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Biomedical subjects

C A Haas

Publications and source records attributed to C A Haas.

At least 19 recordsLinked to original sources

Penile fracture and testicular rupture.

Traumatic injuries to the penis and testicles are uncommon, likely due to the well-protected location and degree of mobility of these organs. Because of this the management of these injuries has historically been controversial. However, current literature supports immediate evaluation and surgical repair of these traumatic injuries to prevent complications such as erectile dysfunction or testicular loss. Herein the diagnostic and therapeutic options for both traumatic penile fracture and testicular rupture are reviewed with emphasis on immediate evaluation and repair.

Humans

Intraurethral alprostadil for treatment of erectile dysfunction in patients with spinal cord injury.

OBJECTIVES: To assess the efficacy of intraurethral prostaglandin E1 (alprostadil, MUSE) in treating erectile dysfunction in patients with spinal cord injury (SCI). METHODS: Intraurethral alprostadil was tested in 15 patients with SCI to evaluate its effectiveness in treating SCI-associated erectile dysfunction. All patients were at least 1 year after injury, and all had previously used intracavernosal injections successfully (Schramek's grade 5 erection). The intraurethral drug was administered in the office, in the presence of a physician, with monitoring of blood pressure. If effective, the patient was then able to use MUSE at home. The first 3 patients underwent gradual dose escalation starting with 125 microg, without the use of a constriction ring. Because of hypotension, the remaining 12 patients all used a penile constriction ring prior to intraurethral drug administration using 1000 microg. The quality of the erection was compared with that achieved with intracavernosal injections using Schramek's grading. RESULTS: The dose escalation (titration) in the first 3 patients demonstrated that the 1000-microg dose was the most effective in creating an erectile response. Transient hypotension was noted in these first 3 patients in whom the constricting band was not used. The highest dose of MUSE (1000 microg) was, therefore, used in the remaining 12 patients, with the constriction band. The quality of the erection varied and appeared to be less rigid in all patients (12 patients with grade 1 to 3; 3 patients with grade 4) than that noted with intracavernosal injection therapy (1 5 patients with grade 5). There was no incidence of priapism. The 3 patients with grade 4 erections tried the MUSE at home. All 3 patients were dissatisfied with the quality of the erection and did not continue to use the MUSE at home and returned to intracavernosal injection therapy. CONCLUSIONS: MUSE appears to be somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction. It should always be used in the patient with SCI after placement of a constriction ring to prevent hypotension. Its ultimate use depends on the patient's level of satisfaction with the quality of the erection compared with intracavernosal injections.

Adult

Differential induction of c-Fos, c-Jun and Jun B in the rat central nervous system following unilateral entorhinal cortex lesion.

In order to identify some of the molecular mechanisms that occur after a central nervous system trauma, the immediate early gene encoded proteins c-Fos, c-Jun and Jun B were analysed by immunocytochemistry following unilateral entorhinal cortex lesion (controls, 30 min, 2, 5, 12 and 24 h, two, six, 10 and 14 days, four weeks and six months postlesion). In the dentate gyrus, c-Fos was induced in some supragranular neurons (30 min), massively expressed in granule cells ipsilaterally to the lesion (2 h), expressed in hilar neurons (5 h and two days) and was absent at all later stages. A basal expression of c-Jun was found in dentate granule cells of controls, which was strongly increased on the lesion side (2 h) and on the side contralateral to the lesion (12 h). c-Jun expression returned to control levels by 24 h. Jun B was induced in granule cells ipsilateral to the lesion within 2 h and was back to control levels by 5 h. In the lateral septal area, c-Fos and c-Jun were induced 30 min postlesion and decreased rapidly thereafter. In the cerebral cortex, a widespread induction of c-Fos and c-Jun occurred within 30 min after entorhinal cortex lesion and this up-regulation lasted until two days postlesion. These data indicate that electrolytic lesion of the entorhinal cortex leads to a rapid and widespread induction of c-Fos, c-Jun and Jun B. Within the denervated fascia dentata, some of these changes may be linked to the reorganization processes following the lesion. Alternatively, the alterations in immediate early gene expression reported here may be due to changes in synaptic activity or postlesional seizures which occur in this lesioning paradigm.

Animals

Limitations of routine spiral computerized tomography in the evaluation of bladder trauma.

