Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0-53.0) years in 2005-2007 to 61.0 (56.0-69.5) years in 2020-2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable. CONCLUSIONS: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Stromal DLK1 promotes proliferation and inhibits differentiation of the intestinal epithelium during development.

The stem/progenitor cells of the developing intestine are biologically distinct from their adult counterparts. Here, we examine the microenvironmental cues that regulate the embryonic stem/progenitor population, focusing on the role of Notch pathway factor delta-like protein-1 (DLK1). mRNA-seq analyses of intestinal mesenchymal cells (IMCs) collected from embryonic day 14.5 (E14.5) or adult IMCs and a novel coculture system with E14.5 intestinal epithelial organoids were used. Following addition of recombinant DLK1 (rDLK) or Dlk1 siRNA (siDlk1), epithelial characteristics were compared using imaging, replating efficiency assays, qPCR, and immunocytochemistry. The intestinal phenotypes of littermate Dlk1+/+ and Dlk1-/- mice were compared using immunohistochemistry. Using transcriptomic analyses, we identified morphogens derived from the embryonic mesenchyme that potentially regulate the developing epithelial cells, to focus on Notch family candidate DLK1. Immunohistochemistry indicated that DLK1 was expressed exclusively in the intestinal stroma at E14.5 at the top of emerging villi, decreased after birth, and shifted to the intestinal epithelium in adulthood. In coculture experiments, addition of rDLK1 to adult IMCs inhibited organoid differentiation, whereas Dlk1 knockdown in embryonic IMCs increased epithelial differentiation to secretory lineage cells. Dlk1-/- mice had restricted Ki67+ cells in the villi base and increased secretory lineage cells compared with Dlk1+/+ embryos. Mesenchyme-derived DLK1 plays an important role in the promotion of epithelial stem/precursor expansion and prevention of differentiation to secretory lineages in the developing intestine.NEW & NOTEWORTHY Using a novel coculture system, transcriptomics, and transgenic mice, we investigated differential molecular signaling between the intestinal epithelium and mesenchyme during development and in the adult. We show that the Notch pathway factor delta-like protein-1 (DLK1) is stromally produced during development and uncover a new role for DLK1 in the regulation of intestinal epithelial stem/precursor expansion and differentiation to secretory lineages.

Reduced salivary gland size and increased presence of epithelial progenitor cells in DLK1-deficient mice.

DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis. Here, we have extended our studies of the salivary gland phenotype of Dlk1 knock-out mice. We have observed that salivary glands are smaller and weigh significantly less in both Dlk1 knock-out males and females compared with gender and age-matched wild-type mice and regardless of the natural sexual dimorphism in rodent salivary glands. This reduced size correlates with a reduced capacity of Dlk1-deficient mice to secrete saliva after stimulation with pilocarpine. However, histological and ultrastructural analyses of both adult and developing salivary gland tissues have revealed no defects in Dlk1 ((-/-)) mice, indicating that genetic compensation accounts for the relatively mild salivary phenotype in these animals. Finally, despite their lack of severe anomalies, we have found that salivary glands from Dlk1-deficient mice present a higher amount of CK14-positive epithelial progenitors at various developmental stages, suggesting a role for DLK1 in the regulation of salivary epithelial stem cell balance.

An expandable prosthesis with dual cage-and-plate function in a single device for vertebral body replacement: the clinical experience on 14 consecutive cases with vertebral tumors.

AIM: The aim of this paper was to test the hypothesis that an expandable prosthesis with dual cage-and-plate function can provide immediate and durable spine stabilization after corpectomy. METHODS: We designed an expandable vertebral body prosthesis with dual cage-and-plate function in a single device (JR-prosthesis). Anatomical studies were performed to design a titanium-made prosthesis. Cadaver assays were done with a stainless steal device to test fixation and adequacy to the human spine anatomy. Then, 14 patients with vertebral tumors (8 metastatic) underwent corpectomy and vertebral body replacement with the JR-prosthesis. RESULTS: All patients had neurological deficit, severe pain and spine instability (mean follow-up: 25.4 months). Mean pain score before surgery in a visual analog scale improved from 7.6 to 3.0 points after operation (P=0.002). All patients achieved at least one grade of improvement in the Frankel score (P=0.003), excepting the 3 patients with Frankel grade A presurgery. Two patients with renal cell carcinoma died during the following 4 days after surgery (renal failure and massive bleeding), the rest attained a painless and stable spine immediately and maintained for long periods. No significant infections or implant failures were registered. A non-fatal case of inferior vena cava surgical injury was observed (repaired during surgery without further complications). CONCLUSION: The JR-prosthesis stabilizes the spine immediately after surgery and for the rest of the patients' life. To our knowledge, this is the first report on the clinical experience of any expandable vertebral body prosthesis with dual cage-and-plate function in a single device. These observations await confirmation in different scenarios.

