Magnetic resonance imaging of traumatic posterior urethral defects and pelvic crush injuries. A total of 18 patients 4 to 71 years old with complete occlusion of the prostatomembranous urethra from pelvic crush injury underwent magnetic resonance imaging (MRI) of the pelvis just before open urethroplasty. MRI studies included T2-weighted sagittal and coronal images as well as transaxial T1 and T2-weighted spin-echo images. Operative findings and erectile function were correlated with MRI findings. All patients underwent conventional cystography and retrograde urethrography. The mean interval from injury to operation was 5.5 months (range 3 to 12 months) and followup averaged 12 months (range 3 to 40 months). Posttraumatic pelvic anatomy can be distorted and imaging in all 3 planes was needed. The severity and direction of prostatourethral dislocation, and the length of the urethral defect could be accurately determined, which often is not possible with conventional radiographic studies. MRI also demonstrated injuries at many locations along the erectile pathway, including sacral and ischial fractures as well as fractures and avulsions of the cavernous bodies. Pelvic MRI can accurately define the pelvic anatomy after crush injury and, therefore, it can provide useful preoperative information that cannot be obtained by conventional radiographic studies. Our results correlating MRI findings of cavernous avulsion with clinical impotence require further study.


Successful outcome of artificial urinary sphincters in men with post-prostatectomy urinary incontinence despite adverse implantation features. A total of 75 men with post-prostatectomy urinary incontinence underwent artificial urinary sphincter implantation with a mean followup of 3.7 years. Average patient age at implantation was 67 years, with 30 men being 70 years old or older. In only 15 men (20%) was there no adverse implantation feature, while the remainder had adverse features, such as detrusor hyperactivity (44), bladder neck or urethral stricture disease (27), previous radiation therapy (11) and metastatic prostate cancer (11). Although men with ideal implantation characteristics, men with normal detrusors and men who underwent prostatectomy for benign disease had slightly better outcome in terms of urinary continence, in general each group of men with and without adverse features had satisfactory urinary continence. Other than men with a benign prostate, who fared better, each group of men with and without adverse features had equal need for device revisions. In conclusion, men with post-prostatectomy urinary incontinence should not be excluded from consideration for artificial urinary sphincter implantation based on the failure to meet ideal implantation criteria provided such adverse features are recognized and appropriately addressed.


The hemodynamic pathophysiology of impotence following blunt trauma to the erect penis. A total of 19 patients provided a history of impotence following blunt trauma to the erect penis during intercourse or masturbation, or after accidents. Corporeal veno-occlusive dysfunction was the most common hemodynamic abnormality (16 of 19 patients, or 84%). A site-specific leak, which consisted of abrupt filling of the dorsal vein and/or corpus spongiosum from a focal site on the penile shaft, was demonstrated in 15 patients (79%). Cavernous artery insufficiency was found less often (7 of 19 patients, or 37%). A focal mid shaft cavernous artery occlusion was demonstrated in 5 patients (28%). It is hypothesized that the aforementioned hemodynamic abnormalities are caused by tunica and intracavernous vasculature injuries induced by the marked short-term pressure increases, which approach or exceed the tunica tensile strength during acute abrupt loading of the erect penis. This hypothesis is supported by direct recording of intracavernous pressures that exceeded 450 mm. Hg in response to angulation and manual compression of the penile shaft. Further evidence was created by a biomechanical model that was based on previously published intracavernous pressure--circumference patient data during dynamic infusion pharmacocavernosometry. Using a typical patient data set a 60% diminution of circumference at the site of abrupt loading was calculated to induce a 15% increase in circumference in the nonloaded portion of the penile shaft and an elevated intracavernous pressure exceeding 900 mm. Hg. The site-specific hemodynamic abnormalities were found to occur not only in patients with a classical penile fracture history but also in patients with injuries during masturbation or following accidents who had no acute penile swelling or ecchymosis. Thus, the erect penis is at risk for injury during any acute loading situation. It is likely that this erect trauma-induced hemodynamic pathology occurs more frequently than previously appreciated and that this type of impotence may be the underlying basis for many cases of idiopathic Peyronie's disease.


Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1. We performed a double-blind, crossover study using objective measurements to compare maximum rigidity and duration of erections with papaverine hydrochloride in combination with phentolamine mesylate and/or prostaglandin E1. The rationale for the protocol was to combine a smooth muscle relaxant (papaverine) with either or both vasodilating agents (phentolamine and prostaglandin E1) commonly used for injection therapy. The 7 volunteer patients with organic impotence documented by abnormal nocturnal penile tumescence testing were injected with 0.5 to 1.0 ml. papaverine (30 mg./ml.) in combination with phentolamine (0.5 mg./ml.) and/or prostaglandin E1 (5 micrograms./ml.). Each patient received 2 injections on each of 2 testing dates; injection 2 was given after tumescence resulting from injection 1 had subsided completely. The medications were given in a randomized, counterbalanced order following double-blind procedures. Patients evaluated the erections subjectively. In addition, the RigiScan device was used to measure maximum rigidity and duration of erections. All patients observed increased duration of erections with both combinations containing prostaglandin E1. Analysis of RigiScan measurements showed no statistically significant differences for maximum rigidity (p greater than 0.1) but significantly greater duration of erections with papaverine plus prostaglandin E1, and papaverine plus phentolamine plus prostaglandin E1 compared to papaverine plus phentolamine (p less than 0.001). There was no statistical difference in rigidity or duration of erections between papaverine plus prostaglandin E1 and papaverine plus phentolamine plus prostaglandin E1. No patient reported significant penile pain with any of the injections. We conclude that the combination of papaverine and prostaglandin E1 produces erections of longer duration than papaverine plus phentolamine and that no additional benefit is gained by adding phentolamine to a combination of papaverine and prostaglandin E1. Further studies are in progress to define optimal dose response curves for papaverine and prostaglandin E1 as individual agents and in combination.


Results of surgical management of Peyronie's disease. Peyronie's disease is often managed surgically when medical management fails and sexual function is impaired due to residual curvature or loss of erectile function. In this study 63 patients were treated surgically, with 25 receiving a penile prosthesis, 25 undergoing a tunica vaginalis graft and 13 undergoing the Nesbit ellipse procedure. The long-term surgical outcome as determined by sexual function indicated that the penile prosthesis group remained the most sexually active, followed by the Nesbit ellipse group with the tunica vaginalis graft group being the least sexually active. Incision of curvature with placement of a penile prosthesis for the surgical management of Peyronie's disease remains an approach that has excellent long-term functional results.


Sclerotherapy with tetracycline for hydroceles in renal transplant patients. A total of 17 patients with hydroceles following renal transplantation underwent sclerotherapy with tetracycline hydrochloride (10 ml. of a 5% solution of tetracycline in 1% lidocaine). A successful outcome was obtained in 15 patients (88%). Post-sclerotherapy hydrocelectomy was necessary in 2 patients (12%). No major complications (testicular loss, scrotal abscess or necrosis) occurred in any patient. Pain at injection was the only adverse effect. Tetracycline sclerotherapy for hydroceles appears to be an effective and safe procedure in the renal transplant population. We recommend this procedure as the initial treatment modality for hydroceles in patients with a renal allograft.


Intraoperative varicocele anatomy: a macroscopic and microscopic study. Varicoceles are found in approximately 15% of all men in the general population and up to 41% of all infertile men. However, the exact location and relationship of internal and external spermatic arteries, veins and lymphatics within the inguinal portion of the spermatic cord have not been previously well described in infertile men. The results of detailed intraoperative macroscopic and microscopic surgical dissections of the spermatic cord and gubernaculum of 83 infertile men with 115 palpable varicoceles are described. Enlarged veins exiting the testis and traversing the gubernaculum were present in 48% of the dissections. Enlarged external spermatic veins were detected in 74% of all spermatic cords. Typically, small internal spermatic veins drained into a large vein more proximally in the spermatic cord. An average of 3.6 lymphatics per spermatic cord was identified and preserved during the dissections. A solitary testicular artery was observed in 69% of the dissections. The testicular artery was adherent to the posterior surface of a large internal spermatic vein in 50% of the dissections and was surrounded by a dense complex of closely adherent veins in 30%. To decrease the incidence of postoperative varicocele recurrences we suggest a surgical approach that addresses all identifiable dilated and connecting veins. These findings suggest that surgical approaches that include intraoperative access to and ligation of low inguinal (external spermatic) and gubernacular veins may cause fewer recurrences, unligated small internal spermatic veins may be a cause of varicocele recurrence, and large internal spermatic veins should be individually identified, dissected and ligated since the testicular artery and lymphatics are often adherent to these veins. Optical magnification is important to facilitate identification of lymphatics, testicular arteries and small internal spermatic veins.


Management of preexisting inflatable penile prosthesis during radical retropubic prostatectomy. A potentially difficult technical situation exists when a man with a functioning inflatable penile prosthesis elects radical prostatectomy as treatment for localized prostate cancer. Between February 1988 and June 1991 we encountered 8 men with a preexisting inflatable penile prosthesis who subsequently underwent radical retropubic prostatectomy. In 2 patients the reservoir portion of the prosthesis was in the perivesical space such that radical prostatectomy could be performed without difficulty. However, in 6 patients removal of the reservoir was necessary to complete the prostatectomy. In 3 of these 6 patients the reservoir was replaced at 3 to 6 months after radical prostatectomy and all 3 systems function well. The remaining 3 patients have not yet elected replacement of the reservoir. Only 1 patient had an infection and a complication attributable to the prosthesis. We believe that a preexisting inflatable penile prosthesis should not preclude successful radical retropubic prostatectomy, although temporary removal of the reservoir may be required.


Retrieval of proximally migrated ureteral stents. Proximal migration of Double-J ureteral stents is a rare complication. An atraumatic and effective method of retrieving the dislodged stent using a ureteral balloon is described.


