Radionuclide Counts Research Articles

Preventing Blind Thyroid Lobectomy in Patients with Intrathyroidal Hyperfunctioning Parathyroid Glands with Radioguided Enucleation

Aim: Hyperfunctioning intrathyroidal parathyroid glands are rare and often result in thyroid lobectomy. This study examines the utility of radioguided surgery to guide enucleation of intrathyroidal parathyroids. Methods: Between December 2002 and March 2018, 2291 patients underwent parathyroidectomy by one surgeon for primary hyperparathyroidism. A total of 74 (3%) patients had an ectopic intrathyroidal parathyroid gland and underwent radioguided. Results: All of intrathyroidal parathyroid glands were localized with the gamma probe. In vivo radionuclide counts were above 120% of the background in all but three patients. All intrathyroidal parathyroids were enucleated with the guidance of the gamma probe. Conclusion: Radioguided surgery is useful for intraoperative identification of hyperfunctioning, intrathyroidal parathyroid glands. This technique allows for enucleation of the abnormal parathyroid gland, avoiding thyroid lobectomy and preserving healthy thyroid parenchyma.

Prevalence of Thymic Parathyroids in Primary Hyperparathyroidism During Radioguided Parathyroidectomy.

Background:Radioguided surgery has been an effective tool for identifying hyperfunctioning parathyroid glands during routine parathyroidectomy for hyperparathyroidism. The purpose of this study was to examine the role of radioguided surgery for the identification of intrathymic parathyroid glands.Material and Methods:Between March 2001 and February 2018, 2291 patients underwent parathyroidectomy by 1 surgeon for primary hyperparathyroidism. Of these patients, 158 (7%) were identified to have an ectopic intrathymic parathyroid gland. All patients underwent radioguided parathyroidectomy. Ex vivo radionuclide counts were used to confirm parathyroid excision with specimen radioactivity of >20% of the background level.Results:The mean age was 56 ± 1 years with 74% of the patients being female. Preoperatively, 122 patients underwent sestamibi scan, which correctly identified the affected gland 61% of the time. Mean background radionuclide count was 208 ± 7, mean ex vivo radionuclide count was 127 ± 9, with ex vivo counts of removed glands >20% in all patients. All ectopic parathyroid glands were successfully identified using gamma probe. Ex vivo counts found to be significantly higher in patients with adenomas. Patients with parathyroid adenomas also were older in age and had higher preoperative calcium levels. While 10% of patients with primary hyperparathyroidism have hyperplasia, 42% of patients with thymic parathyroids had hyperplasia.Conclusions:Radioguided parathyroidectomy is useful in detecting ectopic parathyroid glands in the thymus. Patients with hyperplasia disproportionately have clinically significant thymic parathyroid glands.

Scintigraphic evaluation of abomasal emptying rate in neonatal suckling lambs.

Iranian fat tailed Ghezel lambs, 7-10 days of age, were fasted at least 12 h and then fed with 1 mCi of 99m Tc-DTPA added to 150 cc fresh ewe milk. Scintigraphic images were obtained in the standing position using a parallel hole, low-energy, triple head gamma camera. Images were stored digitally for 90 min and were analyzed using a nuclear medicine software program. The number of radionuclide counts from all three views during scintigraphic evaluations showed a time-dependent decrease in the number of radionuclide counts from the laterals (P<0.01) and the ventral view (P<0.001) of the abomasum. There was no significant difference in the number of radionuclide counts from all three views during scintigraphic evaluations. 51.70 ± 3.54 percent of the abomasum content was emptied after 90 min. Evaluating the ROI showed that half emptying time (T1/2) was 67.13 ± 8.64 min. This study was showed that nuclear scintigraphy can be used to evaluate the abomasal emptying rate in suckling lambs.

