Prenatal tobacco exposure and psychiatric outcomes in adolescence: is the effect mediated through birth weight?

OBJECTIVE: This study aims to examine the associations between prenatal exposure to maternal smoking, birth weight and persistent offspring psychiatric symptoms. Additionally, we aim to examine whether the relationship between prenatal maternal smoking and persistent offspring psychiatric symptoms is mediated by offspring birth weight. METHODS: This study used the Growing Up in Ireland (GUI) longitudinal cohort. The GUI is a nationally representative longitudinal study of children which consisted of three data collection waves, at ages 9, 13, and 17 years. Logistic regression analysis was used to examine associations between prenatal tobacco exposure, and offspring psychiatric symptoms. Linear regression was used to examine associations between prenatal tobacco exposure and offspring birth weight. We conducted a mediation analysis examining potential etiological pathways linking maternal smoking during pregnancy, offspring birth weight, and later offspring psychiatric symptoms. All analyses were adjusted for confounders including household income, maternal level of education, and family psychiatric history. Additionally, examination of birth weight and subsequent psychiatric symptoms also was controlled for prematurity. RESULTS: We found that the association between prenatal tobacco exposure and later psychiatric symptoms is mediated by birth weight. CONCLUSIONS: This work provides further evidence that maternal smoking during pregnancy is an important modifiable lifestyle factor that has an impact not just on the physical health of offspring but also their mental wellbeing. Supporting women with structured smoking cessation programs at the earliest stages of pregnancy should be a public health priority.

The association between subjective maternal stress during pregnancy and offspring clinically diagnosed psychiatric disorders.

OBJECTIVE: Exposure to prenatal stress is a ubiquitous and non-specific risk factor for adverse outcomes in adulthood. In this study, we examined associations between exposure to subjective maternal stress during pregnancy and subsequent diagnosis of psychiatric disorders in offspring. METHOD: This study used the Helsinki Longitudinal Temperament Cohort, a prospective birth cohort of individuals born between 1 July 1975 and 30 June 1976 in Helsinki, Finland. The sample for this study comprised 3626 infants whose mothers had completed health and well-being assessments during pregnancy which included a measure of self-reported stress. We ran logistic regressions to assess potential associations between prenatal stress and offspring psychiatric disorder in adulthood, identified through the Finnish Hospital Discharge Register. RESULTS: Individuals whose mothers reported stress during pregnancy had significantly greater odds of developing a psychiatric disorder (OR = 1.41, 95% CI = 1.10-1.81) particularly a mood disorder (OR = 1.67, 95% CI = 1.10-2.54). These associations remained after adjusting for parental psychiatric history, and other prenatal factors. CONCLUSIONS: Individuals exposed to prenatal stress had significantly increased risk of developing psychiatric disorders later in life. This finding highlights the importance of supporting the mental health and emotional well-being of women during pregnancy.

Fertility preservation in the male: from childhood to adulthood.

Approximately 50% of males will develop cancer during their lifetime. In the past, oncologic therapies have largely been focused primarily on cure of the underlying malignancy. With improvements in both diagnostic modalities and treatments, pediatric and adult cancer patients are routinely surviving their disease. For this large group of patients, survivorship issues have become a major concern. Central among these survivorship issues is fertility. For males diagnosed with a malignancy, impaired reproductive potential is often noted even before any cancer therapy has been initiated. Furthermore, cancer treatments, in the form of chemotherapy, radiation therapy, and surgery, can all have potentially deleterious and lasting effects on male reproductive capability. For these reasons, a change in oncologic treatment paradigms has occurred. Now, the offer of fertility preservation to males diagnosed with cancer is a key component of comprehensive oncologic care.

Ethical, moral, and theological insights into advances in male pediatric and adolescent fertility preservation.

The successful treatment of boys with cancer has led to increasing attention to preserving their quality of life after completing cancer therapy. One of the top priorities for living a full life is keeping open the opportunity to have children. While sperm banking for males facing sterilizing cancer treatment can be effective, this approach requires subsequent use of reproductive procedures such as in vitro fertilization (IVF) or intrauterine insemination (IUI) to achieve a pregnancy. Advances in fertility preservation techniques may allow pre-pubertal boys to conceive using advanced stem cell technologies and stem cell transplantation in the future. This review summarizes the ethical positions of leading medical societies and explores the religious and moral stances of major religious institutions regarding these options.

Protein and gene expression of nitric oxide synthase isoforms I and III in the rat penile shaft.

