Periluminal expression of a secreted transforming growth factor-ß type II receptor inhibits in-stent neointima formation following adenovirus-mediated stent-based intracoronary gene transfer.

Transforming growth factor-ß1 (TGF-ß1) has been shown unequivocally to enhance neointima formation in carotid and ileo-femoral arteries. In our previous studies, however, TGF-ß1 expression in coronary arteries actually reduced neointima formation without affecting luminal loss postangioplasty, while expression of a TGF-ß1 antagonist (RIIs) in balloon-injured coronary arteries reduced luminal loss without affecting neointima formation. These observed effects may be a consequence of the mode of coronary artery gene transfer employed, but they may also represent differences in the modes of healing of coronary, carotid, and ileo-femoral arteries after endoluminal injury. To help clarify whether a gene therapy strategy to antagonize TGF-ß might have application within the coronary vasculature, we have investigated the effect of high-level periluminal expression of RIIs using stent-based adenovirus-mediated intracoronary gene transfer. Porcine coronary arteries were randomized to receive a custom-made CoverStent preloaded with saline only, or with 1×10(9) infectious units of adenovirus expressing RIIs or ß-galactosidase (lacZ). Vessels were analyzed 28 days poststenting, at which time angiographic in-stent diameter was significantly greater in RIIs-treated arteries, and in-stent luminal loss significantly reduced. Computerized morphometric minimum in-stent lumen area was ~300% greater in RIIs-exposed vessels than in lacZ or saline-only groups. This was because of significantly reduced neointima formation in the RIIs group. RIIs had no demonstrable effect on cellular proliferation or apoptosis, but greater normalized neointimal/medial collagen content was observed in RIIs-exposed arteries. These data highlight the qualitatively similar effect of TGF-ß antagonism on neointima formation in injured coronary and noncoronary arteries, and suggest that since cellular proliferation is unaffected, TGF-ß1 antagonism might prevent in-stent restenosis without the delayed healing that is associated with drug-eluting stents in current clinical use.

Development of viral vectors for use in cardiovascular gene therapy.

Cardiovascular disease represents the most common cause of mortality in the developed world but, despite two decades of promising pre-clinical research and numerous clinical trials, cardiovascular gene transfer has so far failed to demonstrate convincing benefits in the clinical setting. In this review we discuss the various targets which may be suitable for cardiovascular gene therapy and the viral vectors which have to date shown the most potential for clinical use. We conclude with a summary of the current state of clinical cardiovascular gene therapy and the key trials which are ongoing.

Retinoid hepatitis.

A 65-year-old woman treated with etretinate for pityriasis rubra pilaris developed chronic active hepatitis. The elevated transaminases were noted 2 months after initiation of therapy and peaked 2 months after discontinuation of etretinate. The spectrum of liver toxicity induced by etretinate is reviewed. We suggest that reported cases of retinoid-induced liver disease can be divided into four distinct categories: nonspecific reactive hepatitis, acute hepatitis, chronic active hepatitis, and severe fibrosis or cirrhosis.

Severe hyponatremia after colonoscopy preparation in a patient with the acquired immune deficiency syndrome.

Disseminated infections with cytomegalovirus have become an increasingly important cause of morbidity and mortality in patients with the acquired immune deficiency syndrome. Herein we describe a male homosexual with the acquired immune deficiency syndrome who became severely hyponatremic during bowel preparation for colonoscopy. Biochemical evidence of adrenal insufficiency and clinical evidence for cytomegalovirus colitis was found. We propose that the patient had clinically significant cytomegalovirus adrenalitis. A random urinary sodium concentration is suggested as a potential screening test before bowel preparation in such patients.

Electrophoretic analysis of the stored histone pool in unfertilized sea urchin eggs: quantification and identification by antibody binding.