Radioguided parathyroidectomy effective in pediatric patients

BackgroundRadioguided parathyroidectomy (RGP) has been shown to be effective in adult patients with hyperparathyroidism (HPT), but the utility of RGP in pediatric patients has not been systematically examined. It is not known if adult criteria for radioactive counts can accurately detect hyperfunctioning parathyroid glands in pediatric patients. The purpose of our study was to determine the utility of RGP in children with primary HPT. Materials and methodsA retrospective review of our prospectively maintained single-institution database for patients who underwent a RGP for primary HPT identified 1694 adult and 19 pediatric patients aged 19 y or younger. From the adult population, we selected a control group matched three to one for gland weight and gender and compared pre- and postoperative laboratory values, surgical findings, pathology, and radioguidance values between the control and the pediatric groups. ResultsExcised glands from pediatric patients were smaller than those in the total adult population (437 ± 60 mg versus 718 ± 31 mg, P = 0.0004). When controlled for gland weight, ex vivo counts as a percentage of background were lower in the pediatric group (51% ± 5% versus 91% ± 11%, P = 0.04). However, ex vivo radionuclide counts >20% of the background were found in 100% of pediatric patients and 95% of the adult-matched control group. ConclusionsAll pediatric patients met the adult detection criteria for parathyroid tissue removal when a RGP was performed, and 100% cure was achieved. We conclude that RGP is a useful treatment option for pediatric patients with primary HPT.

Radionuclide and Angiographic Assessment of Pulmonary Perfusion After Fontan Procedure: Comparative Interim Outcomes

Right-side heart function is essentially externalized during extracardiac total cavopulmonary connection. The Fontan procedure has a certain impact on pulmonary hemoperfusion and may explain various postsurgical complications. In this study, alterations of pulmonary perfusion in patients undergoing the Fontan procedure were analyzed at the 5-year postoperative mark by radionuclide imaging and angiocardiography, and results of both methods were compared. For 43 post-Fontan patients, perfusion ratios of each lung segment were calculated based on radionuclide imaging data. The pulmonary vascular resistance and pulmonary artery index of each patient were also calculated from right angiocardiographic measurements. The radionuclide count and advantage perfusion ratio of right lung at follow-up did not differ significantly from early postoperative values (t=0.38, p>0.05; t=1.12, p>0.05), and superior/inferior vena cava perfusion ratios were stable (t=0.88, p>0.05; t=0.74, p>0.05). The superior/inferior segment perfusion ratio of the whole lung declined significantly (t=2.54, p<0.05), while that of the dorsal lung segment rose significantly (t=2.16, p<0.05). Compared with early postoperative status, the pulmonary arterial index of patients at follow-up were significantly increased (t=2.41, p<0.05), while small pulmonary vascular resistances declined significantly (t=2.08, p<0.05; t=2.69, p<0.05), and arterial oxygen saturation levels were unaltered (t=1.12, p>0.05). The early angiographic and radionuclide perfusion studies of 5 patients did not match. After the Fontan procedure, hypostatic redistribution of pulmonary blood flow is characteristic. The weak pulse of blood, in the absence of ventricular ejection, can promote pulmonary vascular changes, but at later (intermediate) follow-up, the decline in vascular resistance that results carries no benefit in terms of blood perfusion or oxygenation. Microcirculatory arteriovenous shunting is the likely cause. In this study of functional pulmonary hemoperfusion, radionuclide imaging was deemed superior to angiocardiography.

Spectral measurements of imaging plate backgrounds, alpha-particles and beta-particles

Background radiation and radioactive sources have been measured with laser-scanned phosphor imaging plates using an image processing method that produces spectra. This enables distinction between ambient background radiation, alpha and beta radionuclides and provides a means for quantitation. The background counts span a broad spectral continuum, whereas counts resulting from alpha and beta activity are restricted to certain regions within the background continuum spectrum. The alpha-counting spectral region has a background count rate of <0.01 counts mm −2 h −1. The beta-counting region has a count rate of <1 count mm −2 h −1. One region of the background spectrum is attributed to heavy ions from cosmic rays and has a count rate of <1 count cm −2 day −1. With regard to imaging spectrometry, beta-particles from 3H ( E max=0.0186 MeV) could be distinguished from higher energy beta-particles such as those from 14C ( E max=0.157 MeV) and 40K ( E max=1.33 MeV). Beta-particles can be distinguished from alpha-particles, and radionuclide counts can be distinguished from the background. The spectral characterization of the background, alpha-particles and beta-particles is expected to support applications in cosmic ray, heavy ion, radionuclide and electron studies.

