The relationship between klotho, testosterone, and sexual health parameters among US adult men.

BACKGROUND: Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed. OBJECTIVE: Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone). METHODS: Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300 ng/dL). RESULTS: A positive association was observed between serum klotho and testosterone (ß = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statistically significant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (ß = 90.51, p = 0.001, ß = 106.93, p = 0.002, ß = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9 ng/dL, 390 ng/dL, 409.3 ng/dL, and 436.6 ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (ß = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (ß = - 2.28, p = 0.04, ß = - 2.22, p = 0.04, ß = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively). CONCLUSION: Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.

Co-morbidity in a cystic fibrosis population attending a regional clinic.

Pulmonary disease remains the major cause of morbidity in patients with cystic fibrosis (CF). However, of 115 patients attending a regional CF clinic we noted 16 cases (14%) with co-morbid conditions. Of this group, 4 of 115 patients (3.5%) had renal problems including both structural and functional defects and 4 (3.5%) had neurological disorders, 3 of which were types of epilepsy. Notably, 3 of 115 patients (2.6%) had different forms of neoplasia, all of which required significant surgical and/or chemotherapeutic intervention. There is now increasing evidence of the association between digestive tract malignancy and CF, which further complicates management of these already complex cases.

The acute effects of oxygen and carbon dioxide on renal vascular resistance in patients with an acute exacerbation of COPD.

OBJECTIVE: Changes in renal hemodynamics occur in patients with severe COPD, especially during an acute exacerbation. Renal hemodynamics are affected by changes in oxygen and carbon dioxide levels, but these changes have not been well defined, particularly in the acute clinical situation. We wished to determine whether oxygen or carbon dioxide levels have the predominant effect on renal hemodynamics in patients with an acute exacerbation of COPD. DESIGN: Fourteen patients with an acute exacerbation of COPD and a PaO2 < 64 mm Hg were studied. Initially, the patients breathed room air (hypoxemia). Then their arterial oxygen saturation was raised to approximately 95% (normoxemia) and then to 98 to 99% (hyperoxemia). Finally, 1 L/min of carbon dioxide was added to the circuit (hyperoxemic hypercapnia). Using duplex ultrasonography, the pulsatility index (PI) of an intrarenal artery was measured after 10 min at each level of oxygenation. The PI is an index of distal renovascular resistance. RESULTS: The PI fell significantly from room-air values on inducing hyperoxemia (p < 0.05). This suggests decreased renovascular resistance and increased renal blood flow. When hyperoxemic hypercapnia was induced, the PI rose significantly from the hyperoxemia level (p < 0.001). CONCLUSIONS: In hypoxemic patients, renovascular resistance decreased when hyperoxemia was induced. This fall in renovascular resistance was reversed with the addition of carbon dioxide. This suggests that acute changes in carbon dioxide levels might have a more dominant role than oxygen levels in determining renovascular resistance.

Outcome of surgical treatment for forearm pronation deformities in children with obstetric brachial plexus injuries.

Seven children were operated on for pronation contractures of the forearm due to obstetric brachial plexus injuries. All underwent extensive preoperative evaluations to determine the extent of injury, secondary deformities, and capacity to perform a few basic tasks. Sequential video studies were used to document these findings. Operative procedures performed included various combinations of tendon/muscle lengthenings and/or transfers. Postoperative evaluations focused on function rather than gains in active range of motion and the patient/parental assessment of the benefit of the procedure by response to a questionnaire. All patients were followed for a minimum of I year following surgery. The average gain in active supination was 45 degrees. Each patient showed significant functional gains with a high degree of satisfaction.

Acute effects of hypoxaemia, hyperoxaemia and hypercapnia on renal blood flow in normal and renal transplant subjects.

The aim of this investigation was to study noninvasively the effects of hypoxaemia, hyperoxaemia and hypercapnia on renal blood flow in normal subjects and renal allograft recipients, i.e. with denervated kidneys. By comparing these two groups, the influence of renal innervation on any resulting changes in renal blood flow could be ascertained. Nine normal and eight renal allograft recipients were studied. Each subject inhaled the following gas mixtures in order: room air, 10% O2 (hypoxaemia), 10% O2 + baseline CO2 (isocapnic hypoxaemia), 10% O2 + high CO2 (hypercapnic hypoxaemia), 100% O2 (hyperoxaemia), 100% O2 + baseline CO2 (isocapnic hyperoxaemia) and 100% O2 + high CO2 (hypercapnia hyperoxaemia). Using Doppler ultrasonography, the pulsatility index (PI), an index of renovascular resistance, was measured at the various gas inhalation levels. In normal subjects, the renovascular resistance increased in response to hypoxaemia, with a greater increase in response to hypercapnic hypoxaemia. Hyperoxaemia caused a decrease in renovascular resistance but this was abolished with the addition of CO2. There was a similar pattern in the PI response to the different gas inhalations in the renal transplant subjects, but these responses were attenuated in comparison with those of the normals. In conclusion, renal denervation does not completely abolish the renovascular responses to inhaled oxygen and carbon dioxide.

