Agency-offered and officer-utilized suicide prevention and wellness programs: A national study.

Limited research exists in the area of police mental wellness and suicide prevention, especially regarding programs utilized by these agencies. The purpose of this project was to gain a better understanding of the prevalence of use of police officer wellness promotion and suicide prevention programs implemented in the United States and an understanding of the perceptions of program effectiveness (Part A). We also sought to determine whether differences exist in the mental wellness and perspectives of programming of officers from agencies who utilize suicide prevention and wellness programs compared to those agencies who do not (Part B). Data for Part A was collected directly from agencies via a stratified random sample of city police departments and sheriff's offices nationwide. Part B entailed completion of online surveys by individual officers from agencies participating in Part A. The final sample included 55 agencies for Part A and 144 officers for Part B. At the agency level (Part A), Employee Assistance Programs or counseling services were the most common programs offered, and, notably, planning for programming was inconsistent or not well established. At the officer level (Part B), almost 25% of respondents did not know whether their agency had programming; 35% did not feel their agency supports its officers' mental wellness. For officers who did feel their wellness was supported, they reported significantly less stress and higher overall well-being. Of officer respondents, 12.4% indicated it was either "quite" or "very likely" they would attempt suicide someday. Implications and suggestions for law enforcement agencies are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Follow-up after curative treatment for colorectal cancer: longitudinal evaluation of patient initiated follow-up in the first 12 months.

PURPOSE: To compare patient-triggered follow-up (PTFU) for curatively treated colorectal cancer against traditional outpatient follow-up (OPFU). METHODS: Questionnaires were mailed at four time points over one-year post-treatment to two prospectively-recruited cohorts: A, patients entering follow-up and receiving OPFU pre-implementation of PTFU; B, patients entering follow-up (FU) and receiving either OPFU (B1) or PTFU (B2) post-implementation of PTFU. Bi-variate tests were used to compare patient characteristics and outcomes eight months after entering follow-up (generic and cancer-specific quality of life (QoL), satisfaction). Regression analysis explored associations between follow-up model and outcomes. Resource implications and costs of models were compared. RESULTS: Patients in Cohort B1 were significantly more likely to have received chemotherapy (p < 0.001), radiotherapy (p < 0.05), and reported poorer QoL (p = 0.001). Having a longstanding co-morbid condition was the most important determinant of QoL (p < 0.001); model of care was not significant. Patients were satisfied with their follow-up care regardless of model. Health service costs were higher in PTFU over the first year CONCLUSIONS: PTFU is acceptable to patients with colorectal cancer and can be considered to be a realistic alternative to OPFU for clinically suitable patients. The initial costs are higher due to provision of a self-management (SM) programme and remote surveillance. Further research is needed to establish long-term outcomes and costs.

A randomised controlled trial to evaluate both the role and the optimal fractionation of radiotherapy in the conservative management of early breast cancer.

AIMS: Postoperative radiotherapy is routinely used in early breast cancer employing either 50 Gy in 25 daily fractions (long course) or 40 Gy in 15 daily fractions (short course). The role of radiotherapy and shorter fractionation regimens require validation. MATERIALS AND METHODS: Patients with clinical stage I and II disease were randomised to receive immediate radiotherapy or delayed salvage treatment (no radiotherapy). Patients receiving radiotherapy were further randomised between long (50 Gy in 25 daily fractions) or short (40 Gy in 15 daily fractions) regimens. The primary outcome measure was time to first locoregional relapse. Reported results are at a median follow-up of 16.9 years (interquartile range 15.4-18.8). RESULTS: In total, 707 women were recruited between 1985 and 1992: median age 59 years (range 28-80), 68% postmenopausal, median tumour size 2.0 cm (range 0.12-8.0); 271 patients have relapsed: 110 radiotherapy, 161 no radiotherapy. The site of first relapse was locoregional158 (64%) and distant 87 (36%). There was an estimated 24% reduction in the risk of any competing event (local relapse, distant relapse or death) with radiotherapy (hazard ratio = 0.76; 95% confidence interval 0.65, 0.88). The benefit of radiotherapy treatment for all competing event types was statistically significant (X(Wald)(2) = 36.04, P < 0.001). Immediate radiotherapy reduced the risk of locoregional relapse by 62% (hazard ratio = 0.38; 95% confidence interval 0.27, 0.53), consistent across prognostic subgroups. No differences were seen between either radiotherapy fractionation schedules. CONCLUSIONS: This study confirmed better locoregional control for patients with early breast cancer receiving radiotherapy. A radiotherapy schedule of 40 Gy in 15 daily fractions is an efficient and effective regimen that is at least as good as the international conventional regimen of 50 Gy in 25 daily fractions.

