Efficacy of early versus delayed spinal cord decompression in neurological recovery after traumatic spinal cord injury: Systematic review and meta-analysis. / Eficacia de la descompresión medular precoz versus tardía en la recuperación neurológica tras lesión medular traumática. Revisión sistemática y metaanálisis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare early (<24h) versus late (>24h) spinal cord decompression on neurological recovery in patients with acute spinal cord injury. METHODS: A systematic review was performed according to the PRISMA protocol to identify studies published up to December 2022. Prospective cohort studies and controlled trials comparing early versus delayed decompression on neurological recovery were included. Variables included number of patients, level of injury, treatment time, ASIA grade, neurological recovery, use of corticosteroids, and complications. For the meta-analysis, the «forest plot¼ graph was developed. The risk of bias of the included studies was assessed using the ROBINS-I22 and Rob223 tools. RESULTS: Six of the seven studies selected for our review were included in the meta-analysis, with a total of 1188 patients (592 patients in the early decompression group and 596 in the delayed decompression group), the mean follow-up was 8 months, in 5 studies used methylprednisolone, the most reported complications were thromboembolic cardiopulmonary events. Five studies showed significant differences in favor of early decompression (risk difference 0.10, 95% confidence interval 0.07-0.14, heterogeneity 46%). The benefit was greatest in cervical and incomplete injuries. CONCLUSION: There is scientific evidence to recommend early decompression in the first 24h after traumatic spinal cord injury, as it improves final neurological recovery, and it should be recommended whenever the patient and hospital conditions allow it to be safely done.

[Translated article] Relation between the volume of injected cement and the vertebral volume in the clinical outcome and in the appearance of leakage after a percutaneous vertebroplasty.

OBJECTIVES: To assess the connection between the volume of injected cement and the vertebral volume measured through a volumetric analysis with a computed tomography (CT scan) in relation to the clinical result and the appearance of a leakage in patients who underwent a percutaneous vertebroplasty after an osteoporotic fracture. MATERIALS AND METHODS: A prospective study of 27 patients (18 female-9 male) with an average age of 69 years old (50-81), and with a one-year follow-up. The study group presented 41 vertebrae with osteoporotic fractures that were treated with a percutaneous vertebroplasty with a bilateral transpedicular approach. The volume of injected cement was registered in each procedure and it was assessed together with the spinal volume measured through a volumetric analysis with CT scans. The percentage of the spinal filler was calculated. The appearance of cement leakage was proved by means of a simple radiography and a postoperative CT scan in all the cases. The leaks were classified according to the location in relation to the vertebral body (posterior, lateral, anterior and in the disc), and the significance (minor: smaller than the largest diameter of the pedicle; moderate: larger than the pedicle but smaller than the height of the vertebra; major: larger than the height of the vertebra). RESULTS: The average vertebra volume was 26.1cm3, the average volume of the injected cement was 2.0cm3 and the percentage of the average filler was 9%. A total of 15 leaks in 41 vertebrae appeared (37%). The leaks were posterior in 2 vertebrae, vascular in 8 and into the disc in 5 vertebrae. They were deemed as minor in 12 cases, moderate in 1 and major in 2 cases. The preoperative assessment of the pain was as it follows: VAS (8) and Oswestry (67%). The cessation of pain was immediate after a year with the following postoperative results: VAS (1.7) and Oswestry (19%). The only complication was the temporary neuritis with a spontaneous resolution. CONCLUSIONS: The injection of small amounts of cement, lower than the ones referred to by literary sources, obtains clinical results similar to the ones obtained by injecting higher amounts and it reduces the number of cement leaks and further complications.

Relation between the volume of injected cement and the vertebral volume in the clinical outcome and in the appearance of leakage after a percutaneous vertebroplasty. / Relación entre el volumen de cemento inyectado y el volumen vertebral en el resultado clínico y en la aparición de fugas tras vertebroplastia percutánea.