Nitric oxide synthase (NOS) plays a key role in penile smooth muscle relaxation through the regulation of nitric oxide (NO). NO is a major neurotransmitter in the autonomic nervous system, and alteration of its activity has been implicated in erectile dysfunction. The objectives of this study were twofold: 1) to demonstrate and localize the NOS protein isoforms I and III in the normal rat penis, and 2) to identify and quantitate NOS I and III gene expression in the normal rat penis. The gene and protein product of NOS isoforms I and III are expressed in rat penile tissue. Protein expression of NOS I was confined primarily to neuronal tissue, while NOS III protein expression was identified primarily in both cavernosal smooth muscle and endothelium. The presence of both NOS I and III was confirmed in the penile shaft by Western blot. Quantitation of NOS I and III gene expression by reverse transcription-polymerase chain reaction revealed NOS III to be more highly expressed than that of NOS I in the rat penile shaft. NOS I and III protein and gene products are both expressed in normal rat penile tissue. Protein expression is localized primarily to neuronal tissue for NOS I, whereas NOS III is localized primarily to cavernosal smooth muscle and endothelium. NOS III gene expression is greater than that of NOS I in the normal rat penile shaft. These findings support the possibility that penile erection is regulated by different NOS isoforms released from neural, endothelial, and smooth muscle sources.

Nine critical elements of promising violence prevention programs.

To identify approaches to school-based violence prevention that are most promising and those that may not be effective, a review of the literature was conducted. In addition, telephone interviews were conducted with 15 experts on topics related to school-based violence prevention. Nine critical ingredients of promising approaches to violence prevention were identified. Specifically, the approaches are comprehensive and multifaceted; begin in the primary grades and are reinforced across grade level; are developmentally tailored: and cover appropriate content area. Appropriate content areas include information; anger management; social perspective taking; decision making and social problem solving; peer negotiation and conflict management; social resistance skills; active listening and effective communication; and material on prejudice, sexism, racism and male-female relationship. In addition, promising programs use interactive teaching techniques, are culturally sensitive, and provide teacher training. They promote a positive school climate and foster norms against violence. Six violence prevention activities that appear not to be effective are also discussed. The authors conclude with a discussion of the need for more rigorous evaluation of violence prevention programs.

Comparison of tunica albuginea substitutes for the treatment of Peyronie's disease.

PURPOSE: Peyronie's disease is a connective tissue disorder resulting in fibrotic plaque formation on the tunica albuginea of the penis. One approach to repair consists of plaque excision and patching with one of many potential patch materials. Because the optimal patch material for covering the resultant defect has not been determined, this study compares histological and cavernosometric changes in the penis as a result of the placement of three different types of patch grafts used in surgery for Peyronie's disease. MATERIALS AND METHODS: Eleven mongrel dogs were divided into three groups, each receiving a different patch material (superficial dorsal penile vein, silicone fabric, and dermabraded preputial flap). Each dog had dynamic infusion cavernosometry (DIC) performed prior to placement of the patch over a 6 x 3 mm. defect surgically created in the tunica albuginea. Three months later, DIC was repeated prior to sacrifice. Histology of the penis was examined using Masson's trichrome, and hematoxylin and eosin stains. RESULTS: The only difference among the cavernosometric parameters (preop versus postop) was a higher initial pressure in the dermabraded preputial flap group postoperatively. The dogs undergoing vein patch had moderate fibrosis with apparent reformation of the tunica albuginea over the patch site. The normal venous architecture of the graft was no longer recognizable. Those dogs receiving a silicone patch had moderate fibrosis with a fibrous sheath of compressed histiocytes and fibroblasts enveloping the graft site. Finally, the dermabraded preputial flap patch group had mild-moderate fibrosis with focal loss of the cavernosal space underlying the flap. CONCLUSIONS: We feel that continued use of the vein patch for repair of Peyronie's disease is warranted.

One core positive prostate biopsy is a poor predictor of cancer volume in the radical prostatectomy specimen.

PURPOSE: In view of the recent increase in patients presenting with only 1 core positive for prostate carcinoma, we examined the correlation in tumor volume between the biopsy and the subsequent radical prostatectomy specimen. MATERIALS AND METHODS: We studied a total of 169 consecutive prostate biopsies with matched radical prostatectomy specimens and selected 48 patients with only 1 positive core. RESULTS: Cancers found in the biopsy regardless of their size were associated with a wide range of cancer volume in the radical prostatectomy specimens, and the amount of cancer in the biopsy was a poor predictor of the volume of cancer in the prostatectomy specimen. Even with a cancer of 3 mm. or less in the biopsy, 57% of patients had cancer of clinically significant volume (greater than 0.5 ml.). Other modalities for the evaluation of prostate cancer such as Gleason score and clinical stage were not helpful in segregating patients with clinically significant from those with insignificant volume of cancer. However, when combined with a preoperative serum prostate-specific antigen higher than 10 ng./ml., 1 core positive biopsy could reliably predict the presence of cancer of significant volume. CONCLUSIONS: One core only positive prostate biopsy, when accompanied by an elevated serum prostate specific antigen value (greater than 10 ng./ml.), strongly suggests the presence of clinically significant cancer.

Microanatomy and morphometry of the hydronephrotic "obstructed" renal pelvis in asymptomatic infants.