Novel bcl-2 breakpoints in patients with follicular lymphoma.

Using genomic DNA from patients with follicular lymphoma, we performed polymerase chain reaction (PCR) amplifications to detect t(14;18) translocations. Unexpectedly large products of approximately 1 kilobase (kb) were detected by gel electrophoresis in 2 of 50 positive cases. In these 2 cases, sequence analyses showed novel breakpoints in the 3' untranslated region of bcl-2, approximately 800 bp downstream of the major breakpoint region (mbr). The breakpoints in IgH occurred in JH4 in one patient and JH5 in the other. Sequences just upstream of the new bcl-2 breakpoints suggest a mechanism of translocation that may include minisatellite core-mediated recombination. In one of our two patients with novel bcl-2 breakpoints, the approximately 1 kb product obtained using conventional mbr primers was detectable only when a nested PCR was performed. These findings have important implications for diagnosis and minimal residual disease detection in t(14;18)-positive lymphomas.

Effect of dietary n-3 fatty acids on cerebral microcirculation.

The purpose of these studies was to determine the effects of dietary n-3 fish oil on cerebrovascular reactivity and cerebrospinal fluid prostaglandin levels. Adult rabbits (n = 30) received fish oil (200 mg/kg eicosapentaenoic + 143 mg/kg docosahexaenoic acid), corn oil, or water by daily gavage for 6 wk and were then tested for their pial arteriolar diameter response to topical acetylcholine, bradykinin, or systemic asphyxia using the cranial window technique. Plasma and platelet fatty acids were measured by gas chromatography. Cerebrospinal fluid prostaglandin E and serum thromboxane B2 were measured by radioimmunoassay. n-3 Fatty acids were enriched in the plasma and platelets of the fish oil group (P less than 0.05). Serum thromboxane B2 was decreased by 31% in the fish oil group (P less than 0.05). The diameter response to acetylcholine and asphyxia was the same in all groups; however, the dilator response to bradykinin, which is known to be mediated by oxygen radicals, was significantly diminished in the fish oil group (P less than 0.05). Cerebrospinal fluid prostaglandin E concentration increased in response to acetylcholine, bradykinin, and asphyxia; however, the percent increase was less in the fish oil group. In summary, dietary n-3 fatty acids, which are purported to decrease heart disease, appear to selectively affect cerebral arteriolar reactivity, which is normally dependent on cyclooxygenase metabolism of arachidonic acid and formation of vasoactive oxygen radicals.

Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury.

Previous experiments have shown that, following experimental fluid-percussion brain injury, cyclo-oxygenase-dependent formation of oxygen radicals prevents arteriolar vasoconstriction in response to hyperventilation. The oxygen radical scavengers superoxide dismutase and catalase restore normal reactivity; however, they are not routinely available for clinical use. The present study tested whether n-acetylcysteine (Mucomyst), an agent currently available for acetaminophen toxicity, could be used as a radical scavenger to restore reactivity after brain injury. N-acetylcysteine (163 mg/kg) was given intraperitoneally prior to or 30 minutes after fluid-percussion brain injury (2.6 atm) in cats, and reactivity to hyperventilation was tested 1 hour after injury. The authors found either that pre- or postinjury administration led to normal reactivity. Additional experiments supported the hypothesis that n-acetylcysteine is an oxygen radical scavenger, since it reduced or prevented the free radical-dependent cerebral arteriolar dilation normally induced by the topical application of arachidonic acid or bradykinin. The mechanism by which n-acetylcysteine is effective in trauma may involve direct scavenging of radicals or stimulation of glutathione peroxidase activity. The results suggest that n-acetylcysteine may be useful for treatment of oxygen free radical-mediated brain injury.