OBJECTIVES: To assess the connection between the volume of injected cement and the vertebral volume measured through a volumetric analysis with a computed tomography (CT scan) in relation to the clinical result and the appearance of a leakage in patients who underwent a percutaneous vertebroplasty after an osteoporotic fracture. MATERIALS AND METHODS: A prospective study of 27 patients (18 female-9 male) with an average age of 69 years old (50-81), and with a one-year follow-up. The study group presented 41 vertebrae with osteoporotic fractures that were treated with a percutaneous vertebroplasty with a bilateral transpedicular approach. The volume of injected cement was registered in each procedure and it was assessed together with the spinal volume measured through a volumetric analysis with CT scans. The percentage of the spinal filler was calculated. The appearance of cement leakage was proved by means of a simple radiography and a postoperative CT scan in all the cases. The leaks were classified according to the location in relation to the vertebral body (posterior, lateral, anterior and in the disc), and the significance (minor: smaller than the largest diameter of the pedicle; moderate: larger than the pedicle but smaller than the height of the vertebra; major: larger than the height of the vertebra). RESULTS: The average vertebra volume was 26.1 cc, the average volume of the injected cement was 2.0 cc and the percentage of the average filler was 9%. A total of 15 leaks in 41 vertebrae appeared (37%). The leaks were posterior in 2 vertebrae, vascular in 8 and into the disc in 5 vertebrae. They were deemed as minor in 12 cases, moderate in 1 and major in 2 cases. The preoperative assessment of the pain was as it follows: VAS (8) and Oswestry (67%). The cessation of pain was immediate after a year with the following postoperative results: VAS (1.7) and Oswestry (19%). The only complication was the temporary neuritis with a spontaneous resolution. CONCLUSIONS: The injection of small amounts of cement, lower than the ones referred to by literary sources, obtains clinical results similar to the ones obtained by injecting higher amounts and it reduces the number of cement leaks and further complications.

[The morbidity of the posterior iliac crest bone graft harvesting could be an overestimated fact. Study in patients with open posterolateral lumbar fusion]. / La morbilidad del sitio donante de injerto de cresta ilíaca posterior podría ser un hecho sobreestimado. Estudio en pacientes con fusión lumbar posterolateral abierta.

INTRODUCTION: spinal fusion is used to treat, among other pathologies, the degenerative intervertebral disc disease. Autologous iliac crest bone grafting is the golden standard treatment for increasing the rate of fusion; however, it isn't free of complications. OBJECTIVES: to investigate whether patients who have posterior iliac crest graft harvesting and are blinded to the donor site, can identify from which side the graft was harvested, and whether the intensity of this pain is related to the amount of graft obtained. MATERIAL AND METHODS: prospective, experimental, randomized and comparative, single-blind study. Adult patients who underwent primary instrumented open posterolateral lumbar fusion with autologous iliac crest bone graft between July 2019 and April 2020 were included. Patients were divided into two randomized groups. The amount of graft to be harvested was according to surgical needs. The patients were asked about pain according to the visual analogue scale in the first, third and sixth months after surgery, always requesting that the most painful side be identified. RESULTS: a total of 44 patients (n = 23 right crest, n = 21 left crest) were analyzed. Most patients were unable to identify the side from which the bone graft was harvested, with a statistically significant difference (p-value 0.0001). CONCLUSION: iliac crest bone graft harvesting is an effective and safe procedure that improves the rates of fusion without increasing the patient's morbidity.