Renal functional reserve in patients with severe chronic obstructive pulmonary disease.

BACKGROUND: Renal functional reserve is the normal increase in renal blood flow after a protein load, and reduced or absent renal functional reserve is an early index of renal impairment. Renal blood flow is frequently reduced during acute oedematous exacerbations of chronic obstructive pulmonary disease (COPD). It is possible that patients with severe COPD in the stable state may have a reduced or absent renal functional reserve which could be a factor in oedema formation. METHODS: Sixteen stable patients with severe COPD and five normal controls were studied. The mean (SD) arterial oxygen and carbon dioxide tensions (PaO2, PaCO2) and forced expiratory volume in one second (FEV1) of patients with COPD were 8.1 (1.04) kPa, 6.3 (0.69) kPa, and 0.74 (0.27) 1, respectively. The pulsatility index (PI), an index of renovascular resistance, was measured non-invasively by Doppler ultrasonography at baseline and at intervals after a protein load of 250 g steak. RESULTS: The PI fell after the protein load in the normal subjects from 1.04 (0.19) to 0.84 (0.17), mean difference 0.20, 95% confidence interval of difference (CI) 0.14 to 0.27, p < 0.001. In the COPD group there was no change; baseline PI = 1.04 (0.16), PI after protein load = 1.08 (0.19), mean difference = -0.04, 95% CI-0.11 to 0.04, p = NS. Six of the patients with COPD were normocapnic and 10 were hypercapnic (PaCO2 > or = 6.0 kPa). The normocapnic patients had no significant change in PI (baseline PI = 1.07 (0.15), PI after protein load = 1.01 (0.16), mean difference = 0.06, 95% CI -0.03 to 0.15) while in the hypercapnic patients the PI tended to rise (baseline PI = 1.03 (0.17), PI after protein load = 1.12 (0.21), mean difference = -0.09, 95% CI 0.18 to 0.007, p = 0.06). CONCLUSIONS: Renal haemodynamics were unchanged after a protein load in patients with severe COPD, suggesting that they had no renal functional reserve. This may be a factor in the development of oedema frequently seen in patients with severe COPD, particularly in hypercapnic patients.

A one-year prospective audit of an asthma education programme in an out-patient setting.

A prospective randomised trial was performed to evaluate the effectiveness of an asthma education programme administered by an asthma nurse specialist in an out-patient setting. Sixty asthmatic patients (mean age 28.5 years) were enrolled, 30 to a usual care control group and 30 to an education group. The education group underwent an individual education programme lasting at least one hour. The following variables were measured at baseline, one month after the education programme and at one year follow-up: asthma knowledge by MCQ (36 point questionnaire), inhaler technique (7 point scale), peak expiratory flow rate (PEFR) and symptomatology by visual analogue score (0 to 10 score). The education group's inhaler technique and MCQ score both improved significantly at one month, from 5.4 (0.3) (mean [SEM]) to 6.5 (0.3), p < 0.001, and from 7.5 (2.4) to 22 (1.8), p < 0.0001 respectively. Both of these improvements were significantly greater than in the control group, and both were maintained at one year follow-up. The symptom score improved over one year in the education group, from 5.4 (0.6) to 7.6 (0.5), p < 0.05, and was unchanged in the control group. There was no change in the PEFR in either group. This study shows clear objective benefits to an out-patient asthma education programme conducted by an asthma nurse specialist.

Endobronchial hamartoma presenting as massive haemoptysis.

A 53 year old man presented with massive haemoptysis, and chest radiography revealed a left suprahilar mass. At thoracotomy he was found to have a modular mass in the left upper lobe, which was attached to a peripheral bronchus. Histology confirmed a pulmonary hamartoma.

Ventilation and gas exchange during sleep and exercise in severe COPD.

