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Biomedical subjects

T A Broughan

Publications and source records attributed to T A Broughan.

At least 19 recordsLinked to original sources

Donor liver selection. The South-Eastern Organ Procurement Foundation Liver Committee.

Changes in donor liver allotment will not generate more organs. At this time, diverse training and experience are all that guide donor organ selection. Donor variables are now recognized to influence patient and graft survival at 1 year and beyond. Little is known about the molecular biology of hepatic ischemia/reperfusion that might enable informed donor preparation and selection. This study of South-Eastern Organ Procurement Foundation liver transplant centers identifies differences among liver transplant surgeons in donor assessment as issues for further consideration. Sixteen of 25 centers responded. A 170 mEq/L donor serum sodium was the upper limit for acceptance. Selection based on donor vasopressor use lacked uniformity. Preimplantation donor liver biopsy was used selectively, and the maximum acceptable fat content was 30 per cent for most centers. Donor hospitalization for more than 7 days was considered a negative factor by all groups. Surprisingly, five centers were not using donor livers testing positive for hepatitis C. This study points to the great variability in the assessment of organ donors. Greater consensus in this area could lead to increased organ use and/or less retransplantation, a net gain in organ economy.

Health Facilities

The "white clot syndrome" in hepatic transplantation.

Heparin-associated thrombocytopenia and thrombosis (Type II HAT), the "white clot syndrome," has not been previously reported as a cause for fulminant hepatic failure after liver transplantation. Thrombocytopenia and the use of heparin are common events in the newly transplanted patient. A man who was transplanted for sclerosing cholangitis, and re-exposed to heparin, is described with thrombocytopenia, thrombosis of all hepatic vessels, and heparin antibodies. Type II HAT is an immune phenomenon that can apparently occur despite T-cell-directed immunosuppression. Suspicion is a key element in establishing diagnosis. We no longer use heparin routinely in liver transplant cases.

Heparin

Early gene response to hepatic ischemia reperfusion.

The purpose of this study was to define the differences in heat shock protein (hsp)70, albumin, alpha(-1)-acid glycoprotein (AGP), and CCAAT enhancer binding proteins (C/EBP) alpha and beta mRNA between hepatic ischemia and reperfusion, and to begin to explore C/EBP protein production. These genes have been found important in the hepatic response to lipopolysaccharide and inflammation. In two experiments, Sprague-Dawley rats underwent temporary occlusion of the median and left hepatic lobe vasculature. The first experiment included a single sham-operated group and ligation of the right hepatic lobes during reperfusion. It compared 30 and 60 min ischemia to 2 h reperfusion. The second experiment included a sham-operated group for every time point, and the right hepatic lobes were not ligated during reperfusion; a 30-min ischemia group was compared to 2-, 5-, and 24-h reperfusion groups. Total RNA from the ischemic lobes was analyzed by Northern hybridization for hsp70, albumin, AGP, and C/EBPalpha and beta. C/EBPalpha and beta proteins were compared by Western blotting. Differences in experimental design played an important role in interpretation of results. hsp70 mRNA began to increase during ischemia. Albumin mRNA remained constant during ischemia and reperfusion. The ischemic hepatocyte nucleus is not quiescent and retains the ability to upregulate certain genes, e.g., hsp70. Changes in mRNA in response to hepatic ischemia/reperfusion occur rapidly. Hepatic ischemia/reperfusion does not recapitulate the classic acute phase response; albumin is not down regulated during reperfusion.

Animals

Operations for gastric ulcer: a long-term study.

This study assesses the long-term results of operations for benign gastric ulcers. Three-hundred forty-nine patients operated upon between 1950-1979 have been followed over the past 20 years with a mean and median follow-up of 11.8 and 11.1 years. Fifty-five per cent of the patients had a gastric resection without vagotomy; 19.8 per cent had gastric resection with vagotomy; and 20.3 per cent had vagotomy, pyloroplasty, and wedge excision or biopsy of the ulcer. Operations were selected based on the type of ulcer (Types 1-4), whether the surgeon suspected cancer preoperatively, whether the operations was elective or an emergency, and the age and general health of the patient (presence of significant co-morbid disease). Overall mortality was 6.9 per cent, with a mortality for elective operations 3.6 per cent, and for emergency operations of 32.5 per cent. Age and cardiovascular disease were significant factors in operative mortality and morbidity. All operations were equivalent in long-term results. Excellent to good results were obtained in 92 per cent of patients, with an ulcer recurrence rate of 4 per cent. We conclude that vagotomy, pyloroplasty, and wedge excision or biopsy of a benign gastric ulcer is a comparable operation to a more major gastric resection, with or without vagotomy, in the surgical management of gastric ulcer. The addition of vagotomy to gastric resection does not appear to improve long-term results.

