Improvement in the health-related quality-of-life symptoms of hyperparathyroidism is durable on long-term follow-up.

BACKGROUND: Subjective symptoms such as decreased energy, chronic fatigue, and depression are associated with hyperparathyroidism. Studies have shown that these symptoms are improved during short-term follow-up after parathyroidectomy. This study evaluates the durability of this subjective improvement in quality-of-life symptoms in a large population of patients with follow-up greater than 1 year after operation. METHODS: Between 2002 and 2005, 258 patients underwent parathyroidectomy, 100 (81 females and 19 males) of whom were available for this study. The patients were evaluated with a survey based on the Health Outcomes Institute Health Status Questionnaire. Some answers were quantified on a 1 to 6 scale, while others consisted of "yes" or "no" responses. Patients completed a questionnaire prior to parathyroidectomy and postoperatively at 1 month, 3 to 6 months, and 1 to 2 years or greater intervals. Statistical analysis was used to detect changes attributable to parathyroidectomy. A P value <.05 was considered statistically significant. RESULTS: At 1-month follow-up, patients' perceptions of their overall health, energy level, and mood significantly improved. At 6-month follow-up, significant improvements in muscle strength, health, endurance, and relief of anxiety were documented. At the interval of 1 to 2 years, overall health, energy level, endurance, and relief of anxiety were improved. There was no significant decrement in the quality of life in these patients after parathyroidectomy. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is associated with significant lasting improvement in subjective symptoms. The potential durable improvement in these quality-of-life symptoms is a valid indication for parathyroidectomy.

Health-related quality of life in hyperparathyroidism measurably improves after parathyroidectomy.

BACKGROUND: Hyperparathyroidism is associated with subjective feelings of fatigue and depression as well as limitations in physical activity from musculoskeletal complaints. These quality of life symptoms are not widely accepted as an indication for parathyroidectomy. This study quantifies and compares subjective symptoms of patients with hyperparathyroidism before and after surgery. METHODS: Between February 2001 and June 2002, 61 patients (14 males and 47 females, mean age of 60.8+/-14.4 years) underwent parathyroidectomy. There were 45 patients with single-gland adenomas, 9 patients with double adenomas, 3 patients with primary hyperparathyroidism from 4-gland hyperplasia, 3 patients with secondary hyperparathyroidism, and 1 patient with tertiary hyperparathyroidism. Patients filled out a 53-question survey based on the Health Outcomes Institute Health Status Questionnaire 2.0 before surgery, 1 month postoperatively, and 3-24 months postoperatively. The survey included questions on overall health, daily activities, mood, and medical conditions. Surveys were analyzed for changes in symptoms attributable to parathyroidectomy. Serum calcium and intact parathyroid hormone levels were obtained preoperatively and at 1- and 3-month follow-up visits. RESULTS: At both postoperative evaluations, patients' perception of general health, muscle strength, energy level, and mood significantly improved (P<.05). Moreover, there was a significant correlation between the changes in serum calcium and intact parathyroid hormone levels and improvement in symptoms. CONCLUSIONS: Parathyroidectomy for hyperparathyroidism is associated with significant improvement in patient quality of life. These subjective symptoms represent a valid indication for parathyroidectomy.

The effect of glucagon-like peptide 2 on intestinal permeability and bacterial translocation in acute necrotizing pancreatitis.

