Different neuronal types in transneuronally WGA-HRP-labeled premotor interneurons of the rat spinal cord.

Interneurons presynaptic to motoneurons were labeled by retrograde transneuronal transport of WGA-HRP. The tracer was injected either into the quadriceps muscles or into the posterior biceps muscles, thus labeling interneurons presynaptic to the quadriceps motoneurons (QINs) or interneurons presynaptic to posterior biceps motoneurons (PBINs). Statistical cluster analysis of area, perimeter, equivalent diameter and form factor of the labeled interneurons permitted the identification of 4 different types of premotor interneurons in the lumbar enlargement of the rat. Type I are small elongated interneurons which prevail in PBINs. Type II are medium-sized ellipsoidal cells prevailing in the QINs. Type 3 are small ellipsoidal neurons, slightly more frequent in PBINs. Type 4 is the smallest group and it is composed of large multipolar neurons. A different distribution of the 4 morphological neuronal types was found between the population of the QINs and the PBINs and in the laminae of ventral horn for each group.

Effectiveness and safety of multidrug intracavernous therapy for vasculogenic impotence.

A four-drug vasoactive mixture (papaverine hydrochloride, prostaglandin E1, phentolamine mesylate, atropine sulfate) was used for intracavernous injection therapy in 94 patients with vasculogenic impotence as diagnosed by color Doppler sonography and dynamic infusion cavernosometry-cavernosography. At a mean follow-up of twenty months, 66 patients (70%) are using the injections with the initial dose and are satisfied; 14 patients (15%) are using the injections with a smaller dose than initially given; and 14 patients (15%) dropped intracavernous treatment. Only 4 patients (4%) were unable to achieve a sustained rigid erection during the mixture titration phase. Selected cases of vasculogenic impotence can be safely and effectively treated by the association of drugs which rely on different mechanisms of action, producing a pharmacologic synergism which enhances the overall therapeutic effect.

Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study.

OBJECTIVES: The aim of this study was to determine the effectiveness and safety of yohimbine and trazodone used together for the treatment of pure psychogenic impotence. METHODS: Sixty-three patients who had psychogenic impotence diagnosed on the basis of sexual history, results of physical examination, laboratory analysis, polysomnographic recording of nocturnal erections, and dynamic color Doppler sonography of the cavernosal arteries were entered into a randomized, double-blind, placebo-controlled, partial crossover study comparing placebo with yohimbine (15 mg per day orally) and trazodone (50 mg per day orally) used together. Treatment consisted of two 8-week courses. Patients who initially received placebo for 8 weeks were then switched to the 2-drug combination for 8 weeks. Erectile function, ejaculation, interest in sex, and sexual thoughts were investigated at the end of drug treatment and at 3- and 6-month follow-up. For statistical analysis chi-square, McNemar, and Student's t test for unpaired data were used. RESULTS: Fifty-five patients (87%) completed the whole treatment schedule. Positive clinical results (complete and partial responses) were obtained in 39 (71%) patients at the end of the drug treatment phase. These results were significantly better than those obtained with placebo (p < 0.01). Positive results were maintained in 32 (58%) and 31 (56%) patients at 3- and 6-month follow-up, respectively. Minor drug-related adverse effects occurred in 6 (11%) of the patients in the yohimbine-trazodone group and in 2 (4%) in the placebo group. CONCLUSIONS: The combination of yohimbine and trazodone is a safe and effective first-line treatment for psychogenic impotence.

AMS 700 CX inflatable penile implants for Peyronie's disease: functional results, morbidity and patient-partner satisfaction.