INTRODUCCIÓN: la fusión espinal es utilizada para tratar, entre otras patologías, las enfermedades degenerativas discales. El injerto óseo autólogo de cresta ilíaca es el estándar de oro para aumentar las probabilidades de fusión; sin embargo, no está exento de complicaciones. OBJETIVOS: investigar si los pacientes a los que se les recolecta injerto de cresta ilíaca posterior y son cegados al lado del sitio donante, pueden identificar de qué lado se tomó dicho injerto y si la intensidad de este dolor está en relación con la cantidad de injerto obtenido. MATERIAL Y MÉTODOS: trabajo prospectivo, experimental, aleatorizado y comparativo, simple ciego. Se incluyeron pacientes adultos operados entre Julio de 2019 hasta Abril de 2020, a los cuales se les realizó una cirugía primaria de artrodesis lumbar posterolateral abierta instrumentada, con colocación de injerto óseo autólogo de cresta ilíaca. Se dividió a los pacientes en dos grupos aleatorizados. La cantidad de injerto a recolectar fue de acuerdo a las necesidades quirúrgicas. Se interrogó por el dolor según escala visual analógica al primer, tercer y sexto mes de la cirugía, siempre solicitando que se identifique el lado más doloroso. RESULTADOS: se analizaron 44 pacientes (n = 23 cresta derecha, n = 21 cresta izquierda). La mayoría de los pacientes no lograron identificar el lado del cual se obtuvo el injerto óseo, con una diferencia estadística ampliamente significativa (p = 0.0001). CONCLUSIÓN: la obtención de injerto óseo de cresta ilíaca es un procedimiento efectivo y seguro, que mejora las probabilidades de fusión sin aumentar la morbilidad del paciente.

Spinal cord stimulation: beyond pain management.

INTRODUCTION: The gate control theory of pain was the starting point of the development of spinal cord stimulation (SCS). We describe the indications for the treatment in pain management and other uses not related to pain. DEVELOPMENT: There are currently several paradigms for SCS: tonic, burst, and high frequency. The main difference lies in the presence of paraesthesias. SCS is most beneficial for treating neuropathic pain. Patients with failed back surgery syndrome show the best response rates, although a considerable reduction in pain is also observed in patients with complex regional pain syndrome, diabetic neuropathy, radiculopathy, and low back pain without previous surgery. Phantom pain or pain related to cardiovascular or peripheral vascular disease may improve, although there is a lack of robust evidence supporting generalisation of its use. SCS also improves cancer-related pain, although research on this issue is scarce. Non-pain-related indications for SCS are movement disorders, spasticity, and sequelae of spinal cord injury. The main limiting factors for the use of SCS are mechanical complications and the cost of the treatment. CONCLUSION: In its 50-year history, SCS has progressed enormously. The perfection of hardware and software may improve its effectiveness and reduce the rate of complications. Indications for SCS could include other diseases, and its use could be expanded, if the costs of the technology are reduced.

[Application of vancomycin powder on graft. Does the fusion of the rabbits spine is affected?] / Aplicación de vancomicina en polvo sobre el injerto. ¿Afecta la fusión de columna en conejos?

INTRODUCTION: In vitro studies suggest that vancomycin is highly cytotoxic for osteoblasts. However, several clinical studies in vivo have not provided evidence or determined that effect on osteogenesis. The aim of this work was to investigate the effect of topical vancomycin on a lumbar arthrodesis model on New Zealand white rabbits. MATERIAL AND METHODS: Double-blind randomized experimental study. Posterolateral spinal fusion was performed on 30 rabbits, divided into two groups, A: graft/placebo, B: graft/vancomycin. After sacrificing them, the bone callus was evaluated with axial tomography and classified into three groups: no fusion (0), partial/incomplete fusion (1) and fusion (2). The samples were also histologically analyzed. The associations between the presence of fusion (complete/incomplete) and the group tested were estimated using Poisson log-linear models with two covariates. Adherences to histologically obtained responses were studied using contingency tables and 2 tests. The significance level was set equal to 0.05. RESULTS: Treatment with vancomycin has 30% (0.30. CI 95%: 0.12-0.94) less chance compared to the placebo group, of presenting complete fusion. In other words, the vancomycin group has 2.3 times (CI 95%: 1.02-4.91) more likelyhood, compared to placebo, to have incomplete fusion. CONCLUSION: The application of vancomycin powder mixed with graft reduces fusion rates by 30%, but at doses 5 times higher than those routinely used in arthrodesis by the authors medical team.

