Microvascular histopathology in head and neck oncology.

A histological study of both recipient and flap vessels was performed in 30 patients with head and neck cancer, and relevant preoperative risk factors were assessed. A total of 35 free flaps were transferred in 30 patients; 16 patients had preoperative radiotherapy, 13 were smokers, eight had hypertension and six had peripheral vascular disease. No significant venous pathology was found in either the flap or the neck veins. However, over two-thirds of the neck arteries and one-half of the flap arteries were found to have microscopic arterial pathology. The only pre-existing factor significantly influencing vessel pathology was hypertension (P=0.007). All flaps survived, although in two there was some loss of the skin paddle. This study reveals that the majority of patients undergoing microsurgery in the head and neck region have pre-existing arterial damage in both the flap and the recipient arteries, but this does not have a significant effect on the overall patency of the microvascular anastomoses.     

Maculopapular eruption with enlarged macrophages in eight patients receiving G-CSF or GM-CSF

In the last years, granulocyte and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) are being increasingly used and several cutaneous eruptions have been reported in relation to these treatments. In 1991 Horn et al. described three patients with maculopapular eruption that paralleled the time of infusion of GM-CSF. Two of the cases showed an increase in the number and size of macrophages in the biopsy specimen. Since then, several cases have been reported showing this histopathological alteration that has been considered characteristic of reaction to G-CSF or GM-CSF. Although maculopapular eruption with enlarged macrophages can appear after chemotherapy treatment, we have found that the presentation of this eruption after the beginning of cytokine treatment is suggestive of the involvement of G-CSF and GM-CSF in the eruption. We described eight cases of patients treated with G-CSF or GM-CSF that developed maculopapular eruptions with enlarged macrophages.     

Identification of an insulin-like factor in astrocyte conditioned medium

Survival of dissociated 19-day fetal rat telencephalic neurons in a hormone-free defined medium required the addition of insulin at pharmacological concentrations. However, survival of astrocytes cultured from the cerebral cortex of newborn rats in the same medium did not require insulin. When fetal neurons were incubated with astrocyte conditioned medium or plated on a monolayer of astrocytes, their survival was significantly increased in the absence of insulin. This effect of astrocyte conditioned medium was visibly inhibited by affinity chromatography on an anti-insulin protein A agarose column. A 5-30 kDa ultrafiltration fraction of astrocyte conditioned medium also increased neuronal survival. In addition, the 5-30 kDa fraction stimulated [3H]leucine incorporation into the TCA insoluble material from cultured neurons and competed for [125I]insulin binding to intact neuronal cultures. These results indicate that cultured astrocytes produce a factor with biological and immunological properties similar to those of insulin. This factor may in part mediate the observed neurotrophic effects of astrocyte conditioned medium and may play a role in the normal development and differentiation of central nervous system neurons.     

Oral session 9: Cerebrovascular disorders 2

Oral session 9: Cerebrovascular disorders 2     

Balloon dilation of the aortic valve: studies in normal lambs and in children with aortic stenosis

To evaluate the risks of and optimal method for valve dilation in aortic stenosis, balloons of different sizes were used to dilate the normal aortic root in 16 lambs and then stenotic valves in 15 children. In the lambs, inflated balloon to aortic anulus diameter ratios ranged from 0.9 to 1.5. These hearts were examined immediately after the procedure. Ratios of 0.9 to 1.1 did not produce significant damage to the left ventricular outflow tract, whereas those of 1.2 to 1.5 produced tears or hematomas, or both, of the aortic valve leaflets (n = 3), mitral valve leaflets (n = 4) and interventricular septum (n = 4). The 15 patients, aged 10 days to 15 years, underwent 16 balloon aortic valvotomy procedures. The balloon-aortic anulus ratio ranged from 0.67 to 1.1 (mean 0.90). The average pressure gradient decreased 69% and, overall, the peak systolic gradient decreased from 86 +/- 21 to 28 +/- 14 mm Hg (p less than 0.01) and the aortic valve area increased from 0.44 +/- 0.11 to 0.73 +/- 0.22 cm2/m2 (p less than 0.01). Immediately after the procedure an increase in aortic regurgitation was noted in 8 (57%) of 14 patients, but was never greater than 3+ and has been well tolerated. Other early complications encountered consisted of transient left bundle branch block in two patients, temporary femoral artery occlusion in three and femoral artery rupture requiring operative management in one infant. Balloon valvotomy can reduce the transvalvular gradient in most patients with valvular aortic stenosis when a balloon less than 1.1 times the aortic root diameter is used.(ABSTRACT TRUNCATED AT 250 WORDS)     

