E. V. Adlin~ A. H. Maurer, A. D. Marks, and B. J. Chsnnick, Temple University School of Medicine, Philadelphia, Pa., U.S.A. Decreased bone density has been observed in women on long-term treatment with thyroid hormone. We evaluated bone density, calcitonin responsiveness, and thyroid hormone levels in postmenopausal women treated with thyroxine for 5 years or longer for hypothyroidism or for suppression of thyroid nodules or goiter. Bone mineral density in the spine and hip was measured in 19 thyroxine-treated women, between 50 and 75 years of age, and in 12 matching controls. The thyroxine-treated women had lower bone density, by dual-photon ahsorptiometry, in the lumbar spine (95.4 4. 3.0% of normal vs. ii0.0 +_ 4.6, p <0.005), in the femoral neck (90.5 4. 2.6 v. 100.2 43.7, p <0.02), in Ward's triangle (82.2 4-2.8 vs. 99.7 +_ 5.9, p <0.003), and in the trochanteric area (88.7 43.7 vs. 101.9 +_ 6.0, p <0.003). Plasma calcitonin was measured in the thyroxine-treated women by an extraction-concentration radioimmunoassay. Following a five-minute calcium infusion (2 mg calcium per Kg) a twofold or greater increase in calcitonin was observed in four of the 19 patients, but in 31 of 37 normal women. The average dose of thyroxine was 120 mcg/day; 16 of the 19 patients had serum T4 levels in the normal range, and all 19 had serum total T3 levels that were normal. TSH levels, however, were low in 13 of the 19 patients, suggesting that the thyroxine treatment was supraphysiologic. We conclude that long-term thyroxine therapy is associated with decreased density of the spine and hip. Since both subtle hyperthyroidism and decreased calcitonin responsiveness were demonstrated in these patients, both factors must be considered as possible causes of the decreased bone density. 12 HYPERPARATHYROIDISM IN FEMORAL NECK FRACTURES. BIOLOGICAL AND HYSTOMORPHOMETRIC STUDY IN 21 PATIENTS OLDER THAN 75 YEARS.

The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase–polymerase chain reaction (RT—PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT–PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT–PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT–PCR. We conclude that a multimarker RT–PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation.

Meconium ileus equivalent is one of the lesser-known manifestations of cystic fibrosis. It manifests as distant small bowel obstruction caused by meconium-like stool plugs and occurs mostly in adult patients. With the improved overall survival of patients with cystic fibrosis, general surgeons may encounter this condition more often in the future. We treated a 19-year-old woman with cystic fibrosis who presented with complete distal small bowel obstruction. Medical therapy with Gastrografin and N-acetylcysteine failed to resolve the obstruction. At surgery, a meconium-like plug in the distal ileum was manually pushed into the colon with subsequent relief of symptoms. Meconium ileus equivalent should be considered and treated in cystic fibrosis patients presenting with small bowel obstruction.

wenty-five years ago, in 1968, Wilmore and Dudrick1,2 published lmost simultaneously two papers that revolutionized surgery in eneral and gastrointestinal surgery in particular. An infant of 300 g with almost complete atresia of the small bowel and on the rink of death from inanition was fed intravenously for 44 d and emonstrated normal growth and development.1 This pivotal deelopment followed publication of an extensive experimental work y the same group from the University of Pennsylvania proving hat growth, development, and positive nitrogen balance can be chieved by long-term total parenteral nutrition (TPN) in beagle uppies.2 TPN has since been used in millions of patients all over the orld and for a myriad of indications. However, short bowel yndrome is probably the disease state where its effect was (as in he infant described by Wilmore and Dudrick) and still is the most ramatic one. TPN is used to enable intestinal adaptation and ltimately return to short bowel patients, completely or partly, the se of their bowel or is used as home TPN in those unfortunate nough not to be able to achieve adequate intestinal adaptation. Intestinal adaptation is aimed primarily at the restoration of the bsorptive function of the gut and secondarily at restoring intestial barrier function and gut immunologic function. Intestinal adptation is characterized by compensatory growth of all layers of he bowel wall of the intestinal remnant, leading to dilatation, engthening, and thickening. There is increased epithelial cell roliferation in the crypts and migration of cells into the villi. This yperplasic process results in increased mucosal cell mass, DNA, NA, and protein content.3 The stimulation of this complex proess of adaptation is dependent on pancreatobiliary secretions, on-nutritive factors such as enteroglucagon, growth hormone and ther growth factors, and a variety of nutritive factors.3 Some atients’ guts will be too short or too sick to undergo adequate ntestinal adaptation, and these patients will have to remain on