INTRODUCCIÓN: Estudios in vitro sugieren que la vancomicina es altamente citotóxica para los osteoblastos. No obstante, diversos estudios clínicos in vivo no han aportado evidencias o determinado ese efecto en la osteogénesis. El objetivo del presente trabajo fue investigar el efecto de la vancomicina tópica, en un modelo de artrodesis lumbar sobre conejos blancos neozelandeses. MATERIAL Y MÉTODOS: Estudio experimental randomizado doble ciego. Se realizó fusión espinal posterolateral a 30 conejos, divididos en dos grupos, A: injerto/placebo, B: injerto/vancomicina. Luego de sacrificarlos, se evaluó el callo óseo con tomografía axial, clasificándolos en tres grupos: sin fusión (0), fusión parcial/incompleta (1) y fusión (2). Las muestras también fueron analizadas histológicamente. Las asociaciones entre presencia de fusión (completa/incompleta) y el grupo ensayado fueron estimadas con modelos log-lineales de Poisson con dos covariables. Las adherencias con las respuestas obtenidas histológicamente fueron estudiadas usando tablas de contingencia y test 2. El nivel de significación se fijó igual a 0.05. RESULTADOS: El tratamiento con vancomicina tiene 30% (0.30. IC 95%: 0.12-0.94) menos probabilidad respecto al grupo placebo de presentar fusión completa. En otros términos, el grupo vancomicina tiene 2.3 veces (IC 95%: 1.02-4.91) más probabilidad, respecto del placebo, de tener fusión incompleta. CONCLUSIÓN: La aplicación de vancomicina en polvo mezclada con injerto reduce 30% las tasas de fusión, pero a dosis cinco veces más alta que las usadas rutinariamente en artrodesis por el equipo médico de los autores.

Spinal cord stimulation: Beyond pain management. / Estimulación de la médula espinal: más allá del manejo del dolor.

INTRODUCTION: The gate control theory of pain was the starting point of the development of spinal cord stimulation (SCS). We describe the indications for the treatment in pain management and other uses not related to pain. DEVELOPMENT: There are currently several paradigms for SCS: tonic, burst, and high frequency. The main difference lies in the presence of paraesthesias. SCS is most beneficial for treating neuropathic pain. Patients with failed back surgery syndrome show the best response rates, although a considerable reduction in pain is also observed in patients with complex regional pain syndrome, diabetic neuropathy, radiculopathy, and low back pain without previous surgery. Phantom pain or pain related to cardiovascular or peripheral vascular disease may improve, although there is a lack of robust evidence supporting generalisation of its use. SCS also improves cancer-related pain, although research on this issue is scarce. Non-pain-related indications for SCS are movement disorders, spasticity, and sequelae of spinal cord injury. The main limiting factors for the use of SCS are mechanical complications and the cost of the treatment. CONCLUSION: In its 50-year history, SCS has progressed enormously. The perfection of hardware and software may improve its effectiveness and reduce the rate of complications. Indications for SCS could include other diseases, and its use could be expanded, if the costs of the technology are reduced.

Assessment of systemic cellular inflammatory response after spontaneous intracerebral hemorrhage.

