The effect of intravenous dopamine and dobutamine on blood circulation during a microvascular TRAM flap operation

A study was conducted to assess the effect of intraoperatively administered inotropic agents on blood flow in the recipient and donor vessels, during breast reconstruction with a muscle sparing free TRAM flap. Twenty-one consecutive patients were randomized into 3 groups receiving either dopamine, dobutamine, or placebo. When the flap and all vessels had been fully dissected but not yet divided, the study drug was administered intravenously for 15 minutes. Hemodynamic parameters and transit-time flow of the thoracodorsal and inferior epigastric arteries were monitored.Both dobutamine and dopamine infusions resulted in significant raises in cardiac output and mean arterial pressure. However, while dobutamine resulted in a higher cardiac output (P = 0.001) and a decrease in systemic vascular resistance (P = 0.028), the increase in mean arterial pressure was greater with dopamine (P = 0.002). Only the dobutamine group showed increased blood flow, in both the thoracodorsal (P = 0.043) and the inferior epigastric (P = 0.043) arteries.If vasoactive agents are needed during microvascular anesthesia, dobutamine seems to be more advantageous than dopamine.     

Evaluation of exposure to man-made vitreous fibers by nasal lavage

The objectives of this study were to develop a biomonitoring method for the assessment of exposure to man-made vitreous fibers (MMVF), to examine the level of exposure to MMVF in the prefabricated house industry, and to study nasal inflammatory reactions and respiratory symptoms associated with MMVF among workers. Nasal lavage was performed on workers from two factories, and concentrations of MMVF were measured by electron microscopy. Cytokines (IL-6, IL-8, TNF-alpha, and IFN-gamma) were also assayed and inflammatory cells (lymphocytes, eosinophils, neutrophils, and macrophages) were counted microscopically. Concentrations of airborne fibers (longer than 5 microm) were measured for comparison. Moreover, the exposure to MMVF and the related symptoms were studied with a structured questionnaire. In nasal lavage samples, the mean concentration of MMVF (length >1.5 microm) was 3260 f/ mL in Factory 1, 1680 f/mL in Factory 2, and below 500 f/mL in the control group. About 52% of the retained fibers were longer than 100 microm. The group-specific mean concentrations of MMVF in nasal lavage samples correlated with production rates and airborne fiber levels in both plants. The airborne concentrations of MMVF both in the breathing zone and fixed-point samples were low (below 0.1 f/cm(3)). No significant differences in the biological response (inflammatory cells, cytokines) were found between the groups exposed and the control group. The workers complained of some irritation of the skin, eyes, and upper respiratory tract, which could be reduced by appropriate protective equipment. It is concluded that nasal lavage can be used as a biomonitoring method in the assessment of MMVF exposure.     

Diabetogenic T cells are primed both in pancreatic and gut-associated lymph nodes in NOD mice

Activation of an islet-specific immune response is an early yet essential step in autoimmune diabetes. The immune cells and antigen(s) involved in this early step and its anatomical site remain incompletely understood. To directly evaluate the site where islet-specific and diabetogenic lymphocytes are activated, we isolated lymphocytes from spleen and from pancreas-draining, gut-associated and subcutaneous lymph nodes of diabetic NOD mice and of young NOD mice, and transferred these into NOD scid/scid recipients devoid of endogenous islet-specific immune responses themselves. Although spleen lymphocytes from diabetic NOD mice induced diabetes more rapidly than lymphocytes from any other lymphoid tissue, spleen lymphocytes from young NOD donors were not superior to other lymphocytes from the same donors. At a donor-age of 6 weeks, the most-diabetogenic lymphocytes were found in pancreas-draining lymph node whereas gut-associated lymph nodes and the spleen were sources of intermediate diabetogenic activity. Lymphocytes from peripheral lymph nodes were only weakly diabetogenic at this age, and also remained the least efficient later. Surprisingly, lymphocytes isolated even from 3-week-old NOD mice had diabetogenic potential. However, such cells were almost exclusively found in gut-associated lymph nodes. This suggests that initial priming of diabetogenic cells takes place in the gut whereas pancreas-draining lymph nodes may serve as the site of amplification of the autoimmune response.     

Termination of pregnancy with mifepristone and prostaglandin suppresses transiently circulating glucocorticoid bioactivity

Mifepristone is a potent antiglucocorticoid, the administration of which results in a dose-dependent activation of the hypothalamic-pituitary-adrenal axis. However, the net effect of this compound on circulating glucocorticoid activity is not known. We have used a recombinant cell bioassay to study glucocorticoid bioactivity (GBA), measured directly from serum, in 18 women undergoing medical termination of an early pregnancy with 200 mg mifepristone, followed by 0.8 mg misoprostol, a prostaglandin. Increased serum mifepristone was accompanied by an increase in serum cortisol that was insufficient to maintain circulating GBA within the normal (pre-mifepristone) range (34.7-93.8 nM cortisol equivalents); after approximately 43, 46, and 68 h of mifepristone ingestion, the mean serum GBA levels were much lower than the mean pre-mifepristone level (P < 0.0001). At the corresponding times, 16, 13, and 12 women displayed subnormal serum GBA levels (ranges, <15.6-23, <15.6-25.6, and <15.6-32.5 nM cortisol equivalents, respectively). Altogether 11 subjects displayed subnormal serum GBA (range, <15.6-32.5 nM cortisol equivalents) continuously in the presence of high concentrations of mifepristone. Two weeks after mifepristone administration, circulating GBA had returned to normal levels in all subjects. We conclude that 200 mg mifepristone elicits a significant suppression of serum GBA, to one third of the pretreatment value, despite the compensatory increase in the serum cortisol concentration.     

Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans

Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21–30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity.     

Microvascular reconstructions of full-thickness oncological chest wall defects

OBJECTIVE: To evaluate the suitability of microvascular flaps for the reconstruction of extensive full-thickness defects of the chest wall. SUMMARY BACKGROUND DATA: Chest wall defects are conventionally reconstructed with pedicular musculocutaneous flaps or the omentum. Sometimes, however, these flaps have already been used, are not reliable due to previous operations or radiotherapy, or are of inadequate size. In such cases, microvascular flaps offer the only option for reconstruction. METHODS: From 1988 to 2001, 26 patients with full-thickness resections of the chest wall underwent reconstruction with microvascular flaps. There were 8 soft tissue sarcomas, 8 recurrent breast cancers, 5 chondrosarcomas, 2 desmoid tumors, 1 large cell pulmonary cancer metastasis, 1 renal cancer metastasis, and 1 bronchopleural fistula. The surgery comprised 5 extended forequarter amputations, 5 lateral resections, 8 thoracoabdominal resections, and 8 sternal resections. The mean diameter of a resection was 28 cm. The soft tissue defect was reconstructed with 16 tensor fasciae latae, 5 tensor fascia latae combined with rectus femoris, and 3 transversus rectus abdominis myocutaneous flaps. In 2 patients with a forequarter amputation, the remnant forearm was used as the osteomusculocutaneous free flap. RESULTS: There were no flap losses or perioperative mortality. Four patients needed tracheostomy owing to prolonged respiratory difficulties. The mean survival time for patients with sarcomas was 39 months and for those with recurrent breast cancer 18 months. CONCLUSIONS: Extensive chest wall resections are possible with acceptable results. In patients with breast cancer, the surgery may offer valuable palliation and in those with sarcomas it can be curative.