The resistance index represents the corporeal pressure and not the cavernous wall resistance

PURPOSE: We compare the results of the resistance index generated by duplex scanning and the corporeal pressure generated by the intracavernous injection test followed by gravity cavernosometry. MATERIALS AND METHODS: We examined 40 impotent subjects with duplex scanning and gravity cavernosometry. RESULTS: For the entire group a significant correlation (r = 0.77, p < 0.001) was found between the resistance index and intracavernous injection test, and between the resistance index and the gravity cavernosometry (r = 0.62, p < 0.01). Excluding the results of patients who had a full erection during scanning, the correlation between the resistance index and intracavernous injection test remained but the correlation between the resistance index and gravity cavernosometry disappeared (r = -0.02, p > 0.05). CONCLUSIONS: There was no relationship between the value of the resistance index and the cavernous wall resistance, except in patients capable of developing a full erection after vasodilator injection.     

The pharmaco-erection test

Intracavernous administration of vasoactive drugs induces an erection in absence of erotic stimuli; we can use this property in the study of impotent patients, inducing the appearance on an erection to examine it in all its phases (FIC Test). In case of the appearance of a good erection, the test should rule out the presence of a penile arterial disease or of a corpora-veno-occlusive deficiency. When the administration of the drug does not cause complete tumescence, it is very probable that the erectile dysfunction is caused by arterial vascular alterations or by organic disorders of veno-occlusion mechanism, but we cannot exclude for a certainty a psychogenic dysfunction. In fact an excessive noradrenergic autonomic control, as during stress condition, may limit FIC Test response. Therefore we hope that more efficacious molecules will be available in a near future. Nevertheless, we consider the opportunity of enclosing tests in the diagnostic algorithm of impotent patients to reveal an excessive adrenergic tone, such as, for example, psychological tests, study of cavernous potential, or intracavernous catecholamine dosage.     

Intramedullary fixation of forearm fractures in adults

The arrangement of the smooth muscle and elastic and collagen fibers of the minor papilla of the human duodenum was studied on 53 duodenopancreatic specimens obtained from adults of both sexes. Methods included stereological analyses of gross anatomical specimens and thick and thin microscopic sections. The muscular and elastic fibers of the minor papilla have a unidirectional arrangement by which the contraction of its smooth muscular fibers causes opening of its orifice allowing the flow of the pancreatic juice into the duodenum. It is not a typical anatomical sphincter.     

Renal and hepatic nitrogen metabolism during NH4Cl ingestion in protein-deprived rats

PURPOSE: We assessed the morphodynamic features of cavernous arteries and helicine arterioles by power Doppler sonography in vasculogenic and nonvasculogenic impotent men. MATERIALS AND METHODS: A total of 40 impotent patients with and without definite vascular risk factors were studied by penile power Doppler sonography. The test was performed during penile flaccidity, after intracavernous injection of 20 mcg. alprostadil and after subsequent genital and audiovisual sexual stimulation. A second injection and stimulation were given if the erectile response observed after the initial injection was less than the maximum erection seen during sexual activity. Morphodynamic parameters evaluated by power Doppler imaging included vessel course, shape, wall thickness and pulsatility, peak systolic velocity, end diastolic velocity, acceleration time and resistance index. RESULTS: In the nonvasculogenic group all patients who achieved rigid erection showed normal cavernosal artery and helicine arteriole inflow. In these cases the arteriolar picture was characterized by the presence of 3 orders of distal ramifications originating from the cavernous arteries with an acute angle, systolic diastolic flow during penile tumescence and systolic flow alone at full rigidity. In the vasculogenic group patients with normal cavernous artery inflow showed an arteriolar tree that was pathological in 50% and was characterized by a reduced number of ramifications originating perpendicularly from the cavernous arteries and irregular caliber (arteriolar impotence). In the same group patients with reduced cavernous artery inflow also showed normal or pathological arteriolar components (pre-penile arterial impotence and diffused penile arterial impotence). CONCLUSIONS: Power Doppler sonography allows a precise study of the morphodynamics of the cavernous arteries and helicine arterioles. Our preliminary data suggest that the intracavernous arteriolar component may have a significant role in the genesis of some forms of vasculogenic impotence.     