OBJECTIVE: After spontaneous intracerebral hemorrhage (ICH) a local and systemic inflammatory response is activated. Interleukin-6 (IL) is one of most relevant orchestrators of inflammatory responses in the brain and is released from multiple immune cells, including neutrophils. Herby we assessed the relevance of systemic inflammation in patients suffering ICH. METHODS: From October 2010 to October 2011 we included in our routine of laboratory investigations besides to C-reactive protein (CRP), the addition of IL-6 and an analysis of the subpopulation of circulating blood cells. Values at admission, at 3rd and 7th day after admission were evaluated. We analyzed 43 patients with non-traumatic ICH; stroke-related ICH or tumor associated hemorrhage were excluded. Outcome variables were 30 and 90-day mortality and NIHSS at discharge. A natural logarithmic transformation of IL-6, lymphocytes, and monocytes was used. RESULTS: 8.6% died within 30-days and mortality increased to 39.5% at 90th day. Total leukocytes and neutrophils as well as IL-6 at admission were statistically significant increased among patients who died within 30days after ICH onset (p=0.002). IL-6 and CRP in follow-up (3rd and 7th day) were higher among patients with poor outcome (NIHSS >15). The number of circulating lymphocytes and monocytes was not different in measurement. Leukocytes and neutrophils at 3rd day after admission were augmented in patients with respiratory infection and CRP in follow-up increased if some kind of infection was clinically or microbiologically detected. IL-6 at admission and in follow-up and monocytes at 7th day were related to ICH volume. CRP-values at 3rd or 7th day but not at admission were associated to bigger ICH-volume. The values of IL-6 were highly correlated to 30-day mortality and volume of ICH as CRP only with ICH volume. CONCLUSION: After ICH onset a systemic activation of immune system seems to be induced and may be influencing outcome. Peripheral recruitment of leukocytes, especially neutrophils could be a target for future therapeutic interventions. Because of the tighter correlation of IL-6 at admission, it might be more accurate for prognostic issues than CRP.

A mechanistic approach to understanding range shifts in a changing world: What makes a pioneer?

A species' range can be thought of as a manifestation of the ecological niche in space. Within a niche, evolution has resulted in traits that maximize fitness. Across millennia, natural oscillations in temperature have caused shifts in the geographic location of appropriate habitat and with corresponding changes in species' ranges. Contemporary climate change and human disturbance may lead to rapid range expansion or contractions with largely unknown consequences. Birds provide an excellent case study of this phenomenon with some taxa expanding range and others contracting even to the point of extinction. What leads some populations to expand while others contract? Are there physiological and behavioral attributes of "pioneers" at the forefront of a range shift/expansion? The concept of allostasis provides a framework with which to begin to evaluate when a species will be able to successfully expand into new habitat. This tool allows the integration of normal energetic demands (e.g. wear and tear of daily and seasonal routines) with novel challenges posed by unfamiliar and human altered environments. Allostasis is particularly attractive because it allows assessment of how individual phenotypes may respond differentially to changing environments. Here, we use allostasis to evaluate what characteristics of individuals and their environment permit successful range expansion. Understanding variation in the regulatory mechanisms that influence response to a novel environment will be fundamental for understanding the phenotypes of pioneers.

Effect of increased glucose levels on short-term outcome in hypertensive spontaneous intracerebral hemorrhage.

OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) can be a devastating event. Increased glucose levels in the plasma may be related to poor outcomes; however, the precise association remains unclear. METHODS: We retrospectively assessed 116 patients with hypertensive ICH. Glucose level in the plasma was assessed at days 0, 1, and 3. Outcome variables were mortality within 7 and 30days and the National Institutes of Health Stroke Scale (NIHSS) score at day 14 after ICH onset. RESULTS: Twenty deaths had occurred by day 7, and the 30-day mortality rate was 31.9%. Hyperglycemia at day 0 was significantly more common in patients who died within 7days or 30days. Hyperglycemia at day 1 was more common in patients with an NIHSS score >15 on admission and at day 14. No differences in glucose levels were found between diabetic and non-diabetic patients. Among non-diabetic patients, higher glucose levels were related to poorer outcomes (death or an NIHSS score >15). In multivariate analysis, glucose levels >140mg/dL at day 1 were related to the 30-day mortality (hazard ratio=2.65; 95% confidence interval [CI]=1.15-6.12, p=0.02), and glucose levels >160mg/dL at day 1 were associated with an NIHSS score >15 at day 14 (odds ratio=3.08; 95% CI=0.9-10.5, p=0.07). White blood cell counts were directly associated with poorer outcomes and significantly correlated to glucose levels. CONCLUSION: Initially increased glucose levels and increased levels within 24h of ICH onset were related to poorer outcomes. Altered glucose metabolism may be due to inflammatory cell activation. Further studies are needed to clarify the association between immune activation and glucose metabolism after ICH onset.