Selective sacral rhizotomy in the management of the reflex neuropathic bladder: a report on 17 patients with long-term followup. During the last 6 years 24 patients with cervical or thoracic spinal cord injuries and a severe reflex neuropathic bladder underwent selective dorsal sacral rhizotomy with the aid of intraoperative neurostimulation and urodynamic monitoring. Preoperative and postoperative evaluation was available in 17 patients. Followup ranged from 2 months to 5 years (mean 32 months). Mean bladder capacity increased significantly after rhizotomy (from 148 +/- 28.1 to 377 +/- 52.9 ml., p less than 0.001), as did mean volume to first contraction (from 99 +/- 28.6 to 270 +/- 39.3 ml., p less than 0.001). No significant changes in bowel or erectile function were noted. Continence was improved in 94%, with 14 patients remaining completely dry and voiding with electrical stimulation or intermittent self-catheterization. The long-term results of selective sacral rhizotomy compare favorably to more aggressive alternatives, such as augmentation cystoplasty or urinary diversion.


Effect of spinal cord ischemia on vesicourethral function. We studied 9 patients with clinical evidence of spinal cord ischemia or infarction who had altered vesicourethral function. Of the patients 6 had some preservation of bladder and lower extremity sensation, a clinical pattern consistent with the anterior spinal artery syndrome. A total of 3 patients had a clinical picture more consistent with complete transverse myelopathy, since they had no preservation of bladder or lower extremity sensation. Despite sensory levels well above the sacral spinal cord segments, 6 patients had detrusor areflexia (4 with bethanechol supersensitivity and 4 with neuropathic changes in the perineal electromyograph) indicating longitudinal spinal cord involvement. Three patients had detrusor hyperreflexia with vesicosphincter dyssynergia, indicating some preservation of the sacral spinal cord. In 6 patients appreciation of pinprick in the lower extremities was absent or decreased but light touch or position sense was preserved. Bladder sensation was dissociated in 4 of these 6 patients, since they had perception of bladder distention but loss of urge to void. These findings indicate that bladder distention is a sensory modality probably mediated via the posterior spinal cord, while the sense of urgency is probably conveyed by the anterior spinal cord.


Unilateral renal cystic disease: a case presentation. An infant who presented with a unilateral renal cystic process underwent nephrectomy due to hypertension. There was no evidence of any other disease process. Family history and investigation were negative for renal cystic disease or other genetic disease process. The pathology most resembled autosomal dominant polycystic kidney disease or a specific entity described as unilateral renal cystic disease.


Managing apparent ureteropelvic junction obstruction in the newborn. A total of 97 newborns with apparent ureteropelvic junction obstruction was evaluated from mid 1984 to 1989. Evaluation and management are described. Of these patients 39 with an affected kidney showing good initial differential function (greater than 35%) by diethylenetriaminepentaacetic acid scan and 2 showing diminished function (less than 35%) were followed nonoperatively. Six patients (15%) eventually required pyeloplasty for diminishing function (4), urinary tract infections (1) or symptoms of colic (1). The 4 patients with diminishing function improved after pyeloplasty to at least the initial level. A total of 12 patients with good initial function (greater than 35%) of the affected kidney underwent early pyeloplasty (within 6 weeks of diagnosis). They were compared to the similar group of patients managed nonoperatively and followed by sequential renal scans. Eventual changes in percentage differential function in the nonoperative and early surgery groups were +2.8% and +4.1%, respectively. Changes in extraction factor were +0.8% (nonoperative group) and +0.9% (surgery group). No statistically significant difference was found. In the kidney with apparent ureteropelvic junction obstruction and good function, an initial nonoperative approach with sequential renal scan followup and pyeloplasty as needed appears to be reasonable and has resulted in no permanent loss of function.


Postpubertal genitourinary function following posterior urethral disruptions in children. A total of 24 boys sustaining a simultaneous pelvic fracture and posterior urethral disruption was observed from the time of injury through puberty. Average length of followup was 6 years. In contrast to the adult, in whom the urethra is invariably injured at the prostatomembranous junction, the posterior urethral disruptions in the prepubertal patient were at 3 distinct locations: 1) supraprostatic in 4 patients, 2) transprostatic in 4 and 3) prostatomembranous in 16. Prolonged followup through puberty in these children revealed that the frequency of complications was significantly higher for urethral injuries proximal to the prostatomembranous region compared to those at this latter site: impotence 75% versus 31%, intractable strictures following repairs 75% versus 12% and urinary incontinence 25% versus 0%. In summary, the prognosis of children who sustain a posterior urethral disruption should be based on the location of the injury and must remain guarded until the individual attains a postpubertal status.


Transpubic-perineal urethral reconstruction in boys using a substitution graft. A combined transpubic-perineal 1-stage approach was used for urethral replacement and proximal urethral repair in 6 boys: 4 were treated for a long proximal urethral stricture secondary to trauma and 2 with urethral atresia underwent replacement of the entire anterior urethra. All patients underwent a urethral substitution graft of either skin or bladder mucosa. Followup ranged from 2 to 8 years with all patients continent.


Congenital rupture of scrotum: an unusual complication of meconium peritonitis. Congenital rupture of the scrotum caused by meconium peritonitis occurred in a newborn with clinical findings of the Beckwith-Wiedemann syndrome. Ruptured omphalocele and jejunal atresia were present. Surgical repair 3 hours after birth was successful.


Spontaneous regression of histologically proved pulmonary metastases from renal cell carcinoma: a case with 5-year followup. Spontaneous regression of biopsy proved metastatic renal cell carcinoma is rare. We describe a 39-year-old man who had histologically proved metastatic disease to the lungs after nephrectomy. The lesions had spontaneously regressed 3 months later. The patient remained without evidence of recurrence 5 years after diagnosis.


Complete ureteral transection associated with percutaneous lumbar disk nucleotomy. A case of complete ureteral transection complicating percutaneous nucleotomy for disk herniation is reported. The ureteral lesion was contralateral to the percutaneous approach and was treated by intubated ureteroureterostomy, since complete section precluded endourological management.


Paratesticular fibrous pseudotumor in a patient with Gorlin's syndrome: nevoid basal cell carcinoma syndrome. An 18-year-old man with Gorlin's syndrome (the nevoid basal cell carcinoma syndrome) underwent excisional biopsy of a fibrous pseudotumor of the tunica vaginalis. Preoperative ultrasound confirmed the extraparenchymal nature of this paratesticular lesion, permitting a transscrotal approach. The pathophysiological considerations suggest that this finding (to our knowledge the first such case reported in association with Gorlin's syndrome) may be more than coincidental.


Malignant Leydig cell tumor of the testis in complete remission on o,p'-dichlorodiphenyl-dichloroethane. A 56-year-old patient is described who presented with retroperitoneal lymph node metastases 2 years after resection of a Leydig cell tumor of the left testis. The patient did not suffer from endocrinological imbalance. Surgical removal of the metastases alleviated abdominal symptoms for 1 year. o,p'-Dichlorodiphenyl-dichloroethane (o,p'-DDD) treatment was started at the time of recurrence of the retroperitoneal mass and the appearance of a hepatic metastasis. Tumors were remarkably responsive to o,p'-DDD, since 2 complete remissions could be obtained for extended periods. The o,p'-DDD was tolerated reasonably well and serum levels of 15 to 20 mg./l. were sustained for many months. Unfortunately, the patient could not be cured with this effective treatment.


Osteitis pubis as a complication of transrectal needle biopsy of the prostate. We report a case of osteitis pubis complicating transrectal needle biopsy of the prostate. This case best supports direct trauma to the symphysis pubis as an etiology. A literature review of osteitis pubis is presented.


Adenocarcinoma in a müllerian duct cyst. A case of adenocarcinoma involving a müllerian duct cyst is presented. The presentation, treatment, and pathological and radiological appearance are discussed. The embryology and history of this entity are reviewed.


Progression delay of prostate tumor skeletal metastasis effects by bisphosphonates. Prostate tumor cell metastasis to the axial skeleton was induced in male Copenhagen rats using the intravenous injection of syngeneic metastatic R3327-MATLyLu tumor cells and concomitant caval vein clamping. The proliferation of tumor cells in the lumbar region was monitored by the progression, within 19 days post tumor cell injection, of hindleg paralysis which appeared in these animals. Histology confirmed the presence of tumor cells within the lumbar spine in 100% of cases displaying hindleg paralysis. Treatment with either of the bisphosphonate drugs, Cl2MDP or APD, suppressed and delayed the development of hind leg paralysis. Bisphosphonate treatment may be expected to delay the onset of axial skeletal metastasis effects in prostate cancer patients.


Ureteral compliance and histology in partial obstruction in a canine model. Standardized partial ureter obstruction was achieved in 35 mongrel dogs in whom ureteral compliance and its relationship to histologic changes were studied over a period of 26 weeks. The partially obstructed ureter became dilated with thickened wall and showed muscle hypertrophy and connective tissue proliferation. The normal stellate configuration of the ureteral lumen gradually flattened and became entirely circular by the eighth week. The compliance of the obstructed ureter increased gradually after one, 2, 4, and 8 weeks but decreased thereafter at 12 and 26 weeks. At 8 weeks, the ureter was significantly more compliant than both, the unobstructed control ureter (p less than 0.005) and the 12 week and 26 week partially obstructed ureters (p less than 0.005 & p less than 0.05 respectively). The increase in ureteral compliance was proportional to the amount of muscle hypertrophy during the first 8 weeks while the subsequent decrease in compliance (at 12 and 26 weeks) was proportional to the amount of connective tissue proliferation. This study documents ureteral response, both functional and histologic, to partial obstruction in a canine model over 26 week duration.