This study was designed to clarify the functional results, morbidity and the patient-partner satisfaction observed with, the American Medical System 700 CX three-piece inflatable prosthesis in the treatment of impotence associated with Peyronie's disease. Thirty-three patients were treated and additional plaque surgery was performed in 13 cases (40%). Within 10 days of surgery, four patients (12%) developed a wound infection which was treated conservatively and one patient (3%) experienced glandular ischemia. At the 6-week follow-up, complete penile straightening was achieved in 23 patients (70%), while penile rigidity was considered optimal by all patients. On the contrary, the penis was considered short by 10 patients (30%). Five diabetic patients (15%) complained of severe scrotal and penile pain during full activation of the implant and in one of these patients (3%) the implant had to be removed. Due to spontaneous erections occurring after implant activation one patient (3%) required replacement of the reservoir from the Retzius space into the peritoneum. At the long-term follow-up (mean +/- SE: 17 +/- 2.2 months), 23 patients were evaluated and all found to be engaging in intercourse with the prosthesis. However, five patients (21%) and three of the 13 partners (25%) assessed were not yet completely satisfied. The American Medical System CX700 inflatable penile prosthesis obtains complete penile straightening in 70% and rigidity in 100% of impotent patients with Peyronie's disease. Patients should be fully informed about possible surgical morbidity and actual post-operative penile length.

Improved minimally-invasive assessment of penile haemodynamics: the combination of colour Doppler sonography and injection-stimulation test.

The aim of this study was to assess the diagnostic value of erotically enhanced penile colour Doppler sonography as a minimally invasive tool to evaluate penile haemodynamics. Colour Doppler sonography was used to study the cavernosal arteries of 135 consecutive impotent patients after intracavernous injection of a vasoactive mixture (injection phase) and after subsequent genital and audiovisual sexual stimulation (stimulation phase). The erectile response was upgraded after the adjunct of genital and audiovisual stimulation in 36% of patients. Colour Doppler assessment performed after the stimulation phase identified 16% of patients as arteriogenic despite normal erections, and 7% of patients falsely diagnosed as venogenic after the injection phase. When colour Doppler sonography and the injection-stimulation test are performed together as a single diagnostic procedure the overall diagnostic accuracy is significantly enhanced.

Transdermal electromotive multi-drug administration for Peyronie's disease: preliminary results.

The purpose of this study was to clarify the actual therapeutic potential of a new transdermal drug delivery system (electromotive drug administration; EMDA) for selected patients with Peyronie's disease. Forty patients with Peyronie's disease were treated by electromotive administration of the 3-drug association orgotein-dexamethasone-lidocaine in a double-blind, placebo-controlled, partial crossover study (study 1). Another 25 patients were treated by EMDA with a combination of verapamil-dexamethasone in an uncontrolled study (study 2). Treatment sessions lasted 20 minutes each and took place 3 times a week for 3 weeks with a current of 3 mA. Patients were assessed before treatment and at 1- and 3-month follow-up examinations. Assessments were based on sexual history, physical examination, and dynamic color Doppler ultrasonographic results. Adverse effects of EMDA were not reported. In study 1, the clinical results observed after treatment proved to be significantly better than those of the placebo. Penile pain disappeared in all patients in both studies. Penile lesion (nodule or plaque) either disappeared or significantly improved in 79% and 90% of patients treated by the 3- and 2-drug association, respectively. The improvement of penile deformity also was notable although it did not match the effect observed on penile nodules or plaque (62% and 88%, in studies 1 and 2, respectively). In both studies, more than 80% of patients reported a definite amelioration of penile rigidity, which paralleled the improvement of penile dynamic color Doppler ultrasonographic parameters. Overall, the combination of verapamil-dexamethasone achieved better clinical results than the 3-drug combination. Electromotive drug administration is a novel technique capable of safely achieving satisfactory results in selected patients with Peyronie's disease not only in terms of improvement of patient's symptoms but also due to the reduced need for penile surgery.

Neuron-specific enolase and embryology of the trabecular meshwork of the rat eye: an immunohistochemical study.

Neuron-specific enolase (NSE) is a unique form of the glycolytic enzyme enolase found exclusively in neurons and neuroendocrine tissues. Immunohistochemical techniques in which antineuron-specific enolase antibodies are used have made it possible to map out derivatives of the neural crest in humans. By using affinity-purified antibodies against NSE, we investigated whether the contribution of the neural crest cells to the development of the anterior ocular structures in the rat is similar to that in man. We found that filtration structures in rats show morphologically striking similarities with the analogous region of the human eye. Hence, the rat eye, with certain reservations, is a suitable model for experimental studies on ocular diseases that are characterized by chamber angle anomalies or congenital glaucoma.

The ultrastructure of the nucleus of the oculomotor nerve (somatic efferent portion) of the cat.