PURPOSE: We evaluate the accuracy of spiral computerized tomography (CT) in diagnosing traumatic bladder rupture. MATERIALS AND METHODS: Medical records of 24 consecutive patients diagnosed with traumatic bladder rupture at our level 1 trauma center from 1993 to 1998 were retrospectively reviewed. Of the patients 15 underwent retrograde cystography and spiral CT of the abdomen and pelvis. The results of these imaging studies were compared. RESULTS: Retrograde cystography successfully diagnosed all cases of bladder rupture and correctly classified injuries confirmed surgically. Spiral CT successfully diagnosed 9 of 15 bladder ruptures (60%), and correctly classified 4 of 5 intraperitoneal (80%) and 6 of 11 extraperitoneal (55%) ruptures. CONCLUSIONS: Spiral CT is less accurate than retrograde cystography in diagnosing traumatic bladder rupture.

Adolescent

Region-specific activation of microglial cells in the rat septal complex following fimbria-fornix transection.

Studies of postlesional microglial activation may gain insight into microglia/neuronal interactions in processes of neurodegeneration. We compared the microglial response after axotomy of septohippocampal projection neurons with that seen after selective immunolesioning of cholinergic septohippocampal neurons with the immunotoxin 192 IgG-saporin. Using the microglial marker isolectin B4 from Griffonia simplicifolia (GSA I-B4), we found striking differences in the microglial response between these two lesion paradigms. Following axotomy of septohippocampal neurons by fimbria-fornix transection (ff-t), there was only a moderate and short-lasting microglial reaction in the medial septum (MS) in the early postlesion period. Prelabeling of septohippocampal neurons with Fluoro-Gold (FG) prior to axotomy revealed the survival of most neurons, and only very rarely were microglial cells observed that had phagocytosed FG-labeled debris. In the lateral septum (LS) containing the degenerating terminals of hippocamposeptal fibers transected by ff-t, a heavy reaction of lectin-labeled activated microglial cells associated with high phagocytotic activity was noticed. Unexpectedly, after a long survival time (6 months) following ff-t, we observed an increase in microglial GSA I-B4 labeling in the MS. In contrast, an inverse pattern of the microglial response, i.e., a strong initial reaction in the MS and very little microglial activation in the LS, was observed after immunolesioning. Our results indicate that the microglial reaction in the MS following ff-t differs substantially from that seen in other models of axotomy.

Animals

Cultured astrocytes express functional receptors for galanin.

The neuropeptides galanin and calcitonin gene-related peptide (CGRP) are strongly up-regulated in motoneurons following axotomy. Earlier reports have suggested that peptides might be released from injured neurons to recruit surrounding glia. In this study, the effects of galanin and CGRP on cultured rat astrocytes were investigated using the expression of immediate early genes as a model for receptor-mediated transcriptional activation. Galanin was found to induce c-fos, junB, and Tis11 mRNA in cultured astrocytes, providing evidence for the presence of functional galanin receptors on neuroglial cells. In contrast, CGRP only led to the induction of c-fos and junB mRNA. Cholecystokinin (CCK-8) and substance P, which are also up-regulated in select motoneuron populations following axotomy, fail to induce immediate early genes in astrocytes, indicating specificity of neuropeptides in their ability to stimulate glial cells. The differential induction of immediate early gene expression by galanin and CGRP in astrocytes points to differences in intracellular signal transduction mechanisms. Whereas CGRP was found to stimulate the accumulation of cyclic AMP by 10- to 20-fold, galanin had no effect on basal cyclic AMP content. The effect of CGRP on cyclic AMP accumulation was completely reversed by the CGRP receptor antagonist, CGRP(8-37). These results suggest roles for galanin and CGRP in the transcriptional activation of astrocytes.

Animals

Inguinal scrotal incision for penile fracture.

PURPOSE: We report a new incision for repair of penile fracture. MATERIALS AND METHODS: We describe 2 cases in which the inguinal scrotal incision was used for repair of penile fracture. The preoperative evaluation as well as the technical case and rationale for use of this incision are discussed. RESULTS: Preoperative cavernosogram delineated the site of the fracture. Immediate repair of the fracture using the inguinal scrotal incision was successful. CONCLUSIONS: The inguinal scrotal incision should be entertained for cases of penile fracture. It avoids incision into markedly edematous penile skin and allows for excellent visualization of the fracture site.

Adult

Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase.