Adult

Monoethylglycinexylidide formation as an independent measure of warm hepatic ischemia and reperfusion injury.

An accurate serologic measure of hepatic function would be clinically useful in selecting donors for liver transplantation. An experimental model that incorporates varying lengths of total hepatic warm ischemia with reperfusion injury was utilized to compare serologic parameters and mitochondrial performance of oxidative phosphorylation in predicting hepatocellular injury. Monoethylglycinexylidide (MEGX) formation following bolus intravenous lidocaine injection was found to be significantly decreased (P < 0.0001) at all periods of ischemia when compared to that in nonischemic controls. A serum MEGX level of < 50 micrograms/liter suggested severe hepatic damage. No correlation was found between MEGX level and liver viability as measured by animal survival. Serum transaminase (AST and ALT) levels demonstrated progressive, nonsignificant elevations with increasing length of ischemia (P = 0.0779 at the maximum ischemic time). Polarographic measurements of mitochondrial oxidative phosphorylation did not reveal a significant alteration in subcellular metabolism with prolonged ischemic time. These data highlight the comparative sensitivity of MEGX formation as an early quantitative measurement of hepatocellular injury during warm ischemia, although it was not predictive of organ viability.

Adenosine Triphosphate

Pretransplant chemotherapy in pediatric hepatocellular carcinoma.

The prognosis for pediatric patients with hepatocellular carcinoma is poor, except for fewer than half the patients, who can be rendered disease-free with conventional liver resection. Multicentric, bilobar liver cancer remains unresectable, even after radiation and chemotherapy. Liver transplantation alone for primary hepatic cancer has had limited success. Chemotherapy has been reserved for use after transplantation, with little demonstrable benefit. A pilot program of pretransplant chemotherapy was undertaken. Four adolescent patients with unresectable, multicentric, bilobar hepatocellular carcinoma were staged noninvasively, underwent chemotherapy followed by a final staging laparotomy, and then had liver transplantation. Three of the four patients survived and have no evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44 months after transplantation. Pretransplant chemotherapy has four potential advantages: (1) minimized risk of posttransplant opportunistic infections, (2) less tumor bulk at the time of transplantation, (3) fewer local recurrences, and (4) a lower rate of metastasis.

Adolescent

Endoscopic treatment of biliary leakage after laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is an effective and safe treatment for uncomplicated symptomatic cholelithiasis. However, biliary tract injury may be more common with this procedure than with open cholecystectomy. We have encountered 17 patients with a biliary leak among 465 patients undergoing laparoscopic cholecystectomy, the diagnosis being established by clinical and radiographic parameters. The most common site of leakage was the cystic duct stump. Patients underwent endoscopic sphincterotomy and biliary stent placement, with an overall success rate of 96%. No morbidity or mortality related to the endoscopic procedures was encountered. We conclude that biliary leakage after laparoscopic cholecystectomy is uncommon. When it occurs, it can be treated safely and efficaciously by endoscopic means.

Adult

Mouse antibody-coated lymphocytes during OKT3 therapy in liver transplantation.

Flow cytometry has been a technique in search of a use in transplantation. With each new monoclonal antibody, it has been hoped that the secrets of rejection would be unlocked. The usefulness of CD3+ T-lymphocyte counts to predict successful treatment of organ transplant rejection has been called into question. CD2+, CD3+, and mouse antibody-coated CD3 lymphocytes were followed by flow cytometry in 44 liver transplant patients during OKT3 therapy for induction or rejection. CD3+ lymphocyte counts did not predict successful management of rejection by OKT3. When expressed as percentages of the total lymphocyte count, an increasing trend in CD2+ and mouse antibody-coated CD3+ lymphocytes after day 7 of OKT3 therapy portended persistent or recurrent rejection within 2 months of treatment. It is uncertain if the increasing population of mouse antibody-coated CD3 cells is due to an immune phenomen or decreased clearance by an ailing liver. Care should be taken when using CD3 lymphocyte counts as indicators of adequate OKT3 therapy in liver transplantation.

Animals

Lactiferous fistula.

