bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors after resection of ampullary carcinoma: Multivariate survival analysis in comparison with ductal cancer of the pancreatic head
Authors: Klempnauer J , Ridder G J , Pichlmayr R
Published: March 2007

Resection was performed in 85 patients with ampullary and in 150 with ductal pancreatic head carcinoma. Curative resection was achieved in 98 and 87 per cent respectively. Patient survival at 5 years after exclusion of hospital deaths was 38 versus 16 per cent respectively. The patients were compared retrospectively in a multivariate survival analysis. For patients with pancreatic carcinoma, residual tumour stage, tumour size and grading were independent prognostic factors, but for those with ampullary carcinoma only tumour size was a prognostic factor. Lymph node metastasis impaired prognosis, but this effect was demonstrable for both groups only after univariate analysis. The Union Internacional Contra la Cancrum classification system was not a reliable parameter of prognosis after resection of ampullary carcinoma. Patients with ampullary cancer appear to have a better prognosis intrinsically than those with pancreatic head tumours, and not simply because they present at an earlier stage. The difference in prognosis cannot be explained sufficiently by a differential importance of the various survival variables.
Increased monocyte cytokine production in association with systemic complications in acute pancreatitis
Authors: McKay C J , Gallagher G , Brooks B , Imrie C W , Baxter J N
Published: March 2007

Tumour necrosis factor (TNF) α, interleukin (IL) 1β, IL-6 and IL-8 are thought to play a central role in the pathophysiology of sepsis but their role in acute pancreatitis is unknown. In the present study, monocytes were isolated from the peripheral blood of 26 patients with moderate or severe acute pancreatitis without biliary sepsis. Secretion of these cytokines in vitro was measured at intervals during the first week of illness. Sixteen patients developed systemic complications. Peak TNF-α secretion was significantly higher in patients who developed systemic complications (median (interquartile range (i.q.r.)) 18·05 (5·5–28·5) ng/ml) than in those with an uncomplicated course (3·7 (2·3–6·4) ng/ml, P< 0·01). Similarly, peak IL-6 and peak IL-8 secretion were significantly higher in the complicated group (IL-6: complicated median (i.q.r.) 48·9 (12·1–71·0) ng/ml, uncomplicated 16·3 (14·2–37·9) ng/ml, P< 0·05; IL-8: complicated 748 (643–901) ng/ml, uncomplicated 608 (496–749) ng/ml), P<0·05). No significant difference in peak IL-1β secretion was observed between the two groups. Systemic complications of acute pancreatitis are associated with a significant increase in monocyte secretion of TNF-α, IL-6 and IL-8 suggesting that, as in sepsis, these cytokines play a central role in the pathophysiology of the disease.
Surgical strategy and management of infected pancreatic necrosis
Authors: Farkas G , Márton J , Mándi Y , Szederkényi E
Published: March 2007

Infected pancreatic necrosis and sepsis are the leading causes of death in patients with necrotizing pancreatitis. Between 1986 and 1993, 123 patients with infected pancreatic necrosis were treated; in all cases the infected necrosis extended to the retroperitoneal area. Surgical treatment was performed a mean of 18·5 days after the onset of acute pancreatitis. Operative management consisted of wide-ranging necrosectomy through all the affected area, combined with continuous widespread lavage and suction drainage applied for a mean of 39·5 days, with a median of 6·5 litres of normal saline per day. In 56 cases (46 per cent), another surgical intervention (distal pancreatic resection, splenectomy, cholecystectomy, sphincteroplasty or colonic resection) was also performed. Bacteriological findings revealed mainly enteric bacteria, but Candida infection was detected in 21 per cent of patients. The overall hospital mortality rate was 7 per cent (nine patients died). Infected pancreatic necrosis responds well to aggressive surgical treatment, continuous, longstanding lavage and suction drainage, together with supportive therapy combined with adequate antibiotic and antifungal medication.
Operative strategies in pancreatic trauma
Authors: Farrell R J , Krige J E J , Bornman P C , Knottenbelt J D , Terblanche J
Published: March 2007

Pancreatic injuries are relatively uncommon and the choice of an appropriate operative procedure can be difficult. Operations for pancreatic trauma from January 1990 to June 1993 have been reviewed. Fifty-one patients were studied; 13 had blunt trauma, 17 gunshot wounds and 21 stab wounds. The distribution of injuries was: pancreatic head (17), body (15) and tail (19). Most patients had associated injuries of surrounding organs. Operations performed included pancreatoduodenectomy (seven), distal pancreatectomy (seven) and external drainage (35). Five patients (10 per cent) died: two from haemorrhage, one from an acute subdural haematoma and two from multiple organ failure. Ten patients (20 per cent) developed a pancreatic fistula, four following blunt trauma, four after gunshot wounds and two with stab wounds; all but one had undergone drainage procedures. Stab wounds were associated with a low incidence of duct injury and external drainage was usually satisfactory. After blunt trauma and gunshot wounds, duct injuries were common and easily missed; careful exploration by an experienced surgeon is essential. In appropriately selected patients, pancreatic resection can be performed with good result.
Randomized comparison of pulmonary function after the ‘French’ and ‘American’ techniques of laparoscopic cholecystectomy
Authors: Kum C-K , Eypasch E , Aljaziri A , Troidl H
Published: March 2007

