Priapism: a refined approach to diagnosis and treatment

The recent introduction of intracorporeal injections of papaverine and phentolamine for the diagnosis and treatment of impotence has resulted in an increased incidence of iatrogenic priapism. Based on our research into penile hemodynamics we propose a refined approach to all types of priapism. Intracorporeal blood gas and pressure monitoring should be used to differentiate ischemic (low flow) from nonischemic (high flow) types. Most cases of papaverine-induced or phentolamine-induced priapism will respond to aspiration alone or in combination with intracorporeal instillation of a diluted alpha-adrenergic agent. In spontaneous priapism alpha-adrenergic agents can be tried first if patients have only mild or no ischemia. In patients with severe ischemia stagnant blood should be evacuated and a shunt procedure should be performed to allow metabolic replenishment of tissue. Intracorporeal pressure monitoring will help to determine the size and number of shunts needed to re-establish corporeal circulation.     

Immunoregulatory effects of phospholipase A2 (PLA2) on the proliferation of human lymphocytes

Extracellular phospholipase A2 (PLA2) is a proinflammatory enzyme found especially in the inflammatory exudate to modulate blood flow to areas of antigen stimulation. In this study we found that PLA2 exerted a biphasic effect on the proliferation of phytohemagglutinin (PHA)-stimulated human mononuclear cells (PHA MNC). At low concentrations range from 0.001 to 1 U/ml, PLA2 enhanced the proliferation of PHA MNC (maximal increase was 37.0 +/- 5.67%). Conversely, at concentrations over 10 U/ml, PLA2 markedly suppressed the PHA-induced MNC proliferation (maximal decrease was 88.86 +/- 2.89%). PLA2 was non-toxic to lymphocytes after three days culture, unless the concentration was higher than 100 U/ml. The membrane polarization of PHA-stimulated lymphocytes was also increased by PLA2 at a low concentration. In addition, PLA2 displayed a similar effect on the proliferation of streptokinase-streptodornase (SK/SD) or allogeneic cell stimulated lymphocytes. The change of lymphocyte proliferation by PLA2, was parallel to the change of percentage of helper T cells. Furthermore--a CD4-rich population was proved more susceptible to PLA2 effect than a CD8-rich population. Para-bromophenacyl bromide (pBPB), an irreversible inhibitor of PLA2, abrogated the biphasic effect of PLA2 on PHA MNC proliferation. These results suggest that PLA2 plays a regulatory role on immune reactions by modulating the percentage of helper T cells.     

Blood gas analysis in drug-induced penile erection

To elucidate the hemodynamic changes during erection, we measured corporeal blood gases in 6 monkeys before, during, and after erection induced by either papaverine or phentolamine or a combination of the two. Papaverine alone caused a strong erection (maximal tumescence and rigidity) by means of a rapid, large increase in pO2 and pCO2 with a pH drop to the acidic range. Phentolamine alone caused 'delayed' tumescence with less rigidity; the intracorporeal pO2 level increased, but pCO2 and pH values did not change significantly. The combination of both drugs offered no advantage over papaverine alone. We conclude that papaverine is a potent erection-inducing drug that acts in a bimodal manner, namely, it increases the arterial inflow and, at the same time, decreases the venous outflow. Phentolamine affects the arterial component of erectile function only.     

Randomized placebo-controlled trial comparing montelukast and cetirizine for treating perennial allergic rhinitis in children aged 2–6 yr

Leukotriene receptor antagonists (LTRAs) were recently added to the method of treating allergic rhinitis (AR). However, in children under 6 yr old, there has been no study about its efficacy in treating AR. We aim to compare the clinical efficacy of montelukast, cetirizine and placebo in the treatment of children from 2 to 6 yr old with perennial allergic rhinitis (PAR), to see if there are any significant differences. Sixty children were selected and treated with montelukast, or cetirizine, or placebo once daily. The efficacy of the three agents was compared with the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Total Symptom Score (TSS) by diary. In addition, we also examined serum IgE, serum eosinophil cationic protein (ECP), blood eosinophil counts, nasal airway resistance (NAR) and eosinophil percentage in nasal smears. The results revealed that both montelukast and cetirizine were significantly efficacious compared with placebo in NAR, eosinophil percentage in nasal smears, PRQLQ, TSS and all symptom items except nasal itching, throat itching and tearing. For nasal itching, only cetirizine was significantly efficacious. On the other hand, for night sleep quality, montelukast was significantly superior to cetirizine.     

Hemodynamics of penile erection

In the flaccid state, the smooth muscles of the cavernous arterioles and trabeculae are contracted, and minimal blood flow enters the sinusoids. Relaxation of these smooth muscles incites arterial dilation, venous compression, and sinusoidal relaxation and results in penile erection.     

Abnormal electrical properties of myocytes from chronically infarcted canine heart. Alterations in Vmax and the transient outward current.