Localization and identification of T-(Gal beta 1-3GalNAc alpha 1-O-R) and T-like antigens in experimental rat bladder cancer. A mouse monoclonal antibody and a rabbit polyclonal antibody against the T-antigen (Gal beta 1-3GalNAc alpha 1-O-R) were used to study the distribution of T-antigens in an experimental rat bladder cancer model. Neoplasia was induced in 28 rats by intravesical installation of N-nitroso-N-methylurea (NMU) dissolved in acetate buffer. Fifteen rats were installed with acetate buffer, and served as controls. Urothelial samples were taken from all animals, the atypia was graded and detailed data on the location of the antibody binding structures were obtained by immunohistochemical methods. In addition, Western Blots of glycoproteins and thin-layer-chromatography (TLC) immunostainings of glycolipids extracted from normal and malignant tissue were performed to characterize the molecules presenting T-antigens. Examination of the histologic distribution of T-antigens showed that both the monoclonal and the polyclonal reagents reacted with atypical cells in proportion to the grade of atypia, but showed no reaction in invasive cells. These results confirm previously obtained data on the T-antigen using peanut (arachis hypogaea) agglutinin (PNA), and support the structure identity as being the classical O-linked mucin type T-antigen. Western blots of tumor glycoproteins showed that the monoclonal and the polyclonal antibody reacted with epitopes different from that of PNA, but all the probes correlated with atypia. In addition PNA, as the only anti-T reagent, bound to glycolipid. By using well characterized and highly specific immunological reagents the present study shows that the T-antigen is a highly selective marker of urothelial atypia.


Mechanism of ammonium transport: inhibition by potassium and barium. Elucidating the precise mechanism of intestinal ammonium transport is critical to the understanding of the acidosis associated with intestinal urinary diversion. Unfortunately, it is incompletely understood and controversial. Recently, we have shown that furosemide and Ba2+ significantly inhibit ammonium absorption in the ileum. On the basis of this and other data, we have suggested that ionized ammonium absorption occurs via K(+)-transport pathways. The present study examines intestinal ammonium absorption and its inhibition by K+ and Ba2+ utilizing a simplified in vivo system in rat distal ileum. Ammonium absorption demonstrates a tendency towards saturation at initial concentrations between 0 and 300 mM/l. Above 300 mM/l. there was a marked increase in ammonium absorption suggesting a possible biological effect of high NH4+ concentrations on the intestinal segment. Potassium inhibits ammonium absorption. K+ (50 mM/l.) significantly inhibited ammonium at an initial concentration of 100 mM/l. (p less than 0.05) and K+ (100 mM/l.) inhibited ammonium absorption at both 50 and 100 mM/l. (p less than 0.05 and p less than 0.01 respectively). Potassium inhibition of ammonium absorption was lost at concentrations above 200 mM/l. suggesting that K+ inhibition occurs via a competitive mechanism. Ba2+ (25 mM/l.) was shown to be a potent inhibitor of ammonium absorption. This significant inhibition persisted at high initial ammonium concentrations suggesting a complex, noncompetitive mechanism of inhibition. In conclusion, this study provides important data further suggesting that ammonium transport in the intestine occurs via K+ transport pathways, and suggests that the traditionally held mechanism of nonionic ammonium diffusion needs reevaluation.


Alterations in bile following urinary intestinal diversion. In order to determine whether alterations in bile occur which make it more lithogenic when intestinal segments are interposed in the urinary tract, 42 female Sprague-Dawley rats had intestinal and urointestinal manipulations followed by analysis of bile constituents. Timed collections were obtained from the common bile duct which were analyzed for bile acids, phospholipids, cholesterol, bilirubin, volume, osmolality, pH, calcium, chloride, sodium, and potassium. Changes in bile constituents were identified following urinary diversion which were specific for the type of diversion and the segment of bowel used, but they were not of sufficient degree to cause significant changes in the lithogenicity of bile. This correlates well with the lack of clinical findings of cholelithiasis in children with urinary intestinal diversion.


Endothelin in the urinary bladder. I. Synthesis of endothelin-1 by epithelia, muscle and fibroblasts suggests autocrine and paracrine cellular regulation. The synthesis and localization of endothelin-1 were studied in human and rabbit bladder. In addition, the effects of endothelin-1 on smooth muscle tone and cholinergic neurotransmission were investigated in rabbit bladder. Endothelin-like immunoreactivity was localized in the transitional epithelium, serosal mesothelium, and vascular endothelium; smooth muscle of the bladder (non-vascular) and that of blood vessels; and fibroblasts. With in situ hybridization, transcripts of endothelin messenger ribonucleic acid (mRNA) were localized with the same cellular distribution as endothelin-like immunoreactivity, in bladder tissue. Northern blot analysis of bladder RNA confirmed the expression of preproendothelin-1 mRNA. Rabbit bladder strips in organ chambers contracted when exposed to endothelin-1 and this response was partially attenuated by calcium channel blockers or by removal of extracellular calcium. Transmural electrical stimulation of rabbit bladder strips elicited contractions that were greatly reduced by atropine. The remaining atropine resistant component was blocked by alpha, beta-methylene ATP, which desensitizes purinergic receptors. Endothelin-1 caused a small but consistent attenuation of the atropine sensitive component of the neurogenic contraction, while it had no effect on the atropine resistant component. The localization of endothelin synthesis in epithelia, smooth muscle, and fibroblasts suggests that endothelin may act as an autocrine hormone in the regulation of the bladder wall structure and smooth muscle tone. In addition, endothelin-1 may regulate cholinergic neurotransmission by a paracrine mechanism.


Endothelin in the urinary bladder. II. Characterization of endothelin receptor subtypes. Endothelins (ET-1, ET-2, ET-3) are a family of regulatory peptides with diverse biological functions, including modulation of smooth muscle tone. To evaluate the possible role of endothelins in the control of the detrusor smooth muscle of urinary bladder, we have investigated the responses of isolated strips of bladder dome and base to endothelins, in organ chambers, and characterized the receptors for these isopeptides in bladder membranes. ET-1, ET-2 and to a lesser extent ET-3 caused sustained concentration-dependent contraction of bladder dome and base. The contraction to endothelins, unlike the short-lived contraction produced by cholinergic agents, was long lasting and difficult to wash out. Equilibrium binding studies demonstrated that endothelin isoforms bound to bladder membrane receptors specifically, with high affinity (KD of 0.4-0.6 nM) and limited capacity (60-420 fmol/mg protein). Competition analysis showed two populations of receptors: one with high affinity for ET-1 and ET-2 and low affinity for ET-3 and another with high affinity for ET-1, ET-2 and ET-3. Chemical affinity labeling of endothelins to bladder membranes demonstrated that ET-1 and ET-2 were cross-linked to three proteins (75, 52 and 34 kDa, respectively), whereas ET-3 was cross-linked mainly to a 34 kDa protein. The data obtained from equilibrium binding studies, competition analysis and cross-linking experiments suggest that at least two endothelin receptor subtypes exist in bladder tissue. These observations further suggest that bladder smooth muscle tone may be modulated by endothelin or an endothelin-like substance via interaction with specific receptor sites.


A mechanism of retrograde ejaculation after bilateral hypogastric nerve transections in the dog. To pursue the mechanism of retrograde ejaculation after bilateral hypogastric nerve transections, the disability of the lumbosacral sympathetic trunk and the spermatic nerve to compensate bladder neck closure was investigated while both act as compensatory pathways for seminal emission. Five mongrel dogs were used for each experiment. By manual penis-stimulation, all dogs showed only retrograde ejaculation one month and six months after transection of bilateral hypogastric nerves. Bladder neck closure did not occur by electrical stimulation of either the lumbosacral sympathetic trunk or the spermatic nerve before and one month after transection of bilateral hypogastric nerves in all dogs examined and persistent relaxation of bladder neck was observed one and six months after transection of bilateral hypogastric nerves. The present results and our previous data indicate that retrograde ejaculation after bilateral hypogastric nerve transections is attributable to the absence of effective compensatory sympathetic pathways for bladder neck closure under the recovery of seminal emission by compensatory pathways.


The expression of C-jun and junB mRNA in renal cell cancer and in vitro regulation by transforming growth factor beta 1 and tumor necrosis factor alpha 1. The proto-oncogene C-jun acts as a transcriptional activator or repressor for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. JunB inhibits c-jun's transforming activities. We investigated the expression of jun genes in renal cell cancer (RCC) and their regulation by cytokines and transforming growth factor beta 1 (TGF-b1). The constitutive expression of c-jun was detected in 39 of 43 fresh frozen RCC, 5 of 10 normal kidneys, and the expression of junB detected in 28 of 34 RCC, 5 of 6 normal kidneys. C-jun was also found expressed in all 10 RCC tumor lines examined and junB was expressed at low levels in 6 of 10 renal tumor lines. TGF-b1 and tumor necrosis factor alpha (TNF-a) have been shown to alter the expression of jun genes in other tissue types. Additionally, TGF-b1, TNF-a, and gamma interferon (g-IFN) were shown to inhibit the growth of RCC. We found that TGF-b1 highly augmented the expression of junB (mean of 34 folds, p less than .05), but did not significantly alter the expression of c-jun, the transforming gene. In contrast, TNF-a significantly enhanced the expression of both c-jun (mean fold enhancement of 2.1, p less than .05) and junB (2.2 folds, p less than .05). Interleukin-2 (IL-2), interleukin-4 (IL-4) and g-IFN did not significantly alter jun expression. The findings presented suggest that c-jun may have a role in inducing malignant transformation in RCC and a novel mechanism by which TGF-b1 may exert its anti-tumor effects, via the activation of junB. Additionally, although TGF-b1, TNF-a, and g-IFN all have anti-proliferative actions on RCC in vitro, they were found to have different effects in altering jun expressions.


Effects of adenosine on canine penile erection. We investigated the hemodynamic effects of intracavernous injection of adenosine on canine penile erection. In all ten dogs studied, adenosine induced a dose-dependent increase of intracavernous pressure (ICP). Adenosine (0.67 to 15 micrograms/kg., B.W.) increased arterial blood flow by 83 to 325 percent above baseline levels and also increased venous resistance, which resulted in a full erection (ICP = 80 to 140 cm. H2O) for one to 7 minutes. The repeatability of the adenosine effect was confirmed in eight dogs. We found that adenosine, by virtue of its smooth muscle relaxation properties, can induce a dose-dependent increase of ICP and cause a full erection in dogs.