Ventilation and gas exchange were studied during sleep and incremental treadmill exercise in 19 patients with severe stable COPD with the primary aim of comparing the pathophysiology of oxygen desaturation in the two conditions. A secondary aim was to determine whether exercise studies could aid in the prediction of sleep desaturation. Full polysomnography was used, and ventilation, arterial oxygen saturation (SaO2), and transcutaneous PCO2 (PtcCO2) were monitored continuously during sleep. No patient had significant sleep apnea. Mean (SD) FEV1 was 32 (9.1)% predicted, PaO2 was 71.2 (12.4) mm Hg, and PaCO2 was 44.5 (4.6) mm Hg. SaO2 fell twice as much during sleep as during maximum exercise: 13.1 (8.9) vs 6.0 (3.6)% (p < 0.001). The mean sleep and exercise SaO2, and minimum sleep and exercise SaO2 were well correlated on linear regression (r = 0.81 and 0.78, respectively, p < 0.001), but on multiple regression analysis, awake PaO2 was a better predictor of sleep desaturation than was exercise desaturation. The 12 major desaturators (minimum sleep SaO2 < 85%) had twice as great a fall in exercise SaO2 as the 7 minor desaturators (3.6 +/- 2.8 vs 7.4 +/- 3.3%, p < 0.05). The major desaturators also had a greater fall in estimated sleep PaO2: 19.8 (5.1) vs 6.4 (7.1) mm Hg (p < 0.01), which suggests that their greater sleep desaturation is not simply due to their position on the steep portion of the oxyhemoglobin dissociation curve. The rise in PtcCO2 during sleep was similar among major and minor desaturators: 7.5 (2.9) vs 5.8 (3.7) mm Hg (p = NS), suggesting that all patients had a similar degree of hypoventilation during sleep, and that the greater fall in SaO2 and estimated PaO2 among some patients was secondary to other factors such as increased ventilation-perfusion mismatching.

Tuberculosis of the sternum presenting as metastatic disease.

The case is presented of a 59 year old Saudi Arabian woman with sternal and vertebral tuberculous osteomyelitis and a benign breast mass simulating metastatic disease. This case illustrates the diagnostic difficulties that may be encountered in the diagnosis of tuberculous osteomyelitis.

Topical oropharyngeal anesthesia in patients with obstructive sleep apnea.

Topical oropharyngeal anesthesia (TOPA) increases obstructive sleep apnea (OSA) frequency in both normal subjects and loud snorers. The effects of TOPA in established OSA were assessed in six male patients with a mean age (+/- SEM) of 50 +/- 5.3 yr. Following an acclimatization night, each subject underwent two overnight sleep studies, randomly assigned to TOPA (10% lidocaine spray and 0.25% bupivocaine gargle) and control (C) (saline placebo). Patients demonstrated sleep efficiencies of 93 +/- 2.9% (mean +/- SEM) during C and 88 +/- 2.9% during TOPA. Overall apnea-hypopnea (AH) frequency, using inductance plethysmography, showed little change: 21.2 +/- 3.6 on C versus 25.1 +/- 3.5 events/h on TOPA nights (p = 0.12). There was no significant increase in AH duration with TOPA, and oxygen desaturation (> or = 4%) frequency was similar: 21.1 +/- 3.9 per hour during TOPA versus 23.6 +/- 5.9 during C. However, obstructive AHs showed a change in thoracoabdominal motion from C to TOPA nights, with an increase in events with abdominal paradox from 3.1 +/- 1.1 to 10.3 +/- 3.1 per hour (p = 0.03), and a reduction in events with ribcage paradox from 13.1 +/- 1.6 to 8.2 +/- 2.4 per hour (p = 0.08). Central and mixed AHs demonstrated similar frequencies on both nights. These data support an impairment of upper airway (UA) protective reflexes among patients with OSA.

Oxygen desaturation during sleep and exercise in patients with severe chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have varying degrees of arterial oxyhaemoglobin desaturation during sleep, which have been shown to correlate with awake oxygen levels. We wished to ascertain if exercise desaturation was a better predictor of nocturnal oxygen desaturation than daytime blood gases. We studied 25 COPD patients with PaO2 < 10 kPa (mean = 8.6 kPa), 12 of whom were normocapnic (PaCO2 < or = 6 kPa, Group A), and 13 of whom were hypercapnic (PaCO2 > 6 kPa, Group B), by means of overnight oximetry and maximum treadmill exercise testing. The overall group desaturated significantly more during sleep than exercise [12.9 +/- 10.5 fall in nocturnal oxygen saturation (SaO2) vs. 4.5 +/- 3.7, P < 0.01]. Group B had a lower minimum SaO2 during sleep than Group A (74.3 +/- 13.4 vs. 84.6 +/- 5.8, P < 0.05), despite very similar pre-sleep SaO2 (91.9 +/- 3.2 vs. 92.8 +/- 2.9, P = n.s.). Awake SaO2 correlated well with both mean values (r = 0.7, P < 0.001), and minimum sleep SaO2 (r = 0.44, P < 0.05), but not with the fall in sleep SaO2 (r = 0.21, P = n.s.). Minimum sleep and exercise SaO2 were also significantly correlated (r = 0.44, P < 0.05), but the fall in SaO2 during sleep and exercise was not (P = n.s.). We conclude that exercise studies add no extra information to awake blood gas analysis in predicting the likelihood of nocturnal oxygen desaturation in patients with COPD.