Quantitative analysis of scintigraphic findings in tibial stress fractures in Thoroughbred racehorses

To develop a quantitative method of interpreting tibial scintigrams of Thoroughbred racehorses with tibial stress fractures that may facilitate diagnosis of fractures and to provide prognostic information regarding future performance of affected horses. 35 Thoroughbred racehorses. Static bone-phase scintigrams of tibial stress fractures were quantitatively analyzed by use of ratios of the mean radionuclide counts per pixel in a region of interest (ROI) drawn around the area of increased uptake of radiopharmaceutical to mean counts per pixel in a second ROI drawn around an apparently normal area of the tibial diaphysis. In horses with unilateral fractures, ratios for the contralateral tibia were determined by use of 2 ROIs drawn at the same positions as the ROIs in the fractured tibia. Ratios were compared between fractured versus apparently normal tibias, between horses that returned to racing versus those that did not, and among horses with various grades of lameness. The association between ratios for fractured tibias and intervals between diagnosis and return to racing was also assessed. Mean ratio of ROIs in apparently normal tibias was 1.35 (95% confidence interval [CI], 1.21 to 1.50); that in tibias with stress fractures was 3.55 (95% CI, 2.50 to 4.60). These ratios were significantly different. None of the associations between ratios for fractured tibias and grades of lameness or performance outcomes were significant. Tibial stress fracture scintigrams can be quantitatively analyzed. A prospective study with a controlled rehabilitation period is necessary to evaluate the possible applications of this method.

Assessment of Differential Pulmonary Blood Flow Using Perfusion Magnetic Resonance Imaging

We sought to assess the agreement between lung perfusion ratios calculated from pulmonary perfusion magnetic resonance imaging (MRI) and those calculated from radionuclide (RN) perfusion scintigraphy. A retrospective analysis of MR and RN perfusion scans was conducted in 23 patients (mean age, 60 +/- 14 years) with different lung diseases (lung cancer = 15, chronic obstructive pulmonary disease = 4, cystic fibrosis = 2, and mesothelioma = 2). Pulmonary perfusion was assessed by a time-resolved contrast-enhanced 3D gradient-echo pulse sequence using parallel imaging and view sharing (TR = 1.9 milliseconds; TE = 0.8 milliseconds; parallel imaging acceleration factor = 2; partition thickness = 4 mm; matrix = 256 x 96; in-plane spatial resolution = 1.87 x 3.75 mm; scan time for each 3D dataset = 1.5 seconds), using gadolinium-based contrast agents (injection flow rate = 5 mL/s, dose = 0.1 mmol/kg of body weight). The peak concentration (PC) of the contrast agent bolus, the pulmonary blood flow (PBF), and blood volume (PBV) were computed from the signal-time curves of the lung. Left-to-right ratios of pulmonary perfusion were calculated from the MR parameters and RN counts. The agreement between these ratios was assessed for side prevalence (sign test) and quantitatively (Deming-regression). MR and RN ratios agreed on side prevalence in 21 patients (91%) with PC, in 20 (87%) with PBF, and in 17 (74%) with PBV. The MR estimations of left-to-right perfusion ratios correlated significantly with those of RN perfusion scans (P < 0.01). The correlation was higher using PC (r = 0.67) and PBF (r = 0.66) than using PBV (r = 0.50). The MR ratios computed from PBF showed the highest accuracy, followed by those from PC and PBV. Independently from the MR parameter used, in some patients the quantitative difference between the MR and RN ratios was not negligible. Pulmonary perfusion MRI can be used to assess the differential blood flow of the lung. Further studies in a larger group of patients are required to fully confirm the clinical suitability of this imaging method.

Radioguided Parathyroidectomy Is Equally Effective for Both Adenomatous and Hyperplastic Glands

To determine the utility of radioguided parathyroidectomy for patients with hyperparathyroidism, we studied the properties of 180 resected, hyperfunctioning parathyroid glands. Radioguided resection of hyperfunctioning parathyroid glands has been shown to be technically feasible in patients with parathyroid adenomas. Radioguided excision may obviate the need for intraoperative frozen section because excised parathyroid adenomas uniformly have radionuclide ex vivo counts >20% of background. The feasibility and applicability of radioguided techniques for patients with parathyroid hyperplasia are unclear. Between March 2001 and September 2002, 102 patients underwent neck exploration for primary (n = 77) and secondary/tertiary (n = 25) hyperparathyroidism. All patients received an injection of 10 mCi of Tc-99m sestamibi the day of surgery. Using a gamma probe, intraoperative scanning was performed, looking for in vivo radionuclide counts > background to localize abnormal parathyroid glands. After excision, radionuclide counts of each ex vivo parathyroid gland were determined and expressed as a percentage of background counts.RESULTS Although patients with single adenomas had higher mean background radionuclide counts, the average in vivo counts of all enlarged glands were higher than background. Notably, in vivo counts did not differ between adenomatous and hyperplastic glands, suggesting equal sensitivity for intraoperative gamma detection. Ectopically located glands were identified in 22 cases and all were accurately localized using the gamma probe. Postresection, mean ex vivo radionuclide counts were highest in the single parathyroid adenomas and lowest in hyperplastic glands. Importantly, in all hyperplastic glands, the ex vivo counts were >20%. In patients with hyperparathyroidism, radioguided surgery is a sensitive adjunct for the intraoperative localization of both adenomatous and hyperplastic glands. In this series, all 180 enlarged parathyroids were located with the gamma probe. We have also shown that the ">20% rule" for ex vivo counts not only applies to parathyroid adenomas but also to hyperplastic glands. Therefore, radioguided resection is equally effective and informative for both adenomatous and hyperplastic glands.

