Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review. / Síndrome ROHHAD (obesidad de rápida progresión, disfunción hipotalámica, hipoventilación y disregulación autonómica). Presentación de un caso y revisión de la literatura.

INTRODUCTION: ROHHAD syndrome (rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation) is a rare and complex disease, presenting in previously healthy children at the age of 2-4 years. Up to 40% of cases are associated with neural crest tumours. DEVELOPMENT: We present the case of a 2-year-old girl with symptoms of rapidly progressing obesity, who a few months later developed hypothalamic dysfunction with severe electrolyte imbalance, behaviour disorder, hypoventilation, and severe autonomic dysregulation, among other symptoms. Although the pathophysiology of this syndrome remains unclear, an autoimmune hypothesis has been proposed for ROHHAD. Therefore, after obtaining a limited response to intravenous immunoglobulins, we decided to test the response to a high dose cyclophosphamide (low dose was not effective either). Unfortunately our patient experienced many severe complications (among them central pontine myelinolysis, from which the patient recovered, and failure to wean from the ventilator requiring tracheostomy and long term ventilation) that required a prolonged ICU stay. Although her behaviour improved, our patient unfortunately died suddenly at home at the age of 5 due to respiratory pathology. CONCLUSIONS: ROHHAD syndrome is a rare and little-known disease which requires a multidisciplinary approach because it involves complex symptoms and multiple organ system involvement. Alveolar hypoventilation should be identified early and appropriate treatment should be started promptly for the best possible outcome. Immunomodulatory treatment with immunoglobulins, cyclophosphamide, or rituximab has previously resulted in symptom improvement in some cases. Because of the low incidence of the syndrome, multi-centre studies must be carried out in order to gather more accurate information about ROHHAD pathophysiology and design an appropriate therapeutic approach.

Squamous cell carcinoma over pilonidal chronic disease. A new therapeutic approach.

INTRODUCTION: Pilonidal sinus is a very common disease. Malignant transformation occurs in 0,1% of patients. We present a case of squamous cell carcinoma arised from recurrent pilonidal disease, managed by multimodal treatment. PRESENTATION OF CASE: We present a 70-year-old man with chronic pilonidal sinus. Inflammation had worsened in previous months and exploration revealed a large ulcerative mass which biopsy showed a squamous cell carcinoma. CT scan and MRI imaging showed tumoral invasion of the coccyx and both gluteus major muscles. Neoadjuvant radiotherapy, chemotherapy as radiosensitizer and surgery with intraoperative radiotherapy was decided in the multidisciplinary tumor committee. Post neoadjuvant therapy MRI showed partial response with a decrease of the mass but persistence of the coccyx infiltration. Surgery consisted in en-bloc resection of the tumor with presacral tissues, coccyx and partial gluteal resection. Intraoperative radiotherapy was administered over the sacrum and in the bed of the coccyx resection. One week later, reconstructive surgery was practiced using a latissimus dorsi free flap, advancement of gluteal flaps and skin graft. Histological examination showed no residual tumor. The patient is currently asymptomatic and he has a satisfactory quality of life. DISCUSSION: Although squamous cell carcinoma is rare, it must be suspected in patients with recurrent pilonidal disease. Diagnosis is done by histological examination of biopsies. This type of tumors have a high local recurrence rate. CONCLUSION: We propose a multimodal treatment that includes neoadjuvant radiotherapy and chemotherapy as radiosensitizer and surgery plus intraoperative radiotherapy with the aim to decrease local recurrence rate.

Active and reactive behaviour in human mobility: the influence of attraction points on pedestrians.

Human mobility is becoming an accessible field of study, thanks to the progress and availability of tracking technologies as a common feature of smart phones. We describe an example of a scalable experiment exploiting these circumstances at a public, outdoor fair in Barcelona (Spain). Participants were tracked while wandering through an open space with activity stands attracting their attention. We develop a general modelling framework based on Langevin dynamics, which allows us to test the influence of two distinct types of ingredients on mobility: reactive or context-dependent factors, modelled by means of a force field generated by attraction points in a given spatial configuration and active or inherent factors, modelled from intrinsic movement patterns of the subjects. The additive and constructive framework model accounts for some observed features. Starting with the simplest model (purely random walkers) as a reference, we progressively introduce different ingredients such as persistence, memory and perceptual landscape, aiming to untangle active and reactive contributions and quantify their respective relevance. The proposed approach may help in anticipating the spatial distribution of citizens in alternative scenarios and in improving the design of public events based on a facts-based approach.

Antioxidant enzyme activities and the production of MDA and 8-oxo-dG in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a neoplastic disease susceptible to antioxidant enzyme alterations and oxidative stress. We have examined the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the oxidized/reduced glutathione (GSSG/GSH) ratio together with the levels of malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG) in lymphocytes of CLL patients and compared them with those of normal subjects of the same age. SOD and CAT activity decreased in CLL lymphocytes while GPx activity increased. GSH content of CLL lymphocytes also increased, and GSSG concentration remained constant. Thus, a reduced GSSG/GSH ratio was obtained. The oxidation product MDA, and the damaged DNA base 8-oxo-dG were also increased in CLL. The observed changes in enzyme activities, GSSG/GSH ratio, and MDA were significantly enhanced as the duration of the disease increased in years. The results support a predominant oxidative stress status in CLL lymphocytes and emphasize the role of the examined parameters as markers of the disease evolution.

Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients.

With the availability of new, broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations in the management of febrile, neutropenic cancer patients. The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients, and to examine the frequency with which second-line antibiotics (amikacin, vancomycin, or both) were required. A prospective clinical trial was carried out in a single centre. Eligible patients with solid tumours or lymphoma were randomised to receive monotherapy with ceftazidime or imipenem. In the event of no response, amikacin and/or vancomycin were added in 48-72 h intervals (sequentially, or according to clinical or microbiological data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days. Febrile episodes were classified as microbiologically (34%) or clinically documented (42%), and fever of unknown origin (24%). Gram-negative infections (57%) predominated over gram-positive isolates (30%). The overall success rate with monotherapy (69% versus 70%), or with modification (20% versus 23%) were equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours. Early addition of amikacin and/or vancomycin resolves most failures of the first step.

Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Fifty percent of lung cancers arise in patients over 65 years old and 30% in those over 70. The aim of this study was to evaluate response, survival and tolerability of the combination carboplatin-gemcitabine in elderly patients with advanced non-small cell lung cancer (NSCLC). METHODS: Between May 1998 and December 2000, 88 patients were included. Median age was 74 (range 65-83). Treatment consisted of gemcitabine 1250 mg/m(2) (1000 mg/m(2) in the first six patients) on days 1 and 8, and carboplatin AUC=4 on day 1, every 21 days. Prognostic factors for survival were analysed. Performance status (PS) and symptoms were evaluated before and after three and six courses. RESULTS: A total of 400 cycles were administered (median of four per patient). WHO grades 3-4 toxicities were: neutropenia in 13% of the cycles, thrombocytopenia and anaemia in 4.5 and 14.7% of patients in any cycle. There was one treatment-related death. According to the intent-to-treat analysis, 33 patients achieved objective response, 33 had stable disease, and 22 had treatment failure (progression in 18 patients). Median and 1 year survival were 9 months and 34%, respectively. Median time to progression was 8 months. Only disease stage and PS showed independent prognostic value. Comorbidity and PS displayed no close correlation. Symptom improvement was seen as follows: pain (61.7%), dyspnea (50%), haemoptysis (80%), anorexia (62.5%) and asthenia (61.5%). CONCLUSIONS: The combination carboplatin-gemcitabine at these doses is feasible in elderly patients with advanced non-small cell lung cancer. Tolerability and toxicity are acceptable. Response rate and survival stand in the range of the most active regimens. Comorbidity and PS showed prognostic independence.

Oxidative stress induces the expression of the major histocompatibility complex in murine tumor cells.

The effect of t-butyl hydroperoxide (t-BOOH) on the induction of the Major Histocompatibility Complex (MHC) class I genes has been studied in two cell clones (B9 and G2) of the methylcholanthrene-induced murine fibrosarcoma GR9. These two clones were selected based on their different biological and biochemical behavior specially related to their tumor induction capability when injected into a BALB/c mouse. t-BOOH (0.125 mM) induced the expression of H-2 molecules in both cell clones. In B9 cell clone, in which MHC basal expression is very low or absent, t-BOOH significantly induced H-2Kd, H-2Dd and H-2Ld molecules. In G2 cell clone the expression of MHC class I genes was also enhanced by the xenobiotic, the effect being especially significant on the H-2Ld molecule which is not expressed under basal conditions. H-2 molecules expression was accompanied by the activation of the transactivator factor NF kappa B. These results suggest that oxidative stress may modulate the antigen expression of tumor cells and thus the immune response of the host organism. Basal levels of oxidative parameters, such as anti-oxidant enzymes, malondialdehyde (MDA) and the DNA damaged base 8-hydroxy-2'-deoxyguanosine (8-OHdG), showed differences between the two fibrosarcoma cell clones.

