Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells.

We have developed a method, using nuclear transplantation, to produce transgenic embryonic stem (ES)-like cells from fetal bovine fibroblasts. These cells, when reintroduced into preimplantation embryos, differentiated into derivatives from the three embryonic germ layers, ectoderm, mesoderm, and endoderm, in 5-month-old animals. Six out of seven (86%) calves born were found to be chimeric for at least one tissue. These experiments demonstrate that somatic cells can be genetically modified and then de-differentiated by nuclear transfer into ES-like cells, opening the possibility of using them in differentiation studies and human cell therapy.

Cloned transgenic calves produced from nonquiescent fetal fibroblasts.

An efficient system for genetic modification and large-scale cloning of cattle is of importance for agriculture, biotechnology, and human medicine. Here, actively dividing fetal fibroblasts were genetically modified with a marker gene, a clonal line was selected, and the cells were fused to enucleated mature oocytes. Out of 28 embryos transferred to 11 recipient cows, three healthy, identical, transgenic calves were generated. Furthermore, the life-span of near senescent fibroblasts could be extended by nuclear transfer, as indicated by population doublings in fibroblast lines derived from a 40-day-old fetal clone. With the ability to extend the life-span of these primary cultured cells, this system would be useful for inducing complex genetic modifications in cattle.

Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats.

Parkinson's disease symptoms can be improved by transplanting fetal dopamine cells into the putamen of parkinsonian patients. Because the supply of human donor tissue is limited and variable, an alternative and genetically modifiable non-human source of tissue would be valuable. We have generated cloned transgenic bovine embryos, 42% of which developed beyond 40 days. Dopamine cells collected from the ventral mesencephalon of the cloned fetuses 42 to 50 days post-conception survived transplantation into immunosuppressed parkinsonian rats and cells from cloned and wild-type embryos improved motor performance. Somatic cell cloning can efficiently produce transgenic animal tissue for treating parkinsonism.

Outcome of carotid endarterectomy performed at a community medical center.

From 1990 to 1992 there was a 43% increase in the number of carotid endarterectomies (CEAs) performed at our institution. Not coincidentally the North American Symptomatic Carotid Endarterectomy Trial study was published in August 1991. To determine whether CEAs could be performed safely at community medical centers, records of 181 consecutive CEAs performed during a 30-month period at a suburban community medical center were reviewed. CEAs were performed by 14 surgeons: six vascular, three thoracic, and five general surgeons. Among all patients 87% had lesions with > or = 70% stenosis. Seventy percent of CEAs were performed on symptomatic patients, 84% of whom had stenoses > or = 70%. Among asymptomatic patients 96% had stenoses > or = 70%. There were five instances of neurologic complications in the perioperative period--two transient ischemic attacks, two reversible ischemic neurologic deficits, and one permanent neurologic deficit. One patient died. The mortality rate was 0.6%, the combined major stroke/mortality rate was 1.2%, and the any stroke/mortality rate was 2.2%. There were five patients with nonfatal major complications--one with myocardial infarction, one with pulmonary edema, one with congestive heart failure, and two with postoperative arrhythmia. Thirteen minor complications included eight cases of cranial nerve dysfunction. These data demonstrate that CEAs can be performed safely at community medical centers.

Frequency and significance of early postoperative silent myocardial ischemia in patients having peripheral vascular surgery.

Coronary disease causes the majority of perioperative complications after peripheral vascular surgery. Twenty-four patients with stable coronary disease undergoing peripheral revascularization were studied using continuous electrocardiographic monitoring to determine the incidence of perioperative asymptomatic myocardial ischemia and its relation to postoperative clinical ischemic events. Patients were monitored preoperatively (17 +/- 1 hours), intraoperatively and postoperatively (29 +/- 2 hours) using 4-channel calibrated amplitude-modulated units. Fifteen patients (63%) had early postoperative silent ischemia; 3 also had preoperative silent ischemia and 5 intraoperative transient ischemia. Patients with and without silent ischemia had similar clinical characteristics, perioperative antianginal medications and postoperative episodes of hemodynamic instability. However, 8 of 15 patients (53%) with silent ischemia had postoperative clinical ischemic events (2 had myocardial infarction, 2 had new congestive heart failure and 4 had new rest angina), versus only 1 of 9 patients (11%) without silent ischemia who had angina (p less than 0.05). Early postoperative silent myocardial ischemia occurs frequently after vascular surgery and is associated with postoperative clinical ischemic events.

Lymphoscintigraphy to confirm the clinical diagnosis of lymphedema.

Confirmation of the diagnosis of lymphedema often requires lymphangiography, a procedure that is painful for the patient and technically demanding. Radioisotope lymphoscintigraphy is a relatively new technique that uses technetium 99 m antimony trisulfide colloid to produce a diagnostic image similar to a lymphangiogram. The procedure requires a single subcutaneous injection in the involved extremity, and images are obtained 3 hours later. It is technically easy to perform, produces minimal discomfort for the patient, and has no adverse effects. We have recently used radioisotope lymphoscintigraphy to evaluate 17 patients with extremity edema. These patients initially had a presumed diagnosis of lymphedema involving the upper or lower extremity. Lymphoscintigraphy confirmed the diagnosis of lymphedema in 12 (70.6%) patients. In five of the 17 patients (29.4%) the clinical impression of lymphedema was not supported by lymphoscintigraphy, leading to alternative diagnoses such as lipomatosis, venous insufficiency (two patients), congestive heart failure, and disuse edema. In all patients with secondary lymphedema the lymphatic system in the involved extremity could be partially visualized. Conversely, three of four patients with primary lymphedema had no ascent of the tracer from the foot and no lymphatic channels could be visualized. Lymphoscintigraphy is relatively easy to perform, safe, minimally invasive, and not uncomfortable for the patient. It is useful in differentiating lymphedema from other causes of extremity edema, allowing institution of appropriate therapy.

