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Biomedical subjects

A J Greenfield

Publications and source records attributed to A J Greenfield.

At least 19 recordsLinked to original sources

The cysteine-rich and C-terminal domains of dystrophin are not required for normal costameric localization in the mouse.

Dystrophin has a modular structure and is believed to be critical for muscle cell cytoarchitecture by linking the cytoskeleton to the extracellular matrix. The N-terminus binds to actin and two domains at the C-terminus, the cysteine-rich and C-terminal domains, are associated with the sarcolemma indirectly via the dystroglycan complex. We have generated a mutation in mouse embryonic stem (ES) cells which serves to delete the cysteine-rich and C-terminal domains to address directly their role. We show that these two domains are not necessary for normal costameric organization at the sarcolemma in myotubes derived from the mutant cell line. Furthermore sarcolemmal localization is also apparent in mouse chimaeric muscle in vivo.

Alleles↗

Perineal abscess after embolization for high-flow priapism.

High-flow priapism is unusual and is most often due to blunt perineal trauma with resultant laceration of the cavernosal artery, creating an arteriocavernosal fistula. Although few cases have been reported, the consensus on management appears to be embolization of the fistula with autologous clot, alone or in combination with Gelfoam. We present a case of high-flow priapism treated in this manner. The embolized pseudoaneurysm evolved into an abscess that eventually spread to the perineum. The rarity of this entity and the postprocedural morbidity are reported.

Abscess↗

Multicenter investigation of the role of transjugular intrahepatic portosystemic shunt in management of portal hypertension.

PURPOSE: To determine the safety and efficacy of transjugular intrahepatic portosystemic shunt (TIPS) placement, a prospective multicenter trial was undertaken. MATERIALS AND METHODS: In eight institutions, 96 patients underwent TIPS placement after failed sclero-therapy (Child-Pugh class A [n = 24], class B [n = 38], and class C [n = 34]), with follow-up for 6 months (with ultrasonography and angiography and clinical and laboratory studies). RESULTS: TIPS placement was successful in all patients (mean initial portosystemic pressure gradient, 22.8 mm Hg + 6.7 [standard deviation]; mean decrease after placement, 12.8 mm Hg + 5.2), with variceal embolization in 25 patients. Complications included liver capsule puncture (n = 12), hepatic artery puncture (n = 3), main portal vein puncture (n = 1), and increased encephalopathy (n = 28). The 30-day mortality rate was 0% for patients with Child class A disease, 18% for class B, and 40% for class C. At 6 months, primary patency was 88% and assisted patency was 94%. CONCLUSION: The risk associated with TIPS placement is reasonable, and it is an effective procedure for the treatment of portal hypertension.

Case-Control Studies↗

Increase in copy number of an integrated vector during continuous culture of Hansenula polymorpha expressing functional human haemoglobin.

Recombinant human haemoglobin A (rHbA) was produced by a leucine-requiring strain of Hansenula polymorpha which had been transformed with an integration vector containing the Saccharomyces cerevisiae LEU2 gene and cDNAs for the expression of alpha and beta globin each driven by the H. polymorpha MOX promoter. After 40 generations in a chemostat it was found that the integrated vector had become amplified in the host strain. In some cases this led to an increase in LEU2 gene dosage, but a loss of globin expression cassettes. In other cases the globin gene dosage also increased. These changes coincided with an increase in rHbA production in the culture, which was reversed when the dilution rate was increased. Isolates from a chemostat culture producing elevated levels of rHbA were grown in fed-batch fermentations, resulting in higher productivities than when inoculated with the parent strain. The rHbA produced was purified and characterized. Oxygen binding studies and electrospray mass spectrometry showed that the rHbA had been processed and assembled correctly, and behaved as a fully functional co-operative tetramer.

Genetic Vectors↗

Sequence analysis of two exons from the murine dystrophin locus.