Granulocyte colony-stimulating factor enhances killing of translocated bacteria but does not affect barrier function in a burn mouse model.

Granulocyte colony-stimulating factor drives the proliferation and differentiation of granulocytes and also enhances their bactericidal and phagocytic activity. The present study was undertaken to investigate the effects of murine granulocyte colony-stimulating factor (mG-CSF) on bacterial translocation and gut-derived sepsis after burn injury. In experiment I, BALB/c mice were randomized into two treatment groups, which received 1 microgram/mouse of mG-CSF subcutaneously for either 1 (n = 16) or 2 days (n = 15). Controls received saline (n = 16). After treatment, all animals were gavaged with 10(10) 111In Escherichia coli and then given a 20% burn. All groups were observed 10 days for survival. In experiment II, three additional groups (n = 6/group) received the same treatment as above but were killed 4 hours after burn injury. Mesenteric lymph nodes, liver, and spleen were harvested to measure radionuclide counts (disintegrations per minute per gram of tissue) and colony-forming units (CFU/g of tissue) and to calculate the percentage of viable bacteria (% alive). Experiment I: 10-day survival was significantly higher in groups treated with mG-CSF for 1 or 2 days (75% and 73%, respectively), compared with controls (43.7%), p = 0.001. Experiment II: no differences in translocation to the tissues were observed among any of the groups, according to radionuclide counts. However, quantitative colony counts and calculated percentage of viable bacteria showed that killing was enhanced in the mesenteric lymph nodes and liver of animals that received mG-CSF, but this was significant only in the liver for both treatment times (1 day, p = 0.021 and 2 day, p = 0.009). These data suggest that treatment with mG-CSF does not improve gut barrier function, but does enhance the host's ability to kill translocated organisms and improve survival in a gut-derived sepsis model.

Polymeric Surface Modifications of Tantalum Stents

To compare two kinds of polymer-coated tantalum stents with bare tantalum stents (control) to determine if the coatings can improve thromboresistance. Twenty-seven Fontaine-Dake stents were balloon expanded in three 8-mm x 80-cm polytetrafluoroethylene (PTFE) grafts; 9 stents were bare tantalum (T); 9 were coated with polyetherurethane (PL); and 9 were coated with parylene (PA). There were 9 stents placed in each graft as follows: 3 tantalum, 3 polyetherurethane, and 3 parylene. In swine whose platelets had been radiolabeled with indium 111, the ends of each stented graft were connected to 14F femoral and venous sheaths to create an ex vivo fistula. Each graft was exposed to blood for 30, 60, and 120 minutes. At the end of each test period, the stented grafts were disconnected from the sheaths, flushed with saline until clear, and then flushed with formalin. The stents were removed from the grafts, and a radionuclide well counter recorded radionuclide counts from each stent type at each period of blood contact. These values were converted to platelet density per 1000 microns 2. Stents were then photographed and scanned with electron microscopy (EM) for qualitative analysis. Possible significant differences in platelet adhesion with the three types of stents (both between stent groups and within stent groups) were examined using a two-tailed Student's t-test. There were significantly fewer platelets adsorbed on PA versus T at all time periods (p < 0.005); on PL versus T at 60 and 120 minutes (p < 0.005); and on PA versus PL at 30 and 120 minutes (p < 0.0005). There was no significant difference in platelet density within each stent group (p = 0.1). Mean platelet density (number of platelets per 1000 microns 2 +/- SD) was as follows: at 30 minutes: T = 1891 +/- 965; PL = 373 +/- 193; and PA = 27 +/- 3; at 60 minutes: T = 6226 +/- 1621; PL = 1573 +/- 793; and PA = 1185 +/- 710; at 120 minutes: T = 5307 +/- 591; PL = 3164 +/- 318; and PA = 180 +/- 100. Gross inspection of the 120-minute groups demonstrated focal areas of thrombus on T, less on PL, and none on PA. Scanning EM demonstrated extensive platelet accumulation covering T at all time periods, less on PL, and even less on PA.