BACKGROUND. Reentrant ventricular arrhythmias can occur in the surviving muscle fibers of the epicardial border zone of the canine heart 5 days after coronary artery occlusion. To understand the cellular basis of these arrhythmias, we developed a method of dispersing myocytes (IZs) from the epicardial border zone. METHODS AND RESULTS. We compared the electrophysiological properties of IZs with those of cells dispersed from the epicardium of control noninfarcted (NZs) and of sham-operated animals (NZsham). Transmembrane action potentials of IZs are reduced in total action potential amplitude and maximum upstroke velocity compared with NZs. However, resting potential of IZs is no different from that of NZs. Action potential duration at -10 mV is significantly reduced in IZs compared with control, and IZ potentials do not show the typical "spike and dome" morphology that is evident in all NZs. Using Vmax as an indirect measure of the peak inward current available for the upstroke of the action potential, we found that the availability curve for IZs is significantly different from the NZ curve. Furthermore, the time course of recovery of Vmax after a depolarizing voltage clamp step was significantly altered in IZs. Using whole-cell voltage clamp techniques, we determined that the voltage-dependent, Ca(2+)-independent, 4-aminopyridine-sensitive transient outward current (ito1) occurred in all NZs (n = 16) but existed in only 37% of IZs (n = 16). There was a significant reduction in the density of ito1 elicited by depolarizing steps in those IZs showing ito1 compared with ito1 density in NZs. CONCLUSIONS. We have developed a single-cell model of cells that survive in the infarcted heart. Our studies indicate that there are changes in Vmax in IZs. In addition, there is no prominent phase 1 of repolarization in IZ action potentials. This is consistent with the dramatic loss in the function of the ionic channel responsible for the voltage-dependent transient outward current, ito1.     

Sleep and posttraumatic rheumatic pain modulation disorder (fibrositis syndrome)

The clinical features and sleep physiology of 11 female patients with "fibrositis syndrome" or rheumatic pain modulation disorder (RPMD) were compared with 11 female postaccident pain (PAP) patients who complained of widespread musculoskeletal pain, fatigue, and nonrestorative sleep following a nonphysically injurious motor vehicle or work-related accident. Both groups had similar musculoskeletal pain, fatigue, sleepiness and an alpha (7.5-11 Hz) EEG non-rapid eye movement (NREM) sleep anomaly. A psychophysiologic arousal mechanism during NREM sleep induced by the emotional stress of the accident may mediate the subsequent nonrestorative sleep, musculoskeletal pain, and fatigue symptoms in the posttraumatic pain disorder.     

GABAergic boutons establish synaptic contacts with the soma and dendrites of cuneothalamic relay neurons in the rat cuneate nucleus

This study investigates the synaptic relation between -aminobutyric acid-immunoreactive (GABA-IR) and cuneothalamic relay neurons (CTNs) in the rat cuneate nucleus. Retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase complex (WGA-HRP) was used to label CTNs while anti-GABA immunogold serum was used for the detection of GABA-IR boutons associated with CTNs. With these procedures, immunogold-labelled GABA-IR boutons were found to form axosomatic, axodendritic and axospinous synapses with the WGA-HRP-labelled but immunonegative CTNs. Quantitative estimation showed that the mean ratios of GABA-IR to GABA-immunonegative boutons making synaptic contacts with somata, proximal dendrites, and distal dendrites were 47.9%, 49.1% and 34.7%, respectively. Statistical analysis showed that the incidence of GABA-IR boutons on the somata and proximal dendrites of CTNs was significantly higher than on the distal dendrites. Our results indicate that GABA is the primary inhibitory neurotransmitter in the cuneate nucleus, thereby emphasizing the importance of postsynaptic inhibition on cuneothalamic relay neurons.     

Diurnal sleep/wake-related immune functions during the menstrual cycle of healthy young women

SUMMARY  Animal and human studies have related the sleeping/waking brain to the immune system. Because women are more susceptible to certain immunological illnesses, and sex steroids regulate immune functions, it was investigated whether the diurnal sleep/wake pattern of aspects of cellular immune functions and interleukin-1 (IL-1) and IL-2-like activities differed during low and high progesterone phases of the menstrual cycle.
Eleven healthy women, mean age 24y, were assessed over 24h with serial venous blood samples. Peripheral blood monocytes were assayed for mitogen responses, i.e. phytohemagglutin (PHA) and pokeweed (PWM) and natural killer (NK) cell activities. Plasma was assayed for IL-1 and IL-2-like activities, cortisol and progesterone. Data were standardized by Z transformation and analysed by repeated-measures analysis of variance by comparing high ( N = 5) vs. low ( N = 6) progesterone phases.
During the high progesterone phase, delayed slow-wave sleep (SWS) onset time and reduced amount of SWS was accompanied by a delay in the decline of NK cell activity, but rise in PHA activity following sleep onset. With the low progesterone phase, the pattern was similar to men with an early sleep decline in NK cell and late sleep rise in PHA activities. PWM rose during the night and plasma IL-1-like activity peaked during midday and during nocturnal sleep irrespective of the amount of progesterone.
Slow-wave sleep and sleep-related NK cell and PHA activities differed over the menstrual cycle, but not PWM response. Increases in plasma IL-1 functions during midday and night are consistent with predisposition to sleepiness during these times.