We have isolated two genomic clones from the murine dystrophin locus, containing single exons encoding protein sequence from the putative actin-binding domain of the amino-terminus and the terminal portion of the triple helical domain. Using interspecific backcross progeny mice, both clones were shown to be X-linked. Sequence analysis indicated that the amino-terminal clone contains a 173 bp exon exhibiting 90% nucleotide sequence identity to human dystrophin exon 6, whilst the C-terminal clone contains a 61 bp exon with 93% nucleotide sequence identity to the human cDNA sequence.

Amino Acid Sequence↗

Arteriography for proximity of injury in penetrating extremity trauma.

Arteriography for proximity of injury was studied prospectively at a trauma center. Findings in 85 patients with penetrating extremity wounds were analyzed to determine the prevalence and types of vascular abnormalities seen with these injuries. Ninety-two limb segments were studied for 77 gunshot and 15 stab wounds. Arteriographic findings were positive in 24% overall but in only 5% for injuries confined to major vessels. A 60% positive rate was seen in a small subgroup of 10 patients with fractures due to gunshot wounds. The most frequently injured vessels were muscular branches of the deep femoral artery (59%); the most common injury was focal, non-occlusive spasm (42%). All patients were treated conservatively, without sequelae at follow-up. In this study, the vascular injuries found at arteriography for proximity of injury in penetrating trauma due to bullets of knives, particularly in the thigh, did not require surgical or radiologic intervention.

Adolescent↗

Cigarette smoking: an independent risk factor for atherosclerosis in the hypogastric-cavernous arterial bed of men with arteriogenic impotence.

We investigated the relationship between cigarette smoking and atherosclerosis of the hypogastric-cavernous arterial bed by evaluating arteriograms of young impotent men referred for selective pudendal angiography. Those patients with hemodynamically significant atherosclerosis had smoked more pack-years than had patients without arterial disease. These differences were statistically significant (p less than 0.05) for the common penile artery (32.8 pack-years, 40 patients versus 22.3 pack-years 57 patients) and the dorsal artery (31.3 pack-years, 48 patients versus 22.0 pack-years, 49 patients). The effect of cigarette smoking as an independent risk factor for atherosclerotic disease in the hypogastric-cavernous arterial bed was evaluated as well. When controlled for age, trauma history, hypertension and diabetes, cigarette smoking was independently associated with atherosclerosis in the internal pudendal artery (p less than 0.05). The relative risk (and 95% confidence interval) of developing internal pudendal artery atherosclerosis for each 10 pack-years smoked was 1.31 (1.05 to 1.64). A third analysis investigated the potential interactive effects of cigarette smoking and pelvic or perineal trauma. A significantly higher incidence (p less than 0.05) of cavernous artery atherosclerosis was found among smokers with a history of chronic perineal trauma (33 patients) compared to nonsmokers with a similar history (25 patients). The findings of this study indicate that cigarette smoking is an independent risk factor in the development of atherosclerotic lesions in the internal pudendal and common penile arteries of young impotent men. Cigarette smoking appears to predispose these patients to early atherosclerotic lesions in the cavernous artery following chronic perineal trauma.

Adolescent↗

Transhepatic cannulation of the inferior vena cava.

Problems frequently develop in maintaining central venous access in patients who require long-term total parenteral nutrition. The authors describe transhepatic placement of a silicone rubber catheter into the inferior vena cava (IVC) in a patient with thrombosis of the superior vena cava, infrarenal IVC, and the great veins. The technique and potential complications are described.

Aged↗

Radiologic assessment of impotence: angiography, sonography, cavernosography, and scintigraphy.

Recent advances in the understanding of erectile dysfunction have led to new treatments for vasculogenic impotence and a need for improved imaging techniques. Although much controversy still exists in this evolving field, we provide a review of the concepts and techniques currently used in cavernosography, sonography, scintigraphy, and angiography to evaluate the impotent patient.

