Histomorphometric changes in the vessel wall at the site of amputation in diabetic patients--do they influence healing of the stump?

PURPOSE: To predict healing of the stump by assessing the microscopic vascular changes at the amputation site. METHODS: A cohort study was conducted on 39 patients, 18 of them had below-knee amputation (group A) and 21 had ray amputation of a single toe (group B). Biopsies were taken from the anterior and posterior tibial arteries and the venae comitantes of group A patients. For group B patients, biopsies of the digital artery and dorsal vein of the toe were taken. RESULTS: In group A, 15 patients required no further amputation (group A1) and 3 underwent a further above-knee amputation (group A2). In group B, 16 required no further amputation (group B1) and 5 underwent a below-knee amputation (group B2). Lumen narrowing caused by intimal thickening of the arteries was significantly different between groups A1 and A2 (p<0.05). Lumen narrowing of the dorsal veins between groups B1 and B2 was also significantly different (p<0.05). The proportion of the vessel walls made up of intima and media was significantly different in both A1 and A2 as well as B1 and B2 groups. The proportion of total wall thickness over the total diameter of the vessel was not significantly different between both subgroups of A and B. CONCLUSION: Intimal thickening and medial thinning in the arteries can be used to predict the stump healing in patients who underwent below-knee amputation. For ray amputation patients, similar changes occurred in the dorsal veins, and this finding can also be used to predict the healing of the stump. However, intimal thickening occurred at the expense of the media; therefore, there is little change in the wall thickness.     

Dietary influences on the kinetics of antipyrine and aminopyrine in human subjects.

The possible dietary influences on in vivo antipyrine and aminopyrine kinetics with reference to energy (1500, 1800, 3000 kcal) and protein (5, 10, 15, 20% protein energy-PE) intake were studied in a carefully controlled metabolic experiment in young healthy adult male volunteers aged between 25-34 years. Antipyrine and aminopyrine were used to evaluate drug metabolism. On 1500 kcal intake with 10% PE, the metabolism of both aminopyrine and antipyrine were significantly reduced whereas on 1800 kcal with 10% PE intake, only aminopyrine metabolism decreased significantly as compared to 3000 kcal with 10% PE. Antipyrine clearance on 1800 kcal with 10% PE however had not decreased to the same extent as on 1500 kcal with 10% PE. The results indicate that on low calorie intake with 10% PE, the drug metabolism is decreased. When the protein intake on 1500 kcal was doubled (20% PE) there was a significant stimulation of both aminopyrine and antipyrine metabolism. Aminopyrine and antipyrine clearances on 3000 kcal with 5% PE were significantly reduced as compared to 3000 kcal with 10% and 15% PE indicating that unlike proteins, carbohydrate and/or fat calories per se do not significantly stimulate drug metabolism. When the protein energy in the diet was increased from 5% to 10% or 15% at 3000 kcal, there was a stimulation of both antipyrine and aminopyrine metabolism. Significant differences between 10% and 15% of protein energy were not observed when the energy was adequate (3000 kcal). Therefore it is necessary to consider both proteins and energy as important variables affecting drug clearances from plasma in malnourished conditions.     

Evaluation of quality of life in indian children with bronchial asthma using a disease-specific and locally appropriate questionnaire

AIM: To evaluate quality of life (QOL) in Indian children with bronchial asthma. METHODS: A disease-specific, locally appropriate QOL questionnaire was administered in asthmatic children and compared with FEV1, FVC, PEFR and asthma symptom score, on three occasions. RESULTS: QOL score had strong negative correlation with symptom score and weaker positive correlation with pulmonary function tests. CONCLUSION: Disease-specific QOL score correlates inversely with symptom score in children with bronchial asthma.     

A prospective study of a focused, surgeon-performed ultrasound examination for the detection of occult common femoral vein thrombosis in critically ill patients

HYPOTHESIS: A focused, surgeon-performed ultrasound examination of the common femoral veins is an accurate screening tool for the detection of common femoral vein thrombosis in high-risk, critically ill patients. DESIGN: A prospective study using a focused ultrasound examination for findings consistent with deep vein thrombosis of the common femoral veins. The results of these examinations were compared with those of duplex imaging or computed tomographic venography studies. SETTING: Surgical intensive care unit. PATIENTS: All critically ill patients who were admitted to the surgical intensive care unit and considered to be at high risk for the development of deep vein thrombosis. MAIN OUTCOME MEASURE: Presence of deep vein thrombosis in the common femoral veins. RESULTS: During a 16-month period, surgeons performed 306 ultrasound examinations on 220 critically ill surgical patients. The results included 295 true negative, 9 true positive, 1 false negative, and 1 false positive, yielding a 90.0% sensitivity, 99.6% specificity, and 99.3% accuracy. CONCLUSION: A focused, surgeon-performed ultrasound examination is a rapid and accurate screening method to detect common femoral vein thrombosis in critically ill patients as well as to examine those patients in whom pulmonary embolism is strongly suspected.     