A maternal store of histones in unfertilized sea urchin eggs is demonstrated by two independent criteria. Stored histones are identified by their ability to assemble into chromatin of male pronuclei of fertilized sea urchin eggs in the absence of protein synthesis, suggesting a minimum of at least 25 haploid equivalents for each histone present and functional in the unfertilized egg. In addition, electrophoretic analysis of proteins from acid extracts of unfertilized whole eggs and enucleated merogons reveals protein spots comigrating with cleavage stage histone standards, though not with other histone variants found in later sea urchin development or in sperm. Quantification of the amount of protein per histone spot yields an estimate of several hundred haploid DNA equivalents per egg of stored histone. The identity of some of the putative histones was verified by a highly sensitive immunological technique, involving electrophoretic transfer of proteins from the two-dimensional polyacrylamide gels to nitrocellulose filters. Proteins in amounts less than 2 x 10(-4) micrograms can be detected by this method.

Upper gastrointestinal series immediately after a nondiagnostic first-dose oral cholecystogram.

In 1,250 consecutive patients with nondiagnostic first-dose oral cholecystograms (OCG), the authors performed an upper gastrointestinal series (UGI) that same day prior to repeating the gallbladder studies. The residual barium from the UGI obscured the gallbladder on the reinforced OCG in only 19 patients (1.5%). This approach can alleviate scheduling problems, shorten the hospital stay for patients, decrease the time lost from work for outpatients, and permit an earlier correct diagnosis when the major problem is upper gastrointestinal rather than biliary.

Endometrial stromal tumors, their varied radiographic patterns.

There is a spectrum of endometrial stromal neoplasms which extends from borderline benign to low-grade malignant. These have a definite tendency to metastasize. Proper diagnosis is important because they have an excellent prognosis with long-term survival even with evidence of recurrence or metastases. Aggressive treatment is mandatory. This represents the first report of the radiographic spectrum of the entity as seen in 7 cases. The patients are usually in middle age and present with vaginal bleeding. Not previously stressed is the presence of diarrhea in many of them. Prior uterine surgery even for "fibroids" should be viewed with suspicion. A pelvic mass was usually seen on plain films, intervenous pyelogram (IVP), or barium enema (BE). Ultrasound showed a mixed cystic configuration of the tumors, whereas computed tomography (CT) demonstrated a definitely solid mass. The lesions simulated primary carcinoma of the colon, retroperitoneal tumor, and pelvic inflammatory disease. Metastases to the lung and the bone were also identified.

Ureteropelvic junction obstruction: its occurrence in 3 members of a single family.

A mother and 2 children with ureteropelvic junction obstruction are described. This is the eighth instance of familial hydronephrosis secondary to ureteropelvic junction obstruction. In this family 10 months elapsed between the diagnosis in the first sister and the realization that an obstruction also was present in the sibling. With the recognition that ureteropelvic junction obstruction can be familial it is hoped that earlier, possibly correctable cases will be found. An autosomal dominant form of inheritance with variable penetrance is suggested in this family.

Acute epiglottitis in adults.

Acute epiglottitis in adults is a serious, often rapidly fatal disease, unless diagnosed promptly. Any adult with pain the the throat out of proportion to the visible signs of pharyngitis should have a right and left lateral soft tissue radiograph of the neck and/or indirect laryngoscopy. When expertly interpreted, the roentgenograms can be of inestimable value. Appropriate therapy, including antibiotics and possibly a tracheostomy, should be started immediately.

Contralateral displacement of abdominal viscera by a retroperitoneal liposarcoma: ultrasonic demonstration.

Occasional reports have described contralateral displacement of the kidney, gall bladder, or liver by masses, but no ultrasonographic description of this phenomenon has been published. To our knowledge, this is the first report of contralateral displacement of all three structures by an encapsulated, well-differentiated low-grade liposarcoma. The significance to the ultrasonographer lies in the fact that he may be the first physician, as we were in this case, to have the opportunity to recognize the true anatomical relationships of all three organs and to suggest that this tumor is more likely to be benign or slowly growing rather than a highly infiltrative process.

Intrahepatic rupture secondary to duct exploration demonstrated by cholangiography.

Seven cases of iatrogenic rupture of the intrahepatic bile ducts were demonstrated on T-tube and/or operative cholangiography. This brings the total of documented case reports to 17. All patients had hepatic duct exploration with either the Fogarty balloon catheter and/or the biliary spoon and/or the biliary forceps and/or Bakes dilators. These extravasations usually occur from the right hepatic duct. The recognition of this entity is important because potentially serious complications may occur. Most of the previous cases of intrahepatic extravasation ascribed to excessive pressures of injection were probably surgically induced.