Diurnal and spatial (vertical) dynamics of nutrients (N, P, Si) in four sampling days (summer, fall, winter, and spring) in a tropical shallow reservoir and their relationships with the phytoplankton community

Variações vertical, nictemeral e entre os dias de amostragem das formas de nitrogênio, fósforo e sílica solúvel reativa (SRS) foram estudadas no lago das Garças, reservatório tropical raso situado na cidade de São Paulo, sudeste do Brasil. Excetuado o N-NH4, todas as demais formas inorgânicas de nitrogênio (N-NO2, N-NO3 e N total) diminuíram de teor no sentido do fundo do reservatório. Da mesma maneira, todas as formas de nitrogênio apresentaram diferenças significativas quanto às horas de amostragem, aumentando seus valores durante a noite, em razão da ausência de fotossíntese nesse período. Essas formas diminuíram seus teores no dia de amostragem da primavera, graças à floração de Microcystis registrada nesse período. Os valores das três formas de fósforo estudadas (solúvel reativo, particulado e total) apresentaram variação vertical significativa, exceto no dia da amostragem de outono. No dia de amostragem de verão ocorreu aumento dos valores de P total e particulado, sendo que este último constituiu mais de 70% do P total durante todos os dias de amostragem. Considerando as horas, a variação dos teores de fósforo foi significativa nos dias das amostragem de primavera, de outono e de inverno. A variação vertical da sílica reativa solúvel foi significativa em todos os dias de amostragem, menos no da primavera. Essa variação também foi diferente entre as horas e os dias de amostragem.

The effects of Neotrofin on septodentate sprouting after unilateral entorhinal cortex lesions in rats.

PURPOSE: Recent research on the purine derivative of hypoxanthine Neotrofin (4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has indicated that Neotrofin treatment elevates the mRNA levels of various neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several previous studies have indicated that NGF may regulate septodentate sprouting after entorhinal cortex lesions in rats. Thus, the objective of this investigation was to determine whether Neotrofin treatment would enhance lesion-induced septodentate sprouting from 4 to 15 days postlesion. METHODS: Sham-operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter until the end of the treatment regimen. Septodentate sprouting, as indicated by intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed with optical densitometry. RESULTS: We observed that Neotrofin elevated the AChE-label in the outer molecular layer of the ventral dentate gyrus at 4 days postlesion and of the dorsal dentate gyrus at 15 days postlesion. CONCLUSIONS: Neotrofin appears to have exerted limited stimulatory effects on lesion-induced sprouting by a cholinergic pathway.

Variation of climatic and physical co-determinants of phytoplankton community in four nictemeral sampling days in a shallow tropical reservoir, Southeastern Brazil

Spatial and temporal variation of climatic and physical characteristics in a shallow tropical reservoir in the city of Säo Paulo, Southeastern Brazil, and their possible influence on the dynamics of the phytoplankton population. Samples were taken at 5 depths of the water column (subsurface: 1 percent Io, 10 percent Io, 2 m, and bottom) and at 4 hour intervals (6:00, 10:00, 14:00, 18:00, 22:00, 2:00, and 6:00 h) during summer (March 3-4), fall (June 13-14), winter (August 29-30), and spring (November 29-30) of 1994 at a single sampling station. Garças Reservoir (23º39'S, 46º37'W) is a kinetic turbulent system, highly influenced by winds, with stratification that may last for days or weeks, and which undergoes mixing periods more than once in a year. A thermal pattern of this type is comparable to the warm discontinuous polymictic. Considering its optical properties, the water body was classified as an ecosystem with moderate turbidity, which decreases basically due to increased phaeopigment concentration during the spring. Also, the reservoir is an ecosystem whose phytoplanktonic community is subjected to stress, the degree of which depends on level of light penetration

Evolutive pattern in Crohn's disease: a simplified index using clinical parameters predicts obstructive behaviour.

