Gambling as a precipitating factor in deaths by suicide in the National Violent Death Reporting System.

OBJECTIVES: The public health burden of gambling remains difficult to estimate, given the lack of relevant, available data. Death by suicide, represents a substantial and quantifiable public health cost. The current study reviews data from the National Violent Death Reporting System to detect cases where gambling was identified as a meaningful contextual factor to a death by suicide. STUDY DESIGN: This study is an exploratory content analysis. METHODS: We analysed narrative data from cases of death by suicide, collected from 2003 to 2020 recorded in the Restricted Access Data of the National Violent Death Reporting System. Gambling-related cases identified in our analysis were compared against all other cases on demographic characteristics, case characteristics, US state, and incident year. Chi-square tests of independence and the Wilcoxon ranked sum tests were used in bivariate comparisons. RESULTS: Overall, 1306 of 296 317 cases were classified as gambling-related. This represented 0.44% of total cases. Gambling-related classification was over-represented among those identified as Asian (7.0% vs 2.2%) and under-represented among those identified as Black or African American (4.0% vs 6.4%) compared with all other deaths by suicide. Gambling-related cases were also over-represented in cases where alcohol use was suspected (28.0% vs 21.2%), where there were significant financial problems (50.3% vs 8.6%), where there were intimate partner problems (31.5% vs 25.6%), and under-represented in cases where there was a previous mental health diagnosis (35.1% vs 38.8%). The rate of gambling-related cases in Nevada was approximately nine times greater than the rate in the overall sample (4.0% vs 0.44%). CONCLUSIONS: Administrative data can be used to study the impacts of gambling on public health in the absence of quality representative survey data. However, these sources are still likely to underestimate the public health burden of gambling with current structures and procedures. Requiring intentional collection of gambling-related information in cases of suicide would be a significant step towards better quantifying the public health burden of gambling in the United States.

The value of sildenafil as mode of stimulation in pharmaco-penile duplex ultrasonography.

The purpose of this work was to assess whether a single intracavernous injection (ICI) of a low dose of the combination of papaverine-phentolamine is replaceable by a high dose of the oral erectogenic agent sildenafil as mode of stimulation during pharmaco-penile duplex ultrasonography (PPDU). Eleven patients with complaints of erectile dysfunction were included in a crossover study. With an interval of two weeks the patients were exposed to ICI with papaverine/phentolamine (3.75 mg/0.125 mg) and oral administration with sildenafil (100 mg) preceding PPDU. Five patients started with ICI. Six patients started with sildenafil. In the sildenafil stimulation mode, visual erotic stimulation (VES) was used to initiate erection. VES was applied by personal LCD monitor. Cut-off values to define sufficient arterial response were: peak flow velocity (PSV) >25 cm/s and acceleration time (AT) <72 ms. Cut-off value to define sufficient veno-occlusion was a resistance index > or =1.00. Statistical analysis of PPDU parameters shows no significant difference between the two modes of stimulation for arterial response (PSV, AT), whereas the resistance index, as a parameter of veno-occlusive response was significantly higher in the sildenafil mode. This finding is confirmed in the clinical translation of the results: two patients with an insufficient arterial response to ICI had a sufficient arterial response to sildenafil and only one patient showed an insufficient arterial response following sildenafil, whereas the response following ICI was sufficient. Analysis of veno-occlusive responses shows remarkable differences between both modes of stimulation. Whereas following the administration of sildenafil all veno-occlusive responses were classified as sufficient, seven patients showed an insufficient veno-occlusive response following ICI. As mode of stimulation in PPDU, high dose sildenafil yields significantly less false positive diagnoses of 'veno-occlusive dysfunction' than intracavernous injection of the combination papaverine/phentolamine. No difference was found in the quality of the arterial response. Based on this study we conclude that sildenafil may replace ICI as mode of stimulation during PPDU.

Production of specific macrophage-arming factor precedes cytotoxic T lymphocyte activity in vivo during tumor rejection.

Recently we published a hypothesis on the immunological events occurring during tumor rejection. One of the implications of this hypothesis is that specific macrophage-arming factor (SMAF) is produced early during the initiation of the immune response, whereas the "classical" cell-mediated immune response components, such as cytotoxic T lymphocytes (CTL), are produced later, that is, during the amplifier-effector phase. In this paper we establish the kinetics of the induction of (a) lymphocytes producing SMAF and (b) CTL. Groups of DBA/2 mice were injected i.p. once, twice or three times with irradiated and/or non-irradiated syngeneic SL2 tumor cells, the injections being given at intervals of 10 days. After each of these injections the production of SMAF and the expression of CTL activity were established. The results showed that in the peritoneal cavity SMAF-producing lymphocytes appeared earlier than cytotoxic lymphocytes (CTL). In addition, it was shown (a) that SMAF does not interfere with the in vitro cytotoxicity expressed by CTL and (b) that in addition to CTL memory cells, SMAF-producing memory cells were also induced after injection of syngeneic tumor cells. These data support the hypothesis that SMAF is involved in the early phase of the cellular immune response against tumors, whereas CTL are induced later.

Mechanism of the tachycardia following systemic alpha-methyldopa administration in conscious rats.