A quantitative study of daytime sleepiness induced by carbamazepine and add-on vigabatrin in epileptic patients

Improvement in natural erections has been reported in approximately 9% of impotent men using intracavernous injections of vasoactive drugs for erection induction. The mechanisms which may account for this improvement are psychogenic, improved cavernous hemodynamics, prostaglandin-induced angiogenesis, improved cavernous oxygenation, cavernous smooth muscle hypertrophy and/or normal episodic fluctuations in erectile function. A review of the basic science literature on this subject reveals several theoretical explanations for this phenomenon but a review of the clinical literature reveals little convincing evidence that physiologic and/or pharmacologic factors are responsible for improvement in natural erections with intracavernous injection therapy. Furthermore, the prevalence of a placebo effect from impotence therapy exceeds the reported rate of improvement in natural or spontaneous erections. The most plausible explanations for spontaneous improvement in erections during or after intracavernous injection therapy are psychogenic and episodic variations in erectile function, rather than physiologic or pharmacologic factors. However, intracavernous injection therapy started soon after radical prostatectomy may have a protective effect in preserving normal cavernous physiology and erectile function in men being treated for prostate cancer.     

Quantitative analysis of smooth muscle fibers in corpus cavernosum of human fetuses

PURPOSE: Quantify objectively the normative distribution and the percentage of smooth muscle fibers in the corpus cavernosum of human fetuses with 24 weeks post-conception (WPC) of gestational age. MATERIAL AND METHODS: We studied 7 penises taken from 7 fresh human fetuses. We analyzed 5 randomized sections from each penis and in every section we analyzed 3 fields, totaling 15 fields per penis and 105 fields for the final results. Immunohistological staining for the smooth muscle fibers was used to accentuate the differences between the intracavernous structures (smooth muscle fibers and collagen fibers). The fields studied were digitized with a final magnification of 450X and a computerized analysis of the smooth muscle fibers was performed with image analyzer software. The percentage of smooth muscle fibers per standard square area was estimated and the mean value was used for each penis. RESULTS: The distribution of smooth muscle fibers in the corpus cavernosum of human fetuses with 24 WPC of gestational age ranged from 17.52% to 27.76% of the total area. The mean value was 22.72% and the standard deviation was 3.56. CONCLUSIONS: Our results show that the percentage of smooth muscle cells in corpus cavernosum of human fetuses with 24 WPC of gestational age is significantly smaller when compared with the data available for adult cadavers.     

Relation of intracorporal pressure and end-diastolic velocity during duplex Doppler sonography in the evaluation of veno-occlusive dysfunction

In 37 patients 25 to 69 years old (mean age 49.6 years) with suspected 'vasculogenic erectile dysfunction', diagnosed on the basis of repeated negative reactions to intracavernous pharmacological stimulation, duplex Doppler measurements and pharmacocavernosometry were performed in one session under simultaneous pressure registration. A statistically significant difference between patients with and without veno-occlusive dysfunction was found by combining end-diastolic velocity and pressure in time. We conclude that color Doppler scanning in combination with simultaneous pressure registration can predict veno-occlusive dysfunction in 83-95% of the patients.     

Corpus cavernosum electromyography (CC-EMG): a new technique in the diagnostic work-up of impotence

We have studied cavernous electrical activity in 42 subjects, healthy volunteer controls and groups of impotent patients using a nonspecific electromyographic device (PICO-MENFIS) and a specific one, the SPACE-recorder 7500 designed to achieve electric recordings from the corpora cavernosa. In all of the patients, we detected under basal conditions a mean amplitude of 583 +/- 323 microV, a mean duration of 4.9 +/- 7 s, a mean polyphasicity of 3.5 +/- 1.4. It should be emphasized that a significant reduction of potential amplitudes was recorded after pharmacological stimulation in both the controls and the impotent patients. The healthy controls showed amplitudes significantly higher than the impotent patients after radical cystectomy (715 +/- 141 microV versus 381 +/- 227 microV, p < 0.01). The patients after a "nerve-sparing" radical cystectomy with a mean amplitude similar to the controls (500-700 microV) reacted well to the intracavernous drugs in a high percentage of cases. In our experience, CC-EMG seems to be a reliable method which can pinpoint directly lesions to the cavernous smooth muscle and penile autonomic nerves. It has also been able to assess the effects of stress, anxiety and pain on the erectile mechanisms.     

