Rearrest following residential treatment for repeat offender drunken drivers

Multiple offenders are at high risk for continued drunken driving. Massachusetts, therefore, mandated that individuals convicted of a second drunken driving offense either be committed for a minimum of 7 days in a house of correction or enter a 14-day residential alcoholism treatment program for second offenders. A 2-year follow-up study of arrest rates assessed the impact of the two sentencing options on subsequent arrests for driving under the influence of liquor (DUIL). The incarcerated sample (N = 190) was slightly younger, had more prior DUIL charges and exhibited greater criminality than those who entered treatment (N = 199). Offenders admitted to the 14-day program were significantly less likely to be rearrested for drunken driving (10 vs 20%). A summary odds ratio suggested that when adjusted for differences in prior arrests, the risk of rearrest was 1.9 times greater among incarcerated offenders. Although a 2-year follow-up is insufficient to assess the complete impact of the 14-day program, the two-fold difference in the risk of rearrest suggests that mandated short-term residential treatment may provide an effective intervention among repeat offender drunken drivers.     

Nitric oxide/redox-based signalling as a therapeutic target for penile disorders

Oxidative and/or nitrosative stress is implicated in the pathogeneses of assorted penile disorders of clinical significance, notably erectile dysfunction, priapism and penile fibrosis. It is becoming increasingly recognised that the generation and activity of reactive oxygen and nitrogen species in the penis influence vascular homeostasis of this organ, with adverse effects exerted at cellular and molecular levels. Furthermore, these elements may interact with molecular signalling pathways operating in the penis, modulating their functional roles. This interaction in particular suggests that by accessing molecular targets associated with oxidative/nitrosative stress in the penis, new pharmacotherapeutic approaches may be developed to promote normal erectile ability and preserve erectile tissue health. This notion pertains to, but also extends beyond, interventions which predictably target components of the nitric oxide-based signal transduction pathway for the on-demand treatment of erectile dysfunction. The next line of pharmaceuticals for disorders of the penis, in general, may well spawn from an integrative understanding of the complex regulatory interactions influenced by, as well as influencing nitric oxide signalling in this organ.     

Nitric oxide/redox-based signalling as a therapeutic target for penile disorders

Oxidative and/or nitrosative stress is implicated in the pathogeneses of assorted penile disorders of clinical significance, notably erectile dysfunction, priapism and penile fibrosis. It is becoming increasingly recognised that the generation and activity of reactive oxygen and nitrogen species in the penis influence vascular homeostasis of this organ, with adverse effects exerted at cellular and molecular levels. Furthermore, these elements may interact with molecular signalling pathways operating in the penis, modulating their functional roles. This interaction in particular suggests that by accessing molecular targets associated with oxidative/nitrosative stress in the penis, new pharmacotherapeutic approaches may be developed to promote normal erectile ability and preserve erectile tissue health. This notion pertains to, but also extends beyond, interventions which predictably target components of the nitric oxide-based signal transduction pathway for the on-demand treatment of erectile dysfunction. The next line of pharmaceuticals for disorders of the penis, in general, may well spawn from an integrative understanding of the complex regulatory interactions influenced by, as well as influencing nitric oxide signalling in this organ.     

Pembrolizumab for advanced penile cancer: a case series from a phase II basket trial

Investigational New Drugs - Background: Treatment options for unresectable, locally advanced or metastatic penile squamous cell carcinoma (SCC) are limited. Previous studies have shown that...     

Combination of docetaxel and cetuximab for penile cancer: a case report and literature review

Guidelines on the treatment of metastatic squamous cell carcinoma of the penis are limited to a few prospective trials. Cisplatin-based regimens represent the standard of treatment with promising activity of taxanes. Recently, epidermal growth factor receptor overexpression has been shown in these patients. We treated an elderly man with a docetaxel-cetuximab combination after failure of the cisplatin regimen. We observed a necrosis of the inguinal lymph nodes and a reduction of (18)F-fluorodeoxyglucose uptake at PET/CT scan. Only mild mucositis and skin toxicity had been detected. Our case report, the first in the literature, shows that this combination is active and well tolerated in penile squamous cell carcinoma.     

Novel targeted therapies for the treatment of penile cancer

Introduction: The treatment of penile cancer has changed over the past decade in that it was primarily a surgically managed disease and those with locally advanced or metastatic disease uniformly had a very poor prognosis. However, with the use of better traditional systemic chemotherapeutic agents in the neoadjuvant and adjuvant settings, the disease-specific survival and general outlook has improved. However, there is still a large group of patients who will progress even while on systemic therapy. It is in those patients where the application of targeted therapies has been investigated with some experiencing partial or even complete responses. With the improvement seen in patients with chemotherapy refractory disease, the application of novel targeted agents in the neoadjuvant setting may have a resultant positive impact on patient survival.

Areas covered: This review includes research pertaining to targeted therapies, biomarkers and signaling pathways involved with penile cancer. The article was based on a literature search using the keywords ‘penile cancer’ and ‘targeted therapies’.