Diagnostic Imaging↗

Hot-tip laser. Results and complications.

The hot tip laser system for atheroablation has been used since mid-1984 as a device for broadening the indications for and extending the applicability of angioplasty in the management of lower-extremity atherosclerosis. It has been a controversial device. Although the system demonstrates that it can occasionally be useful for the management of occlusive as opposed to stenotic disease of the infrainguinal arteries, a close examination of the published data fails to demonstrate a consistent improvement in either the primary success or long-term patency rates for thermal energy applied to atheroma for recanalization of the lower extremity arteries.

Angioplasty, Laser↗

Establishment of the mouse chromosome 7 region with homology to the myotonic dystrophy region of human chromosome 19q.

A number of genetic markers, including ATP1A3, TGFB, CKMM, and PRKCG, define the genetic region on human chromosome 19 containing the myotonic dystrophy locus. These and a number of other DNA probes have been mapped to mouse chromosome 7 utilizing a mouse Mus domesticus/Mus spretus interspecific backcross segregating for the genetic markers pink-eye dilution (p) and chinchilla (cch). The establishment of a highly syntenic group conserved between mouse chromosome 7 and human chromosome 19q indicates the likely position of the homologous gene locus to the human myotonic dystrophy gene on proximal mouse chromosome 7. In addition, we have mapped the muscle ryanodine receptor gene (Ryr) to mouse chromosome 7 and demonstrated its close linkage to the Atpa-2, Tgfb-1, and Ckmm cluster of genes. In humans, the malignant hyperthermia susceptibility locus (MHS) also maps close to this gene cluster. The comparative mapping data support Ryr as a candidate gene for MHS.

Animals↗

Combined transluminal angioplasty and infrainguinal reconstruction in multilevel atherosclerotic disease.

Patients with multilevel atherosclerotic disease represent a difficult surgical challenge. This report is a retrospective review of 46 patients who were treated using a combination of iliac transluminal angioplasty and infrainguinal reconstruction. There were 42 male and 4 female patients with an average age of 62 years (range: 40 to 74 years). Follow-up ranged from 1 month to 10 years (mean: 27.3 months). These patients had multiple health problems typical of patients with peripheral vascular disease, including coronary artery disease (67%), hypertension (61%), and diabetes mellitus (42%); 80% of the patients were smokers. Forty-one patients were treated for rest pain and/or tissue loss, while five were treated for incapacitating claudication. Forty-three patients had a combination of angioplasty and distal bypass, while 3 patients had a form of femoral endarterectomy. Iliac artery pressure gradients were reduced from 35.4 +/- 4 mm Hg preangioplasty to 0.6 +/- 0.3 mm Hg postangioplasty. The procedures were well tolerated with no mortality and four serious complications. Vascular laboratory studies showed an improvement in the mean ankle-brachial index from 0.35 +/- 0.03 preoperatively to 0.71 +/- 0.04 postoperatively (p less than 0.05). Life-table analysis revealed a 72% 5-year primary patency rate, with a 93% 5-year limb salvage. Eight patients required a secondary procedure to maintain limb salvage. Five patients underwent amputation, three due to early graft thrombosis and two due to late graft failure. We conclude that combined iliac angioplasty and infrainguinal reconstruction is a safe and effective method for managing the patient with severe multilevel atherosclerotic disease.

Adult↗

Arteriographically determined occlusive disease within the hypogastric-cavernous bed in impotent patients following blunt perineal and pelvic trauma.