Continued statin therapy could improve the outcome after spontaneous intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) often represents a devastating event despite maximal therapeutic efforts. Statins are drugs primarily used as cholesterol reducers with several pleiotropic effects that may result in neuroprotection. In this study, we assessed the continued use of statins after acute ICH. From January 2008 to October 2010, we analyzed a retrospective cohort of 178 patients with acute ICH. Patients with head injury, cerebral tumors, hemorrhage after ischemic stroke, and having a National Institute Health Stroke Scale (NIHSS) score of greater than 30 points on admission were excluded. In 29 patients, statins were continued within the first 24 h after onset of ICH and, subsequently, given daily until discharge, whereas 149 nonusers were used as controls. Inpatient mortality, NIHSS, and Glasgow Outcome Score (GOS) at discharge as well as mortality after 10 days, 3 months, and 6 months were recorded as outcomes. Additionally, changes of C-reactive protein (CRP) and white blood cell (WBC) counts, as well as aspartate transaminase and alanine transaminase levels were assessed. Except for the number of hypertensive and diabetic patients, characteristics on admission were similar between both groups. No mortality was observed in statin users, whereas 19 controls (12.7 %) died (p = 0.04) until discharge; after 10 days, 3 months, and 6 months, a similar trend was found. After 6 months, statin use was associated to lower mortality in regression models (OR = 0.32, 95 % CI = 0.11-0.95, p = 0.04). In the same way, statin use was related to NIHSS reduction (-3.53, 95 % CI = -7.59 to 0.42, p = 0.07). In mixed models, changes of WBC counts and CRP levels were associated with statin use. The hepatic enzymes were similar between groups. The continued use of statins after ICH could be associated to early neurological improvement and may reduce mortality within 6 months. Immunomodulation as a pleiotropic effect of statins may represent one of the underlying mechanisms.

Laparoscopic treatment of heterotopic pancreas in the prepyloric region.

Heterotopic pancreas is a rare condition and its diagnosis is often difficult. Traditionally the condition is treated by open surgery. We report two young women with symptomatic heterotopic pancreas located in the prepyloric region. In the first patient, upper gastrointestinal endoscopy identified a round sessile lesion with a central umbilication of the mucosa without bleeding and in the second endoscopy showed a lesion with intraluminal protrusion. In both cases, a diagnostic laparoscopy identified masses amenable to laparoscopic excision. Intraoperative histology confirmed ectopic pancreatic tissue in both. In the treatment of heterotopic pancreas, laparoscopic excision provides a feasible, safe and effective treatment option.

Un estudio completo sobre la obtención de 99mTc-UBI 29-41 y su comportamiento in vitro e in vivo: su potencial uso en imágenes de infecciones / A complete study about the procurement of 99mTc-UBI 29-41 and its in vitro and in vivo behaviour: potential use in infection imaging

El objetivo del presente trabajo es investigar como se modifica el comportamiento in vitro e in vivo (localización de sitios de infección experimental con Staphilococcus aureus (S.a.)) del UBI 29-41 cuando es marcado con 99mTc por cuatro métodos distintos: a) con borohidruro de potasio y pirofosfato de estaño, b) con hidróxido de sodio y cloruro estañoso (métodos directos), c) con NHS-MAG3 y d) con NHS-HYNIC (métodos indirectos). En segundo lugar comparar los valores PI/PN (Pata Infectada / Pata Normal) del 99mTc-UBI 29-41 (método a), con el 99mTc-scrambled (Sc) UBI 29-41 (péptido control) y con 99mTc-IgG (radiofármaco no específico para infecciones) en ratones infectados con S.a. viables; y los valores pata inflamada/ PN del 99mTc-UBI 29-41 99mTc (método a) con 99mTc-IgG en ratones con inflamación estéril. Cuando el 99mTc-UBI 29-41 fue obtenido por el método a, se obtuvieron los mejores resultados in vitro y las biodistribuciones mostraron la máxima acumulación en sitios con S.a. viables y muy baja acumulación en sitios con inflamación estéril, demostrando su potencial uso en el diagnóstico de infecciones.

