Nitric oxide pathway in the nucleus raphe magnus modulates hypoxic ventilatory response but not anapyrexia in rats

Nucleus raphe magnus (NRM) is one of the cellular groups of the brainstem that is involved in the physiologic responses to hypoxia and contains nitric oxide (NO) synthase. In the present study, we assessed the role of NO pathway in the NRM on the hypoxic ventilatory response (HVR) and anapyrexia (a regulated decrease in body temperature). To this end, pulmonary ventilation (VE) and body temperature (Tb) of male Wistar rats were measured before and after microinjection of N-monomethyl-L-arginine (L-NMMA, a nonselective nitric oxide synthase inhibitor, 12.5 microg/0.1 microl) into the NRM, followed by hypoxia. Control rats received microinjection of saline. Under resting conditions, L-NMMA treatment did not affect pulmonary VE or Tb. Typical hypoxia-induced hyperventilation and anapyrexia were observed after saline treatment. L-NMMA into the NRM reduced the HVR but did not affect hypoxia-induced anapyrexia. In conclusion, the present study indicates that NO in the NRM is involved in HVR, exerts an inhibitory modulation on the NRM neurons but does not mediate hypoxia-induced anapyrexia.     

Living with pain: an existential focus

In the routine of a hospital, during my nursing practice of providing care to patients with pain, it was shown to me as reaching beyond a biological sphere included in an existential dimension. Something in this experience disturbed me and I felt the need to understand these people suffering from pain, asking how they understand their pain and what is the meaning of experiencing painful chronic situations. In the attempt to find a way to obtain such understanding, I searched for some ideas stemming from phenomenology. Then, I interviewed the subjects individually based on the central question: "How is your experience with pain? Tell me about this". After the analysis, I was able to understand that pain is a way to narrow the horizon of possibilities and transformations in existence. It is not only the physical body that is ill, but also life is affected in its various dimensions, fundamentally with regard to the family, work and self-relation world.     

Evaluation of adult papillary thyroid carcinomas by comparative genomic hybridization and microsatellite instability analysis

To clarify the mechanism of tumorigenesis in papillary thyroid carcinoma (PTC) and ascertain whether genomic changes correlate with histologic features, we conducted a comprehensive molecular evaluation of PTC using comparative genomic hybridization (CGH) and microsatellite instability (MSI) analysis in a set of 17 histologically well-characterized PTC specimens. To our knowledge, this is the first study that evaluates chromosomal and nucleotide instability in the same PTC tumor specimens. Four of 15 samples (27%) had aberrations detected by CGH. All four had a partial or complete gain of chromosome 20, and 3 of 4 had a partial or complete loss of chromosome 13. No MSI was detected in any of the PTC samples (n=16), and all samples examined by immunohistochemistry (n=9) expressed the DNA repair enzymes hmlh1 and hmsh2. All PTC samples with abnormal CGH had vascular invasion or invasion of the thyroid capsule, and there was a significant correlation between the presence of chromosomal aberrations and capsular/vascular invasion (P=0.026). We conclude that although chromosomal and microsatellite instability are uncommon in PTC, tumors with chromosomal aberrations are more likely to be associated with invasion.     

Serum gamma-glutamyltransferase alteration in hepatic schistosomiasis doesn't correlate with parasitic load and precedes ultrasound alterations

BACKGROUND: Liver disorders are the major manifestations of schistosomiasis mansoni. Factors that account for increased concentrations of cholestasis-indicating enzymes in the hepatosplenic form of the disease are unknown. OBJECTIVE: To assess the correlation between increased gamma-glutamyltransferase serum levels and both the parasitic load and ultrasound alterations in patients with schistosomiasis. PATIENTS AND METHODS: Twenty-five patients with the chronic form of schistosomiasis were assessed for the presence or absence of increased enzymatic levels, for the parasitic load (low x medium/high) and for ultrasound parameters. Furthermore, analysis of prothrombin time and a platelet count were performed. RESULTS: Of the 25 patients, 13 showed increased gamma-glutamyltransferase plasma levels. No significant correlation was found between increased gamma-glutamyltransferase levels and the parasitic load, or between increased enzyme levels and ultrasound alterations. Nor did the prothrombin index or the platelet count differ between the two groups (normal gamma-glutamyltransferase levels and increased gamma-glutamyltransferase levels). CONCLUSION: The parasitic load explains no rise in gamma-glutamyltransferase plasma levels in patients with the chronic form of schistosomiasis, and conventional ultrasound is not a sensitive method to detect the alteration suggested by the increased enzyme level in those patients.     

Phase II trial and pharmacokinetic study of thalidomide in patients with metastatic colorectal cancer

Introduction. This study was designed to estimate the percentage of objective tumor responses, toxicity profile, and obtain additional information about the plasma pharmacokinetics of thalidomide in patients with refractory and progressing metastatic colorectal cancer. Study design. This phase II clinical trial was conducted according to the two-stage Simon method with the inclusion of consecutive patients. The study protocol was approved by the Institutional Review Board (IRB) of the Academic Hospital (HCPA) of the Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. Patients and methods. Seventeen patients with previously treated, refractory progressive metastatic colorectal cancer were eligible. Six patients had prior radiotherapy. The patients had a median of one previous chemotherapy regimen. Patients were initially treated with 200mg/day of thalidomide with an increase in dose by 200mg/day every 2 weeks until a final daily dose of 800mg/day was achieved. Patients were evaluated every 8 weeks for response by radiographic criteria. Plasma pharmacokinetics studies were performed in four patients at 200mg level and in one patient at 600mg during the first 24h. Main outcome measures and results. A total of 17 patients were accrued, all of them being evaluable for toxicity and 14 for response. Thalidomide was well tolerated, with constipation, somnolence, dizziness, and dry mouth being the major toxicities. There were no objective response or stable disease. The median survival was 3.6 months. Single-agent thalidomide is a generally well-tolerated drug that showed no antitumor activity in patients with advanced pretreated metastatic colorectal cancer. Although thalidomide did not show antitumor activity in this patient population, future studies of this agent in patients at initial stages of the disease (when its antiangiogenic properties may be more relevant to disease progression) could be considered.     

Tretinoin Peeling

BACKGROUND: Topical tretinoin has been used for a long time to improve photoaged skin, but this therapy takes quite a few months to show some clinical changes. Because of that, we think tretinoin peeling would be an excellent choice for improvement of photoaged skin. OBECTIVE: Our objective was to show the clinical and histologic modifications of the skin after five sessions of tretinoin peeling. METHODS: The authors studied the clinical and histologic modification that occurred in 15 female patients after conducting tretinoin peeling procedures twice a week in concentrations of 1-5%. Conventional sectioning of punch biopsy specimens was conducted before and after the treatment. RESULTS: Clinical improvement was observed in the skin texture and appearance. Through histologic examinations, a decrease in the corneous layer and an increase in the epidermal thickness were noticed, inducing an improvement of its stratification, as well as the formation of cristae cutis. CONCLUSION: It was concluded that the peeling conducted with serial tretinoin showed good clinical and histologic results, especially for the treatment of photoaged skins I and II, melasma, ephelis, and acne degree I, as well as being practical, quick, and easily accomplished with no side effects.     

Orthodontic space closure of lost traumatized anterior teeth – case report

Abstract – This case report refers to an 11‐year‐old boy with avulsion of the upper left central and lateral incisors. The teeth were replanted after 4 h, splinted with a semi‐rigid splint for 12 days, and then endodontically treated. Severe progressive root resorption was seen after 2 years and the teeth were extracted. The boy had a normal occlusion with spacing in both jaws and slight protrusion of the anterior teeth. The treatment objectives were to close some of the spaces by mesial movement of the buccal segments in the upper jaw to minimize bone loss for a future single osseointegrated implant. Fixed appliance in combination with a removable plate was used for the mesial movements, levelling, and alignment of the upper jaw. Fixed appliance in the lower jaw and Class II traction were used for the final adjustment of the occlusion. A good occlusion with coincident upper and lower midlines and up‐righted anterior teeth were achieved. A Maryland bridge was performed as a temporary solution for a future osseointegrated implant.     

Acute effects of low doses of melatonin on the sleep of young healthy subjects

This study was undertaken to evaluate the acute effects of single low doses of melatonin given to healthy volunteers in the evening. Six healthy male volunteers (age range 22-24 years) participated in this study, after signing an informed consent form. They received in a double-blind fashion placebo or 0.3 or 1.0 mg melatonin at three fixed times: 18:00, 20:00, and 21:00 hr. Polysomnographic recordings began immediately thereafter, with their being allowed to sleep. Prior to each experimental session and in the following morning, subjects completed a sleep quality questionnaire, the Profile of Mood States, the Stanford Sleepiness Scale, and underwent a visual reaction test. Significant decrease on sleep latencies was found following melatonin treatment at 18:00 and 20:00 hr. In addition, melatonin tended to improve sleep efficiency and to reduce intermittent wakefulness. However, at 21:00 hr, 0.3 mg melatonin increased latency to sleep onset and 1.0 mg melatonin had no effect on sleep variables. Furthermore, melatonin given at different times did not alter subjective sleepiness, mood, and reaction time in the following morning. The results from the present study support the notion that administration of low doses of melatonin, mimicking the nocturnal physiological concentration of this hormone may exert immediate sleep-inducing effects.