The ultrastructure of the somatic efferent portion of the nucleus of the oculomotor nerve was studied in four adult cats. The neuronal population is composed of neurons of variable size. A continuous pattern of morphological aspects is evident between the large neurons, which show abundant cytoplasm with well developed organelles, and the small neurons which have a reduced amount of cytoplasm. The dendrites are generally smooth, with few short spines. Axo-dendritic synapses are numerous. Synaptic boutons are also present on the axon hillock. The neuropil is characterized by the occurrence of small groups of dendrites which may be in direct touch with their membranes. Direct membrane appositions may also occur between neighbouring neurons and between the cell somata and tangentially running dendrites. Generally beneath the site of apposition there is accumulation of mitochondria, multivesicular bodies, coated vesicles and moderately dense amorphous material. The morphological features suggest the possibility of cellular interchanges at the sites of direct membrane apposition. Five types of synaptic boutons were recognized on the basis of their vesicular content, the presence of abundant filaments in the pre-synaptic bag, the occurrence of post-synaptic specializations. The different synaptic types and their distribution are similar to those reported in the spinal motor nuclei. Many of the synapses make synaptic contacts with two or more post-synaptic elements. Axo-axonic synapses were also observed.

Electron microscopic demonstration of cerebello-oculomotor fibres in cat.

Few synaptic buttons with the typical changes of "electron-dense degeneration" were found in the nucleus of the oculomotor nerve of cats, which underwent complete bilateral ablation of the cerebellum. The degenerating buttons were mainly found in the neuropil, contacting small dendritic profiles. For the scanty number of degenerating buttons observed and for the particular location of its terminal buttons, the direct cerebello-oculomotor connection appears to be an ancillary route in the cerebello-oculomotor linkage, which involves mainly polysynaptic routes.

Clinical reliability of multi-drug intracavernous vasoactive pharmacotherapy for diabetic impotence.

The aim of this study was to assess the effectiveness and safety of intracavernous injections of a four-drug vasoactive mixture in diabetic patients with organic impotence. A group of 60 diabetic patients with either pure neurogenic, pure vasculogenic or mixed neurovasculogenic impotence were treated with intracavernous injections of a combination of 12.1 mg/ml papaverine hydrochloride, 1.01 mg/ml phentolamine mesylate, 10.1 micrograms/ml prostaglandin E1 and 0.15 mg/ml atropine sulphate ('full-dose' mixture). A mixture of the same drugs but at one-third concentrations ('reduced-dose' mixture) was also used. The mean (+/- SEM) volumes of the full-dose and reduced-dose mixtures used were 0.21 +/- 0.03 ml and 0.31 +/- 0.02 ml, respectively. All the patients were able to sustain a rigid erection at the end of the titration phase of the study. At a mean follow-up of 18 months, 48 patients (80%) were successfully using the mixture, 6 patients (10%) were using the mixture at a dose lower than the initial dose and 6 patients (10%) had dropped out from the injection therapy. No major complications were seen. The association of multiple vasoactive drugs which use different mechanisms of action, thus exerting a pharmacological synergism, is an effective and safe procedure in intracavernous pharmacotherapy for diabetic patients with organic impotence.

Is there a role for transrectal microwave hyperthermia in the treatment of benign prostatic hyperplasia? A critical review of a six-year experience.

We critically reviewed our 6-year experience with transrectal microwave hyperthermia of the prostate for benign prostatic hyperplasia (BPH) in 320 patients either at high surgical risk or refusing surgery. Transrectal prostatic hyperthermia was given in five to ten 60-minute sessions with an intraprostatic temperature ranging from 42 degrees to 43.5 degrees C. Although an amelioration of symptoms and urodynamic measures was seen initially in most patients, only residual urine volume showed a statistically and clinically significant improvement at the long-term follow-up. According to maximum flow nomograms, bladder outlet obstruction was not resolved by the treatment. We conclude that although the transrectal hyperthermia proved to be a safe procedure, it did not cure BPH in the long term. Considering the results seen with newer nonsurgical procedures such as prostatic stents and prostatic lasers, we believe that transrectal hyperthermia should not be recommended to symptomatic BPH patients.