High protein diets are associated with increased bacterial translocation in septic guinea pigs

During sepsis, body protein stores are decreased due to an increase in protein catabolism. The utilization of nutritional support with high-protein diets has been used as a solution to the problem of sepsis-induced protein loss. Work from our laboratory, however, has shown that diets low in protein (5% of total calories) improve survival in septic animals as compared to high protein (20%) diets. The present study investigated the relationship between low-protein diets and improved survival by determining whether septic animals receiving high-protein diets have increased bacterial translocation. Sepsis was induced in guinea pigs by the implantation of an osmotic minipump into the peritoneal cavity containing an equal mixture of Escherichia coli (10 8) and Staphylococcus aureus (10 8) or saline. On Day 3 postlaparotomy, the animals were randomized to one of four groups. The groups consisted of septic and nonseptic animals that received a diet with 5 or 20% of total calories as protein. Following 4 days of diet all animals received an instillation of 14C labeled E. coli (10 10). Four hours later the animals were sacrificed and blood, mesenteric lymph nodes, spleen, lungs, and liver were removed for determination of radionuclide counts. Results indicated that the septic animals that received the high protein diet had more bacterial translocation, as indexed by higher radionuclide counts in the MLN, liver, lung and blood. These findings suggest that a low protein, enterally fed diet may improve survival in septic patients by decreasing the incidence of bacterial translocation.

IN VIVO EVALUATION OF TIMING, DEGREE, AND DISTRIBUTION OF BACTERIAL TRANSLOCATION FOLLOWING EXPERIMENTAL SMALL BOWEL TRANSPLANTATION

These studies were designed to evaluate the correlation between morphologic and functional changes after heterotopic auxiliary small bowel isograft with systemic venous drainage and two ostomies in 20 Lewis rats. Morphologic damage of the graft was scored by full-thickness biopsies before surgery and 1, 3, 5, and 7 days after transplant. Functional evaluation of the graft was done, at the same time points, by urinary excretion of lactulose and mannitol injected in the proximal ostomy. The intestinal permeability was also studied by injecting Escherichia coli labeled with indium-111 oxine in the proximal ostomy. Translocation of radiolabeled bacteria was quantitated in extraintestinal tissues by radionuclide counts and number of viable organisms and in vivo by scintigraphic imaging. One day after transplant, significant graft damage (score 17.2 +/- 4.2) was observed when compared with the pretransplant value (7.3 +/- 2.6). The degree of tissue injury was similar on days 3 (15.8 +/- 3.5) and 5 (16.1 +/- 3.9) after transplant and remained high on day 7 (11.8 +/- 2.8). The lactulose to mannitol ratio showed a significantly increased permeability on day 1 (17.5) versus pretransplant values (2.6), remained high on day 3 (8.6), and returned to normal values on day 5 (2.8). Translocation of bacteria to distant organs, as measured by both radionuclide counts and number of viable organisms, was strikingly enhanced on day 1 after transplantation, compared with control animals, but returned to the pretransplant value on day 3. A good qualitative and quantitative correlation was observed between radionuclide counts in the extraintestinal organs and in vivo images obtained by scintigraphic scanning. In conclusion, in this model, timing and degree of bacterial translocation do not seem to correlate well, with the exception of the acute post-transplantation phase, with morphologic and permeability changes of the graft. Evaluation of translocation by scintigraphic imaging appears a suitable approach to study in vivo the kinetics and distribution of this process.

Translocation and survival of Bacteroides fragilis after thermal injury.

B. fragilis and E. coli were labeled with tritiated (3H) thymidine, and 10(10) of each were given separately by gavage in Balb/c mice immediately before a 20% burn injury was inflicted. Control groups received gavage with 3H-B. fragilis or 3H-E. coli without burn. Four hours after burn or gavage was administered, the animals were killed, and the radionuclide and colony counts were determined in the mesenteric lymph nodes, liver, and spleen. Additional groups of mice receiving gavage (B. fragilis or E. coli) and burn were observed for 10 days to study survival. The results showed that 3H-B. fragilis translocated to a greater extent than 3H-E. coli but that fewer B. fragilis than E. coli survived in tissues. Survival was 86% for animals challenged with B. fragilis versus 53% for animals challenged with E. coli. It is concluded that in this model B. fragilis translocates extensively after burn injury and that survival is closely related to the destruction of translocated bacteria.

