Reduction of postischemic brain damage and memory deficits following treatment with the selective adenosine A1 receptor agonist.

Agonists of adenosine A1 receptors have been frequently proposed as candidates for clinical development in treatment of cerebral ischemia and stroke. Numerous experimental studies have shown that pre- and postischemic administration of these drugs results in a very significant reduction of postischemic brain damage. However, only a few studies determined the impact of cerebral ischemia and drug treatment on postischemic recovery of spatial memory. The present paper demonstrates that preischemic i.p. administration of adenosine amine congener (ADAC) at 100 micrograms/kg in gerbils results in a significant (P < 0.05) reduction of postischemic mortality and hippocampal, cortical and striatal morbidity. Postischemic Morris' water maze tests show that preischemic treatment with ADAC also leads to a very significant (P < 0.001) reduction of postischemic spatial memory loss. Our results indicate feasibility of further consideration of adenosine A1 receptor agonists as a clinically applicable acute treatment of brain ischemia. Recent development of neuroprotective adenosine A1 receptor agonists that are free of cardiovascular side effects supports such development.

Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A1 receptors.

It is known that stimulation of adenosine A1 receptors has a modulatory effect on the excitability of postsynaptic NMDA receptors. Conversely, acute stimulation of NMDA receptors results in release of adenosine via calcium-independent mechanisms. These findings indicate a close functional relationship between these receptors. It is, therefore, possible that chronic, low level stimulation of the NMDA receptor may have a negative impact on these modulatory processes. To investigate this possibility, we have subjected C57BL mice either to an acute injection of a N6-cyclopentyladenosine (CPA, 0.01 mg/kg) or deoxycoformycin (1 mg/kg) followed by a convulsant dose of N-methyl-D-aspartate (NMDA) (60 mg/kg) or to chronic, low level (20 mg/kg i.p. daily) exposure to NMDA for 8 weeks. One day after the last injection of NMDA, animals were injected either with a convulsant dose of NMDA alone, or with either CPA at 0.001 or 0.01 mg/kg, or with 1 mg/kg deoxycoformycin followed 15 min later by 60 mg/kg NMDA. Neither CPA nor deoxycoformycin were protective when NMDA was given acutely at 60 mg/kg. Chronic treatment with NMDA alone or chronic administration of NMDA followed by 0.001 mg/kg CPA had no significant effect on mortality following a convulsant dose of NMDA. However, when the chronic regimen of NMDA was followed by either 0.01 mg/kg CPA or 1 mg/kg deoxycoformycin, mortality was reduced to 10% (CPA), or eliminated completely (deoxycoformycin). Moreover, combination of chronic NMDA treatment with either CPA (both doses) or deoxycoformycin produced a significant improvement in other measures, i.e., seizure onset, intensity of neurological impairment, and extension of time to death.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous abdominal aortic aneurysm repair and nephrectomy for neoplasm.

BACKGROUND: Abdominal aortic aneurysm and renal neoplasm are occasionally discovered concurrently. Simultaneous operative therapy may be an effective alternate management strategy to a staged procedure. PATIENTS AND METHODS: The medical records of 10 consecutive patients undergoing abdominal aortic aneurysm repair and nephrectomy for renal neoplasm were reviewed. Data collected included mode of presentation, preoperative evaluation, renal pathology, and in-hospital morbidity and mortality. Long-term follow-up was obtained through office records and telephone contact. RESULTS: In 7 patients, the renal mass was identified during evaluation of abdominal aortic aneurysm. The aneurysm was identified during evaluation of hematuria in 2 patients. One patient was discovered to have both conditions simultaneously. All patients underwent successful aneurysm repair and nephrectomy. Pathology revealed 6 renal cell carcinomas, 2 complex cysts, 1 hemangiopericytoma, and 1 oncocytoma. Four patients have died in the follow-up period: 1 of metastatic cancer and 3 of unrelated causes. There have been no cases of graft infection. CONCLUSION: Simultaneous abdominal aortic aneurysm repair and nephrectomy for neoplasm is an appropriate management strategy for selected patients.

The effects of adenosine A3 receptor stimulation on seizures in mice.