OBJECTIVES: To evaluate whether alterations in nitric oxide (NO) synthesis or activity contribute to age-related erectile dysfunction and to elucidate the mechanisms causing these alterations using the rabbit as our model of aging. METHODS: We compared the ability of the rabbit cavernosal smooth muscle to relax in the organ bath in response to acetylcholine (Ach, endothelium-dependent vasodilator), sodium nitroprusside (SNP, an NO donor), and A23187 (a calcium ionophore) in young (6 month old) and aged (2.5 to 3.5 year old) rabbits. In addition, the immunohistochemical expression of endothelial nitric oxide synthase (eNOS) in both young and aged rabbit cavernosal tissue was examined. Endothelial integrity was examined immunohistochemically with JC70. RESULTS: Ach-mediated relaxation of penile corporal tissue was significantly attenuated from a maximum of 68.39 +/- 6.27 (0.1 mM Ach, n = 4) in young rabbits to 39.02 +/- 4.88 (0.1 mM Ach, n = 6) in aged rabbits (P < 0.04). No statistically significant difference (P > 0.05) was noted between cavernosal relaxation to sodium nitroprusside between young rabbits (97.8%, 0.1 mM SNP, n = 5) and aged rabbits (76.1%, 0.1 mM SNP, n = 5). This suggested that the defect in the Ach-NO pathway was at the level of NO synthesis, not activity. Immunohistochemical staining for eNOS demonstrated upregulation in both the vascular endothelium and corporal smooth muscle of aged rabbit tissue compared with young rabbit cavernosal tissue (n = 5). Anatomic endothelial integrity was demonstrated in the young and aged rabbits by the presence of JC70. This suggested that the defect in the Ach-NO synthetic pathway was not at the level of eNOS and was not due to anatomic endothelial cell disruption. Finally, Ach-mediated cavernosal smooth muscle relaxation in the young rabbit was not significantly augmented (P > 0.05) in the presence of the calcium ionophore A23187 (10 microM). A23187, however, significantly augmented (P < 0.04) Ach-mediated relaxation in the aged rabbit from a maximum of 33.93 +/- 6.58 to 41.55 +/- 6.58 (10 microM Ach, n = 5). This suggested that a potential defect in the Ach-NO synthetic pathway was at the level of intracellular calcium flux and possibly at the level of the calcium-eNOS interaction. CONCLUSIONS: Endothelium-dependent relaxation is attenuated in the aging rabbit; eNOS is upregulated in the aging rabbit; and no difference is noted in response to direct NO donation between the young and aged rabbit. The endothelium is anatomically intact in both the young and aging rabbit. The calcium ionophore A23187 augmented the attenuated vasorelaxation in the aging rabbit cavernosum (although not to the levels seen in the young rabbit cavernosum) and had no effect on the young rabbit cavernosum. These data suggest that erectile dysfunction in the aging rabbit cavernosum appears to be related to endothelial dysfunction and is characterized by eNOS upregulation and aberrant intracellular calcium fluxes.

Acetylcholine

Hepatotoxicity related to intracavernous pharmacotherapy with papaverine.

OBJECTIVES: To determine the incidence of hepatotoxicity related to self-administration of intracavernous papaverine or papaverine/phentolamine (bimix). METHODS: From October 1994 through June 1996, we retrospectively reviewed the medical records of 71 consecutive patients diagnosed with organic erectile dysfunction (ED) and receiving intracavernous injection therapy. Inclusion criteria were documentation of normal baseline liver function tests (LFTs), a minimum of 6 months of follow-up that included LFTs, at least one self-injection every 2 weeks, and no other prior or concurrent treatment for ED. Thirty evaluable patients satisfied the inclusion criteria and formed group 1. Mean age was 63 years (range 40 to 77), mean follow-up was 18 months (range 6 to 32), and mean number of injections per month was 5.7 (range 3 to 12). An age-matched population of 20 patients (mean age 69 years, range 46 to 90) without ED but with similar comorbid risk factors formed the control group (group 2). All patients in group 2 had routine long-term follow-up of LFTs (mean 52 months, range 10 to 1 14). RESULTS: Two patients (6.67%) from group 1 had elevated LFTs during treatment: one experienced a mild elevation in alanine aminotransferase and the other developed transient elevations of total bilirubin and aspartate aminotransferase 6 months after beginning therapy. Both patients reported a history of alcohol abuse. Both patients remained asymptomatic. Neither patient required discontinuation of therapy. One patient (5%) from group 2 developed an elevation of total bilirubin at a follow-up of 12 months. CONCLUSIONS: Routine monitoring of LFTs is probably unnecessary during intracavernous pharmacotherapy. Patients with a history of alcohol abuse or liver disease, however, should be followed up more closely when papaverine is selected for intracavernous injection. In these patients, LFTs should be obtained before initiating treatment and at 6-month intervals.