To determine the presence, location and pattern of arterial occlusive disease within the hypogastric-cavernous arterial bed in impotent men following blunt perineal and pelvic trauma, we reviewed the selective internal pudendal arteriograms of 20 patients with a history of blunt perineal and 7 with blunt pelvic trauma who had immediate development of impotence. Arteriographic studies of 104 other impotent patients also were reviewed and compared. Patients with persistent impotence immediately after blunt pelvic and perineal trauma had significantly different patterns of arteriographically demonstrated occlusive disease within the distal hypogastric-cavernous arterial bed consistent with the site of the traumatic injury. Those who sustained blunt pelvic trauma and complained of immediate impotence revealed arterial occlusive lesions mainly in the internal pudendal, common penile, cavernous and dorsal arteries. The incidence of arterial lesions in the distal internal pudendal or common penile artery was significantly higher (p less than 0.01) in patients with blunt pelvic trauma (92%) than in those with blunt perineal trauma (35%). Patients who sustained blunt perineal trauma and complained of immediate impotence demonstrated a more focal pattern of pathological arterial occlusion primarily in the cavernous and dorsal arteries. The incidence of a solitary arterial lesion in the cavernous artery without proximal disease was significantly higher (p less than 0.05) in patients with blunt perineal trauma (48%) than in those with blunt pelvic trauma (8%). It is hypothesized that blunt trauma without immediate impotence may be a potential risk factor for later development of arterial vasculogenic impotence, and that unrecognized or seemingly innocuous trauma may be a factor in cases of idiopathic impotence. Patients without trauma and with vascular risk factors have a more diffuse pattern of arteriographically demonstrated arterial lesions.

Adult↗

Arteriogenic impotence: findings in 195 impotent men examined with selective internal pudendal angiography. Young Investigator's Award.

Selective internal pudendal angiography was performed in 195 men (average age, 35.4 years +/- 10.3) who were suspected of having arteriogenic impotence. In the majority of patients, disease was localized to the cavernosal arteries. A previous series that involved older patients had demonstrated significant disease in the hypogastric and internal pudendal arteries. When controlled for trauma, the data revealed no significant difference (X2 test, P greater than .10) in the distribution of hemodynamically significant penile arterial disease. However, in patients who had sustained major pelvic trauma, the common penile artery was frequently hemodynamically compromised. There is a great deal of variation in the origin of the internal pudendal artery. An accessory pudendal artery was demonstrated in 7% of the patients. If a selective internal pudendal artery injection fails to demonstrate the penile arterial anatomy, a less selective injection should be performed. Bilateral injections should always be performed, as unilateral arterial disease was present in 15% of the patients.

Adolescent↗

"High-flow" priapism: treatment with superselective transcatheter embolization.

Hemodynamically, most cases of priapism occur as a result of venous outflow obstruction producing engorgement of the corpora cavernosa. In a small number of patients, however, the cause is uncontrolled arterial inflow, often from direct arterial trauma. The authors report two cases of arterial or "high-flow" priapism that were successfully treated with selective transcatheter embolization with autologous clot.

Adult↗

Peripheral laser-assisted balloon angioplasty. Initial multicenter experience in 219 peripheral arteries.

In this multicenter clinical series of peripheral laser-assisted balloon angioplasty with an argon laser-heated, metallic-capped fiberoptic, angiographic and clinical success was achieved in a total of 155 (71%) of 219 attempted lesions. When the anatomy of the lesion was subjectively categorized by the angiographer into those considered possible or impossible to treat by conventional balloon angioplasty, clinical success was achieved in 116 (78%) of 149 lesions considered possible to treat with balloon angioplasty (39 [95%] of 41 stenoses and 77 [71%] of 108 occlusions). More importantly, clinical success was achieved in 39 (56%) of 70 lesions considered impossible to treat by conventional means. The incidence of complications, including vessel perforation (4.1%), with this new technique was equal to that reported for conventional balloon angioplasty, decreased with operator experience, and was less than that reported for argon laser angioplasty with bare fiberoptics. Thus, laser thermal angioplasty with a laser-heated, metallic-capped fiberoptic is a safe procedure that is easily learned by physicians skilled in interventional techniques. It allows for nonsurgical treatment of lesions considered difficult or impossible to treat by conventional balloon angioplasty.

Angioplasty, Balloon↗