]. / [Sentinel lymph node diagnosis in prostatic caricnoma: I: Technique and clinical evaluation]

AIM: Evaluation of the significance of lymphoscintigraphy and intraoperative probe measurement for the identification of the sentinel lymph node (SLN) in prostate cancer. PATIENTS AND METHOD: In 117 patients with prostate cancer scintigrams in various projections were acquired till approximately 6 hours p.i. after ultrasound guided transrectal intraprostatic injection of 99mTc-Nanocoll. On the following day the SLNs were identified in the operation theatre with a gamma probe and removed. Pelvic standard lymph node dissection followed SLNE. RESULTS: In three of 117 patients with preoperative lymphoscintigraphy no SLN was scintigraphically detectable. These three patients had antecedent transurethral resection of the prostate. In 113 of the residual 114 patients SLN could be intraoperatively localized. In the mean four SLNs per patient were removed. 28 of 117 patients had pelvic lymph node metastases. In 25 cases SLN were right-positive, in one false-negative and in one intraoperatively not detectable. In one patient we found macrometastasis of up to 4 cm diameter (one SLN was tumour positive). In 15 cases only the SLN was bearing tumour. CONCLUSION: The SLNE with preoperative lymphoscintigraphy and intraoperative gamma probe measurement is suitable for detecting lymph node metastasis in prostate cancer. SLNE is superior to the surgical techniques commonly used in pelvic lymphadenectomy.

Hypercalcemia in patients with esophageal cancer.

Hypercalcemia is a paraneoplastic syndrome that is associated with squamous cell cancers and which may be of life-threatening proportions. We investigated the incidence and prognostic importance of hypercalcemia in patients with esophageal cancer at the Department of Veterans Affairs Medical Center, Washington, DC, USA. The medical records of 170 patients with esophageal cancer from January 1988 to January 1998 were examined. Of the 170 patients with esophageal cancer, 47 (27.6%) had hypercalcemia during the course of their disease. Five (10.6%) of the 47 hypercalcemic patients were found to have hypercalcemia at the time of diagnosis. Forty-six of the 47 hypercalcemic patients had squamous cell carcinoma and 1 had adenosquamous cell carcinoma. Seven (14.8%) had bony metastasis. The median survival of patients with hypercalcemia and esophageal cancer was 12.4 months and 12.6 months for patients without hypercalcemia. Hypercalcemia is a common complication of squamous cell esophageal carcinoma. The survival of patients with or without this complication is similar; thus, it may not be a poor prognostic factor.