Dorsal sympathectomy for hyperhidrosis--the posterior paravertebral approach.

Definitive therapy for hyperhidrosis is sympathectomy. The authors have used a posterior approach to perform 36 dorsal sympathectomies for upper extremity hyperhidrosis in 18 patients (12 female, 6 male). All 18 patients suffered from excessive sweating of the upper extremity (17 palmar, 1 axillary) that caused significant psychological and occupational problems. Eleven patients (61.1%) had lower extremity involvement as well. For all 18 patients conservative medical treatment had failed. Bilateral operations were performed, via a posterior extrapleural approach, through the bed of the third rib. All 36 limbs were relieved of excess sweating. There were no deaths and only two minor wound complications. In no patient did Horner's syndrome develop. Long-term follow-up did not reveal any recurrence of hyperhidrosis. Two patients did complain of compensatory hyperhidrosis of the lower extremities. Dorsal sympathectomy was effective in all of the patients with upper extremity hyperhidrosis in this series. The posterior approach is technically simple, allows simultaneous bilateral operations, and is associated with only infrequent minor complications.

Interruption of the vena cava by means of the Greenfield filter: expanding the indications.

Between 1978 and 1985, 88 patients underwent insertion of the Greenfield vena cava filter. In 21 of the 88 patients (23.9%) the filter was inserted prophylactically. Sixteen of the 21 prophylactic insertions were performed before total joint replacement in patients with a history of venous thromboembolism. Operative morbidity (4.6%) was minor and occurred only early in the series. The operative mortality rate was 4.6%. None of the deaths were related to filter insertion or pulmonary embolism. Follow-up in 65 patients (73.9%) ranged from 1 to 60 months (mean, 16.4 months). Leg edema developed in 9.2% (6/65), stasis ulceration in 3.1% (2/65), caval occlusion in 7.5% (3/40), and recurrent nonfatal embolism in 3.1% (2/65) of the patients. In the patients who received prophylactic filters before total joint replacement, there were no filter-related complications or episodes of pulmonary embolism. This series confirms the safety and effectiveness of the Greenfield filter and suggests that the indications for its use might be liberalized to include prophylactic insertion of the device in certain high-risk patients.

Intussusception following abdominal trauma.

We reviewed the charts of 21 patients on the Trauma Service who were operated on for intestinal obstruction for the years 1983 through 1985. Six (28.6%) of the 21 patients had intussusception as the cause of their obstruction post-laparotomy for trauma. All were males ages 17 to 25 years. The mechanisms of injury were gunshot wounds in three, stab wounds in two, and blunt trauma in one. Five patients were hypotensive on admission with systolic BP less than 70, and two patients received uncrossmatched blood preoperatively. Injuries at exploration included liver laceration (six patients), gastric perforation (two patients), and diaphragmatic lacerations, splenic laceration, renal injury, and ventricular injury, one each. No patient suffered small intestinal injuries and we cannot explain the occurrence of intussusception. Intussusception occurred in the first 8 postoperative days in four patients and at 21 days, and 10 months, in the remaining two. The diagnosis was made twice by CT scan preoperatively. Jejunojejunal intussusception was common (five patients), jejunoileal in one and ileocolic in one (who also had a jejunojejunal intussusception). All patients were treated with manual reduction alone and none recurred. There were no postoperative complications and all patients were discharged by the eighth postoperative day. Our study suggests that early postoperative obstruction is caused by intussusception with unexpected frequency in trauma patients, and can be diagnosed by CT scan in some cases. Treatment with operative reduction has an excellent prognosis.

Tinnitus originating from an abnormal jugular bulb: treatment by jugular vein ligation.

Tinnitus and hearing loss can occur in patients with a high-riding abnormal jugular bulb. Jugular vein ligation in selected patients can cure tinnitus and reverse hearing loss. A 39-year-old woman reported a 4-year history of right-sided tinnitus of increasing intensity associated with a mild hearing loss. Extensive evaluation revealed only an enlarged right jugular bulb with dehiscence of the normal petrous bony septum between the bulb and the middle ear. The patient underwent ligation of the right internal jugular vein and noted immediate cessation of tinnitus and the return of normal hearing. Review of the literature suggests that jugular vein ligation is appropriate in selected cases of venous tinnitus.

Routine versus selective exploration of penetrating neck injuries: a randomized prospective study.

In an effort to settle the controversy regarding the optimal management of penetrating trauma to the neck, a randomized prospective study was conducted in which 160 patients with penetrating neck injuries admitted to Kings County Hospital between 1977 and 1982 were placed, by protocol, into two groups. Group A patients were explored routinely for all injuries to the neck violating the platysma muscle. Group B patients were managed selectively with operation based on clinical or radiographic evidence of major vascular, visceral, or airway injury. Data were collected retrospectively. Length of hospital stay, morbidity, and mortality were compared between groups A and B, as well as between patients explored or not, and no statistical difference was noted. Since there is no clear advantage to either routine or selective exploration in the management of penetrating neck wounds, we conclude that surgeons should base their treatment on their own experience, house staff and nursing support, and radiologic and operating room availability.