Adult

Stimulation of P2Y-purinoceptors on astrocytes results in immediate early gene expression and potentiation of neuropeptide action.

The action of adenosine-5'-O-(2-thiodiphosphate), a non-hydrolysable purine analogue and potent P2Y1-purinoceptor agonist, was studied on immediate early gene expression in rat astrocyte cultures. A rapid and transient increase in c-fos, junB, c-jun and Tis11 messenger RNA was observed in cultured astrocytes after treatment with adenosine-5'-O-(2-thiodiphosphate). Maximal induction of immediate early gene expression was obtained within 30 min of stimulation and c-fos was the most sensitive indicator of P2Y-purinoceptor activation. Calcitonin gene-related peptide has also been shown to be a potent inducer of c-fos messenger RNA in cultured astroglial cells. The combined stimulation of astrocytes with calcitonin gene-related peptide and adenosine-5'-O-(2-thiodiphosphate) resulted in the potentiated expression of c-fos messenger RNA. The superinduction of immediate early gene expression by calcitonin gene-related peptide and extracellular ATP in cultured astrocytes might result from intracellular signal transduction cross-talk, since adenosine-5'-O-(2-thiodiphosphate) was found to increase calcitonin gene-related peptide-induced cyclic AMP accumulation by 35%. Phorbol 12-myristate 13-acetate also increased calcitonin gene-related peptide-evoked cyclic AMP accumulation and led to the induction of immediate early gene expression, suggesting that protein kinase C might be at least in part involved in purinergic cross-talk. Our results demonstrate synergistic roles for extracellular ATP and calcitonin gene-related peptide in the transcriptional activation of astroglial cells.

Adenosine Diphosphate

Axotomy-induced c-JUN expression in young medial septal neurons is regulated by nerve growth factor.

In the present study we investigated the axotomy-induced expression of the proto-oncogene c-jun in young rat medial septal neurons and its regulation by nerve growth factor. First, medial septal neurons were retrogradely labelled by Fast Blue injection into the hippocampus at postnatal day 1 (P1). Rats of different developmental ages (P6, P9, P14, P21, P28 and P42) were then subjected to bilateral fimbria-fornix transection resulting in the axotomy of septohippocampal projection neurons. After the lesion, c-JUN immunoreactivity was observed in the nuclei of axotomized medial septal neurons of all stages examined, suggesting that c-JUN induction is an age-independent feature of axotomized medial septal neurons. Double immunolabelling for choline acetyltransferase and c-JUN or parvalbumin and c-JUN, respectively, revealed that both cholinergic and GABAergic septohippocampal projection neurons express c-JUN after axotomy. In addition, a co-localization of immunostaining for c-JUN and the neuropeptide galanin was found after lesion, as both proteins were induced in the same medial septal neurons following fimbria-fornix transection. Next, the regulation of c-JUN expression in axotomized medial septal neurons was studied in organotypic cultures of the medial septum. Axotomized medial septal neurons in culture did not express c-JUN in contrast to the in vivo situation. With the concept that nerve growth factor suppresses c-JUN expression, slice cultures of the medial septum were treated with antibodies against nerve growth factor. This treatment caused a dose-dependent increase in c-JUN-positive cells in these slice cultures. Simultaneous addition of nerve growth factor and antibodies against nerve growth factor resulted in the reversal of this effect. These data suggest an age-independent induction of c-JUN in axotomized medial septal neurons and its regulation by nerve growth factor.

Acetylcholine

Use of ureteral stents in the management of major renal trauma with urinary extravasation: is there a role?

Five patients with major (Grade IV) renal trauma required ureteral stent placement to facilitate urinary drainage. Three of these patients had stents placed for recurrent gross hematuria with flank pain. All three had obstructing blood clots present at the time of stent placement. The fourth patient had a stent placed because of persistent extravasation at 2 weeks postinjury. The last patient was considered at risk for persistent urinary extravasation because of a partial ureteropelvic junction obstruction and had a ureteral stent placed as part of the initial management. All patients were followed radiographically for resolution of extravasation. Long-term clinical follow-up consisted of serum creatinine evaluation and blood pressure monitoring. Urinary extravasation resolved in all five patients, as determined by radiologic evaluation, at a mean of 8 days after stent placement. Ureteral stents were left indwelling an average of 4 weeks. No patient developed hypertension, and all serum creatinine values were normal at a mean 26 months' follow-up. No patient developed urinoma or abscess, and none required open surgical exploration. Ureteral stents may be used safely and effectively to treat persistent or recurrent urinary extravasation resulting from major blunt renal trauma in appropriately selected patients. In addition, ureteral stents may avoid the need for surgical exploration in patients with Grade IV renal trauma who develop recurrent gross hematuria, flank pain, and persistent or recurrent extravasation secondary to clot obstruction.

