Use of oral ketoconazole to prevent postoperative erections following penile surgery.

Analgesics and topical agents ineffectively inhibit painful erections after penile and urethral surgery. Oral ketoconazole reversibly inhibits testosterone production and has been used empirically at our institution to decrease postoperative erections. We performed a retrospective review of 38 patients who had undergone penile and urethral reconstructive surgery. In all, 31 patients received 400 mg of ketoconazole three times daily for 10-14 days postoperatively (the study group) and seven patients did not receive ketoconazole (the control group). The incidence of postoperative erections, pain, side effects, surgical outcomes and patient satisfaction in each group were compared. Of the control group, 71% reported erections in the immediate postoperative period, and all these patients reported the erections were painful. Only 23% of the patient taking ketoconazole reported postoperative erections, and only 16% reported the erections were painful. We conclude that ketoconazole effectively prevents painful postoperative erections with minimal side effects.

Effect of caesarean section on breast milk transfer to the normal term newborn over the first week of life.

OBJECTIVE: To determine the effect of caesarean section on breast milk transfer (BMT) to the normal term infant over the first week of life. METHOD: A sample of 88 healthy nursing mothers who had a normal vaginal delivery, and 97 mothers who had a caesarean section were recruited from a teaching hospital. Mothers and midwives were instructed to weigh the infants before and after each feed throughout the study period using calibrated portable electronic scales. RESULTS: The volume of milk transferred to infants born by caesarean section was significantly less than that transferred to infants born by normal vaginal delivery on days 2 to 5 (p < 0.05), but by day 6 there was no difference between the two groups (p = 0.08). The difference could not be explained by any of the maternal and infant variables measured. Birth weight was regained by day 6 in 40% of infants born vaginally compared with 20% in those born by caesarean section. CONCLUSION: There is a lag in the profile of the daily volume of breast milk transferred to infants delivered by caesarean section compared with those born by normal vaginal delivery. This study also challenges the widely followed schedules of milk volumes considered to be suitable for the term infant, which appear to be excessive, at least for the first four to five days post partum.

Neural correlates of voluntary breathing in humans.

To investigate the functional neuroanatomy of voluntary respiratory control, blood O2 level-dependent functional magnetic resonance imaging was performed in six healthy right-handed individuals during voluntary hyperpnea. Functional images of the whole brain were acquired during 30-s periods of spontaneous breathing alternated with 30-s periods of isocapnic hyperpnea [spontaneous vs. voluntary: tidal volume = 0.5 +/- 0.01 vs. 1.3 +/- 0.1 (SE) liters and breath duration = 4.0 +/- 0.4 vs. 3.2 +/- 0.4 (SE) s]. For the group, voluntary hyperpnea was associated with significant (P < 0.05, corrected for multiple comparisons) neural activity bilaterally in the primary sensory and motor cortices, supplementary motor area, cerebellum, thalamus, caudate nucleus, and globus pallidum. Significant increases in activity were also identified in the medulla (corrected for multiple comparisons on the basis of a small volume correction for a priori region of interest) in a superior dorsal position (P = 0.012). Activity within the medulla suggests that the brain stem respiratory centers may have a role in mediating the voluntary control of breathing in humans.

Functional MRI localisation of central nervous system regions associated with volitional inspiration in humans.

1. Functional magnetic resonance imaging (fMRI) provides a means of studying neuronal circuits that control respiratory muscles in humans with better spatial and temporal resolution than in previous positron emission tomography (PET) studies. 2. Whole brain blood oxygenation level-dependent (BOLD) changes determined by fMRI were used to identify areas of neuronal activation associated with volitional inspiration in five healthy men. Four series of scans of each subject were acquired during voluntary breathing (active task) and mechanical ventilation (passive task). Ventilation and end-tidal PCO2 were similar between tasks. Scan data were re-aligned to correct for movement artefacts and cross-referenced breath by breath to respiratory data for selective averaging of inspiratory and expiratory images. 3. Group analysis identified significant increases in the fMRI signal with volitional inspiration in the superior motor cortex, premotor cortex and supplementary motor area at loci similar to those detected in earlier studies that used PET. Additional regions activated by volitional inspiration included inferolateral sensorimotor cortex, prefrontal cortex and striatum (these foci were only revealed by PET under significant inspiratory load). 4. This study represents the first synchronised breath-by-breath analysis of respiratory-related neuronal activity with whole brain imaging in humans. Temporal resolution is sufficient to distinguish individual breaths at a normal breathing frequency.

Stimulus-response characteristics of CO2-induced air hunger in normal subjects.

Hypercapnia evokes an uncomfortable sensation, termed 'air hunger'. We examined the relationship between PETCO2 and ratings of air hunger intensity under three conditions in 16 subjects: 1) mechanical ventilation with hyperoxic gas mixtures at fixed frequency and tidal volume (twice resting ventilation), 2) the same mechanical ventilation, but with hypoxic gas mixture, 3) spontaneous breathing with hyperoxic gas mixture. In each case, PETCO2 was varied randomly among several levels, each held for 5 min. During hyperoxic mechanical ventilation, the mean threshold for air hunger sensation was 43 Torr, i.e., 4 Torr above resting PETCO2; intolerable air hunger was evoked by 50 Torr. The threshold and tolerable levels of PETCO2 varied among individuals, but were not well correlated with their ventilatory responses to CO2. Hypoxia (PETO2 60-75 Torr) shifted the PETCO2 at both threshold and tolerance down by only 2 Torr. Breathing greatly reduced the air hunger experienced at any given PETCO2 (threshold increased 5 Torr, and sensitivity decreased 50%).

Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: implications for the pathogenesis and treatment of Alzheimer disease.

The apolipoprotein E4 (APOE4) allele is associated with an early age of onset of the nonfamilial form of Alzheimer disease (AD) and with increased beta protein amyloid deposition in the brain. These two observations may both arise from an effect of the apoE family of proteins on the rate of in vivo amyloidogenesis. We report here that apoE3, the common apoE isoform, is an in vitro amyloid nucleation inhibitor at physiological concentrations. A significant delay in the onset of amyloid fibril formation by the beta-amyloid protein of AD (beta 1-40) was observed at a low apoE3 concentration (40 nM), corresponding to an apoE3/beta protein molar ratio of 1:1000. The inhibitory activity of a proteolytic fragment of apoE3, containing the N-terminal 191 amino acids, is comparable to the native protein, whereas the C-terminal fragment has no activity. ApoE4 is equipotent or slightly less potent than apoE3, which may be due to its inability to form a disulfide dimer, since the apoE3 dimer is a significantly more potent nucleation inhibitor than apoE4. Neither apoE3 nor apoE4 inhibits the seeded growth of amyloid or affects the solubility or structure of the amyloid fibrils, indicating that apoE is not a thermodynamic amyloid inhibitor. We propose that the linkage between the APOE4 allele and AD reflects the reduced ability of APOE4 homozygotes to suppress in vivo amyloid formation.

Validation of a modified one-step rebreathing technique for measuring exercise cardiac output.

A modification of the Farhi one-step rebreathing technique (1) is described for determining submaximal exercise cardiac output (Q). Factors critical in the estimation of Q are initial rebreathing bag volume and constant bag volume during the maneuver. By substituting a high flow rate analyzer (500 ml.min-1) for the recommended low flow rate mass spectrometer (60 ml.min-1), adding a recirculation circuit from the outlet of the analyzer to an inlet at the base of the rebreathing bag, and reducing the length of sample tubing to the analyzer, we were able to recirculate the subject's expired gas and achieve no loss of bag volume. No statistically significant differences in estimate of cardiac output were noted between the mass spectrometer and LB-2 analyzer with recirculation circuit during submaximal cycling. Heart rate and oxygen uptake were highly correlated with cardiac output and agreed well with the literature, irrespective of the CO2 analyzer system used. A unique feature of our method is that the subject's tidal volume is measured prior to the maneuver and then used as the initial rebreathing bag volume. Varying the bag volume by +/- 0.2 L from the tidal volume had no significant effect on the estimate of cardiac output during exercise. Now quick, reliable, and noninvasive measurements of cardiac output are feasible in subjects--not only in the laboratory but also in the field where a mass spectrometer is not readily portable.