There has been limited histological study of the obstructed ureteropelvic junction in patients less than 1 year old. We present our prospective studies on the histomorphometry of the ureteropelvic junction complexes of 35 infants, of whom 23 underwent pyeloplasty for obstruction and 12 were age matched autopsy normals. Qualitatively, the major abnormalities of the pelvic microanatomy in the hydronephrotic obstructed kidneys included a lamina muscularis that was significantly thicker than normal and the presence of collagen fibers between muscle fascicles. Additionally, variable amounts of elastin were present in the adventitia and lamina muscularis. At the ureteropelvic junction the abnormalities were an increase in the number of inner longitudinal muscle bundles, collagen between muscle bundles (p less than 0.016) and elastin in the adventitia. Quantitatively, for the pelvis the lamina muscularis was significantly thicker in 18 obstructed kidneys compared to 7 controls (1,075 +/- 79 mu. versus 420 +/- 63 mu., mean +/- standard error of mean, p less than 0.001). The percentage area density of smooth muscle in the obstructed versus normals was increased (45.1% versus 35.2%, p less than 0.039). The percentage area density of collagen in the obstructed specimens versus normal showed an upward trend (38.6% versus 27.6%), which was not significant. In conclusion, the obstructed ureteropelvic junction complexes of kidneys in asymptomatic infants show significant qualitative and quantitative differences from normal.

The usefulness of touch preparation cytological evaluation and prostatic capsule involvement in prediction of prostate cancer recurrence.

PURPOSE: Touch preparation cytology has been used in oncology as a technique to assist in predicting local tumor recurrence. We prospectively investigated the relationship between this cytological evaluation and the standard histological method of assessing specimens, measuring the distance from the tumor to the various anatomical boundaries and disease recurrence in radical retropubic prostatectomy patients. MATERIALS AND METHODS: In a prospective study of 91 consecutive clinical stages T1c and T2 cancer cases radical retropubic prostatectomy touch preparation cytology was performed intraoperatively in an anatomical fashion (apex, posterior, lateral right and left, and base). A single blinded cytopathologist reviewed all prostate touch preparation specimens and categorized them as malignant, benign or atypical cells. Benign or atypical cells were classified as negative cytology. Detailed histological margin analysis of the surgical specimens was also done in which distances between the tumor front, and prostate capsule (inner and outer edge) and surgical margins (apex, posterior, right and left lateral, and base) were measured. All specimens were re-staged by the same pathologist. Median followup was 38 months. Disease recurrence was determined biochemically (prostate specific antigen), and with bone scans, prostatic fossa biopsies and digital rectal examinations. RESULTS: Of the 91 specimens 25 were excluded from study because distance measurements could not be made for technical reasons. Multivariate analysis was performed on the remaining 66 patients based on the variables of stage, age, cytology status, distance from tumor to the inner prostatic capsule, distance from tumor to the surgical margin and postoperative Gleason sum. The only variable with independent prognostic value was postoperative Gleason sum (p = 0.04). Cytology status was not statistically significant (p = 0.07) nor were distance data to the inner capsule (p >0.05) and surgical margin (p >0.05). CONCLUSIONS: Although touch preparation cytology does not enhance prognostic information already provided by Gleason sum, it does correlate highly with postoperative Gleason sum. Other gross macroscopic variables, that is pathological stage, margin status and distance measurements, although lacking in independent predictive value, correlated with postoperative Gleason sum. The constancy of Gleason sum leads us to believe that the key to predicting prostatic cancer behavior lies not on the macroscopic but on the molecular or cellular level. Of the various factors analyzed in this study postoperative Gleason sum remains the most powerful predictor of recurrence risk.

Side-effect profile of sildenafil citrate (Viagra) in clinical practice.

OBJECTIVES: Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction. Initial studies reported a high tolerability and low incidence of certain characteristic adverse reactions. We sought to evaluate the incidence of side effects of sildenafil citrate, independent of industry support and constraints, utilizing a heterogeneous cohort of patients from a university-based practice. METHODS: A prospective, open-label, flexible-dose study of 256 patients treated with sildenafil citrate for erectile dysfunction was performed at a single institution. The patients were questioned explicitly about the occurrence of headache, flushing, dyspepsia, nasal congestion, visual changes, and other side effects. RESULTS: The adverse reactions most commonly observed were flushing (30.8%), headache (25. 4%), nasal congestion (18.7%), and heartburn (10.5%). All events were short lived and mild in nature. In the present study, 31.6% of patients experienced one or more adverse events. However, no one withdrew from the study because of the severity of these events. There was a significant association between higher doses and the occurrence of side effects. CONCLUSIONS: The incidence of adverse events attributable to sildenafil citrate may be higher than initially reported, but an explanation may be the methodology of data collection and the industry-independent nature of this study. The side-effect profile is dose related and mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile dysfunction.