We have previously shown that acute preischemic adenosine A3 receptor stimulation results in an increased postischemic damage, while chronic stimulation of this receptor diminishes it. Since several pathophysiological phenomena are common for both ischemia and seizures, we have explored the effect of acute and chronic administration of the adenosine A3 receptor selective agonist IB-MECA (N6-(3-iodobenzyl) adenosine-5'-N-methylcarboxamide) prior to seizures induced by N-methyl-D-aspartate (NMDA), pentamethylenetetrazole, or electric shock. At 100 micrograms/kg, acutely injected IB-MECA was protective in chemically but not electrically induced seizures. In chronic administration of IB-MECA, significant protection against chemically induced seizures was obtained in all studied measures, i.e., seizure latency, neurological impairment, and survival. Although threshold voltage was unchanged in electrically induced seizures, a chronic regimen of IB-MECA significantly reduced postepileptic mortality. Since the combination of an arteriole-constricting compound 48/80 and hypotension-inducing clonidine injected prior to NMDA results in a significant protection against seizures, and since acute stimulation of adenosine A3 receptor causes both arteriolar constriction and severe hypotension, there is a possibility that the protection obtained by the acutely administered drug may result from inadequate delivery of chemoconvulsants to the brain. It is, however, unknown whether the protective effect of chronically administered IB-MECA is related to the effect of the drug on blood flow, neuronal mechanisms, or both.

The double-barreled wet colostomy: long-term experience with the first 11 patients.

We describe our experience with a technique for simultaneous urinary and fecal diversion using a single abdominal stoma. The procedure requires the construction of a diverting loop colostomy with division of the colon approximately 15 cm. distal to the stoma. This distal segment of colon acts as a urinary conduit, and allows internal separation of the urine and fecal streams. The procedure has been used in patients without a prior stoma as well as those with existing loop and end colostomies. Unlike the watery diarrhea associated with the wet colostomy described previously, these patients experience a continuous urine output and intermittent semiformed bowel movements. Complications have been minimal: there have been no episodes of clinical pyelonephritis, no new electrolyte problems and no significant stomal complications. In 1 patient late radiographic evidence of hydronephrosis developed associated with advancing metastatic disease, while in another late bilateral ureterocolonic strictures developed. The majority of patients died of the underlying cancer but 1 died of a myocardial infarction 2 weeks postoperatively. This procedure has now been performed in 11 patients with followup from 0.5 to 80 months. The results are gratifying for a group of highly complex cases.

Adenosine A3 receptor stimulation and cerebral ischemia.

Chronic treatment with the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A1 nor A2 receptors are involved in these actions. The data indicate that stimulation of adenosine A3 receptors may play an important role in the development of ischemic damage, and that adenosine A3 receptors may offer a new target for therapeutic interventions.

Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia.

The effect of chronic administration of selective adenosine A1 receptor agonists and antagonists on the outcome of cerebral ischemia is entirely unknown. Therefore, we have investigated the impact of such regimens on the hippocampal adenosine A1 receptor density, and on the recovery from 10 min forebrain ischemia in gerbils. While acutely administered N6-cyclopentyladenosine (CPA) given at 0.02 mg/kg resulted only in a significant reduction of mortality, at 1 mg/kg it improved both survival and neuronal preservation in the hippocampal CA1 region. Acute treatment with 1,3-dipropyl-8-cyclopentylxanthine (CPX) significantly worsened the outcome and enhanced neuronal destruction. The effects of chronic administration of these drugs (15 days followed by 1 drug-free day) were opposite. Thus, although chronic CPA at 0.02 mg/kg did not have any effect at all, at 1 mg/kg both survival and neuronal preservation were significantly poorer than in controls, while chronic CPX resulted in a significant improvement of both measures. These results were not accompanied by adenosine A1 receptor up- or downregulation. Our study indicates that highly selective adenosine analogues may have therapeutic potential in treatment of cerebral ischemia/stroke and possibly other neurodegenerative disorders as well.

Computerized tomography in the preoperative staging for pulmonary metastases in patients with renal cell carcinoma.

Computerized tomography (CT) is the state of the art technology for pulmonary staging of many extrathoracic malignancies. From 1976 to 1990, 120 of 330 patients with renal cell carcinoma treated at our hospital underwent chest radiography and chest CT. These patients were reviewed to evaluate the role of CT in examining the chest for staging of renal cell carcinoma. Median followup was 24 months. Agreement between the 2 imaging modalities was found in 105 patients. The results of chest radiography and chest CT were normal in 82 and abnormal in 23 patients. Of the 15 patients with disagreement between the 2 studies 13 had normal chest radiography with abnormal chest CT and 2 had abnormal chest radiography with normal chest CT. The 13 patients with normal chest radiography and abnormal CT were further divided into 2 groups: 8 patients with small borderline lesions seen on CT only and 5 patients with evidence of advanced, bulky disease outside the chest at presentation. A substantial agreement, more than chance alone, between chest radiography and CT existed (p < 0.0001). Followup records and survival data have shown no significant impact as a result of the disagreement between the 2 imaging modalities on the treatment decision or ultimate outcome. Based on this information, we believe that in patients with a relatively small tumor (stage T1) a normal chest radiograph suffices for pulmonary staging. The indications for additional chest CT would include solitary nodule on chest radiograph before salvage resection of metastasis, chest symptoms suggestive of endobronchial metastasis or extensive regional disease.