The metabolic and cardiovascular effects of intravenous infusion of glucose or intralipid in normal humans

This study was performed to determine whether the administration of intravenous fluids, isosmolar with plasma, activated the sympathetic nervous system, thereby causing changes in cardiovascular variables. On four separate occasions, six young, healthy men were studied for 30 min before and, for 40 min after a 60 min period of either (a) intravenous infusion of 500 ml of 5% dextrose, (b) intravenous infusion of 500 ml of a mixture of 10% Intralipid and saline (154 mmol NaCl 1(-1)), (c) intravenous infusion of 500 ml of saline (154 mmol NaCl 1(-1)) or (d) no intravenous infusion. Venous plasma noradrenaline and adrenaline concentrations did not change significantly during any of these interventions. The venous plasma insulin level rose during infusion of 5% dextrose (p<0.001). The respiratory exchange ratio rose during the dextrose infusion and fell during the infusion of the Intralipid and saline mixture (p<0.01). Hand and calf blood flows and vascular resistances were not significantly affected by any procedure. Similar, small, changes in heart rate, arterial blood pressure, metabolic rate, core temperature and mean skin temperature were observed during the four protocols. The provision of small amounts of metabolic substrate, as either glucose or fat, led to rapid changes in fuel utilisation. However, under the conditions of the present experiments, there was no evidence of activation of the sympathetic nervous system.     

Characterization of chemokine receptors expressed in primitive blood cells during human hematopoietic ontogeny

Chemokines are capable of regulating a variety of fundamental processes of hematopoietic cells that include proliferation, differentiation, and migration. To evaluate potential chemokine signaling pathways important to the regulation of primitive human hematopoietic cells, we examined chemokine receptor expression of highly purified subpopulations of uncommitted human blood cells. CXCR1-, CXCR2-, CXCR4-, and CCR5-expressing cells were detected by flow cytometry among human blood subsets depleted of lineage-restricted cells (Lin(-)) derived from adult bone marrow, mobilized peripheral blood, cord blood (CB), and circulating fetal blood. Although these chemokine receptors could be detected on Lin(-) cells throughout human development, only CXCR4 could be detected in CD34(-)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) subfractions enriched for stem cell function, suggesting that independent of ontogeny, CXCR4-mediated signals are critical to primitive hematopoiesis. Distinct to other stages of human hematopoietic development, primitive CB cells expressed higher levels of CXCR1, CXCR2, CCR5, and CXCR4 on both CD34(-)CD38(-)Lin(-) and CD34(+)CD38(-)Lin(-) subsets. Isolation of these fractions revealed expression of additional chemokine receptors CCR7, CCR8, and Bonzo (STRL133), whereas BOB (GPR15) could not be detected. Our study illustrates that rare uncommitted hematopoietic cells express chemokine receptors not previously associated with primitive human blood cells. Based on these results, we suggest that signaling pathways mediated by chemokine receptors identified here may play a fundamental role in hematopoietic stem cell regulation and provide alternative receptor targets for retroviral pseudotyping for genetic modification of repopulating cells.     

Oocyte morphology predicts outcome of intracytoplasmic sperm injection

To examine the influence of cytoplasmic morphology on the success rate of intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II oocytes was assessed after cumulus stripping. The main abnormalities detected were excessive granularity, cytoplasmic inclusions such as vacuoles, smooth endoplasmic reticulum clustering and refractile bodies. Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out of 161 with excessive granularity and 112 out of 138 with cytoplasmic inclusions. Very poor oocytes were not injected. No difference was found in fertilization rate. The embryos achieved cleaved normally and a similar number of good quality embryos among the three groups was noted. The outcome of transfer of embryos derived solely from normal oocytes (group A: 72 patients, 183 embryos) was compared with those from oocytes with cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A, 17 clinical pregnancies (24% per patient, implantation rate 10%) were established. In group B, only one clinical pregnancy (3% per patient, implantation rate 1%) was established, from the transfer of embryos derived from oocytes with homogeneous granularity of the cytoplasm. No pregnancy resulted following the transfer of embryos from eggs with cytoplasmic inclusions. The difference was statistically significant. The outcome of ICSI is dependent on the quality of the oocytes retrieved. Normal fertilization and early embryo development were achieved in oocytes with abnormal cytoplasm morphology, but the resulting embryos failed to demonstrate the same implantation potential as those derived from oocytes with normal cytoplasm.