Lactiferous fistula, or Zuska's disease, is a rare recurrent condition characterized by draining abscesses about the nipple on one or both breasts. Because little is known about the disease, it is often misdiagnosed and inappropriately treated. We reviewed the medical records of 51 women diagnosed as having lactiferous fistula at The Cleveland Clinic Foundation between 1961 and 1991. The clinical features were tabulated. An experienced breast pathologist reviewed the specimens of all the patients, and surgical techniques were compared. Patients ranged in age from 14 to 66 years, with a mean age of 40 years. Thirty-six patients had a swelling or mass at the areola, 51 had a draining fistula from the subareolar tissue, 40 had a chronic thick, pasty discharge from the nipple and 35 reported pain with the discharge. Fourteen patients had unsuccessful operations elsewhere, including four women who had subcutaneous mastectomies before coming to us. The average duration of symptoms was 3.2 years and the average follow-up period postoperatively was 51 months. On histologic examination, we found that, in all instances, keratinizing squamous epithelium had replaced the lining of one or more lactiferous ducts for a variable distance into the subareolar tissue. Core excision of the fistula and all of the retroareolar fibroglandular tissue and the ductal tissue within the nipple proved to be the definitive therapy in 47 of the 48 patients who had follow-up evaluation.

Abscess

Long-term results of the surgical management of chronic pancreatitis.

To investigate the long-term results of surgical management of chronic pancreatitis, we reviewed the hospital records of 50 consecutive patients who underwent surgery for chronic pancreatitis between 1975 and 1985. The principal indications for surgery were abdominal pain (100%), pseudocyst (24%), and biliary obstruction (42%). Surgeries included pancreatic duct drainage (56%), distal pancreatic resection (20%), and drainage of a pancreatic pseudocyst (24%). Follow-up averaged 5.2 years (range 5 to 11 years). Reoperation was required in 31 patients during the extended follow-up period. Principal indications for reoperation were abdominal pain (93%), recurrent pancreatic pseudocyst (32%), and uncertainty of the diagnosis of chronic pancreatitis (26%). Subsequent operations included cholecystectomy (35%), pseudocyst drainage (32%), splanchnicectomy (16%), and pancreatic biopsy (16%); and eliminated abdominal pain in 24 patients (83%). The diagnosis of chronic pancreatitis was not revised in any case. At most recent follow-up, 30 patients (60%) were well and without abdominal pain, 12 (24%) experienced intermittent abdominal pain, and one (2%) had continued abdominal pain that required narcotics. Five patients (10%) died of other causes, and two (4%) were lost to follow-up. We conclude that pain, the principal symptom of chronic pancreatitis, can be eliminated or reduced in the majority of patients by appropriate surgical therapy.

Adult

Fascial closure in the management of infected pancreatic necrosis.

Reports have focused on the perceived benefit of a new method of managing pancreatic necrosis and sepsis: leaving the abdomen packed open after debridement, the "marsupialization" technique. We have continued to treat infected pancreatic necrosis with aggressive pancreatic debridement and drainage, closure of the abdomen, and prompt reoperation as often as necessary if further sepsis is identified. We report 52 consecutive patients with infected pancreatic necrosis operated upon between July, 1972 and March, 1990. Postoperative organ failure and APACHE II scoring correlated with survival. Patients with APACHE II scores less than 15 had an operative mortality rate of 4 per cent, whereas patients with scores greater than 15 had a 44 per cent mortality rate. We recognize that no two retrospective series are truly comparable, but in comparison to published reports on the open technique, fascial closure after pancreatic debridement appeared to produce fewer wound complications (only one dehiscence and one incisional hernia) and fewer trips to the operating room.

Abdomen

Vascular invasion by hepatic inflammatory pseudotumor. A clinicopathologic study.

BACKGROUND: Unusual lesions composed of fibrous tissue, lymphocytes, histiocytes, and plasma cells, called inflammatory pseudotumors (IPT), are being increasingly recognized in many organs and tissues. A hepatic IPT extending into the inferior vena cava has never been reported before to the authors' knowledge. The patient in this study underwent liver resection with cardiopulmonary bypass and circulatory arrest to excise the IPT. METHODS: The tissue was studied extensively using histologic, immunohistologic, flow cytometric, and gene rearrangement analysis and electron microscopic methods. RESULTS: On gross examination, the large hepatic tumor resembled a malignancy invading the vena cava. Microscopically, a mixture of T-lymphocytes, B-lymphocytes, and plasma cells were scattered throughout the tumor. DNA flow cytometry did not reveal aneuploidy suggestive of neoplasia. Genetic analysis of the immunoglobulin and T-cell receptor genes did not detect evidence of clonal expansion of B-cells or T-lymphocytes. CONCLUSIONS: This experience with the vascular invasive and biliary obstructive nature of IPT and the difficulty in diagnosing it before or during surgery underscores the potentially adverse impact of this lesion on patients. The authors believe that an aggressive approach should be taken when evaluating and treating hepatic masses, even though they may later be confirmed as being IPT.

