Exercise Compared to Mindfulness for Physical and Mental Wellbeing in Medical Students.

Aim Physical Activity (PA) and Mindfulness-Based Stress Reduction (MBSR) both have positive effects on medical student well-being. The 'MED-WELL' programme is a curricular intervention that combines PA and education on exercise as medicine. This trial evaluates whether there is a mean difference in outcomes of participants of an exercise intervention, the 'MED-WELL' programme, versus a control group which engages in a MBSR programme. Methods All second-year medical students were voluntarily allocated into the intervention or control group. Data on overall health and well-being, sleep quality, loneliness, current level of PA, and confidence in prescribing exercise as medicine was analysed from both groups at baseline and after eight weeks. Results Within groups the intervention and control groups showed statistically significant improvements in overall well-being (p=0.010, p=0.005 respectively) and in sleep quality (p<0.001, p=0.007 respectively). The intervention group had statistically significant improvements in levels of PA (p=0.003) and confidence in prescribing exercise (p<0.001). However, there were no statistically significant differences in changes in outcome measures between groups. Conclusion This study has shown that participants in an exercise intervention, the 'MED-WELL' programme, had similar improvements in overall wellbeing and sleep quality to those in a control group who participated in a MBSR programme of the same duration.

Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients.

The presence of CD19 in myelomatous plasma cells (MM-PCs) correlates with adverse prognosis in multiple myeloma (MM). Although CD19 expression is upregulated by CD81, this marker has been poorly investigated and its prognostic value in MM remains unknown. We have analyzed CD81 expression by multiparameter flow cytometry in MM-PCs from 230 MM patients at diagnosis included in the Grupo Español de Mieloma (GEM)05>65 years trial as well as 56 high-risk smoldering MM (SMM). CD81 expression was detected in 45% (103/230) MM patients, and the detection of CD81(+) MM-PC was an independent prognostic factor for progression-free (hazard ratio=1.9; P=0.003) and overall survival (hazard ratio=2.0; P=0.02); this adverse impact was validated in an additional series of 325 transplant-candidate MM patients included in the GEM05 <65 years trial. Moreover, CD81(+) SMM (n=34/56, 57%) patients had a shorter time to progression to MM (P=0.02). Overall, our results show that CD81 may have a relevant role in MM pathogenesis and represent a novel adverse prognostic marker in myeloma.

Short communication: Biological and genetic characterization of HIV type 1 subtype B and nonsubtype B transmitted viruses: usefulness for vaccine candidate assessment.

Due to the extraordinary degree of genetic diversity of HIV-1 and the structural complexity of its envelope glycoproteins, designing an effective vaccine is difficult, requiring the development of viral reagents to assess vaccine-elicited neutralizing antibodies. The aim of this study was to improve on our previously developed panel of HIV-1 strains of different genetic forms, focusing on strains from acute and recently acquired infections as the most representative of the transmitted viruses. HIV-1 primary isolates were expanded in peripheral blood mononuclear cells. Viral stocks of 40 ml each were produced. Syncytium-inducing (SI) phenotype, coreceptor use, and TCID(50)/ml were determined. Near full-length HIV-1 genomes were amplified by RT-nested PCR in four overlapping segments. Phylogenetic analyses were performed with neighbor-joining trees and bootscanning. Forty-four HIV-1 strains were included in the panel. Twenty-four (54.1%) strains were from early infections (16 acute and 8 recent); of them, 21 (87%) were sexually transmitted. NSI/R5 phenotype was detected in 37 (84.1%) viruses and SI/R5,X4 in another 7 (15.9%). TCID(50)/ml ranged between 10(4) and 10(6.6). Twelve different genetic forms constituted this panel: subtypes A1, B, C, F1, and G; circulating recombinant forms CRF02_AG, CRF14_BG, and CRF24_BG; and unique recombinant forms CRF02_AG/A3, BF1, CRF12_BF/B, and DF1G. In conclusion, in this study, we report the development of a comprehensive and well-characterized panel of HIV-1 isolates for assessing neutralization in HIV vaccine research. This panel is available for distribution through the Programme EVA Centre for AIDS Reagents, National Institute for Biological Standard and Control (NIBSC).

Development of a panel of well-characterized human immunodeficiency virus type 1 isolates from newly diagnosed patients including acute and recent infections.