Two-temperature PCR and heteroduplex detection: application to rapid cystic fibrosis screening.

We describe a rapid two-temperature PCR protocol for amplification of genomic DNA applied to the region of the most common mutation (delta F508) of the cystic fibrosis gene. Amplification products are detected as homo- or heteroduplexes on polyacrylamide gels as previously described. Data using two-temperature PCR show complete concordance with allele-specific hybridization after classical three-temperature PCR in 105 normal, carrier and affected individuals. Clinical application is demonstrated in a family which was uninformative by traditional RFLP linkage analysis. Two-temperature PCR may offer advantages of speed and specificity over three-temperature PCR in many clinical and research applications.

Randomised blind controlled trial of a high fibre, low fat and low sodium dietary regimen in mild essential hypertension.

Thirty-four patients with essential hypertension were allocated, in a controlled trial, to a treatment diet of high fibre, low fat and low sodium composition, or to a control diet by the hospital dietitian. Clinical observations were made by a separate 'blinded' nursing sister. After three months treatment, the modified diet-treated group showed a significant reduction in mean systolic (169.4 +/- 23.4 to 150.6 +/- 16.1 mmHg) and diastolic blood pressure (101.5 +/- 7.3 to 89.4 +/- 6.8 mmHg), accompanied by significant reductions in urinary sodium excretion (140.4 +/- 34.6 to 93.7 +/- 44 mmol/day) and weight (73.1 +/- 10 to 71.2 +/- 8.4 kg). The changes in control were; systolic 171.2 +/- 14.1 to 162.1 +/- 19.5 mmHg and diastolic pressure 97.2 +/- 10.8 to 91.7 +/- 9.7 mmHg. The mean differences in reductions between treated and control were 8.8 mmHg Systolic (95% confidence intervals: -2.6 to 21.2 mmHg) and 7.0 mmHg diastolic blood pressure (95% confidence intervals: 0.4 to 14.4 mmHg). The number of patients with normal blood pressure in the diet treated group at three months was double that in the control (eleven versus five). No relationships were shown between blood pressure changes and those of weight or urinary sodium excretion during the trial. The findings in this study are broadly in agreement with similar ones in essential hypertension and suggest that this form of dietary regimen has a clinically worthwhile hypotensive effect and this should be readily achievable in routine clinical practice.

RecA-mediated cleavage activates UmuD for mutagenesis: mechanistic relationship between transcriptional derepression and posttranslational activation.

The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli. It has been shown that the UmuD protein shares homology with LexA, the repressor of the SOS genes. In this paper we describe a series of genetic experiments that indicate that the purpose of RecA-mediated cleavage of UmuD at its bond between Cys-24 and Gly-25 is to activate UmuD for its role in mutagenesis and that the COOH-terminal fragment of UmuD is necessary and sufficient for the role of UmuD in UV mutagenesis. Other genetic experiments are presented that (i) support the hypothesis that the primary role of Ser-60 in UmuD function is to act as a nucleophile in the RecA-mediated cleavage reaction and (ii) raise the possibility that RecA has a third role in UV mutagenesis besides mediating the cleavage of LexA and UmuD.

Survival and mutagenesis of bacteriophage T7 damaged by methyl methanesulfonate and ethyl methanesulfonate.

