Smoking Could Harm Sperm


Two new studies provide evidence that smoking can harm sperm – both in smoking men who may become fathers, and in sons born to women who smoked during pregnancy.

The research also suggests that both men and women who hope to conceive should kick the habit.

“The results of the present study suggest a negative biological effect of smoking on spermatozoa DNA integrity,” said the lead author of one study, Dr. Mohamed E. Hammadeh, head of the assisted reproductive laboratory in the department of obstetrics and gynecology at the University of the Saarland in Saar, Germany.

Research by Hammadeh and his colleagues showed that men who smoke heavily may experience fertility problems stemming from a drop in levels of a protein crucial to sperm development, as well as damage to sperm’s DNA.

Another study suggests that women who smoke early in their pregnancy may ultimately compromise their sons’ reproductive health.

In the first study, Hammadeh’s team compared sperm from 53 heavy smokers (more than 20 cigarettes a day) against that of 63 nonsmokers.

After three to four days of sexual abstinence, a single semen sample was taken from all study participants, to measure levels of two forms of a specific type of protein found in sperm, called protamines. According to the researchers, protamines are key players in sperm development, helping to spur on the process by which chromosomes are formed and packaged during cell division.

Hammadeh and colleagues found that in the smoking group, one form of protamine appeared at levels that were 14 percent below concentrations observed in the sperm of nonsmoking men. This was enough to constitute a form of “protamine deficiency” and, in turn, raise risks for infertility among the smokers.

What’s more, smoking-linked “oxidative stress” appeared tied to an increase in damage to sperm DNA, the team reported.

According to Hammadeh, past attempts to clarify the relationship between cigarette smoking and male infertility have had trouble identifying a molecular mechanism underlying any such link. So he believes the new finding should help convince male smokers struggling with infertility to kick the habit.

“Because of the fact that cigarette smoke contains mutagens and carcinogens, there have been concerns that smoking may have adverse effects on male reproduction,” Hammadeh noted. The new findings help bear that out, he said.

The second study was led by Dr. Claus Yding Andersen, a professor of human reproductive physiology at the University Hospital of Copenhagen in Denmark. It focused on the impact of maternal smoking during the first trimester of pregnancy upon the development of the male fetus.

In this case, the authors analyzed tissue from the testes of 24 embryos that had been aborted between 37 and 68 days following conception.

After classifying the prospective mothers according to smoking habits, the research team found that the number of so-called “germ cells” — cells that develop into sperm in males and eggs in females — were 55 percent lower in the testes of embryos obtained from women who smoked. This observation held regardless of the mother’s alcohol and coffee consumption habits.

As well, embryonic levels of so-called “somatic cells” (those that go on to form other types of tissue) were 37 percent lower among those women who smoked.

In both the case of germ and somatic cells, drop-offs in levels appeared to be “dose-dependent,” meaning that the more the prospective mother smoked, the lower the number of cells grown by the embryo.

Based on these findings early in fetal growth, Anderson and his colleagues conclude that the apparent impact of smoking on cellular production might continue in male offspring carried to term. And that could mean a higher risk of impaired fertility in sons.

According to the Danish team, their earlier research involving female embryos also revealed “germ cell” reductions of about 40 percent for embryos taken from women who smoked during pregnancy. This suggests that maternal smoking in pregnancy may harm the reproductive health of both male and female offspring.

“Our results provide health care professionals who talk to women who are considering conceiving, or have conceived just recently, with a ‘here and now’ argument to convince them to stop smoking,” Anderson said. “Because the negative effect of smoking appears to take place right from conception and during the early days [of gestation], when the human embryo becomes differentiated into either a girl or a boy.”