The ‘French’ and ‘American’ techniques of laparoscopic cholecystectomy, which differ in the position of the surgeon and ports, have not been compared directly. The authors' hypothesis was that the ‘French’ technique results in better postoperative pulmonary function than the ‘American’ technique. Patients undergoing elective cholecystectomy were randomized, 25 patients to have the ‘French’ method and 24 the ‘American’ method. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were measured before operation, and 6, 24 and 48 h after surgery. Postoperative pain and fatigue were also measured. Both FVC and FEV1 at 6 h, 24 h and 48 h after operation were significantly less in the ‘American’ group (FVC at 24 h: 71 versus 86 per cent of preoperative value; P = 0·001, Student's t test; 95 per cent confidence interval 7–24). Two cases of atelectasis occurred in the ‘American’ group and none in the ‘French’ group. Differences in access to Calot's triangle were also noted. One patient in the ‘French’ group sustained a diathermy injury of the duodenum, related to defective equipment. It is concluded that the ‘French’ method leads to less impairment of pulmonary function.
Changes in the management of critical limb ischaemia
Authors: Varty K , Nydahl S , Butterworth P , Errington M , Bolia A , Bell P R F , London N J M
Published: March 2007

A prospective study of all patients with critical limb ischaemia (CLI) who presented to a single vascular unit was undertaken for a 12-month period. There were 222 referrals in 188 patients, 80·2 per cent of which were emergency or urgent admissions. The majority (72·5 per cent) were initially investigated with colour duplex scanning to characterize the arterial lesion. Diagnostic angiography was performed in 35·1 per cent. An attempt at revascularization was made in 73·0 per cent of cases using percutaneous transluminal angioplasty (PTA) in 42·3 per cent, surgery in 24·3 per cent, and a combination of surgery and PTA in 6·3 per cent. Primary major amputation was required in 22 cases (9·9 per cent) and conservative treatments were used in 38 (17·1 per cent). The in-hospital mortality rate was 10 per cent with a limb salvage rate of 79 per cent. Diabetes was an independent risk factor for amputation (odds ratio 2·4, 95 per cent confidence interval 1·22–4·79, P = 0·012). Median hospital stay was much shorter for patients treated by PTA (4·5 days) than surgery (16 days) or primary amputation (18 days). The complication rate of PTA requiring surgery was 5·5 per cent. CLI represents a large non-elective workload for a vascular unit. The increasing use of non-invasive duplex assessment and angioplasty plays a major part in the successful management of these patients.
Prospective randomized controlled study of clinical function and anorectal physiology after low anterior resection: Comparison of straight and colonic J pouch anastomoses
Authors: Ho Y-H , Tan M , Seow-Choen F
Published: March 2007

Clinical function and anorectal physiology were studied prospectively in patients with rectal cancer after low anterior resection, randomized to either a straight anastomosis or an 8-cm colonic J pouch anastomosis. Sixteen patients (mean(s.e.m.) age 61·2(3·2) years; ten men, six women) had a straight anastomosis and 17 (mean(s.e.m.) age 61·2(3·8) years; six men, 11 women) a colonic pouch anastomosis. At 1 year after low anterior resection, a bowel function questionnaire was administered and anorectal physiology tests were performed. Patients with a straight anastomosis had significantly more frequent stools (median 6 (range 3–7) daily) compared with those who had a pouch (median 3 (range 2–7) daily; P = 0·02). A frequent sensation of incomplete defaecation was found in three patients with a straight anastomosis compared with ten who had a pouch anastomosis (P = 0·02). The mean resting anal pressures were lower after colonic pouch anastomosis (P = 0·049) but there were no differences in anal squeeze pressure, rectal sensation, volume of first sensation and compliance between the two groups. The decreased stool frequency with an 8-cm colonic pouch was not associated with measured improvements in rectal reservoir function. It is possible that reversed propulsive activity may be important in smaller colonic J pouches.
Technetium-99m sestamibi parathyroid localization is accurate enough for scan-directed unilateral neck exploration
Authors: Borley N R , Collins R E C , O'Doherty M , Coakley A
Published: March 2007

A retrospective study was conducted into technetium-99m sestamibi imaging of primary hyperparathyroidism to determine the accuracy of identification and localization of parathyroid pathology. Of 56 patients studied, 48 had full preoperative scan data, operative data and pathological results analysed. Overall scan accuracy was 96 per cent. For single gland pathology (adenoma) imaging had a sensitivity of 97 per cent, a specificity of 100 per cent and a positive predictive value of 100 percent. For single gland disease the side was correctly identified in 100 per cent of cases and the site in 94 per cent, but the respective values were only 82 and 79 per cent for multiple gland pathology. Technetium-99m sestamibi imaging is highly sensitive and accurate for primary hyperparathyroidism, with sufficient positive predictive value and accuracy in single gland disease to allow scan-directed unilateral neck exploration.
Breast conservation or mastectomy: Treatment choice of women aged 70 years and older
Authors: Sandison A J P , Gold D M , Wright P , Jones P A
Published: March 2007

Fifty women aged 70 years and older with newly diagnosed carcinoma of the breast were prospectively studied after being offered a choice of four treatment options. Thirty-four of 38 patients who chose their own treatment had breast conservation; four opted for mastectomy. At 12-month follow-up only two women were unhappy with their choice of treatment. It is concluded that elderly women should be involved in deciding the treatment of their breast cancer.
Reduced hepatic acute-phase response after simultaneous resection for gastrointestinal cancer with synchronous liver metastases
Authors: Kimura F , Miyazaki M , Suwa T , Kakizaki S , Itoh H , Kaiho T , Ambiru S , Shimizu H
Published: March 2007