Impact of enteral nutrition on intestinal bacterial translocation and mortality in burned mice

The aim of these experiments was to study the effect of early enteral nutrition with either standard or enriched (arginine, n-3 fatty acids, RNA) enteral formulas on translocation of bacteria from the gut and acute mortality rate following thermal injury. In the first experiment 60 Balb c mice were gavaged with 10 10 Escherichia coli and received a 20% burn injury. In 40 mice enteral nutrition (20 standard, 20 enriched) was started immediately after injury and stopped 36 h later. In the control group (n = 20) aliquotes of Ringer's solution was administered intragastrically. Mortality rate was observed for 10 days post-injury. In the second experiment 60 Balb c mice were gavaged with 10 10 E. coli labelled with biotin 111 Indium and then burned. In 40 mice enteral nutrition (20 standard, 20 enriched) was started immediately after burn. The control group (n = 20) received aliquotes of Ringer's solution. 4 h after injury all animals were sacrificed and liver, lungs, kidneys, spleen and systemic blood were harvested, and radionuclide counts were measured. No animal died after day 3 post-burn. The mortality rate was significantly lower at day 1 in the groups infused with both enteral solutions (15%) compared to controls (30%; p = 0.05). At day 3 the animals fed with the enriched diets showed a lower mortality (5%) versus the standard and control groups (10%). Bacterial translocation to the liver and lungs was significantly higher in Ringer's group than in both enterally fed groups. Early post-burn enteral nutrition reduces both translocation and acute mortality. Supplementation of the diets with specific nutrients appears to exert additional advantages on outcome.

Role of early enteral feeding and acute starvation on postburn bacterial translocation and host defense

To investigate the effect of: a) starvation during the preburn period and b) immediate postburn enteral nutrition on the permeability of the gut to microorganisms and the ability of the host to kill translocated bacteria. Prospective, randomized, experimental trials. Laboratory. Balb/c mice and Hartley guinea pigs. In the first experiment, mice were starved for 0, 6, 12, 18, or 24 hrs before receiving gavage with 10(10) 14C-labeled Escherichia coli and a 20% burn injury. In the second experiment, guinea pigs received a 40% burn injury and were randomized to receive a complete enteral diet (175 kcal/kg/day) or infusion of an equal volume of lactated Ringer's solution via a previously placed gastrostomy for 6, 24, or 48 hrs. After each feeding period, 10(10) 14C Escherichia coli were infused intragastrically. In both experiments, the animals were killed 4 hrs after gavage, and mesenteric lymph nodes, spleen, liver, lungs, peritoneal fluid, and blood were harvested aseptically. For each tissue or fluid, the number of viable E. coli and radionuclide counts of the 14C E. coli were measured and the percentage of translocated bacteria that remained alive was calculated. In mice, 18 and 24 hrs of preburn starvation increased translocation only to the mesenteric lymph nodes, but it also enhanced bacterial killing in all tested tissues. Guinea pigs that were fed enterally for 6, 24, and 48 hrs postburn had significantly lower bacterial translocation in all tissues compared with animals infused with lactated Ringer's solution. Additionally, enhanced killing of translocating organisms was observed after 24 and 48 hrs of feeding. Starvation preburn has different consequences than starvation postburn on translocation and bacterial killing. Postburn enteral nutrition decreases the load of viable bacteria in the tissues via a double mechanism: an initial decreased translocation and a subsequent improved ability to kill bacteria that do translocate.

The primary site of bacterial translocation.