Prophylactic and therapeutic carboprost tromethamine bladder irrigation in rats with cyclophosphamide-induced hemorrhagic cystitis. Recently, prostaglandins have been shown to be effective agents for the treatment of cyclophosphamide-induced hemorrhagic cystitis. Among the prostaglandins studied is carboprost tromethamine, a PGF2a analog. To determine the effectiveness of carboprost tromethamine therapy on the urothelium, we induced hemorrhagic cystitis in 81 rats. These were divided into two treatment arms. One arm was treated prophylactically at the time of cyclophosphamide injection, and the other started treatment only after hemorrhagic cystitis was established. Animals were divided equally into groups receiving 0, 0.4, 0.8, and 1.6 mg.% carboprost tromethamine in 0.9% normal saline by continuous bladder irrigation. All bladders were examined grossly for edema and hemorrhage, then histologically for mucosal ulceration, congestion, and perivascular hemorrhage. Results from the prophylactic arm, as compared to those for controls, revealed that all groups except those treated only with 0.9% normal saline had a lower incidence of hemorrhagic cystitis (p less than 0.05). In the established hemorrhagic cystitis arm, the group treated with 1.6 mg.% carboprost tromethamine showed the best response (p less than 0.05), whereas the group treated with 0.9% normal saline showed the poorest response. This study reveals that hemorrhagic cystitis in the rat model may be prevented by prophylactic continuous bladder irrigation with carboprost tromethamine, whereas established hemorrhagic cystitis may be treated effectively with intravesical instillation of carboprost tromethamine. Although the mechanism of action of this prostaglandin on the urothelium is unknown, it appears grossly and histologically to decrease ulceration, perivascular hemorrhage, and congestion in the mucosa and submucosa.


Synergy of radiation therapy and immunotherapy in murine renal cell carcinoma. The treatment of metastatic renal cell carcinoma with immunotherapy has resulted in objective anti-tumor responses in 15-30% of patients. To enhance the therapeutic effects of immunotherapy, it is becoming evident that this approach should be combined with other treatment modalities. In this study, a spontaneously metastasizing murine renal adenocarcinoma (Renca), transplanted under the renal capsule, was treated with either radiation therapy, immunotherapy or a combination of both. In order to distinguish between the local and systemic effects of radiation therapy, total body irradiation was compared to irradiation of the tumor-bearing kidney only, or irradiation of the whole mouse with the tumor-bearing kidney shielded. Immunotherapy was administered with interleukin-2 (IL-2) alone or with IL-2 and lymphokine activated killer (LAK) cells. Combined radiation and immunotherapy induced a better anti-tumor response than either modality alone. The best response was obtained by local tumor irradiation and IL-2 therapy and resulted in a significant reduction in primary tumor size, elimination of lung metastases and a significant increase in survival.


A new porphyrin photosensitizer (PH1008) in model membranes, normal cells, and bladder cancer cells. Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.


Effects of acute in vitro overdistension of the rabbit urinary bladder on DNA synthesis. Urinary bladder outflow obstruction induces a myriad of structural and functional changes in the organ. Among the morphological responses to outlet obstruction is both hyperplasia and hypertrophy of specific cellular elements. The initial event which has been implicated in the initiation of the response to outflow obstruction is an initial period of high intravesical pressure and subsequent distention of the bladder. In a previous study, it was shown that at one day following partial outlet obstruction there was a marked increase in thymidine labelling of the urothelium, at 3-5 days, the labeling shifted from the urothelium to the interstitial and serosal elements. The current study was designed to determine if acute distention of the urinary bladder can induce an increase in DNA synthesis (3H-thymidine incorporation), and localize the increased DNA synthesis via autoradiography of 3H-thymidine. In this study, the bladders of adult male New Zealand white rabbits were mounted in isolated in vitro baths. Each control bladder was filled to either 5 or 20 ml. with saline, or distended to 120% of capacity. The bladders were incubated for 7 hours at which time 3H-thymidine was placed both within and outside the bladder for an additional one hour. At the end of the time the bladder was divided at the ureteral orifices into bladder body and base, and each body and base divided into two sections. One section of bladder body and base was quantitatively analyzed for both labelled and unlabelled DNA; the second section was fixed and prepared for autoradiography. The results can be summarized as follows: 1) Acute overdistention for 8 hours induced a slight decrease in the DNA concentration which was mediated by edema of the bladder wall. 2) Acute overdistention induced a 5-fold increase in 3H-thymidine incorporation in the bladder body and a 3-fold increase in the bladder base. Radioautoradiography of the overdistended bladders showed significant and substantial labelling which was confined to the urothelial basal cells. The control bladders showed little or no labelling. These results are consistent with the theory that acute distention following partial outlet obstruction initiates the proliferative response of the bladder to outlet obstruction, and the urothelium is the initial target of the proliferative response. Functionally, the proliferative response may serve to maintain the structural as well as functional integrity of the bladder.


Three-dimensional intravascular ultrasound imaging of normal and diseased canine and human arteries. This study reports three-dimensional reconstruction of two-dimensional intravascular ultrasound images obtained along 5 cm vessel segments. Each three-dimensional image was produced by computerized "stacking" of a set of consecutive two-dimensional images (mode 90 images per set; range 32 to 256). Three-dimensional images (n = 26) were obtained from 11 human normal and atherosclerotic arteries (three in vitro and eight in vivo) and five in vivo canine studies. In vivo human examinations included three iliac, one deep, and three superficial femoral arteries and one aortic dissection. Five in vivo canine vessels (three iliac stenoses and two aortic dissections) were imaged before and after intraluminal stent deployment. Images were displayed on a gray-scale monitor, allowing examination of vessel images as complete cylinders or longitudinal hemisections in any user-defined plane. This enabled global examination of vascular segments and identified luminal shape, wall thickness, and distribution and morphology of plaques. Reconstructions of aortic dissections illustrated the extent of the dissection and produced an anatomic picture of the false lumen. Three-dimensional imaging enhanced stent deployment by identifying the site for deployment, dimensions of the vessel lumen, and changes in morphology after stent insertion. There was good correlation in vessel dimensions measured by angiography, two-dimensional intravascular ultrasonography and longitudinal gray-scale reconstructions (r = 0.74 to 0.95; p = 0.34 to 0.001) but poor correlation with measurements from three-dimensional surface-rendered images (r = 0.13 to 0.48; p = 0.42 to 0.87). We conclude that three-dimensional intravascular ultrasound imaging is an innovative new method for identifying the type, extent, and spatial configuration of arterial disease, with promising diagnostic and therapeutic applications.


Accuracy of duplex scanning for measurement of arterial volume flow. This study examined the accuracy of duplex ultrasound measurements of volume flow in a baboon model. Volume flow (Vf) through the external iliac artery was calculated from measurements of blood velocity averaged over several cardiac cycles (time-averaged velocity [TAV]) and vessel cross-sectional area (A) measured from the B-mode image: Vf = TAV x A. Fourteen anesthetized baboons were studied with a duplex scanner with a 7 MHz imaging transducer and 5 MHz pulsed Doppler. B-mode ultrasound measurements of external iliac artery diameters (2.5 +/- 0.2 mm) were used for calculation of cross-sectional area. Timed blood collections obtained through a cannula inserted into the common femoral artery and TAV measurements were obtained simultaneously during 6 to 15-second intervals. These measurements were repeated three to five times per animal with different flow rates each time. Flow rates ranged from 56 to 280 ml/min (170 +/- 54 ml/min). Average velocity was 55 +/- 17 cm/sec. There was no significant difference between the two methods of volume flow measurement (Student t test). Linear regression analysis revealed a high degree of correlation (r = 0.90, slope 0.95, and p = 0.0001). The absolute percentage error was 13% +/- 8%. Volume flow measured by duplex scanning correlates highly with timed blood collections. This method has potential application for the evaluation of diseased arteries and bypass grafts whose rates of flow and waveform patterns are similar to those of this experiment.


Color Doppler imaging of infrainguinal arterial occlusive disease. Few reports in the literature validate the use of color Doppler imaging (CDI) for the evaluation of lower extremity arterial occlusive disease, particularly in the tibial and peroneal arteries. This prospective, blinded study compares CDI to arteriography to address the following questions: (1) how well does CDI visualize arterial segments, including those below the knee? and (2) can CDI alone accurately classify the degree of occlusive disease? Twenty-nine men undergoing arteriography before a lower extremity arterial reconstructive procedure were studied with a color ultrasound scanner from the level of the inguinal ligament to the ankle. Color images were examined for the presence or absence of triphasic flow, poststenotic turbulence, color bruits, and collateral vessels. Among 636 arterial segments adequately visualized by arteriography, > or = 90% were identified with color Doppler imaging, including the tibial and peroneal arteries. With color criteria only, specificity was > or = 92% for distinguishing < 50% from > = 50% lesions and > or = 93% for differentiating patent from occluded arteries. Sensitivity for detecting an occlusion was > or = 97% in the superficial femoral (SFA) and popliteal arteries and 83% in the tibial vessels. For identifying a > or = 50% stenosis, sensitivity was > or = 85% in the SFA and popliteal arteries but only 79% and 86% in the posterior and anterior tibial arteries, respectively. CDI reliably identifies vessel location from the level of the groin to the ankle. For the detection of occlusions, CDI is an accurate screening tool in the SFA and popliteal arteries but is less accurate in the tibial vessels.(ABSTRACT TRUNCATED AT 250 WORDS)


Developmental anomalies at the thoracic outlet: an analysis of 200 consecutive cases. Anatomic observations were made during 200 consecutive transaxillary surgical procedures performed in 175 patients because of unremitting signs and symptoms of nerve or vascular compression at the thoracic outlet. There were 160 cases of brachial plexus compression and 40 cases of arterial or venous occlusion. In 132 (66%) of these cases, single or multiple abnormalities were recognized that represented developmental variations previously described in anatomic dissections or in embryologic studies. There were 17 cases of cervical rib or first thoracic rib abnormalities and 20 supernumerary scalene muscles. Developmental variations were identified in 86 scalene and 39 subclavius muscles or their insertions. Comparisons revealed a higher percentage of developmental anomalies in this group of patients than in consecutive anatomic investigations reported in unselected populations. This information was interpreted in light of recent embryologic studies and histochemical and morphometric ultrastructural studies of scalene muscle. The preponderance of evidence suggests that neurovascular compression in the region of the thoracic outlet derives from a combination of these factors: predisposing morphologic variations, structural modifications conditioned by functional requirements, and changes in fiber type or myosin isoform consequent to trauma. The correlation of clinical syndrome with morphologic characteristics alone was significant only for the Paget-Schroetter syndrome.