Serum cytokines and hepatic acute-phase responses were studied in seven patients undergoing simultaneous resection of primary gastrointestinal cancer and synchronous metastatic liver tumours and in 12 undergoing partial hepatectomy alone for metachronous hepatic metastases. The incidence of postoperative infectious complications was significantly higher after simultaneous resection than after partial hepatectomy alone (P< 0·05). Although the peak interleukin 6 level was significantly higher after simultaneous resection (P< 0·05), plasma levels of acute-phase proteins were significantly lower (P< 0·05). The results suggest that simultaneous resections further reduce the hepatic acute-phase response and render patients liable to infection compared with partial hepatectomy alone, and result in a higher incidence of postoperative infective complications.
Emergency transhiatal oesophagectomy for instrumental perforation of an obstructed thoracic oesophagus
Authors: Gupta N M
Published: March 2007

Between 1986 and 1994, 14 patients underwent emergency transhiatal oesophagectomy for iatrogenic instrumental perforation of the oesophagus. Continuity of the alimentary tract was restored immediately with cervical anastomosis by oesophagogastroplasty in 13 and oesophagocoloplasty in one. Six patients had oesophageal perforation with a carcinoma, seven had corrosive strictures, and cardiac achalasia was present in one. Only five patients underwent operation within 24 h of initial trauma. There were two postoperative deaths. Resectional surgery, though aggressive, has given good results for perforations with oesophageal strictures. Transhiatal subtotal oesophagectomy has both theoretical and practical advantages over transthoracic resection in the management of instrumental perforation with a distal stricture.
Peritoneal defences and peritoneum-associated lymphoid tissue
Authors: Heel K A , Hall J C
Published: March 2007

The peritoneum is mainly protected by the innate immune system. This consists of mechanical clearance of the peritoneal cavity, activation of complement, and the actions of polymorphonuclear neutrophils and macrophages. The specific immune system, which is mediated by the activity of lymphocytes, provides a secondary amplification system that may be of great importance for patients with intraperitoneal sepsis. This review provides an overview of the relevant innate immune mechanisms and explores the possible role of peritoneum-associated lymphoid tissue.
Endocrine and paracrine hormones in the promotion, progression and recurrence of breast cancer
Authors: Reid S E , Murthy M S , Kaufman M , Scanlon E F
Published: March 2007

Both normal and neoplastic breast tissues are stimulated by endocrine and paracrine hormones. Epidemiological studies have demonstrated the significant role that hormones, growth factors and cytokines have in the promotion, progression and recurrence of breast cancer. Significant variations in the hormonal environment occur based on age, the cyclical changes occurring during the menstrual cycle and (mammographically determined) variations in breast composition. These variations have a significant influence on rates of local recurrence of breast cancer and survival. This review analyses data relevant to these issues and suggests means by which operative results may be improved.
Pulmonary function after laparoscopic cholecystectomy in the elderly
Authors: Milheiro A , Sousa F Castro , Oliveira L , Matos M João
Published: March 2007

The results of laparoscopic cholecystectomy in a group of 52 patients older than 69 years (group 1) were compared with the results of the same operation in a group of 338 younger patients (group 2). In group 1, 23 per cent of patients had acute cholecystitis and 13 per cent were operated on after an episode of acute pancreatitis. In group 2, 8 per cent of patients had acute cholecystitis and 4 per cent were operated on after acute pancreatitis. Pulmonary function was assessed prospectively before operation, 24 h after surgery and on the seventh day after operation, in 20 patients in group 1 and 30 in group 2. In group 1 there was one death (2 per cent); the morbidity rate was 14 per cent and conversion to laparotomy was required in 15 per cent. In group 2 there were no deaths, the morbidity rate was 11 per cent and the conversion rate 4 per cent. No significant differences were found between the two groups in mortality and morbidity rates. Preoperative values of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were significantly lower in group 1 than in group 2 (P < 0·05); the values of FVC, FEV1 and forced expiratory flow at 50 per cent 24 h after surgery were less depressed in group 1 (P < 0·01) and also recovered more quickly in these patients 7 days after operation. Laparoscopic cholecystectomy gives excellent results in geriatric patients and can be recommended as the treatment of choice for symptomatic cholelithiasis in the elderly.
Surgery for left-sided pancreatic cancer
Authors: Fabre J M , Houry S , Manderscheid J C , Huguier M , Baumel H
Published: March 2007

A total of 590 exocrine pancreatic cancers of the body or tail of the pancreas, operated on between January 1982 and December 1988, were analysed. There were 128 pancreatic resections (group 1), 164 palliative bypasses (group 2) and 293 exploratory laparotomies which included 74 splanchnicectomies (group 3). The mortality rate was lower in group 1 (9 per cent) than in group 2 (19 per cent) (P = 0·012). The mortality rate exceeded 40 per cent in groups 1 and 2 for patients aged more than 70 years with pre-existing organ failure. The morbidity rate was 32 per cent in group 1 and 29 per cent in group 2. Patients with metastases had a median survival of 3·4 months, whatever the operative treatment. In the presence of lymph node involvement there was no significant difference in survival between groups 1 and 2. Patients with no metastases and no lymph node involvement had 1- and 3-year survival rates of 38 and 12 per cent respectively after pancreatic resection. Only patients with a small tumour (⩾ 4 cm), no lymph node involvement and no metastases achieved a significantly better survival after resection (P = 0·049). Curative resection should be reserved for a small tumour confined to the pancreas. Fewer than 10 per cent of patients will be suitable for surgery. For the other cases, resection must be considered as a palliative procedure without a significant improvement in survival. It seems justified to limit palliative surgery to candidates for digestive bypass and to use non-surgical palliation for the remainder.
Proinflammatory cytokine release by peripheral blood mononuclear cells from patients with acute pancreatitis
Authors: de Beaux A C , Ross J A , Maingay J P , Fearon K C H , Carter D C
Published: March 2007