source: nature medicine

Three-dimensional atomic imaging of crystalline nanoparticles


Determining the three-dimensional (3D) arrangement of atoms in crystalline nanoparticles is important for nanometre-scale device engineering and also for applications involving nanoparticles, such as optoelectronics or catalysis. A nanoparticle’s physical and chemical properties are controlled by its exact 3D morphology, structure and composition1. Electron tomography enables the recovery of the shape of a nanoparticle from a series of projection images2, 3, 4. Although atomic-resolution electron microscopy has been feasible for nearly four decades, neither electron tomography nor any other experimental technique has yet demonstrated atomic resolution in three dimensions. Here we report the 3D reconstruction of a complex crystalline nanoparticle at atomic resolution. To achieve this, we combined aberration-corrected scanning transmission electron microscopy5, 6, 7, statistical parameter estimation theory8, 9 and discrete tomography10, 11. Unlike conventional electron tomography, only two images of the target—a silver nanoparticle embedded in an aluminium matrix—are sufficient for the reconstruction when combined with available knowledge about the particle’s crystallographic structure. Additional projections confirm the reliability of the result. The results we present help close the gap between the atomic resolution achievable in two-dimensional electron micrographs and the coarser resolution that has hitherto been obtained by conventional electron tomography.

source: nature naotechnology

State of the art in the endoscopic imaging and ablation of Barrett’s esophagus


Barrett’s esophagus is the result of long-term acid reflux and is a precursor to esophageal adenocarcinoma. Surgical resection of the esophagus has been the mainstay of treatment for high grade dysplasia and early cancer. However, recent advances in the endoscopic imaging and ablation technologies have made esophagectomy avoidable in patients with dysplasia and superficial neoplasia. In this article, we review the most relevant endoscopic imaging technologies, such as chromoendoscopy, narrow band and autofluorescence imaging, and confocal laser endomicroscopy. We also review the various endoscopic ablation technologies, such as endoscopic mucosal resection, photodynamic therapy, radiofrequency ablation, and cryotherapy. Finally, we focus on the studies that evaluate the efficacy of these imaging and ablation technologies in finding and eradicating neoplastic Barrett’s esophagus.

source: science direct

Effects of sildenafil and vardenafil treatments on sleep quality and depression in hemodialysis patients with erectile dysfunction


ED is prevalent in hemodialysis (HD) patients, and closely related to poor sleep and depression. Efficacy of treating ED either with sildenafil or vardenafil has been shown to be beneficial in ameliorating concomitant depression in non-HD patients. It is yet to be shown whether treatment of ED with a PDE-5 inhibitor would improve poor sleep in HD patients. We aimed to compare the effects of sildenafil and vardenafil on sleep quality and depression in HD patients with ED. A total of 32 maintenance HD patients with ED randomized into two groups to receive either sildenafil or vardenafil for 4 weeks. After a 2-week washout and a crossover, each group received the other drug for another 4-week period. Sleep quality and depression were evaluated via post-sleep inventory (PSI) and Beck’s depression inventory (BDI), respectively, at baseline and at the end of the treatment. Sildenafil and vardenafil both improved PSI and BDI scores significantly compared with pretreatment values. However, there was no difference between sildenafil and vardenafil with respect to these parameters. PDE-5 inhibitors, sildenafil and vardenafil, caused a significant improvement in sleep quality and depression in this cohort of HD patients with ED.

source: International Journal Of Impotence

Is there a role for phosphodiesterase type-5 inhibitors in the treatment of premature ejaculation?


Premature ejaculation (PE) is considered to be the most common male sexual dysfunction. The realization that PE may co-exist with ED prompted the use of PDE5-i’s alone or in combination with selective serotonin reuptake inhibitors (SSRIs) for treating ejaculatory disorders. Until recently, there was little evidence that PDE5-i’s alone may have a role in the treatment of PE in the absence of ED, and current available treatments include only on-demand dapoxetine. However, available data indicate that there is clinical, anatomical, physiological, pharmacological and genetic evidence to explain the efficacy of PDE5-i’s. Nine manuscripts that examined the efficacy of PDE5-i’s in the treatment of PE, alone or in combination with SSRIs, were retrieved. All studies reported some significant changes in the intravaginal ejaculatory latency time and sexual satisfaction scores, although not all were clinically meaningful. Well-designed multicenter studies are urgently required to further elucidate the efficacy and safety, as well as the mechanisms of action of PDE5-i’s in the treatment of PE. The aim of this review is to discuss basic rationale and to show clinical evidence sustaining the possibility to use off-label PDE5-i’s to treat PE.

source: International Journal of Impotence

 

Radiotherapy for Breast Cancer and Cardiovascular Mortality


Observational findings confirm a long-suspected increase in long-term risk.