We have examined survival and mutagenesis of bacteriophage T7 after exposure to the alkylating agents methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS). It was found that although both alkylating agents caused increased reversion of specific T7 mutations, EMS caused a higher frequency of reversion than did MMS. Exposure of the host cells to ultraviolet light so as to induce the SOS system resulted in increased survival (Weigle reactivation) of T7 phage damaged with either EMS or MMS. However, after SOS induction of the host we did not detect an accompanying increase in mutation frequency measured as either reversion of specific T7 mutants or by generation of mutations in the T7 gene that codes for phage ligase. Neither mutation frequency nor survival of alkylated phage was affected by the umuD,C mutation in the Escherichia coli host nor by the presence of plasmid pKM101. This may mean that the mode of Weigle reactivation that is detected in T7 is not mutagenic in nature.

Hyperthyroidism following hypothyroidism.

Two patients are presented who developed autonomous thyrotoxicosis following a diagnosis of primary hypothyroidism. In one of these patients, antibodies to the TSH receptor were typical of Graves' disease when measured as thyrotropin binding inhibitor immunoglobulins (TBII) and as human thyroid adenylate cyclase stimulating (HTACS) activity, while a needle biopsy of the thyroid gland was consistent with lymphocytic thyroiditis. Twenty-one other reported cases of this unusual sequence found in the literature are reviewed. This occurrence is more common than is generally appreciated.

Mutagenesis of bacteriophage T7 and T7 DNA by alkylation damage.

We have developed a new assay for in vitro mutagenesis of bacteriophage T7 DNA that measures the generation of mutations in the specific T7 gene that codes for the phage ligase. This assay was used to examine mutagenesis caused by in vitro DNA synthesis in the presence of O6-methylguanosine triphosphate. Reversion of one of the newly generated ligase mutants by ethyl methanesulfonate was also tested.

Cellular responses to DNA damage.

For many years, the study of the regulation of the SOS network was complicated by both the complexities of the responses and the interrelationships of the key regulatory elements. However, recently the application of powerful genetic and molecular biological techniques has allowed us to gain a detailed picture of the regulation of this complex network. The network is now known to consist of more than 17 genes, each of which is repressed by the LexA protein. Induction of the genes in the SOS network occurs when the RecA protein becomes activated in response to a signal generated by DNA damage. Two of the genes in this network, umuD and umuC, are absolutely required for mutagenesis by UV and various carcinogens. The umuD and umuC genes have molecular weights of 16,000 and 45,000 daltons, respectively, and are organized in an operon repressed by LexA. The mutagenesis-enhancing plasmid pKM101 carries two genes mucA and mucB, which are analogs of the umuD and umuC genes, respectively.

SIg-E- ("null-cell") non-Hodgkin's lymphomas. Multiparametric determination of their B- or T-cell lineage.

The authors performed immunophenotypic, functional, and molecular analysis of the neoplastic cells from 20 cases of SIg-, E-("null-cell") non-Hodgkin's lymphoma (NHL) in order to determine their lineage, better define this category of NHL, and evaluate the lineage specificity of selected phenotypic markers and the individual and collective utility of these approaches. They assigned 4 cases to the T-cell lineage, and 15 cases to the B-cell lineage, and 1 case remained indeterminant on the basis of immunophenotypic analysis. The cells from 2 cases assigned to the T-cell lineage expressed unusual phenotypes, but their T-cell derivation was confirmed by the demonstration of helper function in vitro. The 15 cases assigned to the B-cell lineage expressed a variety of B-cell-associated antigens, consistent with various stages of B-cell differentiation. Monoclonal antibodies OKT3, OKT4, OKT6, and OKT8 exhibited T-cell lineage restriction; and monoclonal antibodies OKB2, BL1, and B1 exhibited B-cell lineage restriction. Ia, TdT, cALLa, OKT9, and OKT10 exhibited lineage infidelity. Southern blot analysis for immunoglobulin heavy chain gene rearrangements confirmed 18 of the 19 lineage assignments made by immunophenotypic analysis and suggested that the 1 case of indeterminate phenotype was a B-cell neoplasm. One T-cell (OKT3+, T4+) neoplasm exhibited rearranged immunoglobulin heavy chain genes. Thus, neither immunophenotypic analysis nor the demonstration of rearranged immunoglobulin heavy chain genes alone permitted the satisfactory lineage assignment of every case of SIg-, E- NHL. However, combined immunophenotypic, functional, and genotypic analysis allowed us to assign every SIg-, E-NHL to the B- or T-cell lineage and to demonstrate that truly "null-cell" NHLs are probably very uncommon.