Endotracheal calcineurin inhibition ameliorates injury in an experimental model of lung ischemia-reperfusion

OBJECTIVES: We previously demonstrated that calcineurin inhibitors given intravenously ameliorate experimental lung ischemia-reperfusion injury. This study evaluates whether these effects can be achieved when these agents are delivered endotracheally. METHODS: Left lungs of Long Evans rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received tacrolimus endotracheally at doses of 0.2, 0.1, or 0.025 mg/kg 60 minutes before ischemia. Injury was quantitated in terms of vascular permeability. Additional animals treated at a dose of 0.1 mg/kg were assessed for lung tissue myeloperoxidase content and bronchoalveolar lavage leukocyte content. Bronchoalveolar lavage fluid was assessed for cytokine and chemokine content by enzyme-linked immunosorbent assay. Tissue samples were processed for nuclear factor-kappaB activation, and blood levels of tacrolimus were measured in treated animals. RESULTS: Left lung vascular permeability was reduced in treated animals in a dose-dependent fashion compared with controls. The protective effects correlated with a 47% (0.50% +/- 0.06% vs 0.27% +/- 0.08%, respectively) reduction in tissue myeloperoxidase content (P <.004) and marked reductions in bronchoalveolar lavage leukocyte accumulation. This protection was also associated with decreased nuclear factor-kappaB activation and diminished expression of proinflammatory mediators. Blood tacrolimus levels in treated animals at 4 hours of reperfusion were undetectable. CONCLUSIONS: Tacrolimus administered endotracheally is protective against lung ischemia-reperfusion injury in our model. This protection is associated with a decrease in nuclear factor-kappaB activation. This route of tacrolimus administration broadens its potential clinical use and decreases concerns about systemic and renal toxicity. It may be a useful therapy in lung donors to protect against lung ischemia-reperfusion injury.     

Protective effect of bupropion on morphine tolerance and dependence in mice

Possible reversal of morphine-induced tolerance and dependence by bupropion was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Bupropion (2 and 5 mg/kg) per se, when chronically administered for 9 days, failed to produce any significant change in tail-flick latency compared with the control mice. Chronic administration of bupropion (2 or 5 mg/kg) during the induction phase (days 1-9) delayed the development of tolerance to the antinociceptive action of morphine and also reversed naloxone- (2 mg/kg) precipitated withdrawal jumps. On the other hand, acute administration of bupropion (2 or 5 mg/kg) on day 10, i.e., during the expression phase of morphine dependence, reduced the incidence of naloxone-precipitated withdrawal jumps without affecting tolerance to the analgesic effect. In conclusion, results of the present study suggest the potential use of bupropion in tolerance and dependence.     

Chemotherapy-induced and/or radiation therapy-induced oral mucositis--complicating the treatment of cancer

The term mucositis is coined to describe the adverse effects of radiation and chemotherapy treatments. Mucositis is one of the most common adverse reactions encountered in radiation therapy for head and neck cancers, as well as in chemotherapy, in particular with drugs affecting DNA synthesis (S-phase-specific agents such as fluorouracil, methotrexate, and cytarabine). Mucositis may limit the patient's ability to tolerate chemotherapy or radiation therapy, and nutritional status is compromised. It may drastically affect cancer treatment as well as the patient's quality of life. The incidence and severity of mucositis will vary from patient to patient. It will also vary from treatment to treatment. It is estimated that there is 40% incidence of mucositis in patients treated with standard chemotherapy and this will not only increase with the number of treatment cycles but also with previous episodes. Similarly, patients who undergo bone marrow transplantation and who receive high doses of chemotherapy have a 76% chance of getting mucositis. Patients receiving radiation, in particular to head and neck cancers, have a 30% to 60% chance. The exact pathophysiology of development is not known, but it is thought to be divided into direct and indirect mucositis. Chemotherapy and/or radiation therapy will interfere with the normal turnover of epithelial, cells leading to mucosal injury; subsequently, it can also occur due to indirect invasion of Gram-negative bacteria and fungal species because most of the cancer drugs will cause changes in blood counts. With the advancement in cytology, a more precise mechanism has been established. With this understanding, we can select and target particular mediators responsible for the mucositis. Risk factors such as age, nutritional status, type of malignancy, and oral care during treatment will play important roles in the development of mucositis. Many treatment options are available to prevent and treat this condition, but none of them can completely prevent or treat mucositis. More and more pathological methods are being developed to understand this condition so that better therapeutic regimens can be selected. Emphasis also should be made in assessing the patient's psychologic condition, particular depressive disorders. This is important because treatment with antidepressants will not only contribute in lifting depression but also reduces pain somatization. Although mucositis is rarely life-threatening, it will interfere with treatment of cancer to a great extent.