Proinflammatory cytokine release was measured from peripheral blood mononuclear cells (PBMCs) isolated from six volunteers and, on admission, from 16 patients with acute pancreatitis. Tumour necrosis factor (TNF) release in patients did not differ significantly from that of volunteers, whereas both interleukin (IL) 6 and IL-8 release in patients was raised when compared with that in the volunteer group (mean(s.e.m.) IL-6 20·7(4·6) versus 9·3(1·7) ng/ml, P = 0·03; IL-8 283(40) versus 128(22) ng/ml, P = 0·04). When variation in white cell count was accounted for, IL-6 and IL-8 release but not that of TNF was significantly greater in patients with severe disease than in those with mild disease. These results point to a complex upregulation of proinflammatory cytokine release from PBMCs in patients with acute pancreatitis, components of which relate to the clinical progress of the disease.
Complete resection of the caudate lobe of the liver: Technique and results
Authors: Bartlett D , Fong Y , Blumgart L H
Published: March 2007

The caudate lobe of the liver is a frequent site of involvement by metastatic or primary liver tumours. This study describes the surgical anatomy and analyses the operative technique, results and postoperative morbidity of complete caudate lobectomy. The data represent a retrospective review of 21 consecutive complete caudate lobe resections performed over a 30-month period. The most common diagnosis was metastatic colorectal cancer (nine patients) and the most common procedure was extended left hepatic lobectomy with en bloc caudate lobectomy. Four patients underwent isolated complete caudate lobe resection. The median operating time was 5 h and the median blood loss was 1160 ml. The major complication rate was 38 per cent (nine major complications in eight patients) with 10 per cent mortality rate (two deaths). The median hospital stay was 11 days. This series demonstrates the feasibility of routine complete caudate lobe resection for tumours with general principles of liver resection. Isolated caudate lobectomy can be performed safely and the addition of caudate lobectomy to major liver resection does not add significantly to the morbidity or mortality of the procedure.
Glyceryl trinitrate prevents neutrophil activation but not thromboxane release following ischaemia-reperfusion injury
Authors: Barry M C , Kelly C J , Stokes K , Abdih H , Sheehan S , Burke P , Hayes D Bouchier
Published: March 2007

The aim of this study was to determine whether glyceryl trinitrate (GTN) has a protective effect on neutrophil- mediated lung injury in a model of aortic occlusion (30 min) and reperfusion (120 min). Sprague-Dawley rats were randomized into control (n = 11), ischaemia-reperfusion (IR) (n = 12), and IR treated with GTN (2 μg kg−1 min−1) during reperfusion (n = 10). Myeloperoxidase (MPO) activity measured pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and neutrophil counts. Neutrophil superoxide release was measured by flow cytometry in a further IR versus GTN experiment (n = 6 in each group). The significant increase in MPO activity produced by IR to a level of 7·99 units g−1 was prevented by GTN which reduced the level to 4·73 units g−1. The increase in pulmonary microvascular leakage after reperfusion was also prevented by GTN: BAL protein without GTN was 992 μg ml−1 and with GTN 579 μg ml−1; BAL neutrophil count without GTN was 3219 cells mm−3 and with GTN 820 cells mm−3; the wet:dry lung weight ratio without GTN was 3·8 and with GTN 3·3. Neutrophil superoxide release increased significantly after 40 min of reperfusion in the untreated IR group (P < 0·05). This increase was prevented in the GTN-treated group. GTN administration had no effect on plasma thromboxane production during revascularization. These data suggest that GTN administration during the reperfusion phase has the potential to decrease pulmonary microvascular injury.
Carotid endarterectomy without angiography
Authors: Shifrin E G , Bornstein N M , Kantarovsky A , Morag B , Zelmanovich L , Portnoi I , Aronovich B
Published: March 2007

Between 1 January 1990 and 1 September 1994 a total of 109 carotid endarterectomies were performed without preoperative angiography. Only two cases were considered by the surgeon to have a poor correlation between the duplex examination results and intraoperative findings; the outcome was good in both. The perioperative mortality rate was 1·8 per cent, one patient dying from sudden haematoma causing asphyxia and the other from unrelated causes following a myocardial revascularization procedure. Two non-disabling strokes also occurred. These results suggest that carotid endarterectomy based on carotid duplex scanning alone without preoperative angiography is safe in selected patients.
Prediction of the risk of death by APACHE II scoring in critically ill trauma patients without head injury
Authors: Muckart D J J , Bhagwanjee S , Neijenhuis P A
Published: March 2007