Simultaneous operation of intra-descending aorta bypass grafting and brachiocephalic artery reconstruction in a patient of aortitis syndrome

OBJECTIVE: To determine the intracavernous partial oxygen pressure in different etiological groups of erectile dysfunction: psychogenic (control group), arterial and veno-occlusive and the value of intracavernous gasometry as an indicator of the degree of severity of impotence. METHODS: A total of 16 patients were evaluated according to the diagnostic protocol utilized to determine the etiology of erectile dysfunction. Intracavernous blood samples were obtained during the initial phase of gasometry and PO2 was determined by standard gasometric methods. RESULTS: After injection of the vasoactive drug, the mean intracavernous PO2 was 92.4 +/- 1.27 for the control group, 62.2 +/- 0.85 for the group with arterial impotence, and 76.8 +/- 1.45 for the group with venous impotence, demonstrating a statistically significant difference (p < 0.01). CONCLUSIONS: Intracavernous gasometry, in combination with other diagnostic tests, is useful for evaluating the degree of severity of erectile dysfunction. The reduction in cavernous oxygen tension, which induces cavernous tissue fibrosis, can be considered to be a common mechanism in arterial and venous impotence.     

Minimally invasive therapies in the treatment of erectile dysfunction in anticoagulated cases: a study of satisfaction and safety

PURPOSE: We evaluated patient satisfaction with and the safety of vacuum therapy and self-injection during warfarin treatment of impotent men. MATERIALS AND METHODS: In a 24-week prospective study 33 patients were assigned to vacuum therapy or intracavernous injections with crossover at 12 weeks. Patients maintained diaries, and were followed with physical examinations, coagulation studies and questionnaires. RESULTS: Of the 33 patients 26 completed the study with 706 vacuum applications (mean 1.9 weekly) and 605 injections (mean 1.6 weekly). There are 11 acute minor complications with vacuum therapy (petechiae that resolved spontaneously) and no chronic complications. Only quality of climax was diminished with vacuum therapy. Self-injection resulted in acute minor complications (3 ecchymoses and 1 prolonged erection requiring intervention) and 1 chronic complication (corporeal fibrosis with mild curvature). CONCLUSIONS: The adverse effects of vacuum therapy and intracavernous self-injection in patients on warfarin do not exceed the rate in the general urological population. These therapies appear to be safe in patients receiving warfarin.     

The carcinoid endocardial plaque; an ultrastructural study

Ultrastructural studies disclosed that the plaque-like endocardial thickenings in three patients with the carcinoid syndrome were composed of smooth muscle cells embedded in a stroma that was rich in acid mucopolysaccharides, collagen, and microfibrils, but devoid of elastic fibers. The smooth muscle cells contained variable numbers of myofilaments and cisterns of rough surfaced endoplasmic reticulum, and their basement membranes were greatly thickened, reduplicated, and arranged in layers. The endocardial plaques appeared histologically and ultrastructurally similar regardless of their location in the heart. The smooth muscle cells in these plaques appear to have been derived from primitive mesenchymal cells, which normally are present in the subendocardial endothelial space. These observations are interpreted as indicating that the plaques develop as a result of healing of a superficial endocardial injury, which may be initiated by release of bradykinin from hepatic metastases of a carcinoid tumor.     

Doppler color echography in the diagnosis of impotence

This study reports the experience achieved with duplex and color Doppler ultrasonography in 120 impotent patients. The following morphodynamic parameters of the cavernosal arteries were studies before and after intracorporal injection of a mixture of vasoactive drugs: arterial diameter, wall pulsatility, morphology of the spectral waveform, peak systolic velocity, end diastolic velocity and flow volume. The veno-occlusive mechanism of the corpora cavernosa was studied directly by determination of flow along the deep dorsal vein of the penis and indirectly by serial evaluation of the diastolic flow of the cavernous arteries.     

Arrangement and structure of sinus hair muscles in the big-clawed shrew, Sorex unguiculatus

The arrangement and structure of sinus hair muscles in the snout of the shrew, Sorex unguiculatus, were studied by electron microscopy and serial section light microscopy. Both striated and smooth muscles are directly associated with sinus hair follicles. The striated muscle fibers originate from the base of a follicle and insert onto the superficial portion of adjoining caudally positioned follicles. Some fibers insert into the corium instead of inserting into a follicle. The fibers show a fine structure typical of red fibers. Smooth muscle cells form a network with elastic fibers beneath the corium. Some cells are directly attached to the capsule of the sinus, thus forming a type of M. arrector pili. Striated muscle febers that appear to end in the corium are connected with the smooth muscle network through the elastic fibers which appear to function as the tendon of these two types of muscle cell.     