B-lymphocyte associated differentiation antigen expression by 'non-B, non-T' acute lymphoblastic leukemia.

We investigated the neoplastic cells obtained from 37 cases of 'non-B, non-T' (SIg-E-) acute lymphoblastic leukemia (ALL) for their expression of 13 distinct monoclonal antibody defined B lymphocyte associated differentiation antigens. We correlated the expression of these B cell antigens with terminal deoxynucleotidyl transferase (TdT), HLA-DR antigen, common ALL antigen (cALLa), and cytoplasmic mu heavy chain (Cu) expression by these neoplastic cells. In this way, we were able to describe a hierarchy of B lymphocyte associated differentiation antigens as well as the marked phenotypic heterogeneity of 'non-B, non-T' ALL. TdT and HLA-DR are expressed throughout the stages of B cell differentiation represented by 'non-B, non-T' ALL. The earliest B cell antigen appears to be Leu 12 (B4) followed by BA-2 and then BL2. OKB2, BL1 and BA-1 are acquired next, followed by B1, BL3, cALLa and Cu. BL7 appears just prior to SIg. OKB1, OKB4, OKB7 and BL4 appear at or after the time of SIg expression and hence are not expressed by 'non-B, non-T' ALL cells. This developmental hierarchy is supported by the results of phorbol ester (TPA) induction studies. Thus, cases of 'non-B, non-T' ALL constitute a useful model for probing the hierarchal expression of B cell antigens and delineating the B cell developmental pathway(s).

Mechanisms of rat pancreatic islet allograft rejection.

Since the mechanisms of rat islet allograft rejection are unknown, metabolic, histologic, and immunologic parameters were characterized during rejection. Syngeneic intraportal islet transplants in diabetic Lewis rats normalize glucose values without islet cellular infiltrates; after Wistar-Furth allografts, glucose values rapidly return to diabetic levels and infiltration of islets by mononuclear cells occurs. Using lymphocyte proliferative assays, allogeneic islets induce a 3-fold stimulation of lymphocytes derived from nondiabetic allograft recipients. Using cytotoxicity assays, cell-mediated cytotoxicity of allogeneic islet target cells although inefficient is 2-fold greater in diabetic allograft recipients than in syngeneic recipients. Antibody-dependent cellular cytotoxicity is not observed, whereas 14 days after allotransplantation, complement-dependent antibody-mediated cytotoxicity is elevated. These data suggest that islet allograft rejection using metabolic, histopathologic and immunologic methods is associated primarily with cell-mediated cytotoxicity related to histocompatibility antigens.

Inducible reactivation of bacteriophage T7 damaged by methyl methanesulfonate or UV light.

We examined the effects of host mutations affecting "SOS"-mediated UV light reactivation on the survival of bacteriophage T7 damaged by UV light or methyl methanesulfonate (MMS). Survival of T7 alkylated with MMS was not affected by the presence of plasmid pKM101 or by a umuC mutation in the host. The survival of UV light-irradiated T7 was similar in umuC+ and umuC strains but was slightly enhanced by the presence of pKM101. When phage survival was determined on host cells preirradiated with a single inducing dose of UV light, these same strains permitted higher survival than that seen with noninduced cells for both UV light- and MMS-damaged phage. The extent of T7 reactivation was approximately proportional to the UV light inducing dose inflicted upon each bacterial strain and was dependent upon phage DNA damage. Enhanced survival of T7 after exposure to UV light or MMS was also observed after thermal induction of a dnaB mutant. Thus, lethal lesions introduced by UV light or MMS are apparently repaired more efficiently when host cells are induced for the SOS cascade, and this inducible reactivation of T7 is umuC+ independent.