Theophylline improves gas exchange during rest, exercise, and sleep in severe chronic obstructive pulmonary disease.

The effects of theophylline on pulmonary function and gas exchange during rest, sleep, and exercise were assessed in 10 patients with severe but stable chronic obstructive pulmonary disease (COPD; median FEV1, 31% of predicted). The study was randomized, double blind, placebo controlled, and crossover in design, with each study period lasting 3 wk, and all other usual bronchodilator therapy was continued unchanged. All patients had detailed pulmonary function tests, in addition to exercise testing and overnight sleep studies by standard polysomnography. Theophylline significantly improved gas exchange during rest, exercise, and sleep. Awake resting arterial blood gases showed a higher PaO2 on theophylline (78 [53 to 93] mm Hg, median [range]) than placebo (72 [47 to 83] mm Hg; p < 0.01 by ANOVA), and PaCO2 was lower on theophylline (42 [38 to 54]) compared with placebo (45 [40 to 51], p < 0.05 by ANOVA). Arterial oxygen saturation (SaO2) was significantly higher on theophylline than placebo during exercise and sleep (p < 0.01), and transcutaneous CO2 was lower during sleep (p < 0.05). Theophylline also resulted in significantly improved pulmonary function and reduced trapped gas volume (p < 0.05). Exercise performance was no different during theophylline or placebo phases of the study. Sleep quality, however, was significantly impaired on theophylline. We conclude that theophylline has clinically significant benefits in patients with severe COPD.

Theophylline in obstructive sleep apnea. A double-blind evaluation.

Twelve patients with documented obstructive sleep apnea were enrolled in a double-blind placebo controlled crossover trial of oral theophylline, (Uniphyllin) 800 mg, taken at night for four weeks. Overnight polysomnography, using standard techniques, was performed at the end of each treatment period. The total number of apneas (A) and hypopneas (H) decreased significantly while receiving theophylline compared to placebo, from 398 (69), mean (SEM), to 283 (72), p less than 0.01. Sleep quality was, however, significantly worse while receiving theophylline. Obstructive A and H were very much decreased with theophylline (p less than .001), and even when the data were adjusted for the more disturbed sleep with theophylline, this decrease remained significant; the obstructive A and H index fell from 49 (8.7) on placebo to 40 (9) while receiving theophylline, p = 0.02. There was no difference in the numbers of central or mixed A and H, and mean A and H duration was unchanged on the two study nights. Oxygen desaturations greater than 4 percent were less with theophylline treatment (p = 0.02), but mean overnight SaO2 was unchanged. We conclude that theophylline may be beneficial in patients with OSA, but part of the improvement is due to a deterioration in sleep quality.

Role of theophyllines in severe chronic obstructive pulmonary disease.

Theophyllines are effective bronchodilators, but have other respiratory effects which may be beneficial in patients with chronic obstructive pulmonary disease. These effects include increased diaphragmatic contractility, central respiratory stimulation and anti-inflammatory actions. Some controversy exists however on the precise role of these effects in the clinical setting. We examined the effects of a long-acting theophylline preparation (Uniphyllin Continus) on pulmonary function, and on ventilation and gas exchange during rest, sleep and exercise in a group of 12 patients with severe (FEV1 32 +/- 8.3% predicted), but stable chronic obstructive pulmonary disease. The study was randomised, placebo-controlled, and double-blind in nature. Preliminary analysis of the data indicates a significant improvement in the degree of hyperinflation and gas-trapping with theophylline, and oxygen levels were improved during rest, sleep and exercise while on theophylline. These findings confirm a beneficial effect of theophylline in such patients.

Nitrendipine therapy in asthmatic subjects.

Nitrendipine was given to eight patients with chronic stable asthma prior to a histamine challenge study and compared in a double-blind cross-over fashion with placebo. There were no significant differences in either the bronchoconstrictor effects of histamine, or in oxygen saturation during the histamine challenges, suggesting that nitrendipine should be safely tolerated if used to treat hypertension in patients with airflow obstruction.