The ability of the Acute Physiology And Chronic Health Evaluation (APACHE) II scoring system to predict outcome in 199 critically ill patients with trauma but without head injury was assessed prospectively over an 8-month period. Some 178 patients (89·4 per cent) underwent operation and 50 (25·1 per cent) died, 44 after operation and six without undergoing surgery. The mean(s.d.) APACHE II score was 8·0(5·2) for survivors and 14·5(5·5) for non-survivors (P < 0·001). In patients who underwent surgery the mean(s.d.) scores were 7·7(4·6) and 13·4(5·5) (P < 0·001) and for those managed without operation 11·1(7·2) and 14·7(6·3) (P = 0·31) in survivors and non-survivors respectively. The predicted risk of death and observed mortality rate were 5·1 and 25·1 per cent respectively for the entire group, 5 and 25 per cent for patients undergoing surgery, and 7 and 29 per cent for those not operated on. Although the APACHE II system correctly identified all survivors (specificity 100 per cent), it failed to predict death in any patient (sensitivity 0 per cent). The results suggest that this objective prognostic scoring system is not applicable to the patient with trauma who does not have concurrent head injury.
Anatomical basis of intra-arterial chemotherapy for patients with locally advanced breast cancer
Authors: Doughty J C , McCarter D H A , Kane E , Reid A W , Cooke T G , McArdle C S
Published: March 2007

Twenty-eight patients with locally advanced breast cancer received four doses of regional chemotherapy via angiographically placed percutaneous catheters into the internal mammary artery (IMA) and lateral thoracic artery. Patent blue dye was injected to outline the relative contribution to perfusion of each of these vessels. The IMA was found to perfuse 67 (range 20–95) per cent of the breast and the lateral thoracic artery 15 (range 0–35) per cent. In 33 per cent of patients the lateral thoracic artery did not contribute to breast perfusion and a large area of the lateral aspect of the breast was perfused from a further branch of the subclavian or axillary artery. The blood supply to the breast is extremely variable and must be determined in each patient before delivering regional chemotherapy.
Benefits of D2 lymph node dissection for patients with gastric cancer and pN0 and pN1 lymph node metastases
Authors: Siewert J R , Kestlmeier R , Busch R , Böttcher K , Roder J D , Müller J , Fellbaum C , Höfler H
Published: March 2007

A retrospective immunohistological analysis of 100 patients with pT1–3 N0 and pT1–3 N1 gastric adenocarcinoma demonstrated a high frequency of micro-involvement in the removed lymph nodes. The presence of three or more tumour cells in more than 10 per cent of the lymph nodes was of significant prognostic value in the pN0 cases. Multivariate analysis identified micro-involvement as an independent prognostic factor. The results explain why patients benefit from lymphadenectomy even if the removed lymph nodes are not involved by tumour (pN0) in routine histological examination. The frequent occurrence of micro-involvement is a strong argument favouring routine D2 lymph node dissection in gastric cancer surgery in patients with lymph node metastasis.
Prognostic value of monolayer culture patterning in primary cell culture of oesophageal cancer
Authors: Shimada Y , Kanda Y , Shibagaki I , Kato M , Watanabe G , Tanaka H , Kano M , Imamura M
Published: March 2007

The growth of primary cell cultures of oesophageal cancer was compared with the clinical outcome of patients from whom the cancers were taken. Ninety-three patients underwent curative resection, with no operative deaths, and were divided into three groups according to the monolayer culture pattern of the primary cell culture: culture from 43 patients (46 per cent) grew no malignant cells (group 1), 21 (23 per cent) produced monolayer epithelial growth (group 2) and the rest (from 29 patients) established cell lines (group 3). The 5-year survival rate of patients in group 2 (29 per cent) and group 3 (23 per cent) was significantly lower (P < 0·005) than that of those in group 1 (51 per cent). Monolayer epithelial growth potential is a significant prognostic factor in patients with oesophageal cancer.
Otolith fibers and terminals in chick vestibular nuclei
Authors: Popratiloff Anastas , Peusner Kenna D.
Published: March 2007

The distribution of gravity‐sensing, otolith afferent fibers and terminals was studied in the vestibular nuclei of 4–5‐day hatchling chicks by using single and double labeling of fibers and terminals with biocytin conjugated to Alexa Fluor and confocal imaging. The vestibular nuclei are represented in a series of five transverse sections of the brainstem immunolabeled with MAP2. Saccular fibers entered the medulla posterior to and at the level of the posterior tangential vestibular nucleus and coursed through ventral parts, producing ascending and descending branches. Small saccular terminals contacted a few dendrites in the tangential nucleus. In contrast, small saccular terminals contacted many dendrites and a few neuron cell bodies in the ventrolateral vestibular nucleus, vestibulocerebellar nucleus, and descending vestibular nuclei. Utricular fibers coursed through ventral parts of the central tangential nucleus before bifurcating into ascending and descending branches. In the tangential nucleus, utricular fibers formed a few large axosomatic terminals (spoon terminals) and a few small terminals on dendrites. In addition, small utricular terminals contacted numerous dendrites and a few neuron cell bodies in the ventrolateral, vestibulocerebellar, and descending vestibular nuclei. Thus, there was negligible overlap in the distribution of the otolith nerves, although each otolith afferent shared common regions with the canal afferents, previously shown, suggesting that some second‐order vestibular neurons process convergent inputs from otolith and canal afferents. Taken together with previous results, the present findings identify discrete regions of the chick vestibular nuclei where second‐order vestibular neurons likely process directly convergent otolith and canal inputs. J. Comp. Neurol. 502:19–37, 2007. © 2007 Wiley‐Liss, Inc.
Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas
Authors: Shafritz David A. , Kew Michael C.
Published: March 2007