The mechanism of the tachycardia observed in conscious rats following systemic administration of alpha-methyldopa (alpha-MD) was investigated. Heart rate and mean arterial pressure were monitored following peripheral (i.p. and i.v.) and central (lateral and fourth ventricle and cisterna magna) administration of alpha-MD. As little as 25 mg/kg i.p. produced the maximum tachycardia observed: 136 +/- 30 beats/min within 30 min. However, after central administration of alpha-MD--producing similar reductions in blood pressure--only a gradually developing bradycardia occurred (maximum at 3-4 h), suggesting that the tachycardia was peripheral in origin. Tachycardia following administration of 25 mg/kg alpha-MD i.p. was prevented by pretreatment with propranolol, desmethylimipramine, and the dopa-decarboxylase inhibitor R04-4602, but not by pretreatment with pentolinium, guanethidine, the dopamine-beta-hydroxylase inhibitor FLA-63, or by adrenalectomy or depletion of endogenous catecholamines. In isolated spontaneously beating atria, alpha-MD produced a maximum increase in rate similar to that of isoprenaline. This effect of alpha-MD was blocked by propranolol and R04-4602 but not by FLA-63. These results suggest that the tachycardia observed in conscious rats following alpha-MD administration is caused by stimulation of cardiac beta-adrenoceptors following its conversion to alpha-methyldopamine in cardiac sympathetic neurons.

Specific tumoricidal activity of cytotoxic macrophages and cytotoxic lymphocytes.

The antitumor potency and specificity of syngeneic immune peritoneal exudate cells were tested. Groups of DBA/2 mice were immunized against syngeneic SL2 tumor cells. Then 6 days after the last immunization the antitumor potency, and the specificity of the immunization reaction was tested by injecting groups of the immunized mice with 10(3) to 5 X 10(7) DBA/2 derived L1210, L5178Y, P815 or SL2 tumor cells, and injecting immune peritoneal exudate cells into DBA/2 mice which had been injected 2 h earlier i.p. with 2 X 10(4) or 2 X 10(5) L1210, L5178Y, P815, or SL2 cells. Furthermore the tumor specific cytotoxicity in vitro of isolated immune (vs SL2) peritoneal macrophages was tested against L1210, L5178Y, P815, and SL2 cells. The "reciprocal" experiments (previous immunization against L1210, L5178Y, or P815 cells and 'challenge' with SL2) were also done. Finally, we tested the tumor-specific cytotoxicity of isolated immune peritoneal T-lymphocytes. It was shown that the rejection of tumor cells in previously immunized mice, the antitumor efficacy of the transferred immune peritoneal exudate cells and the in vitro cytotoxicity of purified immune peritoneal macrophages and lymphocytes, were tumor-specific reactions. That is only between the SL2 and L5178Y tumors were cross-reactions observed. However, this cross-reaction was not found at the level of cytotoxic T-cells. This suggests that cytotoxic T-cells and cytotoxic macrophages probably have different mechanisms of recognition of the specific tumor target cells. Treatment of macrophage monolayers, prepared from macrophages of immunized mice, with monoclonal anti-Thy-1 antibodies plus complement caused no decrease in cytotoxicity. This shows that macrophages can really express specific cytotoxicity. Tumoricidal macrophages probably obtain their tumor specificity through the activities of tumor-specific factors produced by sensitized T-cells.

The role of host lymphocytes and host macrophages in antitumor reactions after injection of sensitized lymphocytes and tumor target cells into naive mice.

DBA/2 mice were immunized i.p. against syngeneic SL2 lymphosarcoma cells. At various days after the last immunization peritoneal and spleen lymphocytes were collected. The lymphocyte suspensions were enriched for T-cells by nylon wool filtration. The peritoneal T-cells from immunized mice (a) expressed direct specific antitumor cytotoxicity in vitro, (b) induced macrophage cytotoxicity in vitro, and (c) exerted tumor neutralization measured in a Winn-type assay. Spleen T-cells from these immunized mice (a) expressed no direct specific antitumor cytotoxicity in vitro, (b) only induced moderate macrophage cytotoxicity in vitro, but (c) exerted tumor neutralization in a Winn assay. For effective tumor neutralization in vivo effector target cell ratios of 1000:1 were required. When the effector/target ratio of 1000:1 was maintained but the absolute numbers of effector and target cells were lowered from 10(6) to 10(5) lymphocytes and 10(3) to 10(2) target cells respectively, no tumor neutralization was obtained. The major effect of the sensitized-transferred T-lymphocytes seemed to be the induction of cytotoxic macrophages in the (naive) recipient mice, as the peritoneal macrophages collected from the recipient mice 7 days after i.p. injection of a mixture of sensitized T-cells and tumor cells were cytotoxic. Purified peritoneal T-lymphocytes collected from these recipient mice were able to induce macrophage cytotoxicity in vitro but expressed no cytotoxic T-cell activity. In conclusion, our results show that in the tumor system used, tumor neutralization after transfer of sensitized lymphocytes is not dependent on the presence of cytotoxic T-lymphocytes. Lymphocytes with the strongest potency to render macrophages cytotoxic (in vitro and in vivo) also induce the best tumor neutralization in vivo, suggesting an important role for host macrophages as antitumor effector cells.