BACKGROUND: Two clearly differentiated evolutive patterns of Crohn's disease, obstructive and fistulizing, exist, but the early clinical parameters which can predict the evolution are unknown. AIM: To evaluate whether clinical variables, present at the time of diagnosis, may help in predicting a subsequent evolutive behaviour. PATIENTS AND METHODS: Ninety out of 140 evaluable patients were included. After a median of 50.2 months since diagnosis, 64 patients (71%) followed an obstructive pattern while 26 patients (28.9%) had a fistulizing form. Clinical variables were analysed as predictors of outcome. Logistic regression was carried out in order to obtain a mathematical model that would predict the evolution. The individual ability of the mathematical model to predict evolution was assessed using relative receiver operating characteristic (ROC) curves. RESULTS: The variables which were retained in the model were duration of disease before diagnosis (DD), onset of symptoms (OS), presence of anal disease (AD) and the presence of abdominal mass (AM). The equation z = -9.49 + 2.2643 (AD) - 0.0066 (DD) + 2.5282 (AM) + 1.3433 (OS) was obtained. The probability of evolution towards an obstructive form was P = 1/(1 + e(-Z)). This model can predict 96.88% of obstructive forms but only 53.85% of fistulizing forms. The mathematical point section (ROC curve) corresponds to a probability of 45.2%. Considering an obstructive pattern when the probabilities are above this point, the sensitivity is 98% and the specificity is 50%. CONCLUSIONS: The prediction of an obstructive pattern is feasible using simple clinical variables. The mathematical model obtained is useful for predicting this but not the fistulizing pattern.

Genetic dissection of the signals that induce synaptic reorganization.

Synaptic reorganization of mossy fibers following kainic acid (KA) administration has been reported to contribute to the formation of recurrent excitatory circuits, resulting in an epileptogenic state. It is unclear, however, whether KA-induced mossy fiber sprouting results from neuronal cell loss or the seizure activity that KA induces. We have recently demonstrated that certain strains of mice are resistant to excitotoxic cell death, yet exhibit seizure activity similar to what has been observed in rodents susceptible to KA. The present study takes advantage of these strain differences to explore the roles of seizure activity vs cell loss in triggering mossy fiber sprouting. In order to understand the relationships between gene induction, cell death, and the sprouting response, we assessed the regulation of two molecules associated with the sprouting response, c-fos and GAP-43, in mice resistant (C57BL/6) and susceptible (FVB/N) to KA-induced cell death. Following administration of KA, increases in c-fos immunoreactivity were observed in both strains, although prolonged induction of c-fos was present only in the hippocampal neurons of FVB/N mice. Mossy fiber sprouting following KA administration was also only observed in FVB/N mice, while induction of GAP-43, a marker associated with mossy fiber sprouting, was not observed in either strain. These results indicate that: (i) KA-induced seizure activity alone is insufficient to induce mossy fiber sprouting; (ii) mossy fiber sprouting may be due to the loss of hilar neurons following kainate administration; and (iii) induction of GAP-43 is not a necessary component of the sprouting response that occurs following KA in mice.

Techniques and complications of ileostomy takedown.

OBJECTIVE: We use a loop ileostomy for temporary fecal diversion because of ease of technical construction and assumed low complication rate. Here, we review our complications of loop ileostomy and takedown using three techniques of closure. METHODS: We reviewed charts of all patients who had temporary ileostomies constructed during 1987 to 1995 (n = 366). Ileostomy takedown was performed in 339 patients using one of three closure techniques: enterotomy suture (65%), resection with handsewn anastomosis (20%), and stapled anastomosis (15%). Complications were recorded for pre-takedown and 30-day post-takedown intervals. RESULTS: Overall complication rate was 28%. Pre-takedown complications occurred in 21 patients (5.7%), including small bowel obstruction (2.5%) and dehydration/electrolyte derangement (2.2%). Post-takedown complications occurred in 83 patients (24.5%), including wound infection (14.2%), small bowel obstruction (5%), anastomotic leak (2.9%), and 1 death from a cardiac event. Post-takedown obstruction was higher for closure using resection with sutured anastomosis (12%) compared with enterotomy suture (2.3%), P < or = 0.003. Stapled anastomosis had an intermediate rate of obstruction (7.7%). Anastomotic leak was similar between closure techniques. CONCLUSIONS: Loop ileostomy and takedown are associated with low rates of serious complications (5% or less). As such, we continue to advocate use of loop ileostomy as a diversion procedure. Closure by enterotomy suture is preferred over resection. However, if resection is required, closure by stapled anastomosis is preferred over suture anastomosis.

Elevated expression of Ets2 or distinct portions of Ets2 can reverse Ras-mediated cellular transformation.