99mTc-UBI 29-41: biodistribución y autoradiografía digital en ratones con S.a. viables, S.a. no viables obtenidos por irradiación gamma y S.a. muertos por calor / 99mTc-UBI 29-41: biodistribution and digital autoradiography in mices with viable S.a., non viable S.a. obtained from gamma irradiation and heat killed S.a

El objetivo del presente trabajo es evaluar la capacidad del 99mTc-UBI 29-41 marcado por un método directo en la localización de sitios de infección experimental con Staphilococcus aureus (S.a.). En segundo lugar comparar los valores PI/PN (Pata Infectada / Pata Normal) de las biodistribuciones en ratones portadores de S.a. viables, S.a. no viables obtenidos por irradiación gamma y por calentamiento y en sitios de inflamación estéril y cuantificar las relaciones sitio infectado / sitio normal (SI / SN) através de autorradiografía digital. El UBI 29-41 es un fragmento sintético de la ubiquicidina y el scrambled (Sc) UBI 29-41 es el péptido control. 99mTc-IgG fue el control positivo para inflamaciones estériles. Cuando el 99mTc-UBI 29-41 fue obtenido por este método rápido y reproducible, se visualizaron sitios de infección a 2h p.i.. Las biodistribuciones mostraron mayor acumulación en sitios con S.a. viables que con S.a. irradiados y no hubo acumulación en inflamaciones estériles.

In vivo evaluation of three different 99mTc-labelled radiopharmaceuticals for sentinel lymph node identification.

This work was designed to compare sentinel lymph node (SLN) uptake of 99mTc-labelled human serum albumin colloid (99mTc-HSAC), 99mTc-labelled antimony sulphur colloid (99mTc-SC) and a 99mTc-labelled dextran 70 solution (99mTc-Dx) and their selectivity in the identification of this node in the right rear footpad (RRF) of normal mice and tumour bearing mice. Radiopharmaceutical uptake in the SLN (popliteal lymph node) and the lumbar lymph node (LLN), the second lymphatic node station from RRF, were measured at different time points post-intradermal or intratumoural injection into the RRF of NIH normal mice and of Balb/c mice harbouring the murine mammary tumour M2. 99mTc-HSAC uptake in the SLN was significantly higher than LLN uptake. The 99mTc-SC demonstrated high uptake in SLN, but accumulation in LLN was also high. 99mTc-Dx showed low uptakes in both SLN and LLN. The intradermal injection resulted in a more effective radiopharmaceutical accumulation in SLN than did the intratumoural inoculation. Data also show that increments in tumour volume reduced radiopharmaceutical uptake in the SLN. Our results show that 99mTc-HSAC exhibits the highest uptake in the SLN combined with the smallest amounts of radiopharmaceutical passing through to the LLN. Therefore, 99mTc-HSAC appears to be the best radiopharmaceutical for sentinel node detection.

Development of porphyria cutanea tarda in a hemodialysis patient after reactivation of hepatitis C virus infection.