Ultrastructural aspects of DRG satellite cell involvement in experimental cisplatin neuronopathy.

Different substances may induce neurological impairment, clinically expressed as peripheral neuropathies, due to damage of the neuronal bodies (neuronopathy) of sensory or motor neurons. Neuronopathies have generally been studied referring to neurons, although other cellular components may also be damaged. Cisplatin (CDDP) is known to be neurotoxic to the neurons of the dorsal root ganglia (DRG). The scarcity of information as to the possible involvement and role played by dorsal root ganglion (DRG) satellite cells in neuronopathies prompted this study using the chronic DRG neuronopathy induced by the repeated administration of CDDP in rats as a model. Eighteen female Wistar rats were treated according to 3 different schedules of CDDP administration (6 rats for each group). Six further animals were used as controls. At the end of the experiment the L4-L5-L6 dorsal root ganglia were examined at the light and electron microscope. Ag-NOR reaction was also examined in 4 further CDDP-treated rats and 4 controls. Pathological changes in satellite cells of animals treated with CDDP were remarkable in the nucleus where heterochromatin clumps were reduced or even completely absent. Morphometric analysis of the area occupied by heterochromatin indicated that this nuclear component decreased in an exposure-time dependent manner. Frequently, nucleolar-like structures became apparent in the nucleus of the rats treated with the higher doses of CDDP. Ag-NOR positive regions in the nuclei of treated rats were increased with respect to the controls. Cytoplasmic changes in DRG satellite cells of CDDP treated rats were limited, being characterized by an increased electron-density of the matrix. In treated rats deep invaginations between satellite cells and the neuronal surface were evident, leading to the formation of vacuoli. The interstitial connective space often showed edematous areas. Our observations demonstrate that in chronic cisplatin neuronopathy, DRG satellite cells are also involved in the pathological changes induced by drug exposure, and that these changes may be interpreted as being mainly reactive.

The repeatability of choku-tsuki and oi-tsuki in traditional Shotokan karate: a morphological three-dimensional analysis.

The aim of the study was to quantify the repeatability of the displacement of selected body landmarks while performing two different basic karate attacks. Seven karateka (three men, four women) with different levels of training and knowledge of karate were filmed with an optoelectronic computerized instrument (sampling rate 100 Hz) that allows the three-dimensional reconstruction of the movements of selected body landmarks. Thirteen landmarks (head, hips, upper and lower limbs) were analyzed while performing 10 repetitions each of choku-tsuki (straight punch) and oi-tsuki (lunge punch). For each karateka and punch, the average time of execution was calculated, and the standard deviations of each of the three spatial coordinates x, y, z were computed for each landmark. A total standard deviation of the single karateka and punch was also calculated. For all karateka, the execution of oi-tsuki took longer than the execution of choku-tsuki. For both punches and almost all landmarks, the largest repeatability (smallest standard deviation) was found in the vertical direction, while the smallest was found in the anteroposterior direction (direction of movement). In all karateka, oi-tsuki had a total standard deviation about 3 to 6 times larger than that measured during the performance of choku-tsuki. On average, women had a larger repeatability than men. The method employed in the current study allowed the quantitative analysis of the repeatability of two basic attacks in Shotokan karate by using a landmark based approach. The method could offer valuable help to karateka during training indicating which parts of the body do not repeat a selected movement with sufficient accuracy, thus assisting in the achievement of the most correct body form.

Real complete three-dimensional reconstruction of Golgi-impregnated neurons by means of a confocal laser scanning microscope.

Golgi-impregnated neurons of the human or animal central nervous system were studied with a confocal laser scanning microscope (CLSM). The scanning properties (optical sectioning of the specimen) offered by the CLSM and the capacity of metal granules to reflect the laser beam allow a three-dimensional reconstruction of the impregnated neurons. The volume scanned can be depicted in three different ways: (a) extended focus, i.e., a bidimensional image that contains information from all the optical sections, as if there were an extensive depth of focus; (b) a topographic representation in which the intensity of every pixel is proportional to the calculated z value (as a result, the closer the object section is to the surface, the greater the color intensity becomes); and (c) shadow representation, i.e., a pseudo-three-dimensional image. In addition, a true and complete three-dimensional reconstruction of neurons can be obtained using an extended RAM and quick elaboration (fast CPU) combined with the rotation of the reconstructed image in the different planes. High-magnification, high-numerical-aperture (NA) oil immersion objective lenses with reduced working distance may present some problems in the three-dimensional reconstruction of large neurons with extensive and spreading dendritic branches. This limitation may be overcome by using a low-magnification (10 x) oil immersion lens.