Apoptotic myonuclei in human Duchenne muscular dystrophy

The current view that apoptosis precedes necrosis in death of dystrophin-deficient muscle fibers of the mdx mouse has been well substantiated. Moreover, apoptotic myonuclei have been reported to increase in dystrophin-deficient mice 2 days after spontaneous exercise. To investigate the role of apoptosis in human muscular dystrophy, muscles from 11 patients of different ages with Duchenne muscular dystrophy were analyzed for apoptosis. The amount of apoptosis was assessed by terminal deoxynucleotidyl transferase assay, and the expression of bcl-2 and bax was examined by immunohistochemistry. Although very rare in normal muscles (less than 0.1%), apoptotic nuclei were detected in dystrophic muscles, particularly at the interstitial level. Nevertheless, few dystrophin-deficient myofibers with centrally located nuclei showed a positive reaction for DNA fragmentation. A mosaic pattern of bcl-2/bax-positive myofibers characterized dystrophic muscles, thus the relative proportion of pro- and antiapoptotic proteins differs among muscle fibers in correlation with the presence of apoptotic myonuclei. In the interstitium, apoptotic cells were identified as macrophages and activated satellite cells. This is the first study to show an apoptotic process in adult muscle fibers of patients with Duchenne muscular dystrophy, thereby shedding new light on muscle damage and its progression in dystrophinopathies.     

"Spontaneous" endothelial injury in the rat caudal artery

Numerous spontaneous lesions, characterized principally by a gap in the internal elastic lamina, form with age in the caudal artery of the young, male Wistar rat. Such newly formed lesions were studied, with special reference to the state of the endothelium, using three techniques: "en face" examination of silver-stained caudal artery, [3H]thymidine autoradiography, and light and electron microscopy. In many, but perhaps not all cases, areas of endothelium are damaged or removed either simultaneously or shortly after the formation of the break in the internal elastic lamina and some underlying smooth muscle cells are damaged. Polymorphonuclear cells and monocytes are attracted to the site of injury. A repair process rapidly ensues including rapid regeneration of the endothelium and proliferation of smooth muscle cells in the underlying media and of some adventitial fibroblasts. This process results in the restitution of the endothelial monolayer and the laying down of one or several layers of longitudinal smooth muscle and collagen and elastic fibers in the subendothelial space. This demonstration of naturally occurring damage to fairly large areas of endothelium and the events which occur in the repair process is of interest in view of the "response-to-injury" theory of atherogenesis; observations are discussed in the light of previous studies performed on experimentally removed endothelium.     

Glomerulonephritis in autopsy cases with hepatitis C virus infection

1. The inducible isoform of nitric oxide synthase (iNOS) is expressed in human and experimental cardiac allografts and is localized to infiltrating macrophages, cardiac myocytes, endothelial cells and smooth muscle cells. A recent clinical report proposes a causal link between myocardial expression of iNOS and ventricular contractile dysfunction, a potentially graft- and life-threatening post-transplant complication. 2. Coronary blood flow is elevated in human graft recipients with biopsy proven cellular rejection, indicating that vasodilation accompanies graft rejection. In Lewis-to-F-344 coronary resistance vessels, which show intimal expression of iNOS, pressure-induced myogenic tone is significantly inhibited. Selective iNOS inhibition partially reverses the inhibition of myogenic tone, confirming that iNOS produces vasoactive nitric oxide (NO) and may mediate the rejection-induced vasodilation seen clinically. 3. Endothelial dysfunction, identified as loss of endothelium-dependent dilation, has tremendous prognostic significance in vascular diseases of multiple aetiologies. In transplantation, endothelial dysfunction predicts early cardiac allograft vasculopathy and poor clinical outcome. Lewis-to-F-344 coronary vessels develop endothelial dysfunction at 1 week post-transplantation, but this is preceded by a transient state of endothelial cell hyperfunction, with enhanced endothelial production of NO. 4. The normal interaction between endothelial and smooth muscle cells in coronary resistance vessels is critical for the regulation of coronary blood flow and the maintenance of fluid homeostasis. With allospecific expression of iNOS, the inhibition of vascular tone predicts greatly enhanced intravascular pressure in precapillary arterioles and capillaries; this would be expected to cause a net movement of fluid from the intravascular compartment into the myocardial interstitium, resulting in ventricular oedema, non-compliance and poor contractile performance.     

An electron microscopic study of plasmatic arterionecrosis in the human cerebral arteries

An electron microscopic study of the intracerebral arteries from 9 hypertensive cases was performed in order to elucidate the morphogenesis of the plasmatic arterionecrosis which was considered to be the direct cause of hypertensive intracerebral hemorrhage. In the preceding stage of the arterial lesions, marked necrosis of medial smooth muscle cells and increase of basement membrane-like substance in the intima and media were observed. The lumina of these arteries were slightly dilated. The dilatation and hemodynamic factors were supposed to cause endothelial injury resulting in blood plasma insudation into the intima through the opened spaces between endothelial cells. The insudated blood plasma dispersed and dissolved the basement membrane-like substance, collagen and elastic fibers in the arterial wall, leading to the development of the plasmatic arterionecrosis.     