Long-term results after combined modality treatment for non-metastatic osteosarcoma.

Since the introduction of multimodality treatment, the prognosis of patients with high-grade non-metastatic osteosarcoma has significantly improved. A retrospective review was performed to assess the long-term results of this approach in a single centre setting, and to investigate the impact of potential clinical prognostic factors. Between 1985 and 1993, 35 patients with stage II-A and II-B osteosarcoma underwent preoperative chemotherapy (high-dose methotrexate), wide surgery, and adjuvant chemotherapy (cisplatin-doxorubicin/bleo-mycin-cyclophosphamide-dactinomycin) (modified T-10A protocol). There were 19 males and 16 females. Median patient age was 17 y (range 12-42). Primary tumour sites were the extremities (83%) and axial bones (17%). In spite of an unfavourable grade 3-4 histologic response rate to high-dose methotrexate of 12%, 31 (88%) patients were able to undergo limb-sparing surgery and 28 (80%) were rendered disease free after the planned therapy. Median follow-up was 8 y. The actuarial overall survival and disease-free survival rates were 64% and 49% at 5 y, and 59% and 49% at 10 y, respectively. Tumour size and primary site were significant prognostic factors for survival in univariate analyses. In conclusion, long-term survival after combined modality treatment can be achieved in more than 60% of patients with localised osteosarcoma, including non-appendicular lesions. Limb-sparing surgery is a realistic goal for most cases. The prognostic value of tumour necrosis and the efficacy of neoadjuvant chemotherapy should be interpreted according to individual high-dose methotrexate scheduling.

Metastatic follicular thyroid carcinoma to the kidney: a case report.

Clinically detectable well-differentiated metastatic thyroid cancer to the kidney is rare, with only 12 cases reported in the medical literature. The authors report a case of metastatic thyroid carcinoma to the kidney in a patient with widespread dissemination. She underwent total thyroidectomy, radical left nephrectomy, radioactive ablation with I-131, radiotherapy, and thyroid suppression therapy. Well-differentiated thyroid metastatic cancer can be amenable to treatment with successful long-term results.

[Descriptive epidemiology of transitory ischemic attack: a study in Muro d'Alcoi]. / Epidemiología descriptiva del accidente isquémico transitorio: estudio en Muro d'Alcoi.

A door-to-door survey of transient ischemic attack was conducted in Muro de Alcoi using a randomized sample. We randomly choose 646 people of the 4.525 included in the census. The prevalence ratio found for TIA and stroke were 12.3 per 1,000 people (95% CI 3.9-20.7). The age-specific prevalence rates for male and for women were 12.4 per 1,000 (95% CI 0.3-24.5) and 12.3 per 1,000 (95% CI 0.4-24.2) respectively. The work suggests that methodology of ascertainment strongly influences in the obtained rates, and reinforces the data of our previous whole population work in the same area.

[Descriptive epidemiology of risk factors in cerebrovascular disorders:a study in Muro d'Alcoi]. / Epidemiología descriptiva de los factores de riesgo cerebrovasculares: el estudio en Muro d'Alcoi.

We evaluated cerebrovascular risk factors and the values of cholesterol and triglicerides in the survey in Muro d'Alcoi using a door-to-door randomised interview. We found 14.9% hypertensives, 5.5% persons with diabetes, 1.2% with heart diseases and 42.1 persons with tabaccoism into the 646 persons evaluated. The Serum Cholesterol levels were high and we observed that 62% of males and 63.8% of females had values higher than 200 mg/dl. Our study showed that 24.8% of males and 12% of females presented values of triglicerides higher than 150 mg/dl. The data of risk factors were comparable with the findings described in Beniarres, Lorcha and Planes, located in the same healthy area.

[Epidemiology of urinary lithiasis]. / Epidemiología de la litiasis urinaria.

An epidemiological study of urinary stone disease has been carried out in the districts of La Sierra and Hellín (Albacete, Spain). Between January 1992 and December 1999 a total of 887 patients with urinary lithiasis have been studied, analysing the number of patients discharged from hospital with the primary diagnosis of lithiasis, the distribution of lithiasis by area, age, gender, family history of lithiasis, diet, occupation and concurrent pathology. The geographical, geological, and climatic conditions, the composition of the water supply and the clinical characteristics are described. The incidence of urinary lithiasis in the whole area in 2.66 per thousand inhabitants/year, showing a male predominance with a male:female ratio of 1.26:1. The mean age was 51.34 years (bimodal distribution with peaks in the 4th and 7th decades). 20.41% of the patients had a family history, with the father being the most frequently affected relation. Those occupations associated with a sedentary life style or with a hot, dry workplace show a higher incidence of lithiasis. A hot, dry climate favours the formation of urinary lithiasis and the highest incidence of lithiasis is in the summer, during the months of July and August. No statistically significant influence was shown between at the hardness of the water and the incidence of urinary lithiasis in the study population.

Use of GlideScope for double lumen endotracheal tube insertion in an awake patient with difficult airway.

There is scientific evidence that an anticipated difficult airway must be managed with the patient being awake. The GlideScope has been proven to be a useful device to intubate the trachea in some instances when difficult airway is present, and particularly in the awake patient. It has also been used for double lumen tube (DLT) in the anaesthetized patient, but its use with DLT in both circumstances, awake patients with difficult airway has not been described. GlideScope enabled us to achieve accurate local anesthetic spraying and a successful endotracheal intubation with a double lumen tube (DLT) in an awake patient with predicted difficult airway and bronchoaspiration risk. Different ways to resolve cases like this can be found in the anesthetic literature, but we think this could be another option to bear in mind. We also describe a new variation in the maneuver of introducing a DLT into the trachea under GlideScope view as DLT presents with some difficulties when introduced under normal circumstances. This option could add some risk for the patients when used in inexperienced hands and there is not sufficient scientific evidence in the literature to recommend it for all cases.

Inhibition of complement activity in murine leprosy.

NIH mice infected with Mycobacterium lepraemurium (MLM) show a marked depression in their levels of hemolytic complement that is proportional to the degree of infection. The defect affects more the activation of complement through the classical pathway (CPW) than the activation of complement through the alternative pathway. Although this low activity of CPW-complement may be due to different causes (complement consumption by the infecting microorganism, lack of biosynthesis of complement components, or the presence of complement inhibitory factors), our results seem to support the last possibility. The generation of factors in the infected animals that inhibit the autologous activity of complement as the infection goes on reduces the risk of complement-mediated tissue damage and prolongs the survival time of the host, a wise strategy on the part of the MLM to assure its own survival as a parasite.

Serum enzymatic changes following infection of mice with Mycobacterium lepraemurium.

Mice injected interperitoneally with 1.5 X 10(8) Mycobacterium lepraemurium develop progressive visceral alterations that are reflected in the lactic dehydrogenase (LDH), glutamate-pyruvate transaminase (GPT), and glutamate-oxalacetate transaminase (GOT) levels. The rise in GPT and GOT levels starts earlier (about 30 days post-infection) than the rise in LDH activity (about 70 days), but the latter shows the most impressive increases. Differences between infected and control groups, however, reach statistical significance only at 75 days (LDH), 90 days (GOT), and 150 days (GPT) post-inoculation, still well before the appearance of obvious external signs of infection (about 240 days in our model). It is suggested that the ratio of enzyme levels in infected to enzyme levels in uninfected animals could be taken as a reliable index to follow the progress of the infection with M. lepraemurium.

Transitory macrophage activation in the granulomatous lesions of Mycobacterium lepraemurium-induced lepromatoid leprosy in the mouse.

A kinetic study on the evolution of granulomas that appear in the liver of NIH mice inoculated with 10(8) Mycobacterium lepraemurium by the intraperitoneal route has been performed. The liver was chosen because of its nonlymphoid histology which allowed us to visualize the appearance and maturation of the cell infiltrates generated as a consequence of the mycobacterial infection. The study analyzed both the macrophage activation within the granulomas and the fate of bacilli within the macrophage. The results showed that this mycobacteriosis induces a relatively early macrophage activation (a very likely result of a cell-mediated immune response triggered by the bacilli) that peaks between 45 and 60 days postinoculation, fades thereafter, and practically disappears several days later. Bacilli are susceptible to the microbicidal effects of activated macrophages, but when the macrophages are turned off (probably due to active suppressive mechanisms), the surviving bacilli reinitiate the infection with no further macrophage opposition. As a result, more phagocytes are attracted to the infection sites and the cell infiltrates grow steadily to become confluent, increasing the granuloma fraction and eventually replacing the liver parenchyma. The findings suggest that in murine "leprosy" infection, early immunological changes occur that enable the macrophages present in the granulomas to kill the infecting M. lepraemurium regardless of the eventual lepromatoid evolution of the granulomas. Lepromatoid granulomas in the mouse and lepromatous granulomas in man are equivalent structures in regard to their histology and bacteriology.