Cardiovascular disease remains an important complication of radiotherapy in breast cancer survivors, yet little is known about the impact of breast cancer radiotherapy on the long-term risk for cardiovascular death. To find out more, these investigators studied mortality and causes of death in more than 4500 women who were treated for breast cancer at a single institution in France between 1954 and 1984 and who survived at least 5 years. Median follow-up was 28 years.

Cardiovascular disease was the reported cause of 421 deaths, of which 236 were cardiac. Compared with women who had not received radiotherapy, women who had received radiotherapy had a significantly higher risk for dying of cardiac disease (relative risk, 1.76) and a nonsignificantly higher risk for dying of vascular disease (RR, 1.33). Importantly and unsurprisingly, in women who had been treated for a left-sided breast cancer, the risk for dying of cardiac disease rose with time to nearly double the risk of those treated for a right-sided breast cancer.

Comment: This study confirms that radiotherapy, as practiced over much of the twentieth century, increases the long-term risk for cardiovascular mortality. The increase is of particular concern in survivors treated for left-sided breast cancer. Given these results, we should consider developing strategies that specifically target breast cancer survivors for cardiovascular prevention, diagnosis, and treatment.

JoAnne M. Foody, MD

Published in Journal Watch Cardiology February 16, 2011

Alcohol at Bedtime May Not Help Your Sleep


Study Finds Fault With Popular Notion That a Drink Before Bed Will Help You Sleep Better
woman drinking wine at sunset

Feb. 15, 2011 — Do you drink a nightcap to help you sleep? It may not be as effective as you think, new research suggests.

One of the largest studies to date on alcohol’s effects on sleep shows that drinking alcohol before bed may disrupt sleep and increase wakefulness in healthy adults — affecting women more than men — regardless of family history of alcoholism.

The research is reported in the May 2011 issue of Alcoholism: Clinical & Experimental Research.

In the women studied, alcohol decreased sleep duration and efficiency (ratio of time sleeping in bed to total time spent in bed) and increased how often they woke up during the night. Alcohol deepened sleep during the first half of the night but then disrupted sleep during the second half of the night, a finding that previous studies have reported.

Study researcher J. Todd Arnedt, assistant professor of psychiatry and neurology at the University of Michigan, says in a news release: “It’s clear that a substantial portion of the population uses alcohol on a regular basis to help with sleep problems. This perception may relate to the fact that alcohol helps people fall asleep quickly and they may be less aware of the disruptive effects of alcohol on sleep later in the night.”

The study included 93 healthy adults in their 20s (59 women and 34 men) who were college students or recent college graduates; 29 of the participants had a family history of alcoholism.

The study took place over two nights. On the first night, researchers randomly gave participants an alcoholic beverage containing either vodka or bourbon mixed with caffeine-free cola. On the second night participants were given a “placebo” beverage with a few drops of bourbon or vodka floated on top.

The researchers instructed them to drink to intoxication. After researchers measured their breath alcohol concentration (BrAC), participants slept for eight hours between 11 p.m. and 7 a.m.

The participants were monitored during their sleep. Participants completed questionnaires on sleepiness and sleep quality before bedtime and when awakened the next morning.

Alcohol and Sleep: Men vs. Women

The findings showed that alcohol disrupted sleep more in women than in men at equivalent BrACs. Women’s total sleep time was reduced by 19 minutes, sleep efficiency decreased by 4%, and there was a 15-minute increase in the time they spent awake during the night after drinking alcohol, compared to the placebo.

“It is important to note that the peak BrACs were equivalent between men and women in our study, so the findings are not due to higher BrACs among the female subjects,” Arnedt says in the news release.

Sleep continuity following alcohol compared to placebo was not significantly different in men.  Researchers did not find differences in sleep measures among participants with a family history of alcoholism.

“These differences may be related to differences in alcohol metabolism,” according to Arnedt, “since women show a more rapid decline in BrAC following alcohol consumption than men.”

“We also do not believe that the differences,” Arnedt says, “were due to differences in alcohol experience because the prior alcohol use was also equivalent between the men and women.”