BACKGROUND: Acute pancreatitis (AP) initiates a generalized inflammatory response that increases intestinal permeability and promotes bacterial translocation (BT). Impairment of the intestinal epithelial barrier is known to promote BT. Glucagon-like peptide 2 (GLP-2), a 33 residue peptide hormone, is a key regulator of the intestinal mucosa by stimulating epithelial growth. The purpose of this study was to determine whether GLP-2 decreases intestinal permeability and BT in AP. METHODS: To examine whether GLP-2 can decrease intestinal permeability and thereby decrease BT in acute necrotizing pancreatitis, 34 male Sprague-Dawley rats (200 to 300 g) were studied. AP was induced in group I and group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mg/kg of body weight). The potent analog to GLP-2 called ALX-0600 was utilized. Group I rats received GLP-2 analog (0.1 mg/kg, SQ, BID) and group II rats received a similar volume of normal saline as a placebo postoperatively for 3 days. Group III and group IV received GLP-2 analog and placebo, respectively. At 72 hours postoperatively, blood was drawn for culture of gram-negative organisms. Specimens from mesenteric lymph nodes (MLN), pancreas and peritoneum were harvested for culture of gram-negative bacteria. Intestinal resistance as defined by Ohm's law was determined using a modified Ussing chamber to measure transepithelial current at a fixed voltage. A point scoring system for five histologic features that include intestinal edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. Specimens from MLN, pancreas, jejunum, and ileum were taken for pathology. RESULTS: All group I and group II rats had AP. The average transepithelial resistance in group I was 82.8 Omega/cm(2) compared with 55.9 Omega/cm(2) in group II (P <0.01). Gram-negative BT to MLN, pancreas, and peritoneum was 80%, 0%, and 0%, respectively in group I compared with 100%, 30%, and 20% translocation in group II. CONCLUSION: GLP-2 treatment significantly decreases intestinal permeability in acute pancreatitis.

The effect of interleukin-6 on bacterial translocation in acute canine pancreatitis.

BACKGROUND: Bacterial translocation from the gut to mesenteric lymph nodes and other extraintestinal sites is an important source of infection in acute pancreatitis. Impaired host immunity is known to promote bacterial translocation. Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase reaction, and hematopoiesis. METHODS: Twenty-four mongrel dogs (18-29 kg) were studied in four equal groups. In Groups I and II, acute pancreatitis was induced by direct pressure injection of 4% taurocholate and trypsin into the pancreatic duct at laparotomy. Groups III and IV had only laparotomy. Group I and III dogs were given IL-6 (50 microg/kg/d, sq) daily starting 24 h after operation and Group II and IV dogs received an equal volume of saline administered at similar time. All animals had blood drawn for culture, complete blood count (CBC), platelets, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and amylase on d 0, 1, 4, and 7. On d 7, mesenteric lymph nodes (MLN), spleen, liver, pancreas, and cecum were harvested for pathology study and for cultures of aerobic and anaerobic bacteria. Quantitative cecal cultures of aerobic and anaerobic bacteria were obtained. RESULTS: All Group I and Group II dogs had severe pancreatitis. The increase of plasma CRP in Group I was sustained throughout treatment (1.3+/-0.3 on d 0 vs 3.1+/-0.3*, 3.0+/-0.3*, and 2.9+/-0.3* on d 1,4, and 7, respectively). Plasma CRP was increased in Group II on d 1 and d 4 (1.3+/-0.3 mg/dL on d 0 vs 3.6+/-0.3* mg/dL on d 1, and 3.1+/-0.3* on d 4, *p < 0.05). There were no differences in white blood cell (WBC) count, differential, platelets, and ESR between Groups I and II. Bacterial translocation to MLN was lower in Group I (1/6) than in Group II (6/6) (p < 0.05). All 6 dogs in Group II had bacterial spread to distant sites compared to 2 of 6 dogs in Group I (p = 0.066). Both MLN and other distant organ cultures were negative in Group III and only 1 of 6 MLN cultures was positive in Group IV. CONCLUSIONS: IL-6 treatment decreases bacterial translocation to MLN and may be beneficial in reducing septic complications in acute pancreatitis.