Current knowledge on the morphology and physiology of interstitial cells of Cajal (ICC) is mostly based on animal studies, and information about the function of these cells in humans is scarce. There is ultrastructural evidence that ICC in the myenteric region (ICC-MP) of the small intestine of several species are connected by gap junctions, but these were not observed in the human small intestine. The aim of the present study was to determine whether functional coupling also exists among ICC-MP in the human ileum. We visualized ICC-MP in live tissues using Nomarski optics, and verified their identity by staining for c-Kit. ICC were injected intracellularly with the fluorescent dye Lucifer yellow, which crosses gap junctions. In most cases the labelled cells had oval somata with two primary processes. At normal pH (7.3-7.4) only 20.2% (21/104) of the injected ICC were coupled to other ICC. However, at pH 7.8-7.9 coupling incidence increased to 74.5% (35/47, P < 0.0001). The injected cells were coupled to one to 35 other ICC. Octanol blocked coupling in all cases. Apparently, gap junctions interconnect ICC in the human small intestine. Coupling was enhanced by a small increase in pH, suggesting that it may be under physiological control.

BACKGROUND:Familial dysautonomia (FD) is a hereditary disease of the autonomic and sensory nervous system. A prominent manifestation of FD is gastrointestinal dyscoordination, which contributes to the morbidity and mortality in FD.AIM:As the myenteric plexus is an essential factor in gastrointestinal motility control, we compared its morphology in appendices of FD patients and controls.METHODS:Appendices from FD patients (N=19) were obtained during surgery of fundoplication and gastrostomy; normal appendices (N=17) were obtained from patients suspected to suffer from acute appendicitis, in whom, however, the appendix was found to be normal. Specimens were stained histochemically for NADPH diaphorase (NADPH-d) and in a blinded manner examined under a light microscope for seven morphologic parameters: ganglionic density, neuronal density, ganglionic area, number of stained neurons per ganglion, nerve bundle width, ratio between nervous tissue area and total area, and neuronal area.RESULTS:Ganglionic density was 10.13 per mm(2) in controls versus 5.01 per mm(2) in FD (p<0.05). Neuronal density was 70.12 per mm(2) in controls, compared with 22.09 per mm(2) in FD (p<0.01). The other parameters were not different between the two groups.CONCLUSION:Densities of myenteric ganglia and neurons of FD patients were significantly lower than in controls. This deficiency may contribute to the pathogenesis of FD gastroenteropathy.

Background: The clinical profile of breast cancer may vary among different ethnic groups living in the same country and therefore affect the yield of a breast cancer screening program. The present study attempts to better characterize the breast cancer clinical profile of Arab women compared with Jewish women in the greater Jerusalem area with a future aim of establishing a comprehensive and effective screening program for this population.Methods: Retrospective chart review was conducted and the following covariates were correlated with survival: ethnicity, age at diagnosis, and American Joint Committee on Cancer (TNM) stage at diagnosis.Results: A total of 312 women were operated on for breast cancer between 1994 and 1999; 51% were Ashkenazi Jews (AJ), 26% were Sephardic Jews (SJ), 21% were Palestinian Arabs (PA), and 2% patients did not fit into those ethnic groups. The mean age at diagnosis was 51.5 years for the PA group, 53.4 +/- 1.5 for the SJ group, and 55.9 years for the AJ group (P <0.03 PA versus AJ). The tumor size (mean +/- SEM) was 38.8 +/- 3.7 mm, 31.1 +/- 2.4 mm, and 24.5 +/- 1.6 mm for the PA, SJ, and AJ groups, respectively (P = 0.03 for PA versus SJ and P <0.001 for PA versus AJ). Five-year overall survival was 77%, 72%, and 58% for the AJ, SJ, and PA groups, respectively (P = 0.02); and 5-year disease-free survival was 72%, 51%, and 50% for the AJ, SJ, and PA groups, respectively (P = 0.03, AJ versus SJ).Conclusions: Our data demonstrate younger age and larger primary tumor size for the Arab patients compared with the Jewish patients. These findings were associated with lower 5-year survival and disease-free survival of the Arab patients. (C) 2004 Excerpta Medica, Inc. All rights reserved.

Aging is believed to affect the structure and function of the enteric nervous system, but little specific information on this topic is available, particularly in humans. The aim of this study was to investigate the effect of age on the structure of myenteric ganglia in the human colon. We examined myenteric ganglia in colonic specimens obtained from 168 patients aged 10 days to 91 years. Nerves were stained in whole mount preparations using the vital fluorescent dye 4-(4-dimethylaminostyryl)-methylpyridinium iodide (4-Di-2-ASP) and other staining methods. Human myenteric ganglia were classified into three types: normal, those containing empty spaces (‘cavities’) and those containing large nerve fiber bundles. We found a statistically significant increase with age in the proportion of ganglia with cavities. Conversely, there was a decrease with age in the proportion of normal ganglia. The proportion of fiber-containing ganglia did not change with age. These findings indicate that there is an increase with age in the number of abnormally appearing myenteric ganglia in the human colon, which may contribute to the disturbed colonic motility in the aging population.

Introduction: The sporadic nature of terror-induced mass casualty incidents (MCIs) makes preparation difficult. Hypothesis-Knowledge regarding utilization of hospital resources during prior MCIs is important for planning the initial 24-hour response to subsequent MCIs.

Still debated are the appropriate techniques for the repair of abdominal wall defects and the methods used to measure their strength. Although tension has been used in many studies to test wound strength, bursting pressure reflects more accurately the pathophysiology of wound dehiscence. The aim of the current study was to evaluate three different techniques for closure of abdominal wall defects using a new and more accurate device for bursting pressure measurements. Full thickness abdominal wall defects measuring 2 cm(2) were created in 43 anesthetized rats randomly assigned to three groups: simple primary closure (n = 15), Mayo repair (n = 14), and primary closure reinforced with a mesh (n = 14). Thirty days after surgery, the rats were sacrificed. The abdominal wall was fully excised and placed over a bursting chamber made of a metal cylinder connected to a carbon dioxide source with a control valve and a manometer. Gas was gradually released while the pressure was recorded until bursting occurred. Disruption of all closures occurred at the point where the suture itself penetrated the tissue. The average bursting pressure was 1383 +/- 299 mm Hg for the primary closure group, 1200 +/- 409 mm Hg for the mesh reinforcement group, and 1607 +/- 337 mm Hg for the imbrication repair (Mayo) group (P < 0.03). The data suggests an advantage for the Mayo repair over the other two repairs. The bursting chamber tested is a new and more reliable method to study techniques and conditions influencing the strength of abdominal wall closure.

Despite the widespread use of sentinel lymph node biopsy (SLNBx) in the surgical management of breast cancer patients, several areas remain controversial. The following controversies are reviewed: Learning curves and validation studies. There clearly is a learning curve, and a completion ALND should be done until adequate proficiency is exhibited, both in terms of identification and false-negative rates. Location of injection. Intradermal injection offers superior identification rates compared with peritumoral injection, with comparable false-negative rates. Subareolar injection is as accurate as peritumoral injection. The value of scintigraphy. Routine scintigraphy does not enhance identification or false-negative rates. Mapping agents. Blue dye and radioactive tracer combined to provide a higher identification rate than either used alone. SLNBx in DCIS. In patients with a high risk of microinvasion, such as large tumors, a mass or high-grade DCIS-SLNBx is justified. SLNBx following neoadjuvant chemotherapy. Although there is evidence that SLNBx after neoadjuvant chemotherapy may be accurate, these data should be applied cautiously. Implications of non axillary SLN, especially internal mammary nodes. Data do not support routine resection of internal mammary sentinel lymph nodes outside a clinical trial. Implications of micrometastases in the sentinel lymph node seen only on immunohistochemistry. Since the significance of such metastases is unclear, decisions regarding treatment of these patients should be individualized. The value of completion axillary lymph node dissection. Is being addressed in clinical trials. Until those studies mature, completion ALND should be performed for patients with SLN metastases, but may be abandoned for patients with a negative SLN.

Evidence suggests that branched chain amino acids (BCAAs) are beneficial in treating human disease. It is unknown, however, what impact BCAAs have on outcomes in acute myocardial infarction (MI). This study was performed to test the hypothesis that the specific BCAA leucine mitigates cardiac injury and improves survival post-MI.11–12 week old male C57BL/6 mice were subjected to experimental MI or sham procedure, and provided regular chow (RC; 1.5% leucine) or a high leucine diet (HLD; 5% leucine), and followed for 3½ or 28 days. All mice were studied by echocardiography and cardiac catheterization, and all hearts were collected for histologic measurements of hypertrophy, fibrosis and apoptosis. Inflammation, hypertrophic gene expression, signal transduction, and glucose, palmitate and leucine metabolism were also measured in 3½ day hearts.Except for increased leucine and decreased glucose oxidation, an HLD had no effect on measured outcomes in sham mice. With MI, cardiac structure, function, and survival were significantly improved with an HLD. At 3½ days post-MI, an HLD increased cardiac hypertrophic signaling and decreased inflammation. Cardiac leucine oxidation was decreased in RC mice post-MI, but significantly increased with an HLD. These changes in metabolism were accompanied by a significant increase in cardiac ATP content in the HLD group. Finally, at both 3½ and 28 days post-MI, an HLD increased compensatory hypertrophy, and attenuated cardiac fibrosis and apoptosis.An HLD increases compensatory hypertrophy, attenuates fibrosis and apoptosis, and positively modulates oxidative metabolism to improve cardiac structure, function, and survival post-MI.

We present a series of 27 consecutive unselected patients who underwent 29 retroperitoneoscopic lumbar sympathectomies. There were 21 male patients and six female patients, with a mean age of 45 years (RANGE, 21 to 28 years). Twenty-two patients had ischemia of the lower limb, and five patients had severe reflex sympathetic dystrophy. The retroperitoneal space was developed with a balloon trocar inserted through a small incision in the flank. Additional trocars used for endoscopic instruments. The sympathetic chain from the ganglia second lumbar vertebrae to the fourth lumbar vertebrae was resected. The procedure was successfully accomplished in all the patients without any operative or postoperative complications. The mean operative time Was 136 minutes, and the mean hospital stay was 1.4 days. All the patients had significant improvement of pain or dystrophic changes. Retroperitoneoscopic lumbar sympathectomy successfully combines the advantages of minimally invasive surgery with the effectiveness of the open procedure.

Background: The ultimate therapy for acute cholecystitis is cholecystectomy. However, in critically ill elderly patients the mortality of emergency cholecystectomy may reach up to 30%. Open cholecystostomy performed under local anesthesia was considered to be the procedure of choice for treatment of acute cholecystitis in high-risk patients. In recent years, ultrasound- or computed tomography (CT)-guided percutaneous transhepatic cholecystostomy (PTHC) replaced open cholecystostomy for the treatment of acute cholecystitis in critically ill patients.Methods: The aim of the present study was to evaluate the results of a 5-year protocol using PTHC followed by delayed laparoscopic cholecystectomy for the treatment of acute cholecystitis in critically ill patients. We reviewed the charts of 55 patients who under-went PTHC at the Hadassah University Hospital Mount Seopus during the years 1994 to 1999.Results: The main indications for PTHC among this group of severely sick and high-risk patients, was biliary sepsis and septic shock, in 23 patients (42%) and severe comorbidities in 32 patients (58%). The median age was 74 (32 to 98) years, 33 were female and 22 male. Successful biliary, drainage by PTHC was achieved in 54 of 55 (98% of the patients. The majority of the patients (31 of 55) were drained transhepaticlly under CT guidance. The rest, (24 of 55) were drained using ultrasound guidance followed by cholecystography for verification. Complications included hepatic bleeding that required surgical intervention in 1 patient and dislodgment of the catheter in 9 patients, that was reinserted in 2 patients. Three patients died of multisystem organ failure 12 to 50 days following the procedure, The remaining 52 patients recovered well with a mean hospital stay of 15.5 +/- 11.4 days. Thirty-one patients were able to undergo delayed surgery: 28 underwent laparoscopic cholecystectomy of whom 4 (14%) were converted to open cholecystectomy. This was compared with a 1.9% conversion rate in 1.498 elective laparoscopic cholecystectomies performed at the same time period (P = 0.012). Another 3 patients underwent planned open cholecystectomy, 1 urgent and 2 combined with other abdominal procedures. There was no surgery associated mortality, severe morbidity, or bile duct injury.Conclusions: The use of PTHC in critically ill patients with acute cholecystitis is both late and effective. (C) 2002 Excerpta Medica, Inc. All rights reserved.

INTRODUCTION:Sentinel lymph node biopsy (SLNB) has been recently proven to be an accurate staging method for breast cancer, replacing axillary lymph node dissection (ALND) in selected cases. We present our initial experience and the process of introduction and implementation of SLNB in a University Hospital setting.MATERIAL AND METHODS:46 SLNB were performed in 42 consecutive female patients with invasive breast cancer. Treatment included 0.4mCi-2mCi of Tc-99m rhenium colloid injected either 2 hours before surgery (0.4 mCi) or the night before surgery (2 mCi). Four milliliters of Patent Blue V were injected peritumoral 10 minutes prior to skin incision in all patients. Following SLNB all women underwent subsequent ALND. Sentinel nodes were processed both with multiple (10-15) H&E sections and immunohistochemistry with cytokeratin antibodies stain.RESULTS:Blue dye, isotope or the combination of both identified 43/46 (93%) of the sentinel lymph nodes. ALND was performed only unilaterally in 4 patients with bilateral breast cancer bringing the total evaluable SLNB to 39. In the 39 patients in whom the sentinel node was successfully identified and underwent ALND, the SLNB was true positive (TP) in 17/39 (44%) true negative (TN) in 20/39 (51%) and false negative in 2/39 [(5%), both T2 lesions] with overall accuracy of 95%. In the last 10 cases all sentinel nodes were successfully identified with 70% TP and 30% TN.CONCLUSIONS:Experience with at least 30-40 consecutive cases for safe implementation of SLNB in clinical practice. Specific training and dedication is required for the entire team involved, including surgeons, nuclear medicine physicians and technicians and pathologists.

The high prevalence of protein-energy malnutrition is a critical issue for patients with end stage renal disease (ESRD) on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Levels of plasma and intracellular amino acids are significant indicators of protein metabolism and nutritional status assessment. We measured plasma FAAs in patients on maintenance dialysis and to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction.Fifty-five patients with ESRD were investigated, 25 on HD (male : female = 14 : 11; 48–67 y) and 30 on CAPD (male : female = 17 : 13; 45–64 y). The subjects had been on dialysis for an average of 13 months (range, 9 to 22 months). Their plasma FAAs (including their intermediate metabolites) were measured by ion exchange chromatography before and after HD or during CAPD and were compared with data obtained from 20 age- and sex-matched healthy controls.The total plasma FAA levels (urea and free ammonia, NH3 were excluded) in pre-HD samples (3911 ± 709 μmol/l) was significantly higher than in the other groups (2570 ± 378 in control, 3210 ± 640 in post-HD, and 3468 ± 271 in CAPD samples). The mean plasma FAA concentrations differed significantly between pre-HD and controls and between pre-HD and CAPD samples (p < 0.05). No significant differences were found among the other group comparisons. Comparing individual FAA concentrations, only citrulline differed significantly among all groups (p < 0.05), whereas serine, glutamine, β-alanine, β-aminoisobutyric acid, and γ-aminobutyric acid were not different. Concentrations of some FAAs involved in the urea cycle, e.g., arginine, aspartic acid, citrulline, and ornithines, and solutes urea and NH3, were significantly increased. Ratios of tyrosine / phenylalanine and valine / glycine ratios were markedly reduced in all patients on dialysis compared with controls.FAAs either from dietary uptake or protein catabolism are substantially retained in the plasma of patients with ESRD, possibly producing higher levels of the waste products (urea and NH3) through the urea cycle and ammonia metabolism in liver. Maintenance dialysis can effectively eliminate excess FAAs in plasma, as there was a 17.9% reduction post-HD. The abnormalities in FAA metabolism found in patients with ESRD necessitate careful consideration of dialysis and dietary measures.

The aim of this study was to determine the contribution of intestinal motility and cecal bacterial overgrowth to liquid diet-induced bacterial translocation (BT). Three different commercially available liquid diets were offered to mice for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were examined as well as cecal bacterial counts and populations, small bowel length and weight, and histopathologic changes in the ileal and jejunal mucosa. In addition, the effect of the various diets on intestinal motility was measured by the transit index of a charcoal mixture introduced into the stomach. The incidence of BT to the mesenteric lymph nodes was significantly and similarly increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%) compared with chow-fed controls (0%). Compared with chow-fed controls, all three liquid diets were associated with the development of cecal bacterial overgrowth (p < .01). There were no significant changes in the transit index for the three liquid diet groups compared with the chow-fed controls. BT to the MLN was induced by all three liquid diets tested, casting some doubts as to their role in preventing BT in clinical use. BT was associated with a statistically significant increase in cecal bacterial count but was not associated with gut motility changes in this model. In fact, no significant changes in intestinal motility were noted in all groups tested.