Ets transcription factors are important downstream targets of oncogenic Ras. The transcriptional activity of several Ets family members is regulated by Ras, and interfering with Ets-dependent transcription by expression of just the Ets2 DNA binding domain can inhibit or reverse Ras-mediated cellular transformation. To better understand the role of Ets proteins in Ras transformation, we have now analyzed the effects of stably expressing a variety of Ets2 constructs in Ras-transformed NIH3T3 (DT) cells. Expression of only the Ets2 transactivation domains, which also inhibits Ras or Neu/ErbB-2-mediated activation of Ets-dependent transcription, strongly inhibited anchorage-independent growth, but did not revert the transformed DT cell morphology. Unexpectedly, high expression of full-length Ets2, a transcriptional activator, broadly reversed the transformed properties of DT cells, including anchorage-independent growth, transformed morphology, and tumorigenicity, but did not impair attached cell growth. Increasing full-length Ets2 transcriptional activity by fusing it to the VP16 transactivation domain enhanced its ability to reverse DT cell transformation. Mutational analysis revealed that the mitogen-activated protein kinase phosphorylation site required for Ras-mediated activation, Ets2(T72), was not essential for Ets2 reversion activity. The distinct reversion activities of the highly expressed Ets2 transactivation domains or full-length Ets2, along with the specific reversion activity by Ets2 constructs that either inhibit or activate Ets-dependent transcription, suggests multiple roles for Ets factors in cellular transformation. These results indicate that several distinct approaches for modulating Ets activity may be useful for intervention in human cancers.

GM1-Ganglioside Suppresses Septodentate Sprouting and Enhances Recovery from Entorhinal Cortex Lesions on DRL Perfomance and Locomotor Behavior in Rats.

Administration of gangliosides accelerates recovery of function after entorhinal cortex lesions on open field activity and learned spatial alternation tasks. In the present study, we examined whether GM1 ganglioside might enhance recovery from bilateral entorhinal cortex lesions on a differential reinforcement of low-rate responding tak with a 20 sec delay (DRL-20) as well as on open field activity. Optical densitometry measurements were taken to assess sprouting by the acetylcholinesterase-containing septodentate pathway. Eighteen rats were assigned to sham/GM1, lesion/GM1, or lesion/saline conditions. After preoperative training and testing, the rats received surgery and were then tested post-operatively for thirty days. GM1 injections (20 mg/kg) were given beginning the day before surgery through day 5 postsurgery and then on alternating days. Relative to the lesion/saline group, rats in the lesion/GM1 group showed enhanced recovery on the DRL-20 and the open field tasks. The lesion/GM1 group had significantly less septodentate sprouting than the lesion group treated with saline. GM1 treatment may be facilitating recovery from bilateral entorhinal lesions by reducing the trauma of injury and denervation, reducing heterologous sprouting, or both.

Rapid phosphorylation of Ets-2 accompanies mitogen-activated protein kinase activation and the induction of heparin-binding epidermal growth factor gene expression by oncogenic Raf-1.

Heparin-binding epidermal growth factor (HB-EGF) gene transcription is rapidly activated in NIH 3T3 cells transformed by oncogenic Ras and Raf and mediates the autocrine activation of the c-Jun N-terminal kinases (JNKs) observed in these cells. A 1.7-kb fragment of the promoter of the murine HB-EGF gene linked to a luciferase reporter was strongly induced following activation of deltaRaf-1:ER, a conditionally active form of oncogenic human Raf-1. Promoter activation by deltaRaf-1:ER required a composite AP-1/Ets transcription factor binding site located between bp -974 and -988 upstream of the translation initiation site. In vivo genomic footprinting indicated that the basal level of occupancy of this composite AP-1/Ets element increased following deltaRaf-1:ER activation. Cotransfection of Ets-2 and p44 mitogen-activated protein (MAP) kinase expression vectors strongly potentiated HB-EGF promoter activation in response to deltaRaf-1:ER. Potentiated activation required both p44 MAP kinase catalytic activity and threonine 72 in the Pointed domain of Ets-2. Biochemical assays demonstrated the ability of the p42 and p44 MAP kinases to phosphorylate Ets-2 on threonine 72. Importantly, in intact cells, the kinetics of phosphorylation of Ets-2 on this residue closely mirror the activation of the p42 and p44 MAP kinases and the observed onset of HB-EGF gene transcription following deltaRaf-1:ER activation. These data firmly establish Ets-2 as a direct target of the Raf-MEK-MAP kinase signaling pathway and strongly implicate Ets-2 in the regulation of HB-EGF gene expression.