The aim of this study was the development of a panel constituted by well-defined HIV-1 strains of different genetic forms, with a particular focus on isolates from acute and recent infections. Fourteen HIV-1 isolates, including four from acute and five from recent infections, were expanded in peripheral blood mononuclear cells. SI phenotype, coreceptors use, and TCID(50)/ml were determined. V3 net charge was calculated. Near full-length genomes were amplified by RT-nested PCR in four overlapping segments. Phylogenetic analyses were performed with neighbor-joining trees and bootscanning. Analysis of cysteine residues, lengths of variable regions, and potential N-linked glycosylation sites in gp120 and gp41 was performed. Viral stocks were produced. Thirteen strains were NSI/R5 and one SI/R5,X4. TCID(50)/ml ranged between 10(4.6) and 10(6). V3 net charge was <+5 in 12 sequences and +5 in two sequences. Near full-length HIV-1 genomes analysis identified viruses of the following genetic forms: eight subtype B, three subtype C, two CRF02_AG, and one subtype G. Cysteine residues that form the V1,V2,V3, and V4 loops were highly conserved. The number of potential N-linked glycosylation sites in gp120 and gp41 ranged between 24-29 and 4-6, respectively. Seven potential N-linked glycosylation sites in gp120 and three in gp41 were conserved. V1, V2, V4, and V5 variable regions exhibited substantial length variation. In addition, an analysis of transmitted and natural resistance to current antiretroviral drugs in these strains was performed. It is worth mentioning that the 13S mutation in the V3 sequence, associated with resistance to maraviroc, was observed in a subtype B strain that harbored resistance mutations to nucleoside reverse transcriptase inhibitors and to T20. The availability of a panel including strains from acute and recent infections should be a valuable resource for optimizing and standardizing vaccine candidate assessment. Near full-length genome characterization may be necessary for evaluating clade-specific reactivities.

Robustness of measles immunity in parturient women in Gipuzkoa, Basque Country, Spain, in the post-vaccination era.

The infants of mothers with vaccine-induced immunity lose passive acquired measles antibodies earlier than infants of naturally infected mothers. This study included two cohorts of parturient women: one composed of women who gave birth in 1990 (end of the epidemic period), and another comprising women who gave birth in 2006 (after eight years without virus circulation). Immunoglobulin G (IgG) antibodies against measles (IgG-AM) were investigated by enzyme immunoassay in stored serum samples (-40 degrees C). Measles-IgG titres of >400 mIU/mL were found in all 185 parturient women who gave birth in 1990, all with natural immunity. Of 185 women who gave birth in 2006, most of whom had vaccine-induced protection, measles-IgG were undetectable in 4.9% (<150mIU/mL), values were borderline in 7% (150-299 mIU/mL), and the geometric mean titre was lower (p<0.001), being 3.4 to 3.8 times lower in women aged <28 years. The changing levels of maternal measles antibodies suggest that in Spain, the window of susceptibility to measles in infants is increasing. To protect susceptible infants against measles in countries with long-established vaccination programs where measles immunity in parturient women was artificially acquired, it is essential to ensure that both doses of the routine measles vaccine achieve a coverage of >95%, and that infants receive the first vaccination dose before 15 months of age (e.g. at 12 months).

Marked decrease in the incidence and prevalence of hepatitis A in the Basque Country, Spain, 1986-2004.

The aim of this study was to determine changes in the epidemiology of hepatitis A virus (HAV) infection in the Basque Country, Spain, and to evaluate their implications for vaccination strategies. A total of 1356 persons were enrolled in a study of the prevalence of anti-HAV in 2004 and compared with two previous studies (1986-1987 and 1992). The selection method and the characteristics of the population were similar in the three studies. A marked decline in the seroprevalence in all age groups (P<0.001) and in the incidence of cases/100,000 inhabitants (from 38.0 in 1986-1988 to 2.9 in 2002-2004) were observed. The mean age of patients with hepatitis A increased from 17.7 years in 1986-1992 to 21.2 years in 1993-1998 and 25.3 years in 1999-2004 (P<0.001). Between 1997 and 2004, 20% of patients were hospitalized. The changes observed have occurred rapidly causing a change in the epidemiological pattern from middle-high endemicity (1986) to low endemicity (2004).

Decrease in human fascioliasis in Gipuzkoa (Spain).

From 1981 to 2000 sixty-one cases of human fascioliasis were detected in the province of Gipuzkoa (Spain), most of them during the period of parenchymal invasion. Four family outbreaks were recorded. Thirty, 15, 13 and three cases were detected during the four consecutive 5-year periods. The decrease in this infection over the years is probably related to the change in eating habits.

Autologous stem cell transplantation for poor prognosis Hodgkin's disease in first complete remission: a retrospective study from the Spanish GEL-TAMO cooperative group.

Although more than 50% of Hodgkin's disease patients are cured with conventional chemotherapy, many will relapse and eventually die from their disease. Many efforts have been made to identify poor prognostic factors that could be useful in selecting high-risk patients in 1st CR who may benefit from high-dose chemo/radiotherapy. However, the role of early transplantation in 1st CR remains unclear. We have retrospectively analyzed the results obtained with this procedure in 22 hospitals belonging to the Spanish GEL/TAMO cooperative group. Twenty-seven patients, of whom 19 were males, underwent autologous transplantation for Hodgkin's disease in 1st CR between January 1987 and January 1996. Remission had been achieved after one (n = 22) or two (n = 5) lines of treatment. Twenty-four patients had advanced stage disease, 12 patients bulky mediastinal disease, nine bone marrow involvement and 18 had extranodal disease. Peripheral blood was used as the source of hematopoietic stem cells in 15 patients, BM in nine, and both in three. All but three patients received chemotherapy-based conditioning regimens (16 CBV, four BEAM and four BEAC), while three were conditioned with CY and TBI. There were no transplant-related deaths. Median (range) times to recover >0.5 x 10(9)/l neutrophils and >50 x 10(9)/l platelets were 14 (8-56) days and 16 (8-240) days, respectively. With a median follow-up of 30 (8-66) months, 21 patients are alive and in continuous CR. Four patients who relapsed after transplant at 8, 17.5, 22 and 26 months achieved a second CR with conventional chemotherapy; one patient relapsed 92 months post-transplant and died 5 months afterwards. Another patient died 30.5 months post-transplant from a secondary malignancy. In conclusion, high-dose therapy in poor prognosis Hodgkin's disease in 1st CR was well tolerated with no transplant-related mortalities. Although the follow-up of this series is relatively short, our results seem promising. Nevertheless, late relapses can occur, and the role of this procedure vs conventional treatment in very high-risk patients should be assessed in prospective randomized studies.

A recurrent translocation, t(3;11)(q21;q13), found in two distinct cases of acute myeloid leukemia.

We report two cases of acute myeloid leukemia (M1 and M5B subtypes) with a similar translocation, t(3;11)(q21;q13). We discuss the involvement of these breakpoints in acute leukemia and their putative clinical implications.

A variant t(14;17) in acute promyelocytic leukemia. Positive response to retinoic acid treatment.

We present a case of acute promyelocytic leukemia (APL) carrying an atypical translocation involving chromosomes 14 and 17. This translocation could be considered a variant of the APL-specific t(15;17). Positive response to retinoic acid treatment suggests molecular rearrangement of retinoic acid receptor alpha.

The oxytocin positive elements in the hypothalamic magnocellular nuclei of rats treated with histamine.

The oxytocin positive elements of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, were instigated in 160 male rats through immunohistochemical, morphometric and statistical methods. The rats subdivided into five groups: 20 control rats; 20 rats treated with physiological saline intraperitoneal via (ip); 20 rats treated with physiological saline intracerebroventricular via (icv); 20 histamine (HA) treated rats, ip; and 20 HA treated rats, icv. Some labeled nerve cells appear, mainly, in the lateral part of the SON and the PVN of the control animals. These neurons have central nucleus and oxytocin positive cytoplasmic granulations. After the treatment with physiological saline, ip or icv, no alterations were observed. In HA treated rats, icv, numerous neurons and pathways were observed strongly labeled. Large droplets appear in the SON and in the PVN of these animals. In HA treated rats, ip, the oxytocin positive material is similar to that observed in the control rats. The morphometric and statistical studies confirm these findings. The results are discussed in this paper.

[Non-Hodgkin's lymphoma in childhood. Review of 33 cases]. / Linfoma no Hodgkin infantil. Revisión de 33 casos.

A retrospective study was performed of 33 cases of non Hodgkin's lymphoma in children diagnosed in our hospital. The mean age was 10 years and there were 24 males and 9 females. The distribution, according to Rappaport's diagnostic classification, was: 11 undifferentiated lymphomas, 9 lymphoblastic lymphomas, 6 diffuse histiocytic lymphomas, and 7 cases of other types. Of the 33 patients, 23 had bulky disease (over 5 cm. in diameter). The mean serum LDH and uric acid values were, respectively, 537 (68-2021) and 6.0 (2.7-19). According to Murphy's staging system, the distribution of the cases was as follows: I (1), II (4), III (12), IV (16). Since this study spreads for a long period, several protocols have been used in the treatment of the group, but most patients received the LSA2-L2 regimen. Complete remission (CR) was achieved in 26 cases (78%), this being 100% of the lymphoblastic lymphomas. After a mean follow-up of 45 months, the actuarial survival is 48.1%, and the disease-free survival of patients attaining CR is 60.4%. The prognostic factors analysed, such as histologic type, stage, and serum LDH showed no statistical significance, probably due to the low number of cases studied.

Sequential abdominal reexploration with the zipper technique.

Frequently, several multiple abdominal reexplorations are needed in patients with acute necrotizing hemorrhagic pancreatitis (ANP) or with persistent intraabdominal sepsis (PIAS). Residual undrained necrotic and septic foci lead to multiple organ failure. To provide wide-open drainage of the abdominal cavity, since 1985 we have performed sequential abdominal reexploration with the zipper technique (SARZT) in 24 patients. Apache II score was used to evaluate expected mortality. In the pancreatic necrosis group, with a mean Apache II score of 31, the expected and the observed mortality were 70% and 29%, respectively. In the PIAS group, with a mean Apache II score of 30, the expected and observed mortality were 60 and 28%, respectively. These results are attributed to the sequential reexploration of the abdominal cavity that permits excision and drainage of necrotic and septic foci.

Acetyl-cholinesterase and mono-amine-oxidase activities in the microganglia of the thyroid gland in the rat.

The nervous microganglia of the thyroid gland have been studied in forty adult male rats, their morphology being analyzed by the osmium-zinc iodide technique their acetyl-cholinesterase activity (AChE) by an histochemical specific technique and their mono-amine-oxidase activity (MAO) by a tetrazolium technique. Few but constant microganglia were observed in the thyroid glands. These microganglia are formed by some 4 to 8 nerve cells. Intense mono-amine-oxidase activity (MAO) was found in the nerve cells of these microganglia, being absent in the rest of the thyroid gland. Intense specific acetyl-cholinesterase (AChE) was observed in the nerve cells scattered along nerve branches located in the connective tissue (single nerve cells or small cellular groups). AChE activity was not observed in the microganglia of the thyroid gland.

[The small intestine in the presence of endotoxins in the blood. Effects of splenectomy]. / El intestino delgado durante la endotoxemia. Efectos de la esplenectomía.

We have studied the small intestine by morphologic and histochemical methods of mice treated with Serratia marcescens endotoxin (LD50); the half of the control and endotoxemic animals were splenectomized. We have not observed changes in the only splenectomized animals. We have found important alterations during the endotoxemia in the structure of small intestine, specially in the cells of the mucous membrane, as the cytoplasm and the nucleus. There are an increase of hemorrhagic phenomenons and of mucus, hemodynamic disturbances and loss of continuity of the intestinal wall. These changes are more notable in the endotoxemic and splenectomized animals than in the only endotoxemic animals. These results have be ratified by cytometric and statistic studies. The importance of the intestine in the endotoxemia and the function of the spleen are discussed.

[Effects of extirpation of the piriform area on the ultrastructure of the adrenal cortex]. / Efectos de la extirpación del area piriforme sobre la ultraestructura de la corteza suprerrenal.

We have performed a study about the ultra-structure of the suprarenal cortex in 40 male Wistar rats whose weights oscillated between 200 and 250 grams. The animals were divided in three groups: control group (untouched animals or with simulated operation); experimental group I (animals sacrificed a month after the operation); and experimental group II (animals sacrificed two months after the operation). In the experimental animals, we have performed the bilateral extirpation of the piriform area. We have found a progressive decrease of the lipidic droplets (and of the steroidogenesis) and an increase in the mitochondrial alterations in the cells of fasciculate layer, and also in the cells of reticular layer; what indicates the existence of a decrease in the elaboration of cortex-suprarenal hormones. These results suggest us that the piriform area stimulates the elaboration of hormones by the suprarenal cortex.

[An experimental pain model: the formaldehyde test]. / Un modelo de dolor experimental: el "test" del formaldehído.

Some papers have been published in relation to alternative models of experimental pain in animals. In this work, with the aim of proving the validity, safety, reproducibility and objectivity of this model, we have compared the behaviour of the animal under the formaldehyde test before and after the intracerebroventricular administration of morphine, proving itself as an ideal model for the study of chronic pain caused by an excess of nociception.

Extensive disobliteration of the aorto-iliac and common femoral arteries using the LeVeen plaque cracker.

In 1978 LeVeen et al. described an original technique for extended aortobifemoral disobliteration using a retroperitoneal approach. This technique was introduced to Europe by Widdershoven and Willekens in 1977 and was adopted in Belgium by Suy and Nevelsteen in 1982 and in Spain by Cuesta and Bengoechea in 1984. A group of 228 patients treated by the LeVeen's method from 1982 to 1987 were followed-up for a mean of 21 months (1-54). Disabling claudication (66%) or more advanced ischaemia (34%) was the indication for treatment. An aorto-bifemoral endarterectomy was performed in 124 patients. Aorto-biiliac endarterectomy in 39, unilateral aortofemoral endarterectomy with a contralateral aorto-iliac endarterectomy in 17 and unilateral iliofemoral endarterectomy in 48 cases. There were seven postoperative deaths (3%) and an early thrombectomy had to be performed in 8 patients. There were 14 late deaths. Occlusion occurred in 11 patients giving a 3-year-patency rate of 97%. There were no late complications related to the technique. It is concluded that disobliteration using the LeVeen technique compares well with prosthetic grafting. Since this method does not require the use of foreign material the patient is protected from the complications sometimes seen after the insertion of prosthetic grafts.