Metastatic serous carcinoma of the testis: a case report and review of the literature

Serous tumours of the testis and paratestis are rare, with fewer than 50 cases reported in the literature. The majority of the reported cases have been borderline serous tumours, and these tend not to recur or metastasize. Conversely, serous carcinomas can metastasize but this is often a late event. The presence of invasion in an otherwise borderline tumour has also been associated with the development of metastatic disease several years later, thus highlighting the importance of extensive sampling of all cases of borderline serous tumours. We report a case of a young man diagnosed with serous carcinoma of the testis, occurring 18 years after first diagnosis of a testicular germ cell tumour in the contralateral testis. This pattern has not previously been reported.     

Patterns of Cigarette Smoking Initiation in Two Culturally Distinct American Indian Tribes

Objectives. To better understand patterns of initiation among American Indians we examined age-related patterns of smoking initiation during adolescence and young adulthood in 2 American Indian tribes. Methods. We used log-rank comparison and a Cox proportional hazard regression model to analyze data from a population-based study of Southwest and Northern Plains American Indians aged 18 to 95 years who initiated smoking by age 18 years or younger.Results. The cumulative incidence of smoking initiation was much higher among the Northern Plains Indians (47%) than among the Southwest Indians (28%; P < .01). In the Southwest, men were more likely than women to initiate smoking at a younger age (P < .01); there was no such difference in the Northern Plains sample. Northern Plains men and women in more recent birth cohorts initiated smoking at an earlier age than did those born in older birth cohorts. Southwest men and women differed in the pattern of smoking initiation across birth cohorts as evidenced by the significant test for interaction (P = .01).Conclusion. Our findings underscore the need to implement tobacco prevention and control measures within American Indian communities.Smoking rates in the US population have declined overall in the past several decades, from a high of 42% in 1960 to an estimate of 21% in 2007.¹ However, this decline has not been observed among all racial/ethnic groups nor among all age groups. The prevalence of smoking among American Indians and Alaska Natives, for example, is greater than 50% in many communities, roughly 2.5 times the prevalence in the US general population.^2–7 Furthermore, over the past 3 decades, rates of smoking have been rising in some tribal communities that have historically low rates,^2,8 roughly paralleling the increases in smoking-related diseases, including lung cancer and respiratory and cardiovascular diseases, in American Indians and Alaska Natives.^9,10 Smoking also contributes to the observation that American Indians and Alaska Natives trail only African Americans in years of potential life lost,¹¹ a key indicator of population health. Finally, adverse health outcomes associated with smoking are adding inordinately high health care costs to a dramatically underfunded Indian Health Service.¹²One of the key factors linked to nicotine dependence is age of smoking initiation. Studies have shown that an earlier age of smoking initiation is related to current and daily smoking^13,14 and that the transition from smoking initiation to established smoking generally takes 2 to 3 years.^15,16 However, a more recent study among a cohort of sixth graders reported that youth were susceptible to a rapid loss of autonomy over tobacco. This occurred within 1 or 2 days of first inhalation, and dependency was likely to appear before reaching a consumption rate of 2 cigarettes per day.¹⁷ In addition, smokers who begin smoking at younger ages are more likely than those starting later to develop nicotine dependence, thus making quitting more difficult.^13,14,18Studies among African Americans have revealed major declines in smoking prevalence among adolescents during the 1980s, which were offset by increased initiation among young adults during this period.¹⁹ Such data helped to enhance public health efforts to promote cessation and discourage initiation among African Americans. However, little is known about patterns of smoking initiation among American Indians and Alaska Natives. In a recent survey of South Dakota high school students, more than 45% of American Indian adolescents who were smoking reported starting to smoke before the age of 13 years.²⁰ To better understand the patterns of smoking initiation among American Indians, we conducted a study that examined the age of smoking initiation in 2 culturally distinct American Indian tribal groups across birth cohorts.     

Immunogenicity of biologically-derived therapeutics: Assessment and interpretation of nonclinical safety studies

An evaluation of potential antibody formation to biologic therapeutics during the course of nonclinical safety studies and its impact on the toxicity profile is expected under current regulatory guidance and is accepted standard practice. However, approaches for incorporating this information in the interpretation of nonclinical safety studies are not clearly established. Described here are the immunological basis of anti-drug antibody formation to biopharmaceuticals (immunogenicity) in laboratory animals, and approaches for generating and interpreting immunogenicity data from nonclinical safety studies of biotechnology-derived therapeutics to support their progression to clinical evaluation. We subscribe that immunogenicity testing strategies should be adapted to the specific needs of each therapeutic development program, and data generated from such analyses should be integrated with available clinical and anatomic pathology, pharmacokinetic, and pharmacodynamic data to properly interpret nonclinical studies.     

A facile synthesis of alpha,alpha'-(EE)-bis(benzylidene)-cycloalkanones and their antitubercular evaluations

An economical and facile synthesis of alpha,alpha'-(EE)-bis(benzylidene)-cycloalkanones was achieved by the reaction of cycloalkanones with different aromatic aldehydes using ethanolic KOH in good yields. Few of the selected compounds were reduced with NaBH(4) to the respective alpha,alpha'-(EE)-bis(benzylidene)-cycloalkanols. All these compounds and our earlier synthesized cyclohexyl phenyl methanols were evaluated for their antitubercular, antifungal and antibacterial activities. Several compounds displayed moderate antitubercular activity with MIC=12.5-1.56 microg/mL. However, none of the compounds displayed any significant antifungal activity.     

Gene therapy to prevent occlusion of venous bypass grafts

Revascularization with vein grafts is standard surgical therapy for occlusive arterial diseases. Autologous saphenous vein grafts are important conduits for repairing blocked coronary arteries and are used in the majority of vein graft procedures. Up to 50% of saphenous vein grafts will be occluded during the first decade after surgery. Vein graft occlusion occurs as a result of neointimal hyperplasia, which takes place in response to hemodynamic changes and vessel wall injury, and is characterized by the migration and proliferation of vascular smooth muscle cells. Intimal hyperplasia is further complicated by the concomitant development of atherosclerosis and thrombosis. In the absence of effective pharmacological interventions for the treatment and prevention of occlusive vein graft disease, gene therapy has emerged as a potential therapeutic alternative. Gene therapy could improve vein graft patency by reducing early thrombosis, neointimal hyperplasia and atherosclerosis. In this review we will summarize the emerging applications of gene therapy as a therapeutic tool in occlusive vein graft disease.     

Childhood Vitiligo: Clinicoepidemiologic Profile of 268 Children from the Kumaun Region of Uttarakhand,India

Childhood vitiligo differs from adult vitiligo in many clinical parameters. The objective of the current study was to study the clinicoepidemiologic profile of childhood vitiligo and to compare various clinical characteristics of childhood‐ and later‐onset vitiligo. The clinical presentation of vitiligo was examined and analyzed in 762 individuals attending the Dermatology Clinic of Government Medical College, Haldwani, a referral center for the Kumaun region of Uttarakhand state, India, between January 2006 and December 2010. Of the 762 individuals with vitiligo, 268 (35.2%) were children: 152 (56.7%) female and 116 (43.3%) male. The mean age of onset of vitiligo was 6.9 years. A family history of vitiligo was found in 24.3% of children. The most common site of onset was the head and neck (36.9%), followed by the lower limbs and trunk. The most common type of vitiligo observed was acrofacial vitiligo (38.1%), followed by vulgaris, segmental, focal, and mucosal. Leukotrichia was observed in 32.5% of children and Koebner's phenomenon in 24.3%. On comparison of childhood‐ and later‐onset vitiligo, there were statistically significant differences (p < 0.05) in sex, family history, type of vitiligo (segmental and vulgaris), and site of onset. Atopic dermatitis was one of the important cutaneous diseases associated with childhood‐onset vitiligo. Thirty‐five percent of all patients with vitiligo were children (≤12 yrs). Childhood‐onset vitilgo differs from later‐onset vitiligo in many clinical parameters such as sex, family history, types of vitiligo, and sites of onset.