[Familial prevalence in chronic intestinal inflammatory disease. Differences among groups of patients with and without a familial history]. / Afectación familiar en la enfermedad inflamatoria crónica intestinal. Diferencias entre grupos de pacientes con y sin historia familiar.

OBJECTIVE: To assess the prevalence of familial occurrence in patients with inflammatory bowel disease and to evaluate the differences among groups of patients with and without familial history. PATIENTS AND METHODS: Complete information about sex, age of onset of inflammatory bowel disease, initial location, extracolonic manifestations and perianal disease (in Crohn's disease) was obtained from 187 patients, 99 with Crohn's disease, and 88 with ulcerative colitis. RESULTS: In 9 patients (9%) with Crohn's disease and 11 (12.5%) with ulcerative colitis, at least one first-degree relative also had inflammatory bowel disease. Three relatives of patients with Crohn's disease had ulcerative colitis and no relative of patients with ulcerative colitis had Crohn's disease. As compared with the group of patients with ulcerative colitis and no familial history, patients with familial history had more frequently distal location and extra-colonic manifestations. No differences were observed among patients with Crohn's disease and familial or non familial history. CONCLUSIONS: Prevalence of inflammatory bowel disease in relatives of patients with Crohn's disease or ulcerative colitis is increased. In ulcerative colitis, it is possible to segregate two different groups according to familial history.

[The clinical significance of the magnitude of esophageal dilatation in idiopathic achalasia]. / Trascendencia clínica de la magnitud de la dilatación del esófago en la acalasia idiopática.

The relationship between the diameter of the esophageal body and the clinical profile of the disease and response to treatment was analyzed in 151 patients with idiopathic achalasia by pneumatic dilation of the cardias. Of the 151 patients, 46 presented an esophageal diameter < or = 3 cm (group I), 78 a diameter > 3 cm up to a maximum of 5 cm (group II) and 27 presented a diameter > 5 cm (group III). The result of pneumatic dilatation of the cardias under endoscopic control was analyzed in 117 patients with a minimum follow up of one year after the last dilatation session. Of all the clinical parameters studied, significant statistical differences were only found in group III in respect to the time of symptom evolution and the presence of regurgitation. Manometric data in basal pressure of the esophageal body and in contraction wave width were lower in groups I and III, respectively. The remaining variables were similar in the three groups although group III showed a trend to older age and the frequency of pulmonary complications with lesser thoracic pain and registry of a strict pattern. Endoscopic pneumatic dilation carried out in all the cases was effective in 83% of the patients and was similar in the three study groups. The rate of complications (perforation) was also similar. The therapeutic efficacy of pneumatic dilatation was accompanied by a significant reduction in esophageal diameter. It was concluded that the increase in esophageal diameter in idiopathic achalasia is associated with chronological, clinical and functional parameters which suggest greater disease evolution but do not determine significant changes in the therapeutic response to endoscopic pneumatic dilatation.

[Efficacy of 6-mercaptopurine in the treatment of inflammatory bowel disease]. / Eficacia de la 6-mercaptopurina en el tratamiento de la enfermedad inflamatoria intestinal.

OBJECTIVE: To assess the efficacy of 6-mercaptopurine in I.B.D. treatment. PATIENTS: 21 patients with chronic active disease (8 patients with ulcerative colitis and 13 with Crohn's disease) and mean follow-up 5 years for both diseases (range ulcerative colitis 1-11 and Crohn's disease 1-14 years, respectively). The indications of inmunosuppressor treatment were: corticosteroid dependence (3 ulcerative colitis; 6 Crohn's disease), refractory disease (5 ulcerative colitis; 4 Crohn's disease), fistulae (5 Crohn's disease) and perianal disease (4 Crohn's disease). All patients received a mean dose of 30 mg/day of prednisone. Complete, partial and clinical remission, of failure of treatment are defined. RESULTS: The mean dose of 6-mercaptopurine was 90 mg/day with a response mean time of 3.4 months and 12 months of duration (range 1-36). Complete or partial clinical remission was achieved in 77.7% of all the patients (steroid dependent 88.8%, refractory disease 77.7%, fistulae 40%, perianal disease 100% of all the patients (steroid dependent 88.8%, refractory disease 77.7%, fistulae 40%, perianal disease 100%), in 87% of ulcerative colitis patients (steroid dependent 100%, refractory 80%) and in 61.5% of Crohn's disease patients (steroid dependent 83.7%, refractory disease 75%). Secondary effects were observed in two patients. CONCLUSIONS: Our results suggest that 6-mercaptopurine is an effective and safe drug in the treatment of patients with ulcerative colitis and Crohn's disease in corticosteroid dependent, refractory and perianal disease, its efficacy being less in fistulae.

[Focal nodular hyperplasia of the liver: benign lesion with often surgical treatment. Magnetic resonance and laparoscopic findings]. / Hiperplasia nodular focal del hígado. Lesión benigna con tratamiento frecuentemente quirúrgico. Hallazgos en la resonancia magnética y laparoscópicos.

The diagnosis of benign hepatic tumor lesions is every day more frequent. Three cases of focal nodular hyperplasia (FNH) accidently detected during the performance of echography and/or CAT for other reasons are presented. The difficulty or diagnostic doubts which the different imaging techniques may present before these findings, together with the relatively young age of these patients may lead to the adoption of a surgical attitude in lesions of a clearly benign character. The role of magnetic resonance (MR) as a non invasive diagnostic technique in this type of disease is of note.

Ganglioside-induced alterations in hippocampal cholinergic enzymes and Na,K-ATPase after fimbria-fornix transection.

Previous biochemical findings suggest that exogenous gangliosides enhance cholinergic sprouting in the hippocampus after partial lesions of the septohippocampal pathway. To assess whether GM1 ganglioside accelerates the onset of this sprouting after complete lesions, we measured cholinergic enzymes and Na,K-ATPase activity in the hippocampus of rats with unilateral fimbria-fornix transection. At 14 and 18 days postlesion, histochemical staining showed that acetylcholinesterase (AChE) was almost completely eliminated in the hippocampus ipsilateral to the transection in untreated and GM1-treated rats. Biochemical assays confirmed that GM1 treatments did not increase AChE activity in the denervated hippocampus. Rather, there were significant reductions of AChE and choline acetyltransferase activities in the ipsilateral hippocampus relative to the contralateral value (P less than .001); and the reductions were greater in GM1-treated rats than in untreated controls (P less than .001). Na,K-ATPase activity in the ipsilateral hippocampus increased by 10.1% in GM1-treated rats, whereas it decreased by 21.7% in untreated controls (P less than .05). Since Na, K-ATPase is enriched in synaptic membranes, the increased activity of this enzyme may indicate that GM1 treatments stabilize surviving synaptic membranes and/or accelerate the onset of sprouting in the denervated hippocampus. The reductions in cholinergic enzymes, however, imply that the sprouting pathway must be noncholinergic.

Neonatal brain damage and recovery: intraventricular injection of NGF at time of injury alters performance of active avoidance.

Rats were given lesions of either the ventromedial hypothalamus (VMH) or septal nucleus at 7 days of age and then were tested repeatedly in an active avoidance task (A.A.) from 20 to 80 days. VMH rats were consistently impaired on the A.A. task beginning at 40 days of age. The animals with septal lesions performed the A.A. task consistently better than VMH or control animals throughout the entire test period, the septal syndrome becoming more pronounced as the rats reached maturity. In intact rats a single, intraventricular injection of NGF given at 7 days of age resulted in a greater reactivity, especially as the rats approached maturity. NGF, given at time of surgery, also improved performance of the A.A. task in VMH-damaged rats tested at 40-80 days. In rats given septal lesions, NGF treatment at time of injury attenuated the septal syndrome of improved A.A. performance. The data indicate that NGF treatment, given to neonatal rats, can produce long-lasting effects on CNS functions and can contribute to functional recovery from brain lesions.

Sparing and recovery of spatial alternation performance after entorhinal cortex lesions in rats.

Groups of adult rats were first trained on a spatial alternation task and then subjected to unilateral entorhinal cortex lesions, unilateral entorhinal cortex lesions followed by dorsal psalterium transections, or bilateral entorhinal cortex lesions. After this surgery, the rats were then tested for retention of spatial alternation. Neither unilateral lesions alone nor unilateral lesions followed by dorsal psalterium transections resulted in long-term spatial performance deficits; however, animals with bilateral lesions exhibited severe impairments from which they eventually recovered. The results from animals with bilateral entorhinal damage indicate that extensive postoperative training may facilitate the recovery of spatial alternation performance. Histological analyses indicated that the crossed entorhinal projection proliferated in the dentate gyrus after unilateral entorhinal lesions and such anomalous growth occurred independently of any changes in alternation performance.