DNA extracts from hepatocellular carcinomas of 13 patients from South Africa were examined for hepatitis B virus (HBV) DNA sequences by molecular hybridization using [32P]-labeled recombinant, cloned, and purified HBV-DNA. Eight patients were HBV carriers as demonstrated by the presence of hepatitis B surface antigen (HBsAg) in their serum, and each of these patients had HBV-DNA sequences in hepatocellular carcinoma tissue. Five patients who were not HBsAg carriers, did not have HBV-DNA in their tumors. In DNA extracts from all tumors of patients who were HBsAg-positive, the HBV-DNA was integrated into the host genome. The integration pattern was unique for each tumor, but HBV-DNA bands of a given length were present in more than one specimen and in a human hepatocellular carcinoma cell line (PLC/PRF/5). These results suggest that integration of HBV-DNA into the human genome occurs in conjunction with malignant transformation.
Attenuation of the ethanol-induced hepatic redox change after chronic alcohol consumption in baboons: Metabolic consequences in vivo and in vitro
Authors: Salaspuro Mikko P. , Shaw Spencer , Jayatilleke Elizabeth , Ross William A. , Lieber Charles S.
Published: March 2007

Acute ethanol administration results in increased hepatic NADH/NAD+ ratio and inhibition of galactose elimination, tricarboxylic acid cycle activity, and fatty acid oxidation. To determine how this redox change is affected by chronic alcohol consumption and to assess the resulting metabolic consequences, we studied baboons which were fed alcohol as 50% of their total calories. Redox changes were evaluated through measurement of galactose elimination in vivo and lactate/pyruvate ratios in liver slices in vitro. The metabolic consequences of these changes were assessed through measurement of CO2 production and fatty acid oxidation in liver slices and hepatic lipid accumulation. Chronic alcohol feeding resulted in attenuation of inhibition of galactose elimination, increase in the lactate/pyruvate ratio, and decrease in fatty acid oxidation which were caused by acute ethanol administration. These metabolic adaptations were associated with reduced accumulation of hepatic fat.
Patterns of hypothalamic-pituitary-gonadal dysfunction in men with liver disease due to differing etiologies
Authors: van Thiel David H. , Gavaler Judith S. , Spero Joel A. , Egler Kimberley M. , Wight Carl , Sanghvi Ajitkumar T. , Hasiba Ute , Lewis Jessica H.
Published: March 2007

The hypothalamic-pituitary-gonadal axis was evaluated in two groups of age-matched men with documented biochemical and histologic liver disease and compared to that of age-matched normal controls. Basal testosterone levels (p < 0.05), spermatozoa concentrations (p < 0.01), and seminal plasma volume (p < 0.01) were reduced in the alcoholics studied with liver disease, but not the hemophiliacs with liver disease when compared to the normal controls. No difference in estradiol levels was noted between groups. Basal follicle-stimulating hormone and luteinizing hormone (LH) concentrations were increased (both p < 0.01) in the alcoholics while only LH concentrations were increased (p < 0.01) in the hemophiliacs compared to the normal controls. Gonadotropins (folliclestimulating hormone and LH) and testosterone responses to clomiphene and to luteinizing hormone-releasing factor (LH only) in the alcoholic population studied, further distinguished the alcoholics from the hemophiliacs and the normal controls. The basal levels of the other anterior pituitary hormones (growth hormone and thyroid-stimulating hormone) as well as their provocative responses to thyrotropin-releasing hormone also distinguished the alcoholics from the hemophiliac population. Based upon these results, we propose that factors other than the liver disease per se are responsible for the disturbances of hypothalamic-pituitary-gonadal function observed in men with biochemically as well as histologically advanced stable liver disease.
Idiopathic neonatal iron storage involving the liver, pancreas, heart, and endocrine and exocrine glands
Authors: Goldfischer Sidney , Grotsky Harold W. , Chang Chung-Ho , Berman Errol L. , Richert Robert R. , Karmarkar Sushama D. , Roskamp Jacqueline O. , Morecki Rachel
Published: March 2007

Autopsy studies of two infants, one a newborn, the other 4 months old, revealed massive amounts of iron in lysosomes of hepatocytes and pancreatic acinar cells. Iron, which had been transported across the placenta, accumulated in the same cell types as in adults with primary and secondary hemochromatosis. Hemosiderin was found in cardiac muscle cells, gastric and intestinal glands, and endocrine and exocrine organs including pituitary, thyroid, adrenals, islets of Langerhans, and sublingual and sweat glands. The liver was the most affected organ and the normal hepatic architecture was replaced by hepatocytes which were arranged in clusters, pseudoacinar structures, and multinucleated giant cells embedded in a collagen matrix. The islets of Langerhans were hyperplastic and hypertrophic. Ten similar cases, in five families, have been described; no patients lived longer than 4 months. Neonatal iron storage disease is clinically and pathologically distinct from Zellweger’s cerebrohepatorenal syndrome and hypermethioninemia (tyrosinemia) neonatal diseases in which large stores of iron are present in hepatocytes. No abnormalities in serum iron, ferritin, or transferrin concentrations were detected in five parents of the affected children.
HLA typing in idiopathic hemochromatosis: Distinction between homozygotes and heterozygotes with biochemical expression
Authors: Bassett Mark L. , Halliday June W. , Powell Lawrie W.
Published: March 2007