Expert opinion: Penile cancer at the advanced stages of the disease has a high mortality. The utilization of novel targeted therapies in these situations is warranted in combination with, or sequentially with, traditional cytotoxic chemotherapy to improve the patient survival rate. Personalized therapy is nearly here for penile cancer and should be made real within the next decade.     

磨牙残根修复的临床观察

目的 探讨磨牙残根保留修复的有效方法.方法 对进行磨牙残根修复的81例患者共98颗患牙采用插销式分体桩核+全冠修复磨牙残根,制作单冠或固定桥基牙,进行0.5～2年的临床观察,评价其修复效果.结果 本组98颗患牙无1颗发生桩核或全冠松动脱落,综合其他临床评价指标成功94颗,成功率为95.92%.结论 适应证选择适当,临床操作恰当、插销式分体桩核+全冠修复磨牙残根可取得较好的临床效果,但尚需更长时间观察.     

酮康唑抑制术后阴茎勃起的临床应用

目的:探讨酮康唑抑制阴茎手术术后勃起的临床疗效.方法:78例行阴茎手术的患者于术前检查谷氨酸丙酮酸转移酶和r-谷氨酰转移酶,随机分成3组,A组从术前1d开始至术后第3d;B组从手术当天开始至术后第4d,口服酮康唑400mg/次,3次/d;C组从术前第1d开始至术后第3d,口服乙烯雌酚1mg/次,3次/d,术后观察患者阴茎勃起的次数及持续时间,并复查谷氨酸丙酮酸转移酶(GPT)和r-谷氨酰转移酶(r-GT).结果:A组抑制有效率96.15%,B组有效率88.45%,C组有效率61.54%,三组间比较有显著差异(x2=11.46,P＜0.05),A、B两组间也有显著差异(x 2=4.33,P＜0.05),除C组中有一例患者术后出现谷丙转氨酶异常外,其余患者上述两项检测均正常.结论:酮康唑是一种有效的、防止术后阴茎勃起的药物,其抑制术后阴茎勃起效果比乙烯雌酚好,短期内用药不影响肝功能,术前一日给药效果更佳.     

The impact of a family empowerment intervention on juvenile offender heavy drinking: a latent growth model analysis

We report the results of a growth model analysis of the impact of a Family Empowerment Intervention (FEI) on the heavy drinking over a 36-month follow-up period among youths processed at the Hillsborough County Juvenile Assessment Center. Families involved in the project were randomly assigned to either receive an Extended Services Intervention (ESI) or the FEI. Families in the ESI group received monthly phone contacts and, if indicated, referral information; FEI families received three one-hour, home-based meetings per week for approximately 10 weeks from a clinician-trained paraprofessional. By seeking to improve family functioning by empowering parents, it was hypothesized that target youths' behavior and psychosocial functioning would improve. Although the difference between FEI and ESI was not significant, the reported frequency of getting very high or drunk on alcohol declined more over time for FEI completers than FEI noncompleters. The results provide support for the impact of the FEI services.     

Vascular prosthesis made of polyester threads for microsurgery

The results of experimental and medical application of worked out by the authors synthetic microvascular prosthesis with the internal diameter from 1 to 3 mm. The prostheses were implanted to the abdominal aorta and to the tail vein of rats and also to femoral and carotid arteries of cats for a period of 1 till 15 months. The angiographic and morphologic experiments of blood flow were carried out. The patency of the microprosthesis in the experiments was to 92.7%. The micro-implant adaptation was characterized by complete tissue isolation of a synthetic skeleton with formation of thin and even internal membrane covered with endothelium layer. In fact the possibility of arterial and venous prostheses having a 1-2 mm diameter with synthetic substitutional textile products creates new possibilities for the further development of the microvascular surgery. The microvascular prosthesis was applied to 10 patients in plastic surgery of small circumferential arteries of limbs achieving positive results.     

EP 91073 prevents EP 80661-induced penile erection: new evidence for the existence of specific EP peptide receptors mediating penile erection

The effect of EP 91073, EP 51389, EP 70555 and EP 51216, peptide analogues of the growth hormone releasing peptide hexarelin, on penile erection induced by EP 80661 or EP 60761 injected into the paraventricular nucleus of the hypothalamus, was studied in male rats. Of the above peptides only EP 91073 (0.2-1 microg) was found capable of reducing penile erection induced by EP 80661 or EP 60761, when given into the paraventricular nucleus. Despite its ability to prevent EP peptide-induced penile erection, EP 91073 (1 microg) was unable to prevent penile erection induced by the dopamine receptor agonist apomorphine (50 ng), oxytocin (30 ng) and N-methyl-D-aspartic acid (50 ng), when given into the paraventricular nucleus 10 min prior to the above substances. The EP 91073-induced prevention of penile erection occurred with a reduction in the increase in nitric oxide production that occurs in the paraventricular nucleus concomitant to penile erection induced by EP 80661 and EP 60761, as measured by intracerebral vertical microdialysis. The present results are in line with the hypothesis that EP 80661 and EP 60761 induce penile erection by activating specific receptors in the paraventricular nucleus, located possibly in oxytocinergic neurons mediating penile erection, and show that EP 91073 acts as an antagonist of these EP peptide receptors mediating penile erection.     