Peripheral vascular disease in heart transplant recipients. The improved longevity of heart transplant recipients demands heightened awareness of the long-term complications of the procedure. Between 1979 and 1990, 232 patients received 241 heart transplants at our institution. Accelerated coronary atherosclerosis occurred in 45 (19%) of the 232 patients, typically appearing within 2 years of transplantation, whereas peripheral vascular disease (PVD) appeared in 23 (10%) of the 232 patients, usually within 3 years of transplantation. In the patients with PVD, 13 had occlusive disease, nine had aneurysms, and one patient suffered a vertebral artery dissection. Accelerated coronary atherosclerosis afflicted 12 (52%) of the 23 patients affected by PVD (p < 0.05) and preceded the development of PVD in all 12. Logistic regression analysis revealed risk factors predictive of the development of PVD after transplantation to be a pretransplant history of ischemic cardiomyopathy and posttransplant hypertension and hypertriglyceridemia (p < 0.05), with the presence of more than one risk factor increasing the probability of development of PVD. Those patients thus identified as at risk should be closely monitored for the development of PVD. Aggressive medical management of hypertension and hyperlipidemia in this subpopulation may forestall or prevent the development of peripheral vascular disease after heart transplantation.


Long-term results of compression treatment for lymphedema. Although numerous operations have been devised for lymphedema, most surgeons manage this vexing condition by nonsurgical means. Previous studies by us showed that high-pressure (90 to 100 torr) sequential external pneumatic compression (SEP) reduced both limb girth and volume in a lymphedematous extremity. To assess the long-term effects of a program entailing (1) SEP, (2) elastic compression stockings to maintain the post-SEP girth, and (3) daily skin care, we reviewed the long-term courses of 49 patients managed by one surgeon. Limb girths measured at nine levels on the limb were obtained serially in follow-up (mean 25 months) by an independent observer to provide an objective response to therapy. The relative reduction in lymphedematous tissue was determined by the difference between the pretreatment, postacute treatment, and long-term treatment girths at nine points in the limb. In long-term follow-up, 26 of the patients maintained a full response (reduction at > 3 levels), whereas 10 maintained a partial response (reduction at < or = 3 levels). At late follow-up, calf and ankle girths were reduced by an absolute value of 5.37 +/- 1.01 and 4.63 +/- 0.88 cm in the full-response group and 5.43 +/- 1.58 and 3.98 +/- 1.18 cm in the partial-response group over pretreatment measurements. The degree of subcutaneous fibrosis in relationship to the duration of the edema appeared to influence results greatly. The treatment of lymphedema with SEP and compression stockings is associated with long-term maintenance of reduced limb girth in 90% of patients.


CHAT analysis of the influence of specific risk factors on late results after carotid endarterectomy. The CHAT classification separates various current and historical presentations of cerebrovascular disease in an effort to determine important prognostic clues for management and prognosis. To evaluate known risk factors for late stroke and death, we followed up for an average of 44 months 633 patients who had undergone 714 carotid operations. We analyzed the indication for surgery (by CHAT) and the effect of preoperative risk factors (age, hypertension, cardiac disease, tobacco use, diabetes, hyperlipidemia, renal disease, pulmonary disease, and total risk factor score) on the end points of late stroke and death. Ipsilateral stroke was uncommon after carotid endarterectomy: with life-table analysis, the probability of late stroke at 5 years after carotid endarterectomy was 3%. Among the 127 patients with amaurosis fugax, the incidence of late stroke and of mortality was a combined total of 1% per year, and the 17 patients who had been first seen with permanent ocular stroke (blindness) fared equally well. The 28 patients who were first seen with vertebrobasilar symptoms and were treated by carotid endarterectomy also fared particularly well, with no late strokes or deaths within the first 5 years. Logistic regression analyses revealed that the various indications for carotid endarterectomy were associated with differing patterns of risk factors as significant predictors of late stroke or death. For patients first seen with asymptomatic lesions, only diabetes was an important predictor for late stroke (p = 0.05) and renal disease was the only marker for early death (p = 0.05). On the other hand, those factors were not significant risk factors for patients first seen with amaurosis fugax, for whom tobacco use was a negative predictor for stroke (p = 0.06) and male gender a negative predictor for early death (p = 0.03). After cortical transient ischemic attacks and carotid endarterectomy, there were no risk factors predictive of late stroke or of death. For patients with prior stroke, age was a very strong predictor of stroke (p = 0.01) and both age and a history of cardiac disease were significant risk factors for early death (p = 0.007). In contrast to the results in reports of patients treated medically for transient ischemic attacks and stroke, we found that several risk factors appeared to play relatively minor roles. In conclusion, stroke after carotid endarterectomy was uncommon, least common after ocular symptoms, and most likely after permanent cortical stroke. Specific risk factors were less important for patients after carotid endarterectomy than for the medically treated stroke patient.


Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. The VA Cooperative Asymptomatic Carotid Artery Stenosis Study Group. We prospectively analyzed adverse effects of aspirin in a multicentered cooperative study undertaken to determine the role of endarterectomy in the treatment of asymptomatic carotid artery stenosis. Persons with active peptic ulcer disease or known intolerance to aspirin were excluded from the study. Patients initially received 650 mg aspirin twice daily. After a 54-month recruitment period, 444 patients in 11 centers were followed up for as many as 8 years (mean 47.9 +/- 27.9 months). Patients intolerant to 650 mg aspirin twice daily could be switched to enteric-coated aspirin or "low-dose" aspirin (80 to 325 mg daily). At the conclusion of the study, we performed a cross-sectional analysis of aspirin usage and complications. Overall, there were 757 episodes reported wherein adjustments in study medications were made, including cessation and change in formulation or dosage. At the conclusion of the study, at the time of death, or at occurrence of a neurologic end point, 16% of patients were off medication entirely, 51% had been converted to enteric-coated aspirin, and only 33% were taking regular aspirin with 27% of those having been placed on a reduced dosage. Adverse reactions were ascertained from 4954 patient visit records. In all there were a total of 837 adverse reactions reported, or one in every 5.9 visits. The most frequently reported reaction was heartburn or stomach pain for which 372 episodes were reported in 184 (42%) patients. Nausea or vomiting occurred on 79 occasions in 58 patients, and bloody stools were reported 52 times in 41 patients. We conclude that high-dose aspirin therapy for asymptomatic carotid artery stenosis is poorly tolerated and that adverse reactions even to low-dose enteric-coated aspirin are common even in patients screened for aspirin intolerance.


Polytetrafluoroethylene interposition grafts for carotid reconstruction. Polytetrafluoroethylene interposition grafts were used for carotid reconstruction in 26 operations performed in 23 patients during a 7-year period. There were 10 men and 13 women with a mean age of 66 years. The indication for interposition graft placement was recurrent stenosis with inability to perform endarterectomy in nine operations, a severe kink or technical problem during endarterectomy in nine, aneurysmal changes of the artery in six, and thrombosis of the endarterectomy site segment with stroke in two. There were no perioperative deaths and no further perioperative neurologic complications. Follow-up with performance of yearly duplex scans was obtained in all patients, and the mean duration of follow-up was 36 months. One patient (4%) died of end-stage pulmonary disease during the study interval. Occlusion of the polytetrafluoroethylene graft occurred at 12 months in one patient (4%). Hemodynamically significant restenosis developed in two patients (8%), and two patients (8%) had mild restenosis. Evidence of a second restenosis developed in three of the nine patients who underwent polytetrafluoroethylene interposition graft placement for carotid restenosis. On the basis of our study results, we conclude that polytetrafluoroethylene can be used effectively for carotid reconstruction when an interposition graft is required. However, recurrent stenosis occurs. Patients who undergo polytetrafluoroethylene interposition graft placement for carotid restenosis appear to be at high risk for a second restenosis.


Magnetic resonance angiography of the carotid artery combining two- and three-dimensional acquisitions. To assess the agreement between magnetic resonance angiography and conventional angiography in the evaluation of carotid stenosis, 61 carotid arteries of 40 patients were studied by combined two- and three-dimensional magnetic resonance angiography and conventional angiography. Stenosis of the internal carotid artery was categorized as mild, moderate, severe, critical, or complete occlusion. In 42 arteries, the degree of stenosis according to magnetic resonance angiography correlated exactly to that found by conventional angiography. In the remaining 19 carotid arteries, the magnetic resonance angiographic measurement of stenosis differed from the conventional angiographic measurement by only one size category. The Spearman rank correlation coefficient was 0.95 (p < 0.001). This study showed that by combining information from two- and three-dimensional magnetic resonance angiographic studies and making use of the advantages of each method, magnetic resonance angiography was comparable to conventional angiography in determining carotid stenosis. Magnetic resonance angiography tended to demonstrate a higher level of stenosis when there was a discrepancy. These data demonstrate that magnetic resonance angiography is a steadily improving technology. Although additional studies need to be done, it seems clear that magnetic resonance angiography will be an imaging modality comparable in accuracy to conventional angiography.