Further study may help researchers understand more about the relationship between sleep quality and the development of alcohol use disorders, he says.

source: webMD

ALZHEIMER DISEASE AND OTHER DEMENIA ON IMAGING


Alzheimer disease (Fig. 1A) is the most frequent cause of degenerative dementia. It shows an exponential increase with age. Moreover, the female-to-male prevalence of AD is 70% and is likely to be related to the increased life expectancy of women.

The assessment of the volume of medial temporal lobe on structural MRI can support clinical diagnosis.18 However, atrophy, sometimes found in Parkinson disease and mild cognitive impairment (MCI), remains unspecific.19 Moreover, an overlap between atrophy associated with healthy aging versus AD has been described.2 Brain SPECT reveals a specific pattern of abnormalities in AD by demonstrating reduced CBF in the medial temporal, superior temporal, parietal, posterior cingulate cortex, and precuneus before becoming diffuse and affecting the frontal cortex in advanced stages. Cerebral blood flow decrease is often asymmetric and sometimes unilateral at the beginning of the disease. The relative preservation of the primary cortex, the basal ganglia, and the cerebellum is generally reported. The presentation and severity of abnormalities are relatively well correlated with cognitive impairment and the clinical stage of dementia.3 On the basis of a postmortem pathologic diagnosis, the presence of SPECT abnormalities increases the likelihood of diagnosis of AD by 84% to 92% in patients with a clinical diagnosis of probable AD and 67% to 84% in patients with a clinical diagnosis of possible AD.20 Thus, brain SPECT could improve the validity of clinical diagnosis. Overall, brain SPECT is not useful when the diagnosis is clinically obvious but might help in the differential diagnosis of atypical forms of dementia. The development of new therapeutic strategies justifies the interest in the early identification of patients at risk of developing AD among those affected by amnesic MCI. The presence of hypoperfusion in the parietal cortex, temporal cortex, and posterior cingulate cortex or precuneus has been associated with a higher risk of conversion to AD among MCI patients.3,21,22

The sensitivity of brain SPECT to predict the conversion on the basis of a clinical diagnosis of AD varies among studies from 63% to 90% when a parietal cortex hypoperfusion has been found and the specificity is greater than 75%.3 As for a positive diagnosis, several studies have shown that the sensitivity of brain SPECT in the detection of this conversion is improved when it is combined with clinical parameters (neuropsychological assessment),3 morphological assessment (atrophy),23 or biological data (protein α-amyloid and tau protein in cerebrospinal fluid).24

DEMENTIA WITH LEWY BODIES

Dementia with Lewy bodies (DLB; Fig. 1B) is the second leading cause of degenerative dementia after AD.25 Brain SPECT revealed a diffuse cortical hypoperfusion similar to that found in AD. However, hypoperfusion in the primary cortex and a predominance of occipital abnormalities have been reported but not constantly found. Thus, visual hallucinations frequently observed in this condition are correlated to a marked hypoperfusion in the primary visual areas (Brodmann area 17) and occipital associative areas (Brodmann areas 18 and 19).25,26 More severe frontal hypoperfusion than in AD has also been reported. The sensitivity of brain SPECT in the differential diagnosis between AD and DLB is estimated at 65% with a specificity of about 80%. These values do not consider perfusion brain SPECT as an ideal tool in the differential diagnosis between AD and MCI. By contrast, dopamine transporter brain SPECT I123-Ioflupane (DaTSCAN, GE Healthcare, Velizy, France) increases the sensitivity from 64% to 83% and the specificity from 64% to 100% according to different studies.25

FRONTOTEMPORAL DEMENTIA

Frontotemporal dementia (FTD; Fig. 1C) is rarer than AD, representing less than 8% of dementia cases.27 Brain SPECT reveals the hypoperfusion of frontal and anterior temporal lobes.20 In the early stages of the disease, hypoperfusion might be asymmetric. With disease progression, parietal cortex hypoperfusion has been observed. Alzheimer disease with frontal component might clinically mimic FTD. In this case, brain SPECT might be useful in the differential diagnosis with a sensitivity of 71.5% and a specificity of 78.2%.

 

OTHER DEMENTIAS

In vascular dementia, brain SPECT can reveal the hypoperfusion in the territory of the infarct. White matter lesions, well described on MRI, might disturb the prefrontal subcortical circuit or thalamocortical circuit, leading to subcortical syndrome and executive deficits associated with frontal hypoperfusion. Abnormal vasoreactivity after acetazolamide challenge could be an additional argument in favor of vascular or mixed dementia,20 but this is less used in clinical practice.

Imaging studies of the usefulness of brain SPECT in the diagnosis of rare neurodegenerative dementia remain sparse. Thus, the frontoparietal hypoperfusion contralateral to the apraxia is reported in the corticobasal degeneration, whereas progressive supranuclear palsy is associated with frontal lobe hypoperfusion. Left temporal lobe hypoperfusion has been observed in nonfluent aphasia and temporopolar hypoperfusion in semantic dementia.20

PERFUSION BRAIN SPECT OR 18F-FLUORODEOXYGLUCOSE PET?

The direct assessment of neuronal metabolism by PET with 18F-fluorodeoxyglucose (18F-FDG) and the better spatial resolution suggest the superiority of PET with 18F-FDG in the early and differential diagnoses of dementia. However, this superiority is still a matter of debate.3 In addition, brain 18F-FDG PET is less available in some countries, whereas brain SPECT is widely available.

CONCLUSION

By providing functional information, brain SPECT can detect early neuronal dysfunction. It is complementary to clinical assessment and morphological imaging. Brain SPECT is useful in the early stages of the disease because it can predict the conversion from amnesic MCI to AD and help differentiate between different types of dementia. The recent advance in SPECT technologies, such as the developments in hardware technology and image processing algorithms and the introduction of hybrid SPECT/CT systems, increases the brain SPECT accuracy of the assessment of rCBF.14,29 In addition, the arrival of semiconductor technologies might in the coming years provide substantial reductions in brain SPECT acquisition time without sacrificing diagnostic quality.

Source: journal of CAT

BRAIN SPECT IMAGING


Brain SPECT allows the study of regional cerebral blood flow (rCBF).3 This is correlated at rest to the regional consumption of glucose and, as such, reflects neuronal activity. The functional changes that occur during neurodegenerative diseases might precede the onset of atrophy.4 Thus, the rCBF indirectly reflects neural activity in each brain region at rest, which allows for the earlier detection of functional abnormalities. These functional changes might precede the stage of symptomatic dementia status and thereby are helpful for screening patients at risk of dementia. In addition, brain SPECT could help overcome the mechanisms of cognitive reserve that allow some highly educated patients to achieve good results on psychometric assessments.5 Unlike nondiffusible tracers used routinely in MRI (gadolinium) and CT (iodine contrast agents), which explore the vascular compartment, diffusible tracers exploring the intracellular compartment are used in SPECT, and these allow the detection of neuronal dysfunction.

Hexamethyl-propylene-amine-oxime and ethyl cysteinate dimer are technetium-labeled (99mTc) tracers widely used in clinical practice. They enter cells because of their lipophilic character and remain trapped because of their conversion to hydrophilic compounds after a metabolic process. Most of the radiotracer enters the brain during the first pass; its incorporation is proportional to CBF in the first few minutes after injection. Modifications in CBF after injection do not change the initial distribution of the tracer because of its intracellular trapping.6 The widespread use of these molecules is facilitated by their relative safety. Indeed, its injection can be performed in a patient fasting or not and regardless of their kidney function or allergies. The contraindications remain, that is, lack of cooperation, pregnancy, or breastfeeding. Mothers should interrupt breastfeeding for 24 hours if SPECT is indicated.

The following acquisition parameters for brain SPECT have been recommended by scientific societies7,8: (a) rotational radius (the smallest possible [<15 cm], with appropriate patient safeguards); (b) a matrix (128 × 128); (c) an angular sampling (<3 degrees [360 degrees rotation]); (d) a total detected count of more than 5 million before scatter correction; and (e) a variable total scan time (depending on the imaging device for dual-head cameras, it is closer to 30 minutes, eg, 120 projections, 60 projections per head, 30 s/projection).

If possible, the currently available iterative reconstruction methods, including ordered-subset expectation maximization, should be preferred in data reconstruction because they can improve lesion detection accuracy. Postreconstruction filtering should generally use low-pass (eg, Butterworth) filters. American and European recommendations state that “Attenuation correction (AC) is recommended and should be performed in all cases”.7,8 The AC method is not defined, and only the European recommendations propose several methods including a calculated homogeneous matrix according to the Chang method (linear attenuation coefficient for 99mTc: μ = 0.12 – 0.14 cm−1) or a measured matrix, that is, from a simultaneously assessed transmission scan or x-ray CT scan. Scatter correction (SC) improves the contrast between brain structures9 and has been recommended by the European Society of Nuclear Medicine.8 The triple energy window (TEW) method of SC, which requires data acquisition with a lower and upper scatter window on either side of the 99m Tc photo peak, is widely used.

For AC, the Chang uniform (U-Chang) AC method is the easiest and most frequently used method. When a linear attenuation coefficient of 0.09 cm−1 is used, it assumes a compensation for both scatter and bone attenuation.10,11 However, this method is not perfect and assumes homogeneous attenuation in the whole brain. It also does not take into account specific cytoarchitectural heterogeneity of cerebral parenchyma and differences in skull bone thickness. The nonuniform (NU) AC method assumes a patient’s specific attenuation. The NUAC could be applied according to the CT attenuation map facilitated by the recent emergence of hybrid gamma camera coupled to CT machine.12 The CT-NUAC and triple energy window SC have been reported to give more accurate measures of the rCBF than the U-Chang method.13,14

Although visual interpretation has been reported to have good reader reproducibility and is the most commonly used method in clinical practice,15 the recent implementation of computer-assisted SPECT analyses affords objective and more reliable assessments of functional abnormalities.3 Statistical parametric mapping (SPM) software in its current versions (eg, SPM99, SPM2, and SPM5; Wellcome Department of Cognitive Neurology, London, UK16) is the most widely used and evaluated image analysis software in brain imaging research. Other methods such as 3-dimensional stereotactic surface projection or tomographic z-score mapping are also useful in research.3

Semiquantitative evaluation assists visual interpretation and can be performed using the index method (rCBF in a region of interest / rCBF of reference region [eg, cerebellum, contralateral hemisphere, and total brain]). When NUAC is used, the use of the cerebellar region of interest as a reference is not recommended because it is greatly affected by photon SC and NUAC. The whole brain reference, which offers the least variation in the count ratio, is preferred.

source: the journal of CAT


Chemoembolization in Patients With Hepatocellular Carcinoma


The results of this study comparing chemoembolization with radioembolization in patients with hepatocellular carcinoma showed that survival was similar between the two treatments and that 90Y is at least…

Background: Chemoembolization is one of several standards of care treatment for hepatocellular carcinoma (HCC). Radioembolization with Yttrium-90 microspheres is a novel, transarterial approach to radiation therapy. We performed a comparative effectiveness analysis of these therapies in patients with HCC.

Methods: We collected data from 463 patients who were treated with transarterial locoregional therapies (chemoembolization or radioembolization) over a 9-year period. We excluded patients who were not appropriate for comparison and analyzed data from 245 (122 who received chemoembolization and 123 who received radioembolization). Patients were followed for signs of toxicity; all underwent imaging analysis at baseline and follow-up time points. Overall survival was the primary outcome measure. Secondary outcomes included safety, response rate, and time-to-progression. Uni- and multivariate analyses were performed.

Results: Abdominal pain and increased transaminase activity were more frequent following chemoembolization (P < .05). There was a trend that patients treated with radioembolization had a higher response rate than with chemoembolization (49% vs 36%, respectively, P = .104). Although time-to-progression was longer following radioembolization than chemoembolization (13.3 months vs 8.4 months, respectively, P = .046), median survival times were not statistically different (20.5 months vs 17.4 months, respectively, P = .232). Among patients with intermediate-stage disease, survival was similar between groups that received chemoembolization (17.5 months) and radioembolization (17.2 months, P = .42).

Conclusions: Patients with HCC treated by chemoembolization or radioembolization with Yttrium-90 microspheres had similar survival times. Radioembolization resulted in longer time-to-progression and less toxicity than chemoembolization. Post hoc analyses of sample size indicated that a randomized study with > 1000 patients would be required to establish equivalence of survival times between patients treated with these two therapies.

source: gastroenterology