A size-standardized analysis of soft tissue facial profile during growth.

A method for the quantitative and qualitative analysis of the facial soft tissue profile has been developed and applied to analyze the age differences in lateral cephalograms for the annual Bolton standards from ages 1 to 18 years. To standardize for different facial sizes, profiles were traced in polar coordinates without modifications of facial shape. Most of the soft tissue landmarks showed progressive modifications from birth to 18 years of age. Soft tissue nasion and lower lip had a steep change between 2 and 3 years of life, pronasale between 3 and 5 years of life, A', upper lip, and stomion between 4 and 5 years of life. Hereafter, all these landmarks but N' had several minor modifications progressing toward the adult value. Soft tissue nasion did not modify significantly after 2 years of age. Conversely, changes in the relative positions of B' and Pg' were more scattered in the analyzed period. Age-related size differences were more linear than shape modifications, with gradual increments from 1 to 18 years of age. The method allowed a simple and rapid quantitative evaluation of soft tissue profiles during facial growth. An approximate evaluation of the soft tissue thickness at nose, lips, and chin was also possible. No particular mathematical knowledge was required at any step of the analysis. Results were in good agreement with the well-known patterns of normal growth and development, thus confirming the practical possibilities of the method.

The site of motor corticospinal fibres in the internal capsule of man. A computerised tomographic study of restricted lesions.

The distribution of the motor impairment was correlated to the site and extension of the lesion of 18 patients with restricted lesions of the internal capsule, detectable with computerised tomography (CT). In three cases the lesion was located in the anterior limb of the internal capsule and the patients did not suffer any motor defect. Among the 15 patients with lesions in the posterior limb, 13 presented a distribution of the motor weakness consistent with a location of the corticobulbar fibres in the genu and corticospinal fibres in the anterior half of the posterior limb. Our CT study confirms the classical view on the location of the pyramidal tract in the internal capsule of man, but also evidences the possibility of individual variations.

The organization of corticopontine fibres in man.

Patients with lesions located in the frontal and temporal lobes, in the parieto-temporo-occipital border zone, and in the anterior limb of the internal capsule, did not present ataxia or other cerebellar signs. On the other hand, patients with the ataxic hemiparesis (AH) syndrome had lesions located in the posterior limb of the internal capsule, in the corona radiata and in the central region of the cerebral cortex. These findings in man do not confirm the existence of large frontal (Arnold's bundle) and temporal (Türck's bundle) projections to the pontine nuclei and indicate that the main bulk of corticopontine fibres originates from the central region of the cerebral hemisphere and courses in the posterior limb of the internal capsule. In man, the anatomical organization of corticopontine fibres is therefore similar to that recently demonstrated in animals.

Non-parametric deconvolution provides an objective assessment of GH responsiveness to GH-releasing stimuli in normal subjects.