Adolescent

Crohn's disease of the gallbladder.

In a 57-year-old woman, Crohn's disease involving the gallbladder and duodenum caused biliary tract obstruction and necessitated surgery. The patient's symptoms did not improve postoperatively until corticosteroids provided rapid resolution. Inflammatory bowel disease often involves the hepatobiliary tree, yet the gallbladder is rarely involved directly. This patient highlights a rare complication of Crohn's disease.

Cholestasis, Extrahepatic

Cholesterol crystallization-promoters in human bile: comparative potencies of immunoglobulins, alpha 1-acid glycoprotein, phospholipase C, and aminopeptidase N1.

Concanavalin A (Con A)-binding glycoproteins accelerate the rate of cholesterol crystal formation as a prelude to gallstone formation. Immunoglobulins (IgM, IgA, and IgG), aminopeptidase N (APN), phospholipase C (pcPLC), and alpha 1-acid glycoprotein from this Con A fraction have all been proposed as candidate promoters. We immunopurified each of the six putative promoters and examined their comparative effects by adding equal amounts to a cholesterol crystal growth assay. The effects of immunoabsorptive removal of each of the specific candidate promoters from native bile were also compared. In additional studies, the potency of these proteins was in the following order: IgM > IgA = AAG > IgG. APN and pcPLC showed no effect on cholesterol crystal growth at their apparent physiological concentrations. In subtractive experiments, only a minor loss (< 10%) of net promoting activity from that of the whole Con A-bound fraction was observed after immunoabsorptive removal of pcPLC, APN, or immunoglobulins. Total removal of AAG, however, showed a far greater loss (/33%) of the net promoting activity. These data indicate that AAG accounts for the greatest portion of net biliary Con A-bound promoting activity derived from currently defined and well-identified glycoproteins. However, more than 60% of total Con A-binding promoting activity remains unaccounted for, indicating the presence of other important and still unidentified promoters in human bile.

Aminopeptidases

Partial mastectomy without radiation is adequate treatment for patients with stages 0 and I carcinoma of the breast.

The treatment of potentially curable carcinoma of the breast has changed from one operation, radical mastectomy, to a flexible approach. At the Cleveland Clinic, we use four types of treatment for primary potentially curable carcinoma of the breast (Stages 0, I and II)--modified radical mastectomy, simple mastectomy, partial mastectomy with postoperative adjuvant radiation therapy and partial mastectomy without radiation therapy. The latter treatment (partial mastectomy without adjuvant radiation) is controversial. We recommend this procedure for patients with T(is) and T1 carcinomas that appear to be localized, without lymph node metastases, Stages 0 and I disease. The overall and disease-free survival rates are similar to those of patients having modified radical or partial mastectomy with radiation. Local recurrence is slightly higher at five years (11.0 percent) as compared with the other procedures, but at ten years, is only 16.1 percent, a figure comparable with patients having partial mastectomy with radiation (14.4 percent). For patients with Stages 0 and I carcinoma of the breast, the addition of postoperative radiation therapy after partial mastectomy seems to be unnecessary.

Breast Neoplasms

Neurological complications following liver transplantation.

Neurological complications occurred in 4 (19%) of 21 consecutive patients (Group II) undergoing orthotopic liver transplantation, compared with a 47% (9/19) incidence in our initial series (Group I). In Group II, the neurological problems included new recurrent headaches and delayed intracerebral hemorrhage (1 patient), partial third nerve palsy and brachial plexopathy (1 patient), and ataxic dysarthria with encephalopathy (2 patients). Seizures, noted in 8 of 9 neurologically affected Group I patients, were not encountered in Group II. Of the 4 patients in the entire series with the cerebrocerebellar syndrome, 2 had partial recovery after stopping treatment with cyclosporine, 1 stabilized when cyclosporine was discontinued but later worsened when rechallenged, and 1 had full recovery but died following a second transplantation. Brain magnetic resonance images appeared normal in 3 of the 4 patients. Complications affecting vision included cortical blindness in 2 patients and occipital lobe hemorrhage in 1. All completely recovered. Survival was comparable for patients with and those without neurological complications (69% and 63%, respectively). Immediate withdrawal of cyclosporine at the onset of a change in mental status or dysarthria and improvement in intra- and postoperative management may have contributed to the decreased incidence of neurological complications.

Adult