To establish the primary anatomic site of bacterial translocation in the intestinal tract. Prospective randomized experimental trials. Laboratory. Hartley guinea pigs. In guinea pigs, 10-cm closed loops of upper jejunum, distal ileum, or proximal colon were created. The animals then received intraluminal injections of Escherichia coli labeled with radioactive carbon (14C) before a 50% full-thickness burn was inflicted. Four hours after the burn injury, the animals were killed, and the intestinal loops, mesenteric lymph nodes, spleen, liver, and lung were harvested. Intestinal loops were irrigated and then treated with ethylenedinitroilotetraacetic acid to separate the enterocytes and colonocytes from the lamina propria. Radionuclide counts were determined in the effluents, the enterocytes (or colonocytes), lamina propria, and other organs. Colony-forming units of E coli were also determined in mesenteric lymph nodes, spleen, liver, and lung. No significant differences were noted in the radionuclide counts in the lamina propria and epithelial cell fraction related to the type of loop. In addition, no significant differences were noted in the radionuclide counts in the mesenteric lymph nodes, liver, spleen, and lung related to the type of loop, but more viable bacteria were recovered when bacteria were injected into the jejunal loop. Translocation of bacteria occurred with similar intensity throughout the gut, but more bacteria were killed in the process of translocation across the lower part of the intestinal tract.

The Distribution of Medication along the Spinal Canal after Chronic Intrathecal Administration

Chronic intrathecal drug infusion for the treatment of neurological diseases, such as spasticity and chronic pain, has become an accepted method of therapy in recent years. Concurrent pharmacokinetic studies have shown that the cisternal cerebrospinal fluid (CSF) drug level is considerably lower than the lumbar CSF level during continuous infusion into the lumbar subarachnoid space. One factor that makes analysis of this decline in drug level difficult to quantify is that it is only feasible to sample CSF at the two extremes of the spinal subarachnoid space. Using a radionuclide technique, we have examined the distribution along the spinal canal of a hydrophilic compound, indium-111 diethylenetriamine pentaacetic acid, that was delivered over 72 hours into the lumbar subarachnoid space in five patients with implanted drug pumps. Over a 20-cm distance of the thoracic cord, radionuclide counts decreased gradually so that the indium-111 diethylenetriamine pentaacetic acid concentration surrounding the cord at the T2 vertebral level was 43% of that at the T12 level in four patients. Therefore, it appears that even with a hydrophilic compound, which minimizes spinal cord capillary losses, there is still a considerable reduction of CSF drug concentration along the spinal canal. The clinical implication of this gradual decline in drug level is that for intrathecal infusion of relatively hydrophilic compounds there may not be any advantage in placing the catheter tip at more rostral locations, such as at the midthoracic or cervical cord.

Identification of the blood component responsible for increased susceptibility to gut‐derived infection

It has previously been reported that the transfusion of allogeneic whole blood increases sepsis-related mortality and decreases the ability of the host to kill bacteria that have translocated from the intestinal tract. To determine which blood component contributes to this adverse effect, the impact of the transfusion of white cells (WBCs), red cells (RBCs), and plasma on microbial translocation, bacteria killing, and mortality rate was studied. Blood from C3H/HeJ mice was separated into WBCs, RBCs, and plasma, and these fractions were transfused to Balb/c mice. Controls received sterile saline. Five days after transfusion, all Balb/c mice underwent a 20-percent burn and gavage with 1 x 10(10) Escherichia coli labeled with 14C-glucose. Mortality was observed for 10 days. Four additional groups, receiving the same treatment as above, were sacrificed 4 hours after the burn, and mesenteric lymph nodes, liver, kidney, and blood were harvested aseptically. For each tissue, quantitative colony counts, radionuclide counts, and percentage of translocated bacteria that remained alive were calculated. By radionuclide counts, no difference was observed in the degree of 14C E. coli translocation among the groups. In contrast, the percentage of viable bacteria and the mortality rate were significantly higher in the group receiving allogeneic WBCs than in all other groups (p < 0.05). It is concluded that WBCs are the component in transfused blood that has an adverse effect on host resistance to gut-derived infection.

Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide.

The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow. In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10(10) Escherichia coli and a 20% burn injury. Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor N omega-Nitro-L-arginine (NNA) before gavage and burn. The effect of these diets and NNA on the degree of translocation of 14C-radiolabeled E. coli from the intestine and the ability of the host to kill translocated organisms was also investigated. Mice were fed and received transfusion, gavage, and burn as above. Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn. Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN-76A group and 20% in the chow group (p < 0.02). After gavage and burn, survival was 100% in the arginine-supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01). In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001). Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group. However, there was no difference in translocation to the liver and spleen related to dietary group. Quantitative colony counts and the calculated percentage of remaining viable bacteria showed that the ability to kill translocated organisms was significantly enhanced in animals receiving arginine. Treatment with NNA reversed the beneficial effects of arginine on immune defense. The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway.