Exercise training and atrial fibrillation: a systematic review and literature analysis.

OBJECTIVE: There are concerns in maintaining adequate levels of physical activity in patients with atrial fibrillation (AF). This could be related to the type of exercise delivered, different among studies, as the words used to describe it as treatment. We have analysed the state-of-art of the role of the exercise in AF by a mathematical analysis. This analysis documented the connections between topics and updated the available evidence through a systematic review of the current literature. MATERIALS AND METHODS: A literature search was conducted using specific terms for studies published between 2000 and 2019. For the descriptive analysis of the current literature, we used the LExical Network analysed by the Graph THeory (LENGTH) method, while to perform our review we followed the PRISMA statement. Downs and Black Quality Index was also used to assess the quality of studies. The LENGTH approach indicated nonspecific terms as "exercise", "physical" and "activity" as more representative than "rehabilitation" to describe the intervention. RESULTS: The systematic review identified nine studies on 882 patients of moderate (n=4) to good (n=5) quality. Training consisted of a combination of supervised ambulatory and home-based outpatient programs, focused on aerobic elements (endurance and resistance training, walking, treadmill and bicycle ergometer). Significant improvements in 6-minute walking test distance and peak oxygen uptake and in quality of life were obtained, with high adherence to training and no serious/significant adverse events. Only one trial was based on cardiac rehabilitation principles. CONCLUSIONS: Adequate exercise training can get a favourable cardiovascular outcome in patients with AF.

Polypharmacy is a determinant of hospitalization in Parkinson's disease.

OBJECTIVE: Patients with Parkinson's disease (PD) are at a higher risk of hospitalization and recurrent hospitalizations, with consequent complications. Polypharmacy is associated with several adverse outcomes, including hospitalization, increased length of hospital stay, and mortality. The aim of this study was to evaluate among patients with PD the association between the number of medications and incident hospitalizations. PATIENTS AND METHODS: We analysed the data of 165 patients with Parkinson's disease attending a geriatric Day Hospital who were enrolled in a cohort study and followed for a median of two years. RESULTS: Over the follow-up, 46 participants (46%) were hospitalized at least one time; multiple admissions were observed in 12 subjects (7%). The median number of agents was 5 (4-7). In Cox regression, the number of drugs was associated with increased hospitalization rates (HR=1.23; 95% CI=1.06-1.43), also after excluding non-neurological medications (HR=1.18; 95% CI=1.01-1.38). Using Poisson regression, polypharmacy (i.e., use of >5 drugs) predicted the number of repeated hospitalizations (IRR=2.62; 95% CI=1.28-5.36; p=.008). CONCLUSIONS: Among patients with PD, the number of daily medications is associated with increased risk of hospitalization; an increasing number of drugs is associated with increasing number of hospitalizations.

p16INK4 expression in precursor lesions of squamous cell cervical cancer related to the presence of HPV-DNA.

The purpose of the present study was to identify the expression of p16INK4 in cervical cancer precursor lesions by immunohistochemistry and to correlate it with lesion grade and presence of human papillomavirus (HPV) infection. Cervical specimens from 144 women seen consecutively at the gynecology outpatient clinic of our institution from December 2003 to May 2005 were analyzed by cytopathology, histopathology, polymerase chain reaction for HPV-DNA, and p16INK4 immunostaining. Histologically normal biopsies, HPV-DNA negative by polymerase chain reaction, were used as control. HPV-DNA prevalence, including the control group, was 68.1% and the prevalence of p16INK4 expression was 55.0%. The percentage of cells stained by p16INK4 ranged from 10 to 100%, both in the group consisting of cervical intraepithelial neoplasia (CIN)1/HPV specimens and in the group of CIN2/CIN3 specimens with P value of 0.0001. p16INK4 expression was 48.3% in the CIN1/HPV group, as opposed to 94.3% in the CIN2/CIN3 group (P = 0.001), showing a statistically significant difference between the two groups. The quantitative method used here is simple and less subjective than the different semiquantitative methods described in the literature. In view of the different definitions of a p16INK4-positive case, it is almost impossible to compare the findings reported by different investigators. This study confirms the association between p16INK4 and CIN2 and CIN3 lesions. Moreover, it shows that some low grade lesions expressed high levels of this protein. This may indicate that such low grade lesions may be predisposed to progress to high grade lesions. This means that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker.

p16INK4 expression in precursor lesions of squamous cell cervical cancer related to the presence of HPV-DNA

The purpose of the present study was to identify the expression of p16INK4 in cervical cancer precursor lesions by immunohistochemistry and to correlate it with lesion grade and presence of human papillomavirus (HPV) infection. Cervical specimens from 144 women seen consecutively at the gynecology outpatient clinic of our institution from December 2003 to May 2005 were analyzed by cytopathology, histopathology, polymerase chain reaction for HPV-DNA, and p16INK4 immunostaining. Histologically normal biopsies, HPV-DNA negative by polymerase chain reaction, were used as control. HPV-DNA prevalence, including the control group, was 68.1 percent and the prevalence of p16INK4 expression was 55.0 percent. The percentage of cells stained by p16INK4 ranged from 10 to 100 percent, both in the group consisting of cervical intraepithelial neoplasia (CIN)1/HPV specimens and in the group of CIN2/CIN3 specimens with P value of 0.0001. p16INK4 expression was 48.3 percent in the CIN1/HPV group, as opposed to 94.3 percent in the CIN2/CIN3 group (P = 0.001), showing a statistically significant difference between the two groups. The quantitative method used here is simple and less subjective than the different semiquantitative methods described in the literature. In view of the different definitions of a p16INK4-positive case, it is almost impossible to compare the findings reported by different investigators. This study confirms the association between p16INK4 and CIN2 and CIN3 lesions. Moreover, it shows that some low grade lesions expressed high levels of this protein. This may indicate that such low grade lesions may be predisposed to progress to high grade lesions. This means that p16INK4 may be a strong marker for "neoplastic lesions" induced by HPV and not just an infection marker.

Infection with human papillomaviruses of sexual partners of women having cervical intraepithelial neoplasia.

Epidemiological studies show that human papillomaviruses (HPV) are strongly related to cervical cancer and cervical intraepithelial neoplasias (CIN). Unlike the case for women, there are no consistent data on the natural history of HPV in the male population even though these viruses are prevalent in males. We carried out a prospective study to assess the prevalence of HPV in males as well as the factors that determine such infections in 99 male sexual partners of women with CIN. The genitalia of the males were physically examined and subjected to peniscopy for the collection of scrapings which were subjected to the polymerase chain reaction and restriction fragment length polymorphism to detect HPV. Of the 99 males sampled, 54 (54.5%) were positive for HPV DNA, 24% of whom presented normal peniscopy, 28% presented evident clinical lesions and 48% isolated lesions consistent with subclinical infection. In the HPV-negative group, 53% showed normal peniscopy, 4% presented evident clinical lesions and 42% isolated lesions consistent with subclinical infection. The study detected a statistically significant association (P < 0.02, Pearson chi-square test) between HPV infection and both the mean number of sexual partners which a male had during his life and the mean number of sexual partners in the year prior to testing. Viral types 6 and 11 were most frequently encountered. The study shows that infection with HPV was frequent in male sexual partners of women with CIN.

Infection with human papillomaviruses of sexual partners of women having cervical intraepithelial neoplasia

Epidemiological studies show that human papillomaviruses (HPV) are strongly related to cervical cancer and cervical intraepithelial neoplasias (CIN). Unlike the case for women, there are no consistent data on the natural history of HPV in the male population even though these viruses are prevalent in males. We carried out a prospective study to assess the prevalence of HPV in males as well as the factors that determine such infections in 99 male sexual partners of women with CIN. The genitalia of the males were physically examined and subjected to peniscopy for the collection of scrapings which were subjected to the polymerase chain reaction and restriction fragment length polymorphism to detect HPV. Of the 99 males sampled, 54 (54.5 percent) were positive for HPV DNA, 24 percent of whom presented normal peniscopy, 28 percent presented evident clinical lesions and 48 percent isolated lesions consistent with subclinical infection. In the HPV-negative group, 53 percent showed normal peniscopy, 4 percent presented evident clinical lesions and 42 percent isolated lesions consistent with subclinical infection. The study detected a statistically significant association (P < 0.02, Pearson chi-square test) between HPV infection and both the mean number of sexual partners which a male had during his life and the mean number of sexual partners in the year prior to testing. Viral types 6 and 11 were most frequently encountered. The study shows that infection with HPV was frequent in male sexual partners of women with CIN.

Testicular function and prolactin responsiveness to TRH and cimetidine after renal transplantation.

The hypothalamic-pituitary-testicular axis and the regulation of prolactin secretion were investigated in eleven male renal transplant recipients. Mean serum levels of testosterone and estrone were normal, whereas those of androstenedione and estradiol were low. Mean basal luteinizing hormone (LH) levels were slightly elevated, but the peak responses to 50 micrograms i.v. gonadotropin-releasing hormone (GnRH) were not dissimilar from controls. Both basal and GnRH-stimulated follicle-stimulating hormone (FSH) levels were elevated (p less than 0.02-0.05) and also positively correlated with the time spent on hemodialysis (p less than 0.005-0.002). Basal prolactin (PRL) levels were normal, in all subjects. Nine out of 11 patients had a normal PRL response to Thyrotropin-releasing Hormone (TRH). However only six out of 11 had a normal response to 200 mg i.v. Cimetidine (Cim). Three subjects normally responding to TRH failed to respond to Cim. Uremic primary hypogonadism is not fully reversed by renal transplantation: a slight defect in the pituitary LH release may persist and the impairment of the tubular testicular function is left unchanged. While uremic hyperprolactinemia is corrected, the responsiveness to PRL-stimulating agents, particularly Cim, is not restored to normal, reflecting a derangement at the pituitary as well as the hypothalamic level.

Hyperprolactinemia and psychological distress in women undergoing chronic hemodialysis.

In order to investigate the possible relationship of hyperprolactinemia to psychological distress in patients undergoing chronic hemodialysis, 19 uremic women were evaluated by a semistructured interview and administered the Kellner Symptom Questionnaire. Group A (10 uremic women with hyperprolactinemia) did not differ significantly in anxiety, depression, somatization and hostility from group B (9 normoprolactinemic uremic women). Both groups rated themselves more depressed and hostile than a normal control group of 10 women, and hyperprolactinemic patients were also significantly more anxious than the normal controls.

Male hypogonadism of uremic patients on hemodialysis.

Primary hypogonadism occurring among uremic men on hemodialysis has been widely investigated, yet few data are available concerning the general pattern of steroidogenesis. In 161 hemodialysis patients and in 83 healthy subjects, serum levels of gonadotropins (LH and FSH), prolactin (PRL), testosterone (T), androstenedione (A), estrone (E1), estradiol (E2), and dehydroepiandrosterone-sulphate (DHEA-S) were assessed through RIA methods. Mean +/- SD hormone levels were: LH 45.6 +/- 41.1 mIU/ml, FSH 16.3 +/- 16 mIU/ml, PRL 42.4 +/- 69.1 ng/ml, A 0.83 +/- 0.27 ng/ml, E1 64.3 +/- 31.7 pg/ml, all higher than controls; T 289 +/- 125 ng/100 ml, E2 11.8 +/- 3 pg/ml, and DHEA-S 1.4 +/- 1.4 micrograms/ml, all lower than controls. The A/T and E1/E2 ratios were also higher than controls and showed a good positive linear correlation (r = 0.40; p less than 0.001) between each other. The uremic damage acts at the testis level, impairing the activity of the enzyme 17-beta-hydroxysteroid-dehydrogenase (17-OHSD), even if a derangement of the peripheral interconversion between steroids cannot be excluded.

The permeability of normal, adenomatous, ulcerative colitic and malignant large bowel epithelial cell membranes to inulin.

We measured the permeability of normal, adenomatous, colitic and malignant large bowel epithelial cells by immersing fragments of large bowel mucosa in radiolabelled inulin and comparing autoradiograph grain density inside and outside cells after incubation. All the carcinomas studied showed extensive uptake of inulin within 5 min, while normal, adenomatous and colitic epithelial cells completely excluded inulin for 30 min. We found no difference in the proportion of epithelial cells incorporating uridine into RNA in carcinomatous and normal mucosa, and this suggests that the increased inulin permeability of carcinoma cell membranes was not due to leakage into non-viable cells. Experiments with cytochalasin B also showed that increased pinocytosis by carcinoma cells could not account for the difference. The relative impermeability of adenomatous and colitic cells suggests that increased permeability is not caused by increased proliferation. The consistent finding of increased permeability in the plasma membranes of carcinoma cells suggests that this may be more than an epiphenomenon of malignancy. It also suggests that measurement of cell permeability may have a role in distinguishing malignant from benign epithelial neoplasms.

Effect of short and long-term administration of lisuride in Cushing's disease.

To define the role of dopaminergic drugs on pituitary ACTH secretion, we studied the effect of a dopamine-agonist, lisuride, on a group of 9 patients with pituitary dependent Cushing's syndrome. Lisuride (0.4-0.6 mg/day) was administered for two days: in only two out of eight cases the ACTH levels, sampled every 30 min for 6 h (08:00-14:00 h), showed some reduction when compared with the control day. Two of the nonresponders (R.P.; B.F.) and one untested patient (L.E.) were then treated chronically with a similar amount of lisuride per day for 20 days (L.E.) and for 4 months (B.F.; R.P.). One patient (L.E.) showed a clear decrease in urinary free cortisol without clinical improvement; while in the other two cases, followed for a longer period of time, a clinical improvement was observed together with a decrease of the hormonal parameters. In conclusion, lisuride may occasionally reduce ACTH secretion in patients with pituitary dependent Cushing's syndrome, but the acute test fails to identify the patients who would benefit from this treatment.

Effect of hyperprolactinemia and age on the hypogonadism of uremic men on hemodialysis.

Primary hypogonadism has been commonly reported among uremic men on hemodialysis, characterized by low testosterone levels, increased luteinizing hormone and sometimes follicle-stimulating hormone levels. Little is known about the influence of hyperprolactinemia and age on this hypogonadism. In 149 hemodialysis patients and in 60 healthy subjects the serum levels of testosterone (T), gonadotropins (LH and FSH) and prolactin (PRL) were assessed through radioimmunoassay. Mean +/- SD hormone levels were: T 274 +/- 125 ng/100 ml, lower than controls; LH 44.7 +/- 46.1 mlU/ml and FSH 17.6 +/- 18.4 mIU/ml, both higher than controls. PRL 31.3 +/- 49.4 ng/ml, higher than controls. A positive correlation between LH and FSH, a negative correlation between PRL and both T and LH was found. Moreover T and FSH were correlated with age only in the normoprolactinemic patients. These data suggest: a common damaging mechanism by uremia on both interstitial and tubular structures of the testis; a central antigonadal influence of hyperprolactinemia even if a direct action on the testis cannot be excluded; a worsening action of age on the gonadal function of these patients.

Hyperprolactinemia and sexual disturbances among uremic women on hemodialysis.

The investigation of a sample of 99 women on maintenance hemodialysis has shown the presence of sexual disturbances to a great extent: the rate of sexual intercourse and the ability to reach orgasm were significantly lower than in age-matched control women. 80% declared a reduction in their sexual desire and the frequency of intercourse was also lower as compared to the period prior to dialysis. Ageing decreased the sexual activity in both the ill and healthy population, but in uremic patients the sexual activity ended at an earlier age. The patients with hyperprolactinemia reported lower frequencies of intercourse and lower percentages of orgasm than normoprolactinemic ones. The incidence of sexual dysfunction and the role of hyperprolactinemia in this respect were similar to those which are found among male patients on hemodialysis.

Psychosomatic aspects of hyperprolactinemia.

A review of some recent studies on the psychosomatic aspects of hyperprolactinemia is presented. Women seem to be more prone to suffer from the behavioral effects of prolactin than males. Women with hyperprolactinemic amenorrhea rated themselves significantly more hostile, more depressed and more anxious than women with amenorrhea only and other control groups. Hyperprolactinemic males did not rate themselves more hostile and depressed than matched controls. Psychological distress and hostility appear to remit upon treatment with bromocriptine. Postpartum patients matched for prolactin levels with hyperprolactinemic women showed significantly less depression and anxiety but about the same levels of hostility. Hostility, depression and loss of libido may coexist in the same hyperprolactinemic patient but they may be also present independently.

Pituitary microadenomas: surgical results and morphological findings.

The results of transsphenoidal microsurgery in treating 22 patients with pituitary microadenomas are reported. Histological and ultrastructural comparative studies were performed in attempting to obtain a more accurate morphological classification of pituitary microadenomas.

Psychological correlates of hyperprolactinemia in males.

In a previous study with hyperprolactinemic female patients, self-rated hostility, depression and anxiety were significantly higher than in other female patients. The study was repeated in hyperprolactinemic males, using the same psychological assessments. Hyperprolactinemic males were significantly more anxious but did not differ significantly in hostility and depression from other male patients. The findings support the view that the psychological effects of high serum prolactin levels depend in part on interactions with gonadal hormones.

Depression and hostility in hyperprolactinemia.

1. Patients with hyperprolactinemia offer a unique opportunity to investigate the effects of prolactin on psychological states. Women with hyperprolactinemic amenorrhea rated themselves significantly more hostile, more depressed and more anxious than women with amenorrhea only and normal women. 2. The hyperprolactinemic patients were compared with a group of post-partum (7th day) women, matched for sociodemographic variables and prolactin levels. The post-partum women showed significantly less depression and anxiety than those with hyperprolactinemic amenorrhea but about the same levels of hostility. 3. Hyperprolactinemic males did not rate themselves more hostile and depressed than matched controls.