In a study of 20 families with idiopathic hemochromatosis, relatives of probands were classified as either homozygous, heterozygous, or normal according to their HLA phenotype. An abnormality in the serum iron concentration, total iron-binding capacity, or serum ferritin concentration was present in all homozygotes and in 25% of heterozygotes. In heterozygotes, the mean total iron-binding capacity was significantly decreased, and the mean hepatic iron concentration was significantly increased compared to normals. However, in contrast to homozygotes, clinical evidence of iron overload was not observed in heterozygotes, and there was no biochemical or histological evidence of liver disease resulting from excessive iron stores. Progressive iron overload did not develop in 44 heterozygotes who were studied for up to 16 yr.
Distal splenorenal shunt vs. portal-systemic shunt: Current status of a controlled trial
Authors: Conn H. O. , Resnick R. H. , Grace N. D. , Atterbury C. E. , Horst D. , Groszmann R. J. , Gazmuri P. , Gusberg R. J. , Thayer B. , Berk D. , Wright S. C. , Vollman R. , Tilson D. M. , McDermott W. V. , Cohen J. A. , Kerstein M. , Toole A. L. , Maselli J. P. , Razvi S. , Ishihara A. , Stern H. , Trey C. , O’hara E. T. , Widrich W. , Aisenberg H. , Stansel H. C. , Zinny M.
Published: March 2007

A prospective controlled comparison of portal-systemic (PSS) and distal splenorenal shunts (DSRS) in cirrhotic patients who had survived hemorrhage from esophagogastric varices was undertaken 5 yr ago at five hospitals by the Boston-New Haven Collaborative Liver Group. The clinical and endoscopic criteria for massive hemorrhage were satisfied in 155 patients. Thirty-four patients were excluded, primarily because of uncontrolled hemorrhage. Thirty-four were rejected because they were poor operative risks and 21 because they did not satisfy criteria. Thirteen patients refused to participate; the remaining 53 were randomized; 29 to receive PSS and 24, DSRS. The two groups were similar in clinical, laboratory, and manometric characteristics. The DSRS group was older and tended to have had more previous hemorrhages. Followup ranged from 1 to 56 months (mean 21). After PSS, which was performed by 10 different surgeons, 6 patients died during the hospital admission (21%) compared to 2 after DSRS (12%). There were 6 late deaths in the PSS group and 4 in the DSRS group. Portal-systemic encephalopathy occurred in 5 of the 23 survivors of PSS (23%), and in 6 of the 19 who survived DSRS (32%). Two patients in the PSS group bled (9%), 1 after thrombosis and 1 after stenosis of the shunt. Three patients in the DSRS group bled (16%) and all had thrombosis of the shunt. PSS was associated with an unexplained but inordinately high operative mortality.

Although the DSRS was accomplished with an acceptably low operative mortality, it was associated with frequent portal-systemic encephalopathy, shunt occlusion, and recurrent hemorrhage. Similar incidences of portal-systemic encephalopathy, shunt occlusion, and recurrent hemorrhage were observed in the PSS group. More patients and longer followup are necessary to determine which of these portal decompressive procedures is superior.
A noncollagenous matrix for attachment of rat hepatocytes in culture
Authors: Ponce Patricia , Cordero Javier , Rojkind Marcos
Published: March 2007

Adult rat hepatocytes efficiently attach to intact connective tissue fibers prepared from normal rat liver; this material has been given the name of “biomatrix”. The cells remain alive and differentiated for at least 4 months in culture. The liver biomatrix contains both collagen and noncollagenous glycoproteins. Heretofore, the functions of the different components of the biomatrix in facilitating cell adhesion and promoting survival and differentiation of rat hepatocytes have not been investigated. We now report on an aggregate of glycoproteins which were extracted with dilute acetic acid from liver biomatrix and which facilitate hepatocyte adhesion to plastic dishes and collagen. One protein in the extract, with a molecular weight larger than 300,000, was selectively immunoprecipitated with an antibody prepared against the extract and immunoadsorbed to glutaraldehyde-cross-linked rat serum. The antibody did not cross-react with cold-insoluble globulin and selectively inhibited cell attachment. The protein of molecular weight of 300,000 appears to be specific for liver, since similar extracts prepared from rat lung, kidney, and heart biomatrices did not cross-react with the antibody. Furthermore, the latter extracts did not facilitate cell attachment above values obtained with plain culture dishes. The results suggest that glycoproteins in the biomatrix, which are antigenically distinct from fibronectin, can mediate attachment of rat hepatocytes to plastic dishes and collagen.
A low molecular weight binding protein for organic anions (Z protein) from human hepatic cytosol: Purification and quantitation
Authors: Kamisaka Kazuaki , Maezawa Hidenori , Inagaki Tooru , Okano Kenichi
Published: March 2007