The effect of lexipafant on bacterial translocation in acute necrotizing pancreatitis in rats.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLNs) and other extra intestinal organs is an important source of infection in acute pancreatitis (AP). Lexipafant (BB-882) is a potent platelet-activating factor receptor antagonist that has an anti-inflammatory effect. To examine whether BB-882 could affect BT in acute necrotizing pancreatitis, 48 male Sprague Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the common biliopancreatic duct (1 mL/kg of body weight). Group I rats received BB-882 (10 mg/kg, i.p. qd) and Group II rats received a similar volume of normal saline as a placebo postoperatively for 2 days. Group III and Group IV received BB-882 and placebo, respectively, after an exploratory laparotomy. At 48 hours postoperatively, blood was drawn for culture, serum amylase, and tumor necrosis factor (TNF)-alpha determinations. Specimens from MLNs, spleen, liver, pancreas, and cecum were harvested for culture of gram-positive, gram-negative, and anaerobic bacteria. Quantitative cecal cultures of gram-positive, gram-negative, and anaerobic bacteria were obtained. A point scoring system for five histological features that include interstitial edema, inflammatory cellular infiltration, fat necrosis, parenchymal necrosis, and hemorrhage was used to evaluate the severity of pancreatitis. There was no difference in serum amylase levels (2415 +/- 127 IU/L versus 2476 +/- 170 IU/L), serum TNF-alpha levels (7820 +/- 1396 pg/mL versus 7318 +/- 681 pg/mL), and the mean pancreatic histology score (5.9 +/- 1.2 versus 6.5 +/- 1.1) between Group I and Group II, respectively (P > 0.05). Seven of 12 Group I rats had BT to MLNs, compared with 11 of 12 rats in Group II (P > 0.05). Five of 12 Group I rats had BT to distant sites such as pancreas, spleen, liver, and/or blood, compared with 11 of 12 rats in Group II (P < 0.05). BB-882 treatment decreases bacterial spread to distant sites, but does not reduce serum amylase levels and serum TNF-alpha levels or ameliorate pancreatic damage in rats with AP.

Total thyroidectomy for benign thyroid disease.

BACKGROUND: The goal of this study was to evaluate the safety and efficacy of total thyroidectomy performed for benign thyroid disease. METHODS: A total of 106 consecutive patients undergoing total thyroidectomy for benign disease from October 1982 to July 1995 were reviewed. The 33 men and 73 women had an average age of 46 years (range, 16 to 82 years). Indications for total thyroidectomy were a thyroid nodule with the history of head and neck radiation in 36 patients, bilateral thyroid nodules in 35, needle biopsy of a follicular neoplasm or frozen section diagnosis of a possible malignancy in 18, and toxic goiter in 17. Total thyroidectomy was performed as the primary operation in 98 patients, and 8 patients had a completion reoperation for recurrent disease. RESULTS: Pathology findings revealed benign nodular goiter in 49 patients, follicular adenoma in 26, hyperplasia in 19, and Hashimoto's thyroiditis in 12. Postoperative hemorrhage requiring operative hemostasis occurred in two patients (1.9%). Two patients had unilateral recurrent laryngeal nerve (RLN) palsy before operation (1.9%). Three patients had unilateral postoperative RLN palsy (2.8%). Two cases resolved in 3 and 4 months. The only permanent RLN injury occurred in a patient reoperated for a compressive goiter. Early postoperative hypocalcemia (8.0 mg/dl or less) was found in nine patients (8.5%). No patient had permanent hypoparathyroidism at long-term follow-up evaluation. CONCLUSIONS: Total thyroidectomy for benign thyroid disease can avoid reoperation for nodular goiter and hyperthyroidism and eliminate any subsequent risk of malignant change in radiated thyroid glands. A low complication rate can be achieved with meticulous surgical technique. Total thyroidectomy can be performed safely for bilateral benign thyroid disease.

The effect of epidermal growth factor on the septic complications of acute pancreatitis.

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLN) and other extraintestinal organs is an important source of infection in acute pancreatitis (AP). Epidermal growth factor (EGF), a peptide hormone with trophic effects on gut mucosa, has decreased intestinal mucosal injury in septic rats and decreased burn-induced BT in mice. The purpose of this study is to examine whether EGF could affect BT in acute necrotizing pancreatitis. Forty-eight male Sprague-Dawley rats (250-350 g) were studied. AP was induced in Group I and Group II by pressure injection of 3% taurocholate and trypsin into the biliopancreatic duct (1 ml/kg of body weight). Group III and Group IV underwent laparotomy without induction of acute pancreatitis. Group I rats received human recombinant EGF (100 micrograms/kg, subcutaneously twice daily) and Group II rats received a similar volume of 0.1% bovine serum albumin as a placebo postoperatively. Group III and Group IV received EGF and placebo, respectively. At 48 hr postoperatively, blood was drawn for culture and amylase determinations. Jejunum and ileum were obtained to measure mucosal protein content, mucosal thickness, villus height, and crypt depth. Specimens from MLN, spleen, liver, pancreas, and cecum were harvested for pathology and culture of gram positive (G+), gram negative (G-), and anaerobic bacteria. Ileal mucosal protein levels were increased significantly in Group I (1.96 +/- 0.14 mg/cm) compared to Group II (0.95 +/- 0.15 mg/cm intestinal segment) (P < 0.01). Jejunal and ileal mucosal thickness, villus height, and crypt depth in Group I were significantly increased when compared to Group II (P < 0.05). All 12 rats in Group II had BT to MLN compared to 58% (7 of 12 rats) in Group I (P < 0.05). Thirty-three percent (4 of 12 rats) had BT to distant sites such as pancreas, spleen, liver, and/or blood in Group I vs 83% (10 of 12 rats) in Group II (P < 0.05). EGF treatment minimizes intestinal damage, decreases BT to MLN and bacterial spread to distant sites, and may be beneficial in preventing septic complications in AP.

Tumor angiogenesis in pheochromocytomas and paragangliomas.

BACKGROUND: Angiogenesis correlates with growth and likely metastases in several tumors. To determine whether it has a similar role in pheochromocytomas, immunohistochemical staining of factor VIII was done on the tumor tissue of 42 patients. METHODS: Formalin-fixed, paraffin-embedded tissue was obtained from 29 women and 13 men with 24 primary adrenal and 18 extraadrenal pheochromocytomas. Patients were divided into two groups. Group 1 included 32 patients with benign pheochromocytomas, and group 2 included 10 patients with malignant tumors evidenced by capsular or vascular invasion (six), liver metastases (three), or periaortic lymph node metastases (one). Blood vessels highlighted by factor VIII staining of endothelial cells with labeled streptavidin-biotin were counted under light microscopy. Mean vessel count within a 10 mm2 micrometer disk was calculated under x100, x200, and x400 magnification fields. RESULTS: There were no significant differences in patient age or clinical symptoms between the groups. The mean tumor size in group 2 of 8.8 +/- 5.3 cm was larger than the mean of 4.8 +/- 2.8 cm in group 1 (p < 0.005). The mean counts of vessels in the x100, x200, and x400 magnification fields were 102 +/- 48, 40 +/- 18, and 19 +/- 9 in group 1, and 203 +/- 77, 73 +/- 28, and 37 +/- 15 in group 2. The number of blood vessels in group 2 was significantly higher than in group 1 (p < 0.001) in each studied field. CONCLUSIONS: In this study the number of tumor blood vessels correlated with the invasive behavior of pheochromocytomas. Tumor angiogenesis may be useful in determining the likelihood of malignant behavior in pheochromocytomas.

Effects of granulocyte colony-stimulating factor in severe pancreatitis.

BACKGROUND: The effect of granulocyte colony-stimulating factor (G-CSF) on the rate of secondary infections in acute pancreatitis was evaluated in a canine model. Infectious complications are the major determinant of morbidity and mortality in severe pancreatitis. Bacterial translocation has been shown to be a cause of these secondary infections. The relative immunosuppression found with pancreatitis may promote translocation and the spread of bacteria to the pancreas. METHODS: Thirty-four mongrel dogs were studied. Pancreatitis was induced in 18 dogs; 9 were treated with 100 micrograms G-CSF/day and 9 were given only saline solution. Laparotomy alone was done in 16 dogs of which one half were given 100 micrograms G-CSF/day and one half were given saline solution. Daily blood counts and cultures were obtained. All dogs were killed on day 7, and the mesenteric lymph nodes, pancreas, liver, spleen, and peritoneal fluid were cultured and studied histologically. RESULTS: G-CSF caused a significant and sustained increase in mature granulocytes in dogs given pancreatitis. No difference was found in the rate of translocation to mesenteric lymph nodes in dogs given G-CSF (n = 4) versus dogs given saline solution (n = 6). However, a significant decrease occurred in the spread of bacteria to distant sites in dogs given G-CSF (1 versus 15, p < 0.05). CONCLUSIONS: Although G-CSF does not decrease the rate of translocation, it does decrease the rate of distant infection in severe acute pancreatitis.