Cerebrovascular magnetic resonance angiography: a critical verification. Because simultaneous noninvasive noncontrast imaging of cervical and cerebral vasculature and brain is possible with magnetic resonance angiography (MRA) and imaging (MRI), the following study was undertaken from July 1990 to January 1992. One hundred twenty-eight patients were examined with General Electric 1.5 Tesla MRI systems. Axially acquired volumetric three-dimensional time-of-flight MRA with 0.7 mm3 voxel size with regional maximum intensity projection after processing followed a two-dimensional time-of-flight localizing sequence. These two MRA sequences combined with spin-echo parenchymal brain MRI were compared with duplex scans, contrast angiograms, and surgical findings. Blinded readings by a radiologist and vascular surgeon allowed comparison of grades of luminal diameter narrowing (normal, mild, moderate, severe, and occluded) seen on MRA to be compared with those of Doppler and contrast angiography. Excluding 12 nondiagnostically imaged internal carotid arteries (10 MRA) and limiting duplex correlation to within 5 days of the MRA examination allowed critical appraisal of 182 internal carotid arteries. Exact correlation of grade of stenosis was obtained by the radiologist in 136 (74.7%) of 182 arteries and the surgeon in 138 (75.8%) of 182 arteries. Spearman rank correlation analysis found rank correlation coefficients of 0.88 (p < 0.001) and 0.83 (p < 0.001), respectively, for the radiologist and vascular surgeon. Disagreement one category apart was found by the radiologist in 35 studies (19.3%) and the surgeon in 28 studies (15.4%). Two or more grades of disagreement were found by the radiologist in 11 studies (6%) and the surgeon in 16 studies (8.8%). Contrast angiogram-MRA agreement was found in 86% of 36 internal carotid arteries. The degree of stenosis detected by MRA was concordant with surgical findings in 39 of 40 patients. Thus MRA emerges as a useful and accurate method of obtaining cerebrovascular evaluation in clinical practice.


Upper extremity arterial bypass distal to the wrist. Seventeen arterial bypass procedures distal to the wrist have been performed in 13 men and two women at the Oregon Health Sciences University during the past 9 years. Ten patients had traumatic true or false aneurysms of the ulnar artery with digital embolization. Five patients with end-stage renal disease had severe hand and finger ischemia manifested by rest pain or digital ulceration resulting from widespread forearm and hand arterial occlusions. Patients with aneurysms of the ulnar artery underwent excision and reversed autogenous vein grafting (n = 11) from the distal ulnar artery in the forearm to the superficial palmar arch. All the patients with end-stage renal disease had severe occlusive disease of the forearm and hand arteries and underwent a variety of procedures including radial-radial bypass (n = 2), ulnar-ulnar bypass (n = 2), radial-radial bypass with takedown of a Brescia-Cimino fistula (n = 1), and brachial-radial bypass (n = 1). High-quality upper extremity and magnification hand arteriography was essential for operative planning and was available on all patients. Distal saphenous vein from the ankle or foot was the graft source in 16 procedures and basilic vein the source in one procedure. All operations were performed with headlight illumination, optical loupes, fine sutures, and microvascular instruments. There were no operative deaths or major complications. The mean follow-up period was 14 months. Of the 17 grafts, 16 remained patent by clinical and vascular lab criteria. The single occlusion occurred in an ulnar aneurysm bypass and was accompanied only by mild intolerance to cold.(ABSTRACT TRUNCATED AT 250 WORDS)


Modified polytetrafluoroethylene: indium 111-labeled platelet deposition on carbon-lined and high-porosity polytetrafluoroethylene grafts. Platelet accumulation on carbon-lined (CL) and high-porosity (HP) polytetrafluoroethylene (PTFE) grafts was investigated in vivo. In experiment 1, 20 CL grafts and 20 control PTFE grafts, each 5 cm in length and 4 mm in diameter, were interposed into both carotid and femoral arteries of 10 dogs. In experiment 2, 12 HP grafts (90 microns mean internodal distance) and 12 control PTFE grafts were implanted in six dogs. Indium 111-labeled platelets were injected intravenously and the grafts were retrieved 48 hours later. Radioactivity of the grafts and a control segment of the carotid artery was counted. A graft platelet accumulation index (GPAI) was calculated as the ratio of emission from the graft compared to that from the control segment. The GPAI of the CL graft was significantly less than the GPAI of the control graft in both the carotid (control 29.7 +/- 5.46, CL 22.3 +/- 6.55; n = 9 [p < 0.05]) and the femoral arteries (control 30.7 +/- 9.65, CL 22.0 +/- 6.59; n = 9 [p < 0.05]). There was no significant difference in GPAI between the control and HP grafts in the carotid arteries (control 30.6 +/- 11.8, HP 31.5 +/- 9.71; n = 6) and in the femoral arteries (control 31.5 +/- 7.88, HP 34.0 +/- 4.97; n = 6). Carbon lining decreases platelet accumulation on PTFE grafts in the early postoperative period, and HP grafts do not exhibit increased platelet uptake.


A population-based twin study of alcoholism in women. To clarify the role of genetic factors in the etiology of alcoholism in women. Personal structured psychiatric interviews conducted by researchers "blinded" to the status of the co-twin in an epidemiologic sample of 1030 female-female twin pairs of known zygosity from the population-based Virginia Twin Registry. Three definitions of lifetime prevalence of alcoholism based on Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria: (1) alcoholism with tolerance or dependence; (2) alcoholism with or without tolerance-dependence; and (3) alcoholism with or without tolerance-dependence or problem drinking. Using narrow, intermediate, or broad definitions, the probandwise concordance for alcoholism was consistently higher in monozygotic than in dizygotic twin pairs. Multifactorial threshold models suggested that the heritability of liability to alcoholism in women is in the range of 50% to 60%. The results support the hypothesis that genetic factors play a major role in the etiology of alcoholism in women. Women should be well represented in the efforts currently under way to elucidate the molecular basis of the genetic susceptibility to alcoholism.


Differences in quality of care for hospitalized elderly men and women. To analyze whether important gender differences exist in the quality of hospital care provided to patients with four major medical conditions. Bivariate and multivariate comparisons of clinically detailed sickness at admission, quality, utilization, and outcome measures. Acute care hospitals located in five states. A total of 11,242 patients 65 years or older who were hospitalized with one of four diseases: congestive heart failure, acute myocardial infarction, pneumonia, and cerebrovascular accident. We derived our data from the nationally representative sample used to study the quality of hospital care for Medicare patients before and after the implementation of the prospective payment system. A hierarchical (nested) cluster sampling design was used to draw disease-specific samples of patients hospitalized in 1981, 1982, 1985, or 1986 in one of 297 hospitals located in 30 areas within five states. This was an observational study. Sickness at admission, process, use rates, length of stay, discharge status, discharge destination, and mortality. Sex differences in sickness at admission varied by disease. There was some evidence that women received worse process of care, but the difference was very small. We found many similarities in the process and outcomes of care for male and female patients. After controlling for sickness at admission, age, and other important covariates, the in-hospital experiences of elderly men and women showed greater similarities than differences. The concern that sex bias enters into clinical decision making during hospitalization is eased, although not entirely eliminated.


Environmental and familial contributions to insulin levels and change in insulin levels in middle-aged women. To examine familial and environmental variables associated with elevated insulin levels and changes in insulin levels in healthy, premenopausal women. A population-based sample of 518 women (aged 42 to 50 years) completed baseline assessments of weight, cardiovascular risk factors, exercise behaviors, and glucose and insulin levels (fasting and 2 hours after a glucose load); 495 of the women were reevaluated after 3 years. Plasma insulin levels were related to weight, activity level, race, body fat distribution, and weight gain since age 20 years. Parental history of either diabetes or hypertension was also related to elevated insulin levels, independent of body mass index, with the highest insulin levels occurring in those women with a parental history of both diseases. Increases in plasma insulin levels over the years of follow-up were related to weight gain. This study suggests that importance of using family history to identify women who may have elevated insulin levels and of intervening to prevent weight gain during middle age.


Age at onset for familial epithelial ovarian cancer. To provide age-specific risks for ovarian cancer for relatives of ovarian cancer case patients. To characterize the age at onset for ovarian cancer for women with a single relative vs several relatives affected with ovarian cancer. Three previous studies were reexamined. The cumulative probability of ovarian cancer in first-degree relatives of women with histologically confirmed epithelial ovarian cancer and matched control subjects who participated in the Cancer and Steroid Hormone (CASH) Study was determined. The age of onset of ovarian cancer in women with and without relatives with ovarian cancer in a Washington, DC, case-control study was contrasted with that of women with at least two first-degree relatives studied at the National Cancer Institute (NCI). The CASH Study data showed that first-degree relatives of women with ovarian cancer had an increased risk for ovarian cancer, especially at older ages, when compared with relatives of control subjects. However, the median age at onset was the same among women in the Washington, DC, study with and without an affected relative. Among the women with an extensive family history of ovarian cancer studied at the NCI, the age at onset was considerably younger (47 years) than is typical for this disease (59 years). Of these, 17% had been diagnosed as having primary ovarian cancer by age 40 years. Women who have one first-degree relative affected by ovarian cancer are at greater risk for ovarian cancer but not at an age earlier than the general population. The small proportion of women who have several affected relatives are, however, at a greater risk of early onset of ovarian cancer. Prophylactic oophorectomy may be reasonable for these women.


The postmenopausal estrogen/breast cancer controversy. To provide an overview of the postmenopausal estrogen/breast cancer controversy emphasizing the sources of disagreement in the literature and their clinical and research implications. A MEDLINE search of the English-language literature and a review of bibliographies of meta-analyses describing the association between postmenopausal estrogen use and breast cancer risk. Twenty-four original articles and three meta-analyses were reviewed. In addition, five studies that attempted to minimize detection bias were reviewed to assess the potential role of this bias on risk estimates. Among the original articles, risk estimates ranged from a protective to an adverse effect in women who ever used estrogens; no consistent quantitative effects of estrogens on breast cancer risk were found. In the meta-analyses, summary risk estimates were not significantly elevated in women who ever used estrogen. Findings from European-based studies may account for the increased risk associated with increasing duration of use reported in one meta-analysis. In studies that controlled for detection bias, risk estimates were 1 or less in the ever-used category; there was no consistent effect across other categories of use. These findings do not support an overall increased risk of breast cancer in women who ever used postmenopausal estrogens or a conclusive or consistent effect across other measures of use. Cross-national differences in estrogen use and inequalities in breast cancer detection between estrogen users and nonusers may account for the increased risk estimates reported in some studies. Newer estrogen and progestin-opposed regimens need to be evaluated further.


Reperfusion and revascularization strategies for coronary artery disease in women. One third of all deaths in women in the United States each year are attributable to coronary heart disease. Gender differences exist in the course and management of patients with coronary heart disease. Few randomized trials have been conducted in women to evaluate effective therapeutic strategies. With the aim of developing rational approaches to women with coronary heart disease, we review gender-related outcomes with coronary revascularization and reperfusion therapies. English-language journal articles and reviews on the subject of women with coronary heart disease or gender-specific responses to coronary heart disease management, from 1970 through 1992, identified through MEDLINE searching. Selected studies included only randomized controlled trials for topics related to thrombolysis, and articles considered to contribute significantly to the topic of women with coronary artery disease in the case of angioplasty and coronary artery bypass grafting. Two reviewers participated in extracting the data with the aim of presenting a balanced and comprehensive review of the subject. Thrombolysis in acute myocardial infarction reduces mortality in men and women, although women may have a reduced mortality benefit compared with men. Angioplasty and the newer interventional devices result in greater procedural morbidity but similar if not better long-term outcomes in women. Women may have a greater mortality rate than men with coronary artery bypass surgery, although studies suggest that outcome after bypass surgery may depend more on coronary size and preoperative risk factors than on gender itself. The existence of gender differences in the course of coronary heart disease and response to revascularization and reperfusion strategies suggests the need for unique clinical approaches to the female patient with coronary heart disease and stresses the importance of developing randomized trials that enroll adequate numbers of women and that are designed to answer gender-specific questions.


Factors affecting mammographic visualization of the breast after augmentation mammaplasty. To measure the effect of various parameters on mammographic visualization of the breast after augmentation mammaplasty. Preoperative and postoperative mammography was performed in patients undergoing augmentation mammaplasty. The area of breast tissue visualized on each film was measured. Changes in the area visualized were correlated with a variety of different parameters. The Breast Center, Van Nuys, Calif, a free-standing multidisciplinary breast diagnostic and treatment facility. The 68 women (126 breasts) represent a consecutive sample of patients undergoing augmentation mammaplasty for whom preoperative and postoperative mammograms were available. Area visualized was correlated with degree of capsular contracture, implant position, type of mammography, preoperative breast size, implant size, and implant type. The major factor affecting mammography is capsular contracture. Little or no capsular contracture results in a 30% reduction in the area visualized; moderate or severe contracture results in a 50% reduction. Other important factors include implant position (improved visualization with implant beneath pectoral muscle) and type of mammography performed (slightly more tissue seen with displacement technique). Very small preoperative breast size yields increased visualization. Implant size and type have little or no effect. In most women with breast implants, there is a decrease in measurable breast tissue on the postaugmentation mammogram. Capsular contracture and implant position exert a profound effect; type of mammography performed and preoperative breast size are also significant.


Change in body weight and longevity.

Change in body weight and longevity. To investigate the effect of body weight change on longevity. Cohort analytic study, following men from 1977 through 1988. The study was conducted among Harvard University alumni with mean age of 58 years. Alumni, free of cardiovascular disease and cancer, completed questionnaires on weight, height, cigarette habit, and physical activities in 1962 or 1966 and in 1977 (n = 11,703). We assessed weight change between questionnaires, based on self-reported weights. Mortality from all causes (n = 1441), coronary heart disease (n = 345), and cancer (n = 459), determined from death certificates. Lowest all-cause mortality was among alumni maintaining stable weight (+/- 1 kg). With this category as referent (relative risk = 1.00), relative risks of death associated with losing more than 5 kg, losing between 1 and 5 kg, (more than 1 kg and up to 5 kg) gaining between 1 and 5 kg (more than 1 kg and up to 5 kg), and gaining more than 5 kg were 1.57 (95% confidence interval, 1.34 to 1.84), 1.26 (1.10 to 1.46), 1.06 (0.90 to 1.24), and 1.36 (1.11 to 1.66), respectively. For coronary heart disease mortality, relative risks were 1.75 (1.26 to 2.43), 1.43 (1.05 to 1.93), 1.28 (0.91 to 1.80), and 2.01 (1.36 to 2.97), respectively. Weight change did not predict cancer mortality. Findings were not explained by cigarette habit, physical activity, or body mass index. We observed similar trends for follow-up between 1977 and 1982 and between 1983 and 1988. Those losing or gaining more weight also reported greater total lifetime weight loss, which may indicate weight cycling. Both body weight loss and weight gain are associated with significantly increased mortality from all causes and from coronary heart disease but not from cancer.


Physicians' utilization and charges for outpatient diagnostic imaging in a Medicare population. For 10 common clinical presentations, we assessed differences in physicians' utilization of and charges for diagnostic imaging, depending on whether they performed imaging examinations in their offices (self-referral) or referred their patients to radiologists (radiologist-referral). Using previously developed methodologies, we generated episodes of medical care from an insurance claims database. Within each episode, we determined whether diagnostic imaging had been performed, and if so, whether by a self-referring physician or a radiologist. For each of the 10 clinical presentations, we compared the mean imaging frequency, mean imaging charges per episode of care, and mean imaging charges for diagnostic imaging attributable to self- and radiologist-referral. Depending on the clinical presentation, self-referral resulted in 1.7 to 7.7 times more frequent performance of imaging examinations than radiologist-referral (P < .01, all presentations). Within all physician specialties, self-referral uniformly led to significantly greater utilization of diagnostic imaging than radiologist-referral. Mean imaging charges per episode of medical care (calculated as the product of the frequency of utilization and mean imaging charges) were 1.6 to 6.2 times greater for self-referral than for radiologist-referral (P < .01, all presentations). When imaging examinations were performed--including those performed in both physicians' offices and hospital outpatient departments--mean imaging charges were significantly greater for radiologists than for self-referring physicians in seven of the clinical presentations (P < .01). This result is related to the high technical charges of hospital outpatient departments; in office practice, radiologists' mean charges for imaging examinations were significantly less than those of self-referring physicians for seven clinical presentations (P < .01). Nonradiologist physicians who operate diagnostic imaging equipment in their offices perform imaging examinations more frequently, resulting in higher imaging charges per episode of medical care. These results extend our previous research on this subject by their focus on a broader range of clinical presentations; a mostly elderly, retired population; and the inclusion of higher-technology imaging examinations.


Physician ownership of physical therapy services. Effects on charges, utilization, profits, and service characteristics. To evaluate the effects of physician ownership of freestanding physical therapy and rehabilitation facilities on utilization, charges, profits, and three measures of service characteristics for physical therapy treatments. Statistical comparison by physician joint venture ownership status of freestanding physical therapy and comprehensive rehabilitation facilities providing physical therapy treatments in Florida. A total of 118 outpatient physical therapy facilities and 63 outpatient comprehensive rehabilitation facilities providing services in Florida during 1989. The data from the facilities were collected under a legislative mandate. Visits per patient, average revenue per patient, percent operating income, percent markup, profits per patient, licensed therapist time per visit, and licensed and nonlicensed medical worker time per visit. Visits per patient were 39% to 45% higher in joint venture facilities. Both gross and net revenue per patient were 30% to 40% higher in facilities owned by referring physicians. Percent operating income and percent markup were significantly higher in joint venture physical therapy and rehabilitation facilities. Licensed physical therapists and licensed therapist assistants employed in non-joint venture facilities spend about 60% more time per visit treating physical therapy patients than licensed therapists and licensed therapist assistants working in joint venture facilities. Joint ventures also generate more of their revenues from patients with well-paying insurance. Our results indicate that utilization, charges per patient, and profits are higher when physical therapy and rehabilitation facilities are owned by referring physicians. With respect to service characteristics, joint venture firms employ proportionately fewer licensed therapists and licensed therapist assistants to perform physical therapy, so that licensed professionals employed in joint venture businesses spend significantly less time per visit treating patients. These results should be of interest to the medical profession, third-party payers, and policymakers, all of whom are concerned about the consequences of physician self-referral arrangements.


The crisis in primary care and the role of medical schools. Defining the issues. While a number of issues have diminished the attractiveness of primary care residency programs to USGs, the absolute number of residents in these programs has increased rather than diminished over the past decade, although the proportion of USGs choosing these fields has decreased. In the current arena of medical practice, there are many reasons why these fields are not among the most attractive, and there are several remedies that could be applied to increase their attractiveness. Focusing on medical schools as the sole cause of this dilemma, however, is the least effective way of accomplishing this objective; in addition, this will allow those truly able to increase interest in these fields, such as state and federal governments, to have a reason for not doing so. As long as the medical marketplace is sufficiently large enough to accommodate more than the number of graduates from US medical schools in "desirable" residency training positions, one can never effectively "force" a choice of residency training, nor should one. Primary care can be among the most rewarding of specialties, if adequately supported. It is this support that is lacking and must be addressed.