Human Z protein from liver was purified to homogeneity. The protein has a molecular weight of 11,000 and an isoelectric point of pH 5.8. Circular dichroism spectra of Z protein-bilirubin (uncon-jugated and diglucuronide) complexes revealed two ellipticity extrema, a negative peak at 460 nm, and a positive peak at 410 nm. Human serum albumin had a higher affinity for bilirubin than did Z protein. Fluorescence studies showed the approximate association constants of this protein and bilirubin, bromosulfophthalein, and indocyanine green were 106
M
−1, 105
M
−1, and 106
M
−1, respectively. Immunofluorescence studies revealed that Z protein was localized in the cytoplasm of hepatocytes, proximal tubular epithelium, and epithelial cells of the small intestine. Radioimmunoassay studies were done to assess the amount of Z protein in controls and in various liver diseases. The highest concentrations of Z protein were found in the liver, kidney, heart muscle, and small intestine, in that order. In cases of acute and chronic hepatitis, hepatic Z protein concentrations were generally decreased, whereas serum Z protein concentrations were increased. In contrast, both serum and hepatic Z protein concentrations were decreased in cases of constitutional hyperbilirubinemia.
Ligandinemia in primary liver cell cancer in rat and man
Authors: Ohmi Naohito , Arias Irwin M.
Published: March 2007

Ligandin was quantitated by radioimmunoassay in serum and, when possible, in tumors from patients with primary hepatocellular carcinoma, massive hepatic metastasis or nonhepatic primary neoplasms, and in rats and athymic (nu/nu) mice bearing transplantable ligandin-containing or nonligandin-containing rat hepatocellular carcinomas.

Following transplantation of a ligandin-containing rat hepatocellular carcinoma in rats or athymic (nu/nu) mice, mean serum ligandin concentrations progressively increased and, within 4 months, exceeded normal serum ligandin concentrations by 10-fold.

In 11 of 15 HBsAg negative patients with primary hepatocellular carcinoma, serum ligandin concentrations ranged from 82 to 551 (mean: 298) ng per ml; the mean ligandin concentration in the hepatic neoplasm was 32% of the ligandin concentration in normal liver. In 19 of 22 patients with extensive hepatic metastasis and in each of 20 patients with primary carcinomas without hepatic metastasis, serum ligandin concentrations were normal (7.0 ± 4.0 ng per ml).
The effects of variation in dietary protein and ethanol on hepatic microsomal drug metabolism in the rat
Authors: Mitchell Mack C. , Mezey Esteban , Maddrey Willis C.
Published: March 2007

The effects of chronic ethanol consumption and variations in dietary protein content on microsomal drug metabolism were studied in rats pair-fed liquid diets containing 10, 20, or 30% dietary protein with or without ethanol. In vivo drug metabolism was measured by aminopyrine breath tests and aminopyrine blood elimination kinetics. In vitro drug metabolism was assessed by measuring aminopyrine N-demethylase activity in the hepatic microsomal fraction. The rate of elimination of aminopyrine in vivo was increased in all ethanol-fed animals (p < 0.05) regardless of the protein content of the diet. Animals receiving 10 or 20% protein diets with ethanol showed a 36% increase in drug elimination over pair-fed controls as compared to a 17% increase in drug elimination over controls in animals receiving 30% protein diets. Microsomal aminopyrine N-demethylase activities were similar in ethanol-fed animals and pair-fed controls. Cytochrome P-450 content was increased in all ethanol-fed animals (p < 0.05) but the increase was not dependent on dietary protein content. These results indicate that the effect of chronic ethanol feeding in enhancing drug metabolism in vivo is influenced by the dietary protein content.
Effect of chronic alcohol intake on hepatic fibrosis and granulomas in marine schistosomiasis mansoni
Authors: Orrego Hector , Israel Yedy , Crossley Ian R. , Mahmoud Adel A. F. , Peters Pierre A. , Varghese George , Wanless Ian R.
Published: March 2007

In consideration of the vast prevalence of schistosomiasis and heavy alcohol consumption in many parts of the world, the possibility of an interaction between these two conditions inducing liver disease was studied in mice infected with Schistosoma mansoni. Alcohol consumption significantly reduced by 25% the mean granuloma diameter and by about 60% the extent of fibrous tissue deposition determined chemically as hydroxyproline. DNA, as an expression of the inflammatory and cellular components of the granulomatous reaction in the infected animals, was also significantly reduced by alcohol consumption. These results indicate the need for epidemiological studies in the clinical manifestations and course of schistosomiasis in human alcoholics.
Iepatic vitamin D 25-hydroxylase: Inhibition by bile duct ligation or bile salts
Authors: Bolt Erry J. G. , Sitrin Michael D. , Favus Murray J. , Rosenberg Irwin H.
Published: March 2007

Bone disease and low serum levels of 25-hydroxyvitamin D are prevalent in cholestatic syndromes such as primary biliary cirrhosis and biliary atresia. Defective hydroxylation, along with malabsorption of vitamin D, could be a factor in 25-hydroxyvitamin D depletion. To assess hepatic hydroxylation during experimental cholestasis, we studied vitamin D 25-hydroxylase activity in liver homogenates of rats after 7, 14, and 21 days of bile duct ligation. We have also studied the effects of bile acids on this enzyme in vitro. Hepatic 25-hydroxylation was depressed after 7 days ligation in only 1 of 4 animals, but by 14 days, all animals showed a marked reduction with a mean decrease of 64% in specific activity. Total liver enzyme activity was reduced by 43% at 14 days. In the ligated animals, liver histology showed progressive bile stasis, focal necrosis, bile ductular proliferation, periductular and periportal inflammation, and fibrosis. Addition of bile acids to the in vitro assay in concentrations approximating those found in cholestasis produced marked inhibition of vitamin D 25-hydroxylase activity.