Plasmid labeling confirms bacterial translocation in pancreatitis.

To examine whether the gut is a source of infection in acute pancreatitis, bacterial translocation and alterations of intestinal microecology and morphology were studied in 16 dogs. Dogs were colonized with a strain of Escherichia coli (E. coli 6938K) bearing the plasmid pUC4K, which confers kanamycin resistance. In eight dogs (group I), pancreatitis was induced by sodium taurocholate/trypsin injection. Eight other dogs (group II) underwent laparotomy only. The pancreas, mesenteric lymph nodes, peritoneal fluid, liver, and spleen were harvested 7 days later for culturing and histologic analysis. Identification of E. coli 6938K was accomplished by plasmid DNA analysis. Group I dogs had severe pancreatitis and ischemic changes in small bowel mucosa. Group II dogs had no changes. Translocation to the pancreas occurred in five dogs and to mesenteric lymph nodes in six dogs with pancreatitis. No translocation occurred in group II dogs (p < 0.05). In addition to E. coli 6938K, other gram-negative kanamycin-resistant species were isolated, including E. coli (other than 6938K) and Enterobacter cloacae. Enteric origin of these strains was confirmed by antibiography and plasmid DNA analysis. No overgrowth of cecal gram-negative bacteria was found. This study suggests that the gut is a primary source of infection in pancreatitis and that ischemic damage of intestinal mucosa may promote bacterial translocation.

Secondary pancreatic infections: are they distinct clinical entities?

BACKGROUND: Infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have been proposed as distinct clinical entities in terms of treatment and outcome. To evaluate this classification, we reviewed the clinical course and bacteriologic findings of pancreatic infections. METHODS: Of 1299 patients with pancreatitis or a related complication admitted over a 7-year period, 64 (4.9%) with culture-documented secondary pancreatic infections were reviewed with regard to cause, clinical course, bacteriologic findings, and outcomes. RESULTS: Group I consisted of 23 patients with infected pseudocysts; group II, 20 patients with pancreatic abscesses; and group III, 21 patients with infected pancreatic necrosis. The causes were alcohol in 36%, biliary tract disease in 30%, and postoperative in 16%, with no significant difference between groups. Patients in group I had abdominal pain or a mass without accompanying signs of sepsis, whereas patients in groups II and III had sepsis. In group I, 15 patients were treated with internal drainage, four with percutaneous drainage, and four with external drainage. In group II, three had percutaneous drainage, 15 operative drainage, and two open packing. In group III, 19 patients had operative drainage and two had open packing. Morbidity occurred in 26% of patients in group I, 40% in group II, and 90% in group III (p less than 0.001). Mortality rates were 9% in group I, 25% in group II, and 48% in group III (p less than 0.01). Enteric organisms were present in 66% of isolates, with no difference between groups, suggesting a common mode of infection. CONCLUSIONS: Despite similar bacteriologic findings, infected pseudocysts, pancreatic abscesses, and infected pancreatic necroses have significantly different presentations, clinical courses, and outcomes, confirming that they are distinct entities. This distinction is important when therapeutic outcomes are compared.

Effect of somatostatin analogue and cholecystokinin receptor antagonist on bile-induced acute canine pancreatitis.

To determine whether a synthetic somatostatin analogue, octreotide, and a cholecystokinin receptor antagonist, L-364,718, may be beneficial in acute pancreatitis, 33 dogs were assigned to four groups. Each dog underwent laparotomy with injection of autologous bile into the dorsal pancreatic duct. Thirty minutes after the induction of pancreatitis, Group 1 received a subcutaneous injection of octreotide (200 micrograms/kg), Group 2 received an equal volume of the octreotide carrier, Group 3 received an hourly intravenous bolus of L-364,718 (60 micrograms/kg), and Group 4 received an equal volume of the L-364,718 carrier. Hemodynamic profiles, arterial blood gases, plasma glucose, and serum amylase were obtained before laparotomy, at bile injection, and at hourly intervals. The pancreas was removed after 8 hours for gross evaluation, measurement of water content, and histologic examination. A significant decrease in cardiac index and a significant increase in serum amylase and pancreatic edema occurred in all four groups 8 hours after the induction of pancreatitis (P less than 0.05), but there was no statistical difference between any group. Likewise, there was no difference in gross or histologic changes in the pancreas of any group. The somatostatin analogue, octreotide, and the cholecystokinin receptor antagonist, L-364,718, did not ameliorate the effects of severe, bile-induced pancreatitis in dogs.

Calcitonin gene-related peptide increases coronary flow and decreases coronary resistance.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator, but its effects on in situ ventricular function are unknown. We studied effects of intracoronary CGRP (100, 200, and 600 pmole/min, for 10 min) in 21 open-chest chloralose-anesthetized dogs. Systemic, pulmonary, left ventricular (LVP), central venous, and pulmonary capillary wedge pressures were continuously monitored. Left ventricular wall thickness (WT) and circumflex coronary blood flow were also measured. CGRP was infused into the proximal circumflex artery. During CGRP infusion there were no changes in heart rate, cardiac index, pulmonary artery pressure, or systemic vascular resistance, no percentage change in ventricular WT, and no changes in dWT/dt, peak dP/dt, or the slope of end-systolic points on WT/LVP loops. But there were significant changes in coronary flow (CQ), coronary resistance (CRES) and mean arterial blood pressure (MAP) from control (C)* (P less than 0.05). (table; see text) CGRP is a potent coronary artery vasodilator causing notable dose-dependent decreases in coronary resistance and a rise in myocardial flow, despite a decreased MAP (all P less than 0.05). CGRP does not affect ventricular contractility in vivo.

The effect of parathyroid hormone on the acutely ischemic myocardium.

UNLABELLED: Parathyroid hormone (PTH) is reported to be a potent vasodilator. To determine if this action is beneficial in acute myocardial infarction (AMI) and is due to changes in prostacyclin or thomboxane, thirty dogs were anesthetized and instrumented (left atrial, coronary sinus, left main coronary, pulmonary artery and femoral artery catheters). AMI was induced by ligating the left anterior descending coronary artery. Either pentobarbital or alpha chloralose anesthesia was randomly assigned. Following LAD ligation, animals were randomized to receive PTH 0.008 nm/kg over 10 minutes every 30 minutes during the ischemic period or an equal volume of saline. Cardiac index, regional myocardial blood flow, O2 consumption and lactate production were measured. Infarct size was determined by computerized planimetry. PTH bioactivity was verified by adenyalate cyclase stimulating activity in rat osteosarcoma cells. Myocardial blood flow ranged from 81.5 to 155.2 ml/min/kg for normal myocardium. Cardiac index, O2 consumption, lactate production and myocardial perfusion was unaltered by the PTH administration. PTH reduced infarct size in dogs receiving pentobarbital but was deleterious in those receiving alpha chloralose. There was no difference in prostacyclin and thromboxane levels among groups. CONCLUSION: PTH is not beneficial in acute myocardial infarction.

The effect of somatostatin analogue (SMS 201-995) on pancreatic blood flow.

The effect of somatostatin analogue SMS 201-995 on pancreatic blood flow was studied. In 24 dogs all vessels to the pancreas, except for the pancreaticoduodenal artery and vein, were divided. A flow probe was placed around the pancreaticoduodenal artery. The animals were divided into four groups. Control animals received a subcutaneous injection of 0.5 ml of normal saline solution. Treated animals received 0.002, 0.02, and 0.2 mg/kg of SMS 201-995 at the outset of the experiment. Mean systemic arterial blood pressure, cardiac output, and serum amylase values were monitored, in addition to pancreaticoduodenal blood flow. SMS 201-995 produced a prompt and sustained decrease in pancreatic blood flow in all treated groups compared with control animals without alteration of systemic hemodynamics. This suggests that SMS 201-995 decreases local vascular resistance, which results in decreased pancreatic blood flow.