Adolescent

Traumatic renal artery occlusion: a 15-year review.

BACKGROUND: To better define what constitutes appropriate treatment for traumatic renal artery occlusion, we report our 15-year experience in managing this injury. METHODS: A retrospective chart review was performed to evaluate treatment outcomes and complications of 12 patients (13 injuries) who presented to our trauma centers with renal artery occlusion secondary to blunt injury. RESULTS: Five of 12 patients underwent attempted surgical revascularization with a median warm ischemia time of 5 hours (range, 4.5-36 hours). Of these five patients, one required nephrectomy for inability to establish arterial flow, three demonstrated no function, and one had return to 9% differential function on postoperative renal scan. Seven patients did not have attempted revascularization, and none of them experienced immediate complications. Hypertension developed in three patients (43%) who required nephrectomy to control blood pressure at a mean of 5 months after injury (range, 3-7 months). Four patients remained asymptomatic and normotensive at a mean follow-up of 11 months (range, 4 weeks to 2.6 years). CONCLUSION: Surgical revascularization for traumatic renal artery occlusion seldom results in a successful outcome. Patients who are observed must have close follow-up for hypertension.

Adolescent

Traumatic renal artery occlusion: a review of the literature.

To better define what constitutes appropriate treatment for traumatic renal artery occlusion, we analyzed our experience along with 147 other case reports from the literature. We recently reported our 15-year experience with 12 patients (13 injuries) who presented to our trauma centers with renal artery occlusion secondary to blunt trauma. This experience prompted a review of the literature. From this review, we identified an additional 19 cases of bilateral and 128 cases of unilateral renal artery occlusion that met our inclusion criteria. Of the 20 patients with bilateral renal artery occlusion, surgical revascularization was attempted in 16 and successful in 9 (56%). Of the 139 patients with unilateral renal artery occlusion, surgical revascularization was attempted in 34 and successful in 9 (26%). Evidence of decreased renal function was noted in 67% of those who had a successful revascularization for unilateral injury at a mean 1.8-year follow-up, whereas 12% experienced hypertension at a mean 3.1-year follow-up. Hypertension developed in 34 (32%) of the 105 patients who did not have revascularization attempted and was present by a mean 97 days postinjury. Surgical revascularization for unilateral renal artery occlusion seldom results in a successful outcome. Revascularization is indicated in patients with bilateral renal artery occlusion and in those with injury to a solitary kidney. Patients who are observed must be followed closely for development of hypertension.

Abdominal Injuries

Basal expression, subcellular distribution, and up-regulation of the proto-oncogene c-JUN in the rat dentate gyrus after unilateral entorhinal cortex lesion.

The expression of the transcription factor c-JUN was investigated in the rat fascia dentata under normal conditions and after entorhinal cortex lesion. As shown by immunocytochemistry and in situ hybridization histochemistry c-JUN and its messenger RNA are present in the principal cell layers of the dentate gyrus and Ammon's horn (except hippocampal region CA2). Pre-embedding immunogold electron microscopy revealed an almost exclusive nuclear localization of c-JUN, where it is associated with chromatin. In addition, double immunolabelling for c-JUN and parvalbumin demonstrated that c-JUN immunoreactivity is primarily found in principal neurons since GABAergic parvalbumin-positive interneurons did not express c-JUN. After unilateral electrolytic lesion of the entorhinal cortex c-JUN was strongly up-regulated in the ipsilateral dentate gyrus within 2 h postlesion. This up-regulation was also present in the contralateral fascia dentata 12 h after entorhinal cortex lesion and returned to control levels on both sides 24 h postlesion. The cellular distribution of c-JUN did not change after entorhinal cortex lesion: parvalbumin-positive interneurons never contained c-JUN. These results point to a specific role of c-JUN in the granule cells of the fascia dentata in the normal animal and in rats with entorhinal cortex lesions. The selective induction of c-JUN after entorhinal lesion could be one of the first molecular steps that regulate transneuronal changes within granule cells after their denervation. A different mechanism has to be assumed for GABAergic interneurons known to receive an entorhinal innervation as well.

Animals