First recorded outbreak of yellow fever in Kenya, 1992-1993. II. Entomologic investigations

OBJECTIVES: The physiology of the female sexual response and its molecular mediators remain poorly understood. Nitric oxide (NO) is synthesized in neurons and is a potent relaxor of vascular and nonvascular smooth muscle. In this study, we hypothesize that vaginal atrophy and declining sexual function during menopause may be NO dependent. Using the rat as an experimental model, we examined the expression and topologic localization of vaginal NO synthase (NOS) and the concomitant induction of apoptosis under normal and estrogen-depleted conditions. METHODS: Thirty rats were categorized into six groups on the basis of phase of the estrous cycle or estrogen status after oophorectomy. The expression and cellular localization of NOS was examined in frozen sections using specific antibodies against neuronal (N-NOS) and endothelial NOS (E-NOS). Apoptotic cells were identified in situ using the terminal transferase technique (TUNEL). Trichome staining was performed in all specimens to determine smooth muscle/collagen ratios. RESULTS: N-NOS immunoreactivity was localized to nerve fibers supplying vaginal smooth muscle, perivascular nerve plexuses, and lamina propria. E-NOS was localized to vascular endothelium and perivascular smooth muscle fibers. Both E-NOS and N-NOS expression in intact cycling animals was highest during proestrous and lowest during metestrous. After oophorectomy, levels of both N-NOS and E-NOS declined substantially compared with those of intact animals, and there was a parallel induction of apoptosis. Estrogen withdrawal also resulted in increased vaginal atrophy, intramural collagen accumulation, and perivascular wall thickening, as identified by trichome staining. Estrogen replacement resulted in a significant increase in E-NOS and N-NOS expression, as well as diminished apoptosis and vaginal atrophy. CONCLUSIONS: This cellular distribution of NOS in the rat vagina suggests that NO may modulate both vaginal blood supply and vaginal smooth musculature. Estrogen appears to play a critical role in concomitantly regulating vaginal NOS expression and apoptosis in nerves, smooth muscle, vascular endothelium, and epithelium of the rat vagina. These findings may have significant clinical implications for the pathophysiology of postmenopausal female sexual dysfunction.     

Expression of MHC and cell adhesion molecules in muscular sarcoidosis

Biopsied skeletal muscles from 5 patients with muscular sarcoidosis (nodular type; 1, and myopathic type; 4) were immunocytochemically examined. All biopsies presented granulomatous changes. Atrophic or regenerating muscle fibers adjacent to granuloma demonstrated compression or ischemic changes. In the center of the granuloma, CD68+ epitheloid cells and giant cells, and CD4+ T cells were localized. At the periphery of the granuloma, CD4+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophages were found. Expression of HLA-A,B,C was diffuse in the muscle fibers. Expression of HLA-DR and ICAM-1 was more prominent near the granuloma or perifascicular fibers, and that of LFA-3 was moderate in those lesions. VCAM-1 was expressed in endothelial cells and macrophages near the granuloma. Those findings indicate that interferon-gamma or TNF-alpha produced by infiltrating inflammatory cells may induce expression of these immunologic markers or adhesion molecules. Immunocytochemical differences between the nodular and myopathic forms of sarcoidosis are not evident, but either localization or abundance of granuloma in muscle bulks is relevant to weakness or atrophy of clinically affected muscle.     

A histopathological study of deep dorsal penile vein in venogenic impotence

We have studied the histopathology of 87 dorsal penile veins, obtained from patients who underwent a resection of the deep dorsal penile vein because of proven venous leakage. The amount of muscle tissue and of collagenous connective tissue has been numerically quantified. Special attention has been focused on the muscular/collagenization ratio. We show that this ratio is not correlated to age neither with the outcome of the operation and that no differences exist between veins in venous leakage patients and in potent patients. This study confirms that the reduction of venous outflow-the so called corporeal veno-occlusive mechanism-is probably a secondary passive phenomenon, due to smooth muscular relaxation, and mainly located within the corpora cavernosa, between the expanding sinusoidal wall and the noncompliant tunica albuginea. Our findings also strongly refute the hypothesis that polsters or other venous wall characteristics contribute to the normal physiology of the deep dorsal penile vein.