Cases of porphyria cutanea tarda (PCT) are occasionally reported in hemodialysis patients. Recently, hepatitis C virus has been recognized as a precipitating factor of PCT. The activity of the liver disease may be critical for the appearance of PCT. In this regard, liver disease reactivation after treatment with interferon alpha (IFN-alpha) is a well-known phenomenon. We report the case of a hemodialysis patient who developed PCT coincidentally with reactivation of liver disease, immediately after treatment with IFN-alpha. Therefore, in the present case, reactivation of hepatitis after IFN-alpha withdrawal could be the triggering factor. The occurrence of a bout of PCT should be considered as a possible complication at the end of IFN-alpha therapy, if reactivation of the disease exists.

Lysosomes can fuse with a late endosomal compartment in a cell-free system from rat liver.

The passage of pulse doses of asialoglycoproteins through the endosomal compartments of rat liver hepatocytes was studied by subcellular fractionation and EM. The kinetics of disappearance of radiolabeled asialofetuin from light endosomes prepared on Ficoll gradients were the same as the kinetics of disappearance of asialoorosomucoid-horse radish peroxidase reaction products from intracellular membrane-bound structures in the blood sinusoidal regions of hepatocytes. The light endosomes were therefore identifiable as being derived from the peripheral early endosome compartment. In contrast, the labeling of dense endosomes from the middle of the Ficoll gradient correlated with EM showing large numbers of reaction product-containing structures in the nonsinusoidal parts of the hepatocyte. In cell-free, postmitochondrial supernatants, we have previously observed that dense endosomes, but not light endosomes, interact with lysosomes. Cell-free interaction between isolated dense endosomes and lysosomes has now been reconstituted and analyzed in three ways: by transfer of radiolabeled ligand from endosomal to lysosomal densities, by a fluorescence dequenching assay which can indicate membrane fusion, and by measurement of content mixing. Maximum transfer of radiolabel to lysosomal densities required ATP and GTP plus cytosolic components, including N-ethylmaleimide-sensitive factor(s). Dense endosomes incubated in the absence of added lysosomes did not mature into vesicles of lysosomal density. Content mixing, and hence fusion, between endosomes and lysosomes was maximal in the presence of cytosol and ATP and also showed inhibition by N-ethyl-maleimide. Thus, we have demonstrated that a fusion step is involved in the transfer of radiolabeled ligand from an isolated endosome fraction derived from the nonsinusoidal regions of the hepatocyte to preexisting lysosomes in a cell-free system.

The presence and measurement of secretory component in human bile and blood.

Five monoclonal antibodies which recognized three separate epitopes on the free secretory component molecule were produced using free secretory component obtained from human colostrum. Two-site immunoradiometric assays were developed to measure free secretory component and secretory IgA. Monoclonal antibody M9 was used on coated plates as the capture antibody. Monoclonal antibody M7 was used as the labelled signal antibody for the assay of free secretory component and a commercially available monoclonal anti-IgA antibody was used as the labelled signal antibody for the assay of secretory IgA. Free secretory component was found in human serum and bile. In serum, its concentration was raised in patients with high serum alkaline phosphatase due to liver disorders but not in patients with high serum alkaline phosphatase due to non-liver disorders. In bile from bile duct drains collected during the first week after liver transplantation, free secretory component was found in concentrations of up to 33 mg/l, in vast excess of that found in bile from gallstone patients (up to 0.3 mg/l). Bile from gallstone patients but not from liver transplant patients produced proteolytic degradation of free secretory component when incubated in vitro. The finding of large amounts of free secretory component, the free cleaved fragment of the polymeric IgA receptor in human bile, further supports the existence of the blood to bile transhepatocytic pathway in humans.

The polymeric immunoglobulin A receptor is present on hepatocytes in human liver.

A monoclonal antibody raised against human colostrum secretory component produced even staining of hepatocyte plasma membranes, as well as bile duct lining cells, in all sections examined from eight normal and three abnormal human livers. Human bile samples incubated with free secretory component degraded it to varying extents, probably proteolytically; true levels of free secretory component will therefore often be higher than those reported. It seems likely that human liver resembles that of other mammals in transferring polymeric IgA through hepatocytes to the bile by means of the polymeric IgA receptor.