OBJECTIVE: Deconvolution analysis has been proposed as an effective method for analysing the physiology of GH secretion. In the literature, it has been applied to spontaneous secretion data characterized by long and uniform sampling paradigms. In the present study we investigated the applicability of non-parametric deconvolution to the analysis of response-to-stimuli (RTS) data characterized by infrequent and non-uniform sampling. PATIENTS: Thirty-six healthy adult male volunteers (age range 24-37 years) were randomly subdivided into two groups (group I, n = 30; group II, n = 6). DESIGN: Subjects of group I were tested with a single 1 microgram/kg body weight GH-releasing hormone (GHRH) bolus, administered at 0 minutes. Subjects of group II were tested, in random order, with a 4- or 5-day interval, with (1) two consecutive 1 microgram/kg body weight GHRH boluses at 0 and 120 minutes and (2) two consecutive 1 microgram/kg body weight hexarelin boluses, administered at 0 and 120 minutes. MEASUREMENTS: GH levels were determined at 0, 15, 30, 45, 60, 90 and 120 minutes (group I) and -30, 0, 15, 30, 45, 60, 120, 135, 150, 165, 180 and 240 minutes (group II). A numerically efficient regularization-based non-parametric deconvolution algorithm incorporating non-negativity constraints was used to estimate the time profile of the instantaneous secretion rate (ISR). Confidence limits allowing for both measurement error and kinetic model uncertainty were computed using a Monte-Carlo procedure. In order to validate the deconvolution method, a simulated benchmark problem was set up. RESULTS: The analysis of the benchmark problem showed that the proposed method is capable of providing an accurate reconstruction of the ISR (as measured by the root mean square (RMS) error). Moreover, it appeared that reliable confidence limits cannot be obtained unless the kinetic model uncertainty is taken into account. The analysis of the data showed a clear rise in the ISR subsequent to the first bolus (either GHRH or hexarelin), with most of the response occurring within 60 minutes of the stimulus. In group I, it was also seen that discarding the samples collected at times 90 and 120 minutes only marginally affected the estimate of the cumulated ISR over 0-60 minutes (the variation was always less than 3%). The analysis of GH responsiveness to repeated stimuli (group II) showed that the amount of hormone secreted after the second bolus was clearly reduced in comparison with the elicited by the first stimulus, most of the response occurring within 60 minutes of the injection. The amount of GH secreted after the second stimulus ranged from 13 to 36% (GHRH 17-36%; hexarelin 13-36%) of the overall amount of hormone secreted after time 0 minutes. CONCLUSIONS: Even with relatively few samples, non-parametric deconvolution of response-to-stimulus data is capable of providing a reliable, smooth and non-negative estimate of the GH instantaneous secretion rate that offers a realistic representation of the GH secretory dynamics. The non-parametric approach compares favourably with respect to discrete deconvolution methods, that yield discontinuous instantaneous secretion rates profiles, and parametric methods that would require more stringent assumptions on the shape of the instantaneous secretion rate. When assessing confidence limits it is essential to take into account both measurement error and kinetic model uncertainty. Using deconvolution in normal subjects, the estimated instantaneous secretion rate between 0 and 60 minutes is scarcely affected by samples taken after time 60 minutes. Since most of the secretory response takes place during this time interval, there is motivation for investigating the use of shorter sampling protocols in conjunction with deconvolution analysis. Although pulse detection and the assessment of the shape of spontaneous pulses have not been investigated, it could be interesting to apply non-parametric deconvolution to spontaneous sec

Quantitative analysis of the neuronal population of the red nucleus of the cat.

There is strong evidence in the literature for a correlation between the two parts of the red nucleus, magnocellular and parvocellular, and different functions. Unfortunately in the cat, the species most studied both physiologically and anatomically, there are no morphological criteria distinguishing the two portions. With quantitative techniques applied to Nissl preparations the neuronal population of the Red Nucleus has been studied in serial sections along the rostrocaudal axis of the mesencephalon of the cat. Statistical analysis of the data revealed a horizontal plane dividing the two portions of the nucleus with a high statistical significance level. This plane lies between the caudal two-thirds and the rostral third of the nucleus. Although in the model two portions can be distinguished, it is not possible to assign to either a single type of neuron, whether or considered in terms of shape or size.

Distribution of the cortico-spinal fibres in the cervical and lumbar enlargements of the rat spinal cord.

We examined the distribution pattern of the corticospinal fibres in cervical and lumbar enlargements of the rat spinal cord with the Fink-Heimer silver impregnation method, after extensive cortical ablation. Corticospinal fibres are bilateral and run in the lateral and anterior funiculi. The distribution at the cervical and lumbar levels does not differ. The main area of termination are: 1) the lateral part of the ventral horn basis; 2) an area surrounding the motoneurons group posteriorly. At the electron microscope we were unable to find degenerating boutons of the corticospinal projections contacting HRP labelled motoneurons retrogradely. This indicates that at both levels few monosynaptic corticospinal fibres or none at all end on the motoneurons. Our study does not support the suggestion of differences in the termination pattern of the corticospinal tract of the rat between cervical and lumbar enlargements made on the basis of electrophysiological studies.