Venogenic impotence following dermal graft repair for Peyronie's disease.

Peyronie's plaque excision with dermal grafting generally offers good cosmetic results for patients who require surgical intervention for Peyronie's disease. However, postoperative impotence has been reported in 12 to 100% of such patients. The mechanism of impotence in this setting is not well defined. We present 3 men who had venogenic impotence after plaque excision and dermal grafting for Peyronie's disease. One patient has subsequently responded well to dorsal vein ligation, 1 has chosen an effective nonoperative method of management and 1 continues to consider the options. We report venous leak as an organic cause of impotence after plaque excision and dermal grafting for Peyronie's disease, and its successful management by dorsal vein ligation. The implications of these findings in the surgical management of Peyronie's disease are discussed.

Simultaneous diversion of the urinary and fecal streams utilizing a single abdominal stoma: the double-barreled wet colostomy.

A new technique to achieve simultaneous diversion of the urinary and fecal streams using a single abdominal stoma is described. The procedure consists of the construction of a diverting loop colostomy with division of the colon approximately 10 to 15 cm. distal to the stoma. The segment of colon distal to the stoma, the urine limb, acts as a urinary conduit. To date 3 patients have undergone the procedure with followup of 3, 13 and 18 months. Neither upper tract infection nor upper tract deterioration has occurred. The potential role of this procedure to treat a difficult group of patients is discussed.

Ureteroscopic results and complications: experience with 130 cases.

Since its introduction for general use, the role of rigid ureteroscopy in the diagnosis and therapy of urological disease has been in evolution. We evaluated retrospectively the experience at our institution with rigid ureteroscopy from January 1983 to July 1986 in an attempt to identify clinical situations or techniques that tended to increase the incidence of either success or complications. We determined that ureteroscopic complications were rare in procedures performed for diagnosis compared to those performed for calculi (2 of 33 or 6 per cent versus 27 of 99 or 27 per cent, p less than 0.025). The likelihood of failure or complication was greater for stones above than for those below the pelvic brim (15 of 25 or 60 per cent versus 26 of 75 or 35 per cent, p less than 0.05). Major complications were more common early in our experience (9 of 63 or 14 per cent versus 2 of 69 or 3 per cent for the combined years 1983 and 1984 compared to 1985 and 1986, p less than 0.05). Our success rates in the treatment of calculous disease were similar to those reported previously, and they were somewhat better for stones located below (62 of 75 or 83 per cent) than for those above (17 of 25 or 68 per cent) the pelvic brim. Based on our findings we conclude that carefully performed diagnostic ureteroscopy has little potential for major complications, ureteroscopy for stones above the pelvic brim should be avoided when possible, and an increased rate of complications and failures is expected early in any series owing at least partly to the learning curve effect.

Effect of local alpha-adrenergic blockade on human penile erection.

Recent data suggest that selective local blockade of the alpha-adrenergic receptors of the sympathetic innervation within the corpora cavernosa of the penis will result in erection in normal and impotent subjects. To examine this hypothesis we studied in a randomized, double-blinded fashion 8 impotent patients and 2 normal controls. The organic nature of the impotence was documented with nocturnal penile tumescence testing, sacral latency examination, Doppler penile blood flow measurements, hormonal evaluation and psychological testing. The 2 normal controls had full erections for 5 to 7 minutes after the intracorporeal injection of 5 mg. phentolamine. All of the impotent subjects had tumescence without full erection after a similar injection. The tumescence was augmented by standing upright and diminished by assuming a supine posture, and lasted for several hours. Possible mechanisms, and diagnostic and therapeutic implications are discussed.

Fibroepithelial polyps of the ureter.

We report a case of fibroepithelial polyps of the ureter, which are rare, benign mesodermal tumors. The advantage of ureteroscopic confirmation of this benign tumor is emphasized.

Splenogonadal fusion associated with an anaplastic seminoma.

A case of the rare anomaly of splenogonadal fusion is presented. The literature related to this anomaly is reviewed and the 2 principal classifications are discussed. To our knowledge this is the first reported case of splenogonadal fusion associated with an intra-abdominal testicular neoplasm.

Renal insufficiency in a solitary kidney secondary to hydronephrosis of pregnancy.

A case is reported of renal insufficiency in a solitary kidney secondary to hydronephrosis of pregnancy. Evidence supporting obstruction on a mechanical basis is presented. This entity should be considered when pursuing a correctable cause for functional renal deterioration in pregnant women. The clinical importance of this entity in the management of renal insufficiency in the pregnant woman is discussed.