阴茎背神经切断术治疗早泄临床疗效观察

目的:观察阴茎背神经部分切断术治疗早泄的疗效。方法:从2009年开始运用阴茎背神经部分切断术治疗158例原发性早泄患者,并记录手术前后各项观察指标以评估该手术的临床疗效。结果:158例中有效87例,好转59例,无效12例。患者术前射精潜伏期时间为(0.78±0.35)min,性交满意度为(5.73±1.54)分,阴茎生物震感阈值(2.8±1.1)V;术后6个月射精潜伏期时间为(6.32±4.21)min,性交满意度为(11.93±2.71)分,阴茎生物震感阈值(6.2±1.6)V。结论:阴茎背神经部分切断术有效率高,安全性高。     

Nitrergic-noradrenergic interaction in penile erection: a new insight into erectile dysfunction

Penile erection is regulated by two opposing systems: noradrenergic (anti-erectile) and nitrergic (pro-erectile) neurotransmission. Noradrenaline released from sympathetic nerves causes contraction of the blood vessels and smooth muscle of the penile corpus cavernosum, thus leading to detumescence of the penis. Nitric oxide (NO) released from nitrergic nerves causes relaxation of the smooth muscle of the corpus cavernosum, thus allowing engorgement of blood into the cavernous space and leading to erection. Nitrergic neurotransmission is known to modulate noradrenergic responses. We have recently shown that the degree of this modulation varies among species. In the human corpus cavernosum, noradrenergic responses are under nitrergic control, such that even pharmacological concentrations of noradrenaline fail to show an effect when nitrergic neurotransmission is operating. This situation is similar in the monkey and rabbit, where nitrergic neurotransmission does not merely modulate but actually controls the sympathetic responses; however it differs in the rat, mouse and dog where the sympathetic system is predominant. Our recent work has demonstrated that the interaction between the two systems occurs in the smooth muscle, suggesting a physiological antagonism. Our observations suggest that the key element in this interaction is intracellular calcium in the smooth muscle. The nitrergic pathway causes a decrease in intracellular calcium concentrations thus leading to relaxation of the smooth muscle. Noradrenergic stimulation, in contrast, elicits an increase in the intracellular calcium concentrations thus leading to a contraction. The neuronal pathway which controls the concentrations of intracellular calcium in the smooth muscle determines the dominance of that pathway over the other. Nitrergic dominance over noradrenergic system in the human corpus cavernosum also suggests a key role for this interaction in the pathophysiology of erectile dysfunction. Indeed, a nitrergic-noradrenergic imbalance in favor of the noradrenergic system has been implicated in penile tissues from patients with erectile dysfunction. However, the mechanism of this imbalance is not fully understood. In addition, since the present study has demonstrated that phosphodiesterase type V inhibitors can enhance and prolong the nitrergic control of noradrenergic responses, such compounds may have therapeutic potential in impotence, where defective nitrergic transmission is accompanied by increased noradrenergic activity.     

Insulin resistance in penile arteries from a rat model of metabolic syndrome

BACKGROUND AND PURPOSE

Metabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vascular effects of insulin in penile arteries and whether these effects are impaired in a rat model of insulin resistance and metabolic syndrome.

EXPERIMENTAL APPROACH

Penile arteries from obese Zucker rats (OZR) and their counterpart, lean Zucker rats (LZR), were mounted on microvascular myographs and the effects of insulin were assessed in the absence and presence of endothelium and of specific inhibitors of nitric oxide (NO) synthesis, phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). Insulin-induced changes in intracellular Ca²⁺ concentration [Ca²⁺]_i were also examined.

KEY RESULTS

OZR exhibited mild hyperglycaemia, hypercholesterolemia, hypertryglyceridemia and hyperinsulinemia. Insulin induced endothelium- and NO-dependent relaxations in LZR that were impaired in OZR. Inhibition of PI3K reduced relaxation induced by insulin and by the β-adrenoceptor agonist isoprenaline, mainly in arteries from LZR. Antagonism of endothelin 1 (ET-1) receptors did not alter insulin-induced relaxation in either LZR or OZR, but MAPK blockade increased the responses in OZR. Insulin decreased [Ca²⁺]_i, a response impaired in OZR.

CONCLUSIONS AND IMPLICATIONS

Insulin-induced relaxation was impaired in penile arteries of OZR due to altered NO release through the PI3K pathway and unmasking of a MAPK-mediated vasoconstriction. This vascular insulin resistance is likely to contribute to the endothelial dysfunction and erectile dysfunction associated with insulin resistant states.