Risk of suicide among persons with AIDS. A national assessment. We sought to describe the rate, risk, trends, methods, and distribution of suicide among persons with the acquired immunodeficiency syndrome (AIDS) in the United States. We used National Center for Health Statistics multiple-cause mortality data from 1987 through 1989 to identify suicides among persons with AIDS (PWAs) and public-access AIDS surveillance data to determine person-years of observation of PWAs. Residents of the United States with death certificates indicating suicide. Death certificates indicating both AIDS and suicide. In 1987 through 1989, a total of 165 suicides among PWAs occurred in 45 states and the District of Columbia. All but one case were male. Among males the rate was 165 per 100,000 person-years of observation, 7.4-fold higher than among demographically similar men in the general population. Self-poisoning with drugs was both the most common method (35%) and the method with the highest standardized mortality ratio (35). Suicide risk for PWAs decreased significantly (P < .05) from 1987 to 1989. Persons with AIDS have an increased risk of suicide, and assessment of such risk should be a standard practice in their care. These assessments should be carefully considered when potentially lethal medications are prescribed. The declining trend in suicide rates between 1987 and 1989 is encouraging; possible causes include emerging therapies for human immunodeficiency virus/AIDS, better psychiatric care for these patients, and lessened social stigma against PWAs.


Guidelines for the diagnosis of rheumatic fever. Jones Criteria, 1992 update. Special Writing Group of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young of the American Heart Association. The Jones Criteria for guidance in the diagnosis of acute rheumatic fever were first published by T. Duckett Jones, MD, in 1944 and have been revised over the years by the American Heart Association. The current guidelines are an update of these criteria. For the first time, the guidelines are designed to establish the initial attack of acute rheumatic fever. Major manifestations, minor manifestations, and supporting evidence of antecedent group A streptococcal infection are discussed. These updated guidelines expand on the available tools to diagnose streptococcal pharyngitis and clarify the available antibody tests for detecting antecedent group A streptococcal infection. At the present time echocardiography without accompanying auscultatory findings is insufficient to be the sole criterion for valvulitis in acute rheumatic fever. Finally, this article addresses overdiagnosis of rheumatic fever and lists exceptions to the Jones Criteria, including recurrent attacks in individuals with a history of rheumatic fever.


Guidelines for cardiopulmonary resuscitation and emergency cardiac care. Emergency Cardiac Care Committee and Subcommittees, American Heart Association. Part IX. Ensuring effectiveness of communitywide emergency cardiac care. Cardiac arrest treatment continues to evolve. Adequate treatment of the individual patient requires that the whole ECC system function smoothly, consistently, and rapidly. To maximize communitywide survival rates, a careful evaluation of the entire chain of survival is required using standard measurements of performance. The challenge for the next decade is to establish this infrastructure and to conduct multicenter, prospective, controlled clinical trials to better define the key factors that will improve survival of cardiac arrest in every community.


Socioeconomic status and risk for substandard medical care. To assess whether the socioeconomic status of the patient was associated with the risk of adverse events, defined as medical injuries caused by medical management, and the proportion of these events that resulted from substandard care. 51 hospitals in New York State. Rates of medical injury and substandard care by gender, race, income, and payer status were developed from reviews of 30,195 medical records in New York in 1984. We evaluated these socioeconomic parameters in a multivariate analysis, while controlling for hospital-level factors. We found that uninsured patients (odds ratio, 2.35; 95% confidence interval, 1.40 to 3.95) were at greater risk for substandard care. The characteristics of the hospitals to which patients were admitted did not affect this result. Race, gender, and income were not independently associated with risk for medical injury or substandard care in multivariate analyses. Our findings suggest that the uninsured are at greater risk for suffering medical injury due to substandard medical care.


Rates of avoidable hospitalization by insurance status in Massachusetts and Maryland. To determine whether uninsured and Medicaid patients have higher rates of avoidable hospitalizations than do insured patients. We used 1987 computerized hospital discharge data to select a cross-sectional sample of hospitalized patients. Population estimates from the Current Population Survey were used to estimate rates of admission, standardized for age and sex. Nonfederal acute care hospitals in Massachusetts and Maryland. All patients under 65 years of age who were uninsured, privately insured, or insured by Medicaid. Hospitalizations for obstetric and psychiatric conditions were excluded. Relative risk of admission for 12 avoidable hospital conditions (AHCs) identified by a physician panel. Uninsured and Medicaid patients were more likely than insured patients to be hospitalized for AHCs. Rates for uninsured patients were significantly greater than for privately insured patients in Massachusetts for 10 of 12 individual AHCs, and in Maryland for five of 12 AHCs. After adjustment for baseline utilization, the results were statistically significant for 10 of 12 AHCs in Massachusetts and seven of 12 AHCs in Maryland. For Medicaid patients, rates were significantly greater than for privately insured patients for all AHCs in each state before adjustment, and for nine of 12 and seven of 12 AHCs in each state, respectively, after adjustment for baseline utilization. Our findings suggest that patients who are uninsured or who have Medicaid coverage have higher rates of hospitalization for conditions that can often be treated out of hospital or avoided altogether. Our approach is potentially useful for routine monitoring of access and quality of care for selected groups of patients.


Magnesium administration and dysrhythmias after cardiac surgery. A placebo-controlled, double-blind, randomized trial. To determine whether magnesium administration is effective in reducing postoperative morbidity and mortality after cardiac surgery. Randomized, double-blind, placebo-controlled trial. A tertiary acute-care 500-bed university teaching hospital. Over a 6-month period, 100 patients electively scheduled for cardiac surgery involving cardiopulmonary bypass were studied. Fifty patients were randomized to receive an intravenous infusion of magnesium chloride, 2 g, and 50 patients received placebo intraoperatively after the termination of cardiopulmonary bypass. Magnesium-treated patients had a significantly decreased frequency (P < .04) of postoperative ventricular dysrhythmias (eight [16%] of 50) compared with placebo-treated patients (17 [34%] of 50). Patients who were normomagnesemic postoperatively had new supraventricular dysrhythmias less frequently (P < .03) than patients who were hypomagnesemic postoperatively (eight [17%] of 48 vs 19 [37%] of 52). Compared with placebo-treated patients, magnesium-treated patients had significantly higher (P < .02) postoperative cardiac indices in the intensive care unit (2.8 +/- 0.1 vs 2.5 +/- 0.1 L/min per m2). Patients with postoperative total and ultrafilterable hypomagnesemia had postoperative ventricular dysrhythmias (P < .04) and required prolonged mechanical ventilatory support (P < .01) more frequently than patients without postoperative hypomagnesemia. Total and ultrafilterable hypomagnesemia are prevalent findings in cardiac surgery patients, and postoperative hypomagnesemia is strongly associated with clinically important morbidity. Magnesium administration decreased the frequency of postoperative ventricular dysrhythmias and increased the stroke volume and thereby cardiac index in the early postoperative period.


Bone gain in young adult women.

Bone gain in young adult women. To test whether bone mass increases in healthy nonpregnant white women during early adult life after cessation of linear growth; and to test whether various self-chosen levels of physical activity and nutrient intake or use of oral contraceptives influences this increase in bone mass. Longitudinal prospective study of up to 5 years of 156 healthy college-aged women full-time students attending professional schools in universities in the Omaha, Neb, area. University medical center. A convenience sample of healthy women students from Omaha-area professional schools. Any candidate with an illness, condition, or medication (except oral contraceptives) thought to affect general health or bone mass was excluded. None. Clinical and family histories of disease, particularly osteoporosis; oral contraceptive use; bone mineral densities of the spine, forearm, and total body by dual- and single-photon absorptiometry; estimates of nutrient intake by repeated 7-day diet diaries; and measures of physical activity using a physical activity monitor. The median gain in bone mass for the third decade of life, expressed as a percentage per decade, was 4.8% for the forearm, 5.9% for lumbar bone mineral content, 6.8% for lumbar bone mineral density, and 12.5% for total body bone mass (P < .0001 in all cases). By both bivariate and multiple regression analysis the rate of gain in bone density of the spine was negatively correlated with age and positively correlated with calcium/protein intake ratio and physical activity (multiple r = .31; P = .004). Bivariate analysis showed that use of oral contraceptives was associated with greater gain in total body bone mass (r = .31, P = .01). The estimated age when mineral acquisition ceased ranged from 28.3 years to 29.5 years at the several study sites. Gain in bone mass occurs in healthy young women during the third decade of life. Physical activity and dietary calcium intake both exert a positive effect on this bone gain. Use of oral contraceptives exerts a further independent positive effect. Changes in life-style among college-aged women, involving relatively modest increases in physical activity and calcium intake, may significantly reduce the risk of osteoporosis late in life.


Familial Creutzfeldt-Jakob disease (codon 200 mutation) with supranuclear palsy. To identify a possible gene defect in a large kindred with atypical Creutzfeldt-Jakob disease (CJD). Over 360 kindred members, with and without progressive dementia. Family, hospital, and clinic records were reviewed. The DNA was extracted from paraffin-embedded brain tissue of two deceased patients, and from blood leukocytes of nine healthy persons at risk. DNA was subjected to polymerase chain reaction and then analyzed by restriction endonuclease and single nucleotide primer extension. Nine family members had progressive fatal neurological disease consistent with CJD without myoclonus or typical electroencephalographic findings. Supranuclear gaze palsy was present in all five patients who underwent eye examinations. Two neuropathologically confirmed cases and five of nine at-risk family members had an identical mutation (GAG to AAG, glutamic acid to lysine) in codon 200 of the amyloid gene (PRNP) on chromosome 20. Clinically atypical CJD with early supranuclear gaze palsy but without myoclonus or characteristic electroencephalographic periodicity patterns is associated with the codon 200Lys mutation in the largest CJD kindred yet reported. The clinical concept of familial CJD should be enlarged to include this unusual phenotype.


A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group. To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease. A 12-week, double-blind, placebo-controlled, parallel-group study. Outpatients at 23 centers. Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions. In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d. Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC). Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P = .014), clinician-rated CGIC (P = .014), and caregiver-rated CGIC (P = .006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P = .015), clinician-rated CGIC (P = .016), and caregiver-rated CGIC (P = .028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment-related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%). These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations.