RESUMO
Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.
Assuntos
Respiração Celular , Ecossistema , Aquecimento Global , Tundra , Regiões Árticas , Carbono/metabolismo , Carbono/análise , Ciclo do Carbono , Conjuntos de Dados como Assunto , Concentração de Íons de Hidrogênio , Nitrogênio/metabolismo , Nitrogênio/análise , Plantas/metabolismo , Estações do Ano , Solo/química , Microbiologia do Solo , Temperatura , Fatores de TempoRESUMO
PURPOSE: The demand for objective and outcome-based facts about surgical results after radical prostatectomy (RP) is increasing. Systematic feedback is also essential for each surgeon to improve his/her performance. METHODS: RP outcome data (e.g., pT-stage and margin status) have been registered at Sahlgrenska University Hospital (SUH) since 1988 and patient-related outcome measures (PROM) have been registered since 2001. The National Prostate Cancer Registry (NPCR) has covered all Regions in Sweden since 1998 and includes PROM-data from 2008. Initially PROM was on-paper questionnaires but due since 2018 all PROMs are collected electronically. In 2014 an on-line "dashboard" panel was introduced, showing the results for ten quality-control variables in real-time. Since 2017 all RP data on hospital, regional, and national levels are publicly accessible on-line on "www.npcr.se/RATTEN". RESULTS: The early PROM-data from SUH have been used for internal quality control. As national clinical and PROM-data from the NPCR have been made accessible on-line and in real-time we have incorporated this into our pre-existing protocol. Our data are now internally available as real-time NPCR reports on the individual surgeons' results, as well as ePROM data. We can compare the results of each surgeon internally and to other departments' aggregated data. The public can access data and compare hospital level data on "RATTEN". CONCLUSIONS: The process of quality control of RP locally at SUH, and nationally through the NPCR, has been long but fruitful. The online design, with direct real-time feedback to the institutions that report the data, is essential.
Assuntos
Feedback Formativo , Prostatectomia/normas , Neoplasias da Próstata/cirurgia , Controle de Qualidade , Humanos , Masculino , Prostatectomia/métodos , Suécia , Fatores de TempoRESUMO
Regulation of skeletal muscle blood flow is a complex process, which involves an integration of multiple mechanisms and a number of vasoactive compounds. Overall, muscle blood flow is regulated through a balance between vasoconstrictor and vasodilator signals. In a healthy cardiovascular system, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular function by enhancing vasodilator formation and reducing the levels of vasoconstrictors and ROS.
Assuntos
Diabetes Mellitus/fisiopatologia , Exercício Físico/fisiologia , Saúde , Hipertensão/fisiopatologia , Microcirculação/fisiologia , Músculo Esquelético/irrigação sanguínea , Diabetes Mellitus/patologia , Hemodinâmica , Humanos , Hipertensão/patologia , Microvasos/patologia , Microvasos/fisiologia , Contração MuscularRESUMO
The present study examined if an elevated nitrate intake would improve VO(2) kinetics, endurance, and repeated sprint capacity in elite endurance athletes. Ten highly trained cyclists (72 ± 4 mL O(2) /kg/min, mean ± standard deviation) underwent testing for VO(2) kinetics (3 × 6 min at 298 ± 28 W), endurance (120 min preload followed by a 400-kcal time trial), and repeated sprint capacity (6 × 20 s sprints, recovery 100 s) during two 6-day periods in randomized order with a daily ingestion of either 0.5 L beetroot (BR) juice to increase nitrate levels or a 0.5 L placebo (PLA) drink with blackcurrant juice. Plasma NOx (nitrate + nitrite) levels were higher (P < 0.01) in BR (147 ± 102 and 159 ± 103 µM after 4 and 6 days of beverage intake, respectively) compared with PLA (41 ± 10 and 40 ± 7 µM). VO(2) kinetics and exercise economy were the same in BR and PLA. Time-trial performance was similar with an average completion time of 18:20 and 18:37 min:s in BR and PLA, respectively, with average power outputs of 290 ± 43 W in BR and 285 ± 44 W in PLA. Peak and mean power during repeated sprinting were similar in BR and PLA. In contrast to observations in moderately trained subjects intake of BR juice had no effect on VO(2) kinetics and performance in elite cyclists.
Assuntos
Ciclismo/fisiologia , Suplementos Nutricionais , Nitratos/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Resistência Física/efeitos dos fármacos , Adulto , Atletas , Ingestão de Energia , Humanos , Cinética , Masculino , Nitratos/administração & dosagemRESUMO
The regulation of blood flow to skeletal muscle involves a complex interaction between several locally formed vasodilators that are produced both in the skeletal muscle interstitium and intravascularly. The gas nitric oxide (NO) and the purines ATP and adenosine, are potent vasodilators that are formed by multiple cell types and released into the skeletal muscle interstitium and in plasma in response to muscle contraction. Cellular sources of ATP and NO in plasma are erythrocytes and endothelial cells, whereas interstitial sources are skeletal muscle cells and endothelial cells. Adenosine originates primarily from extracellular degradation of ATP. During exercise the concentrations of ATP and adenosine increase markedly in the interstitium with smaller increases occurring in plasma, and thus the interstitial concentration during exercise is severalfold higher than in plasma. The concentration of NO metabolites (NOx) in interstitium and plasma does not change during exercise and is similar in the two compartments. Adenosine and NO have been shown to contribute to exercise hyperaemia whereas the role of ATP remains unclear due to lack of specific purinergic receptor blockers. The relative role of intravascular versus interstitial vasodilators is not known but evidence suggests that both compartments are important. In cardiovascular disease, a reduced capacity to form adenosine in the muscle interstitium may be a contributing factor in increased peripheral vascular resistance.
Assuntos
Trifosfato de Adenosina/fisiologia , Adenosina/fisiologia , Exercício Físico/fisiologia , Hiperemia/fisiopatologia , Óxido Nítrico/fisiologia , Humanos , Hipertensão/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiologiaRESUMO
Ageing is associated with an impaired ability to modulate sympathetic vasoconstrictor activity (functional sympatholysis) and a reduced exercise hyperaemia. The purpose of this study was to investigate whether a physically active lifestyle can offset the impaired functional sympatholysis and exercise hyperaemia in the leg and whether ATP signalling is altered by ageing and physical activity. Leg haemodynamics, interstitial [ATP] and P2Y(2) receptor content was determined in eight young (23 ± 1 years), eight lifelong sedentary elderly (66 ± 2 years) and eight lifelong active elderly (62 ± 2 years) men at rest and during one-legged knee extensions (12 W and 45% maximal workload (WL(max))) and arterial infusion of ACh and ATP with and without tyramine. The vasodilatory response to ACh was lowest in the sedentary elderly, higher in active elderly (P < 0.05) and highest in the young men (P < 0.05), whereas ATP-induced vasodilatation was lower in the sedentary elderly (P < 0.05). During exercise (12 W), leg blood flow, vascular conductance and VO2 was lower and leg lactate release higher in the sedentary elderly compared to the young (P < 0.05), whereas there was no difference between the active elderly and young. Interstitial [ATP] during exercise and P2Y(2) receptor content were higher in the active elderly compared to the sedentary elderly (P < 0.05). Tyramine infusion lowered resting vascular conductance in all groups, but only in the sedentary elderly during exercise (P < 0.05). Tyramine did not alter the vasodilator response to ATP infusion in any of the three groups. Plasma [noradrenaline] increased more during tyramine infusion in both elderly groups compared to young (P < 0.05). A lifelong physically active lifestyle can maintain an intact functional sympatholysis during exercise and vasodilator response to ATP despite a reduction in endothelial nitric oxide function. A physically active lifestyle increases interstitial ATP levels and skeletal muscle P2Y(2) receptor content.
Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Perna (Membro)/fisiologia , Acetilcolina/farmacologia , Trifosfato de Adenosina/farmacologia , Adulto , Idoso , Endotélio Vascular/fisiopatologia , Epinefrina/sangue , Artéria Femoral/fisiologia , Humanos , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Norepinefrina/sangue , Receptores Purinérgicos P2Y2/fisiologia , Adulto JovemRESUMO
During exercise, oxygen delivery to skeletal muscle is elevated to meet the increased oxygen demand. The increase in blood flow to skeletal muscle is achieved by vasodilators formed locally in the muscle tissue, either on the intraluminal or on the extraluminal side of the blood vessels. A number of vasodilators have been shown to bring about this increase in blood flow and, importantly, interactions between these compounds seem to be essential for the precise regulation of blood flow. Two compounds stand out as central in these vasodilator interactions: nitric oxide (NO) and prostacyclin. These two vasodilators are both stimulated by several compounds, e.g. adenosine, ATP, acetylcholine and bradykinin, and are affected by mechanically induced signals, such as shear stress. NO and prostacyclin have also been shown to interact in a redundant manner where one system can take over when formation of the other is compromised. Although numerous studies have examined the role of single and multiple pharmacological inhibition of different vasodilator systems, and important vasodilators and interactions have been identified, a large part of the exercise hyperaemic response remains unexplained. It is plausible that this remaining hyperaemia may be explained by cAMP- and cGMP-independent smooth muscle relaxation, such as effects of endothelial derived hyperpolarization factors (EDHFs) or through metabolic modulation of sympathetic effects. The nature and role of EDHF as well as potential novel mechanisms in muscle blood flow regulation remain to be further explored to fully elucidate the regulation of exercise hyperaemia.
Assuntos
Exercício Físico , Contração Muscular , Músculo Esquelético/irrigação sanguínea , Vasodilatação , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Fatores Biológicos/metabolismo , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Epoprostenol/metabolismo , Homeostase , Humanos , Hiperemia/metabolismo , Hiperemia/fisiopatologia , Músculo Esquelético/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Óxido Nítrico/metabolismo , Consumo de Oxigênio , Fluxo Sanguíneo Regional , Transdução de SinaisRESUMO
BACKGROUND: Robot-assisted nephroureterectomy (RANU) is the primary treatment for upper tract urothelial carcinoma (UTUC) at our hospital for patients with clinical stage less than T2, and for patients with invasive tumours, but unfit for major surgery. OBJECTIVE: To assess peri-operative conditions and outcomes of RANU at our unit, and to evaluate the safety of the procedure. METHODS: The medical records of all 166 patients undergoing RANU for suspected UTUC and followed for more than three months in a large university hospital in Sweden were reviewed retrospectively. After the exclusion of twenty patients because of previous cystectomy, simultaneous surgical procedure, or other tumour types than UTUC in the pathological report, 146 patients remained for the analyses. The primary endpoint was complication rate according to Clavien-Dindo at 90 days. Secondary endpoints were perioperative bleeding, violation of oncological surgical principles, hospital stay, and re-admission within 90 days. RESULTS: The median age was 75 [(Inter Quartile Range) IQR 70-80] years and 57% of the patients had an ASA score above 2. According to Clavien-Dindo, one patient had a grade 3 complication, and no patient had a grade 4-5 complication. The median blood loss was 50 (IQR 20-100) ml and the median hospital stay was 6 (IQR 5-7) days. Twelve patients were re-admitted to the hospital within 90 days (eight with urinary tract infection/haematuria, one with hematoma, and three with other diseases). CONCLUSION: Robot-assisted nephroureterectomy is a safe procedure for patients with upper tract urothelial carcinoma, with a low risk of major surgical complications.
Assuntos
Carcinoma de Células de Transição , Robótica , Neoplasias da Bexiga Urinária , Idoso , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Estudos de Viabilidade , Humanos , Nefroureterectomia/métodos , Estudos Retrospectivos , Robótica/métodos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
OBJECTIVE: Based on the hypothesis that fetal breathing movements (FBM) enhance sections of the circulation to meet the needs of gas transport, we studied the effects of FBM on the fetal inferior vena cava (IVC), which transports blood with the lowest oxygen saturation in the fetal body. METHODS: One-hundred and ten women with low-risk singleton pregnancies were included in a longitudinal study during the second half of pregnancy. Inner diameter, peak systolic velocity and time-averaged maximum blood velocity were measured in the IVC below the ductus venosus outlet during rest and FBM. Volume flow and pressure gradient were estimated in 55 observations of forced inspiratory movements at 36 weeks of gestation. The results are presented as mean and 95% CI of the mean. RESULTS: Based on 585 observations obtained during fetal rest and FBM, we found no difference in diameter, 0.42 (95% CI, 0.41-0.43) cm vs. 0.41 (95% CI, 0.39-0.42) cm, respectively, apart from during high-amplitude inspiratory movement, when the diameter was 0.15 (95% CI, 0.13-0.17) cm. The peak systolic velocity was different during rest and FBM, 34.0 (95% CI, 32.7-35.3) cm/s vs. 81.5 (95% CI, 76.2-87.5) cm/s, respectively, and correspondingly for time-averaged maximum velocity, 19.7 (95% CI, 18.9-20.5) cm/s vs. 37.2 (95% CI, 34.9-39.9) cm/s, respectively. Forced inspiratory movements at 36 weeks significantly reduced flow in the IVC compared with rest, 63.6 (95% CI, 44.4-88.1) mL/min vs. 186.0 (95% CI, 142.8-238.1) mL/min, respectively. The pressure gradient increased 14-fold during forced inspiration, from 0.64 to 8.76 mmHg. CONCLUSIONS: High-amplitude fetal inspiration substantially constricts the abdominal IVC and creates a negative pressure in the chest. The IVC constriction withholds abdominal blood, thus temporarily giving way to other flows.
Assuntos
Coração Fetal/fisiologia , Feto/fisiologia , Hemodinâmica , Mecânica Respiratória/fisiologia , Ultrassonografia Pré-Natal/métodos , Veia Cava Inferior/fisiologia , Adolescente , Adulto , Feminino , Coração Fetal/diagnóstico por imagem , Movimento Fetal , Feto/irrigação sanguínea , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/embriologia , Adulto JovemRESUMO
OBJECTIVES: In humans, fetal breathing movements affect blood velocities in the umbilical vein and artery, but it is not known whether fetal respiratory activity is associated with increased fetal blood flow through the placenta. We therefore tested this hypothesis in the present study. METHODS: One-hundred and ten women with low-risk singleton pregnancies were each examined three times by ultrasound during the second half of pregnancy. Fetal heart rate, umbilical artery blood velocity, umbilical vein diameter and blood velocity, and umbilical blood flow at the placental end were determined during fetal rest and fetal respiratory movements. RESULTS: Based on 330 observations obtained during fetal rest or breathing activity, no difference was found in the mean fetal heart rate (beats per minute (bpm)) during rest compared with breathing (142 bpm vs. 142 bpm, respectively). Although fetal breathing affected the umbilical artery waveform, there was no difference in the mean time-averaged maximum velocity between rest and breathing: 26.6 (95% CI, 25.1-28.3) cm/s vs. 28.9 (95% CI, 27.2-30.7) cm/s, respectively. The umbilical vein was 27% greater in cross-sectional area and the blood velocity 9% higher during breathing, resulting in a 42% increase in mean umbilical blood flow: 121.8 (95% CI, 109.5-135.0) mL/min at rest vs. 173.0 (95% CI, 158.0-188.6) mL/min during breathing. Venous velocity was calculated from recordings of mean duration 3.7 s at rest and 6.2 s of respiratory activity. Gestational age did not influence the relationship. CONCLUSION: Fetal breathing is associated with increased umbilical blood flow during the second half of pregnancy. Umbilical vein distension during breathing suggests active endocrine regulation.
Assuntos
Coração Fetal/fisiologia , Placenta/irrigação sanguínea , Artérias Umbilicais/fisiologia , Veias Umbilicais/fisiologia , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo/fisiologia , Feminino , Coração Fetal/diagnóstico por imagem , Movimento Fetal , Idade Gestacional , Frequência Cardíaca Fetal , Humanos , Placenta/diagnóstico por imagem , Gravidez , Respiração , Ultrassonografia Pré-Natal , Artérias Umbilicais/diagnóstico por imagem , Veias Umbilicais/diagnóstico por imagem , Adulto JovemRESUMO
Essentials It is unknown how regular exercise affects platelet function after menopause. We studied the effect of 3-months of high-intensity exercise in pre- and postmenopausal women. Platelet sensitivity to the inhibitory effect of arterially infused prostacyclin was increased. Reduced basal platelet reactivity was seen in the premenopausal women only. SUMMARY: Background The risk of atherothrombotic events increases after the menopause. Regular physical activity has been shown to reduce platelet reactivity in younger women, but it is unknown how regular exercise affects platelet function after the menopause. Objectives To examine the effects of regular aerobic exercise in late premenopausal and recent postmenopausal women by testing basal platelet reactivity and platelet sensitivity to prostacyclin and nitric oxide. Methods Twenty-five sedentary, but healthy, late premenopausal and 24 matched recently postmenopausal women, mean (95% confidence interval) 49.1 (48.2-49.9) and 53.7 (52.5-55.0) years old, participated in an intervention study: 3-month high-intensity supervised aerobic spinning-cycle training (1 h, × 3/week). Basal platelet reactivity was analyzed in platelet-rich plasma from venous blood as agonist-induced % aggregation. In a subgroup of 13 premenopausal and 14 postmenopausal women, platelet reactivity was tested ex vivo after femoral arterial infusion of prostacyclin, acetylcholine, a cyclooxygenase inhibitor, and after acute one-leg knee extensor exercise. Results Basal platelet reactivity (%aggregation) to TRAP-6 (1 µm) was higher in the postmenopausal, 59% (50-68), than the premenopausal women, 45% (35-55). Exercise training reduced basal platelet reactivity to collagen (1 µg mL-1 ) in the premenopausal women only: from 63% (55-71%) to 51% (41-62%). After the training intervention, platelet aggregation was more inhibited by the arterial prostacyclin infusion and the acute exercise in both premenopausal and postmenopausal women. Conclusions These results highlight previously unknown cardioprotective aspects of regular aerobic exercise in premenopausal and postmenopausal women, improving their regulation of platelet reactivity through an increased platelet sensitivity to prostacyclin, which may counterbalance the increased atherothrombotic risk associated with the menopause.
Assuntos
Plaquetas/fisiologia , Exercício Físico/fisiologia , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Plaquetas/efeitos dos fármacos , Estudos Transversais , Epoprostenol/farmacologia , Feminino , Humanos , Técnicas In Vitro , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Estudos Prospectivos , Trombose/sangue , Trombose/etiologia , Trombose/prevenção & controleRESUMO
Prostate cancer is the most common cancer for men in the western world. For the first time, a dual-modality probe, combining Raman spectroscopy and tactile resonance technology, has been used for assessment of fresh human prostate tissue. The study investigates the potential of the dual-modality probe by testing its ability to differentiate prostate tissue types ex vivo. Measurements on four prostates show that the tactile resonance modality was able to discriminate soft epithelial tissue and stiff stroma (p < 0.05). The Raman spectra exhibited a strong fluorescent background at the current experimental settings. However, stroma could be discerned from epithelia by integrating the value of the spectral background. Combining both parameters by a stepwise analysis resulted in 100% sensitivity and 91% specificity. Although no cancer tissue was analysed, the results are promising for further development of the instrument and method for discriminating prostate tissues and cancer.
Assuntos
Neoplasias da Próstata/diagnóstico , Análise Espectral Raman/instrumentação , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Neoplasias da Próstata/patologia , Análise Espectral Raman/métodosRESUMO
AIM: The aim was to elucidate whether essential hypertension is associated with altered capillary morphology and density and to what extent exercise training can normalize these parameters. METHODS: To investigate angiogenesis and capillary morphology in essential hypertension, muscle biopsies were obtained from m. vastus lateralis in subjects with essential hypertension (n = 10) and normotensive controls (n = 11) before and after 8 weeks of aerobic exercise training. Morphometry was performed after transmission electron microscopy, and protein levels of several angioregulatory factors were determined. RESULTS: At baseline, capillary density and capillary-to-fibre ratio were not different between the two groups. However, the hypertensive subjects had 9% lower capillary area (12.7 ± 0.4 vs. 13.9 ± 0.2 µm(2)) and tended to have thicker capillary basement membranes (399 ± 16 vs. 358 ± 13 nm; P = 0.094) than controls. Protein expression of vascular endothelial growth factor (VEGF), VEGF receptor-2 and thrombospondin-1 were similar in normotensive and hypertensive subjects, but tissue inhibitor of matrix metalloproteinase was 69% lower in the hypertensive group. After training, angiogenesis was evident by 15% increased capillary-to-fibre ratio in the hypertensive subjects only. Capillary area and capillary lumen area were increased by 7 and 15% in the hypertensive patients, whereas capillary basement membrane thickness was decreased by 17% (P < 0.05). VEGF expression after training was increased in both groups, whereas VEGF receptor-2 was decreased by 25% in the hypertensive patients(P < 0.05). CONCLUSION: Essential hypertension is associated with decreased lumen area and a tendency for increased basement membrane thickening in capillaries of skeletal muscle. Exercise training may improve the diffusion conditions in essential hypertension by altering capillary structure and capillary number.
Assuntos
Pressão Sanguínea/fisiologia , Capilares , Hipertensão/metabolismo , Músculo Esquelético/metabolismo , Capilares/ultraestrutura , Hipertensão Essencial , Humanos , Neovascularização Fisiológica/fisiologia , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To relate the expression of HIV regulatory proteins and HIV-specific mRNA in the brain cells of infected individuals with clinical neurological disease. DESIGN: Formalin-fixed postmortem brain tissue from 14 HIV-infected adult patients, with previous repeated neurological and neuroradiological examinations, was studied by immunohistochemical and molecular biological methods. Samples from non-infected brains served as controls. METHODS: Immunohistochemistry with monoclonal antibodies (MAb) was combined with in situ RNA hybridization. Target cells were identified with MAb to glial fibrillary acidic protein (GFAP; astrocytes), CD68 (activated macrophages) and Ricinus communis agglutinin (RCA-1; microglia, endothelial cells). For HIV, a panel of MAb against HIV Nef, Tat, Rev and Env proteins or probes specific for all classes of mRNA (nef), for singly or non-spliced mRNA (env) and for non-spliced mRNA (gag/pol) were used. RESULTS: Nef protein was detected in subcortical or subpial astrocytes in seven out of 14 samples, and in multinucleated giant cells in two cases. Gag/pol or env mRNA-expressing astrocytes were detected in four cases. In four out of five cases studied, HIV Rev, but not Tat, was also expressed in astrocytes. Six out of the seven patients with Nef-positive astrocytes had suffered from moderate to severe dementia. The patient with most rapidly progressing severe dementia showed extensive HIV mRNA expression together with Nef and Rev expression in astrocytes. CONCLUSION: In adult human brain, astrocytes are infected by HIV and preferentially express HIV Nef and Rev proteins but are also sometimes productively infected. Astrocyte infection is associated with moderate to severe dementia which agrees with recent knowledge on the housekeeping activities of astrocytes and their eventual role in learning and memory.
Assuntos
Complexo AIDS Demência/virologia , Astrócitos/virologia , Encéfalo/virologia , Produtos do Gene nef/genética , Produtos do Gene rev/genética , HIV/genética , Complexo AIDS Demência/patologia , Adulto , Astrócitos/patologia , Encéfalo/patologia , Feminino , Regulação Viral da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , RNA Mensageiro/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana , Produtos do Gene rev do Vírus da Imunodeficiência HumanaRESUMO
Twenty-seven patients sensitive to ragweed pollen were treated with topical imipramine 0.05% in one eye and vehicle in the other in a double-masked fashion. The eyes treated with imipramine showed significantly less redness, tearing, and discomfort after exposure to pollen extract. Imipramine, a tricyclic antidepressant, appears to be an effective antihistamine in the eye.
Assuntos
Conjuntivite/prevenção & controle , Antagonistas dos Receptores Histamínicos/administração & dosagem , Imipramina/administração & dosagem , Pólen , Administração Tópica , Adulto , Conjuntivite/etiologia , Feminino , Humanos , Hipersensibilidade/prevenção & controle , Masculino , Pessoa de Meia-Idade , Extratos VegetaisRESUMO
Blood and tissue were studied for potential infectivity at autopsy of ten patients with human immunodeficiency virus (HIV) infection. Special attention was paid to the possibility of detecting HIV in bone at craniotomy. Postmortem intervals were one to six days. Specimens for HIV isolation included skull bone, brain, blood, bone marrow, spleen, and lymph node, and cerebrospinal fluid in one case. HIV grew in culture from at least one specimen from eight autopsies, one of which was performed six days postmortem. HIV was recovered from the blood of five patients and the tissue of five patients, including three with negative blood cultures. Skull bone contained HIV in two cases. HIV also grew from native spleen specimens stored for up to 14 days postmortem at 20 degrees C. Recommended precautions, including those for bone, are indicated at autopsy of HIV-infected patients even after long postmortem intervals.
Assuntos
Autopsia , HIV/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/transmissão , Humanos , Fatores de Tempo , Cultura de VírusRESUMO
The stability of human immunodeficiency virus (HIV) antibodies was studied for samples of sera, vitreous fluid and bile obtained from eight HIV-positive autopsy cases. The autopsy delay was on average 5 days. The samples were stored at room temperature (20 degrees C) for 51 to 314 days and tested repeatedly. In Western blotting on fresh postmortem samples, the antibodies detected most of the proteins of the virus. Antibodies against all major envelope, core and transmembrane proteins, although weakened, were also detected in stored sera. In stored vitreous fluid and bile the envelope protein gp 160, the transmembrane protein gp 41 and in half of the cases also the major core protein p 24 could still be detected. The disappearance of p 24 was associated with AIDS, but was detected in all samples from patients with early infection. Of screening tests, the enzyme-linked immunosorbent assay applying synthetic peptide as an antigen detected antibodies from all serum samples, but was less applicable to vitreous fluid or bile. Another immunoassay, applying recombinant antigen, succeeded in vitreous fluid and bile but not in sera. The rapid visually read assay detected antibodies in most samples of fresh whole blood, bile and in most of the vitreous samples, but was less useful on stored specimens.
Assuntos
Anticorpos Anti-HIV/análise , Soropositividade para HIV/patologia , Mudanças Depois da Morte , Autopsia , Bile/microbiologia , Western Blotting , Ensaio de Imunoadsorção Enzimática , Soropositividade para HIV/microbiologia , Humanos , Imunoensaio/métodos , Preservação de Tecido , Corpo Vítreo/microbiologiaRESUMO
PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Internato e Residência , Procedimentos Cirúrgicos Oftalmológicos , Propranolol/uso terapêutico , Tremor/tratamento farmacológico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Placebos/uso terapêutico , Qualidade da Assistência à Saúde , Resultado do TratamentoRESUMO
When rabies reappeared in Finland in April 1988, the country had been rabies free since 1959. Soon a picture of sylvatic rabies become evident, its main vector and victim being the raccoon dog (Nyctereutes procyonoides). Between 8 April 1988 and 16 February 1989, 66 virologically verified cases were recorded (48 raccoon dogs, 12 red foxes, 2 badgers, 2 cats, 1 dog and 1 dairy bull) in an area estimated at 1700 km2 in south-eastern Finland. The greatest distance between recorded cases was 67 km. A positive reaction with monoclonal antibody p-41 indicated that the virus was an arctic-type strain. A field trial on oral immunization of small predators was initiated in September 1988 using Tübingen fox baits according to the Bavarian model of bait distribution. Each bait contained 5*10(7) TCID50/ml modified live rabies virus (SAD-B19). The 6 months' surveillance indicate a seroconversion rate of 72% (N = 126) in the raccoon dog population, 67% (N = 56) in the red foxes and 13% (N = 16) in the badgers, when titers greater than or equal to 1.0 IU/ml are considered seropositive. In the whole follow-up period, no statistically significant difference could be detected between the raccoon dogs and red foxes in the rate of seroconversion or in the uptake of tetracycline from the baits. Notably high antibody levels were recorded in both raccoon dogs and red foxes within 4-5 months after vaccination. Of the seropositive animals, the proportion of animals with titers 3.0 IU/ml or greater was higher in raccoon dogs (73%) than in red foxes (51%) (x2 = 5.29, p less than 0.05). The trial shows that raccoon dogs can be immunized against rabies in the field with vaccine baits originally developed for controlling sylvatic rabies in foxes.
Assuntos
Carnívoros , Surtos de Doenças/veterinária , Vacina Antirrábica , Raiva/veterinária , Vacinação/veterinária , Animais , Animais Selvagens , Gatos , Bovinos , Cães , Finlândia/epidemiologia , Raposas , Raiva/epidemiologia , Raiva/prevenção & controleRESUMO
A large Medicare population, a higher than average length of stay, an aging medical staff, and difficulty in retaining professional staff were a few of the indications that Nazareth Hospital, Philadelphia, was headed for financial difficulties. Unfortunately, Nazareth leaders overlooked these warnings because the hospital was concentrating on a major construction project. In 1989 the hospital lost approximately $5 million from operations, resulting in debt covenant violations on a $33 million bond issue. Nazareth then adopted a revitalization program with the following basic components: Establishing extensive cost-cutting measures to help reverse the financial deficits Retaining outside consultants to serve as management advocates and to keep the repositioning effort moving forward Enhancing long-range strategic planning to lay firm groundwork for the hospital's future As a result of these efforts, Nazareth went from a fiscal year 1989 operating loss to a 1990 year-end break-even position. Nazareth leaders attribute this success to the total commitment by the involved constituencies: board, managers, medical staff, and employees.