Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature

BACKGROUND: Cellular angiofibroma (CA) of the vulva is a recently described condition, whose clinical and pathological features are poorly known. METHODS: We have encountered two cases of this very unusual tumor. Their clinical and pathological features were analyzed and compared to those reported in the literature. RESULTS: Both patients were middle-aged women. In each case, the lesion had the clinical appearance of a vulvar cyst, located in the lateral aspect of the clitoris and the right labium majus, respectively. Microscopically, the lesions were well circumscribed but not truly encapsulated. Both were composed of small spindle cells arranged in short fascicles and mixed up with relatively abundant small- or medium-sized rounded vessels. While mitotic activity was perceptible in both cases, no cellular atypia could be demonstrated. A striking feature seen in one case was the presence of pseudoangiomatous changes in the stroma, similar to those occasionally found in spindle cell lipoma. Phenotypically, the tumor cells consistently expressed vimentin, CD99, and both estrogen and progesterone receptors. A discrete CD34 or smooth muscle actin immunoreactivity was also found in one case. No expression of S-100 protein, Bcl-2 protein, CD117 (c-kit gene product), epithelial membrane antigen, desmin, or h-caldesmon could be demonstrated. CONCLUSION: This study further illustrates that CA of the vulva has distinct clinical and pathologic features that set it apart from the other soft tissue conditions involving this area. However, like many soft tissue neoplasms, this tumor also exhibits some variation in its histological or immunohistochemical features.     

Amniotic fluid beta-endorphin: a prognostic marker for gastroschisis?

Purpose: The aim of this work was to study amniotic fluid [beta ]-endorphin as a potential predictor for postnatal morbidity in gastroschisis. Methods: Beta-endorphin was assayed in 43 amniotic fluid samples from 13 pregnant women with fetal gastroschisis undergoing diagnostic amniocentesis or therapeutic amnioinfusion and compared with 33 controls. Within the gastroschisis group, the authors investigated the relationship between postnatal morbidity and the peak value of amniotic fluid [beta ]-endorphin (AFBE). Results: Ten AFBE values in 6 cases of gastroschisis were above the upper limit of the 95% confidence interval derived from controls. Postnatal morbidity was significantly higher when peak AFBE exceeded 10 [mu ]g/L (n = 4 pregnancies) compared with below 5 [mu ]g/L (n = 9 pregnancies), as shown by mean duration of mechanical ventilation (15.2 v 3 days; P = .01), of parenteral feeding (77 v. 18.7 days; P = .04), and of hospitalization (84 v 32.2 days; P = .04). There was no statistically significant association between postnatal morbidity markers and prenatal dilation of fetal bowel. Conclusions: The most severe cases of gastroschisis are associated with high levels of AFBE. The authors speculate that this fetal hormonal response could result from stress or pain caused by prenatal bowel damage.     

Hemodynamic and hormonal responses to the sudden interruption of caval flow: insights from a prospective study of hepatic vascular exclusion during major liver resections

Hepatic vascular exclusion (HVE) combines portal triad clamping and occlusion of the inferior vena cava. Although HVE has been performed for major liver resections during the last 2 decades, little is known about the mechanisms that explain its satisfactory hemodynamic tolerance. Consequently, we performed a comprehensive study of both hemodynamic and hormone responses to HVE. Twenty-two patients who underwent liver resection for secondary tumors developed in noncirrhotic livers were prospectively studied. Heart rate, arterial blood pressure, pulmonary artery pressure, mixed venous saturation, cardiac output, and left ventricular dimensions determined by transesophageal echocardiography were monitored in HVE patients. Blood concentrations of arginine vasopressin (AVP), epinephrine, norepinephrine, dopamine, and atrial natriuretic peptide and plasma renin activity (PRA) were measured before clamping; 5, 15, and 30 min after clamping; and 15 min after unclamping. Hemodynamic response to HVE was characterized by a significant (P < 0.05) decrease in left ventricular dimensions, fractional area change, and pulmonary artery pressure. We also observed a marked decrease in cardiac output (50%) and an increase in heart rate and systemic vascular resistance. After unclamping, there was peripheral vasodilation, assessed by a significant decrease in systemic vascular resistance from the preclamping value to unclamping. An acute and sustained increase in AVP and norepinephrine that returned to baseline after unclamping and the absence of modification in PRA concentrations were noted. The marked decrease in venous return that characterizes HVE is compensated for by an increase in vascular resistance secondary to an important activation of the AVP and sympathetic systems. The PRA system does not play an important role in maintaining arterial blood pressure during HVE. IMPLICATIONS: Hemodynamic and hormonal responses to the acute interruption of caval venous return to the heart were investigated in patients undergoing liver resection with hepatic vascular exclusion. A compensatory role for arginine vasopressin and sympathetic systems that provoked increased vascular resistance was demonstrated.     

Counteraction of type 1 diabetic alterations by engineering skeletal muscle to produce insulin: insights from transgenic mice

Insulin replacement therapy in type 1 diabetes is imperfect because proper glycemic control is not always achieved. Most patients develop microvascular, macrovascular, and neurological complications, which increase with the degree of hyperglycemia. Engineered muscle cells continuously secreting basal levels of insulin might be used to improve the efficacy of insulin treatment. Here we examined the control of glucose homeostasis in healthy and diabetic transgenic mice constitutively expressing mature human insulin in skeletal muscle. Fed transgenic mice were normoglycemic and normoinsulinemic and, after an intraperitoneal glucose tolerance test, showed increased glucose disposal. When treated with streptozotocin (STZ), transgenic mice showed increased insulinemia and reduced hyperglycemia when fed and normoglycemia and normoinsulinemia when fasted. Injection of low doses of soluble insulin restored normoglycemia in fed STZ-treated transgenic mice, while STZ-treated controls remained highly hyperglycemic, indicating that diabetic transgenic mice were more sensitive to the hypoglycemic effects of insulin. Furthermore, STZ-treated transgenic mice presented normalization of both skeletal muscle and liver glucose metabolism. These results indicate that skeletal muscle may be a key target tissue for insulin production and suggest that muscle cells secreting basal levels of insulin, in conjunction with insulin therapy, may permit tight regulation of glycemia.     

A CLA mixture prevents body triglyceride accumulation without affecting energy expenditure in Syrian hamsters

We examined the effects of feeding conjugated linoleic acids (CLA) to adult male hamsters on several components of energy metabolism and body composition. Hamsters (n = 54) were assigned for 6-8 wk to one of three diets: 1) a standard diet (in percentage energy: lipids, 33, carbohydrates, 49, and proteins, 18); 2) to the standard diet augmented with the 9c,11t-isomer of CLA to 1.6% of energy (R group); or 3) the standard diet augmented with the 9c,11t-isomer and the 10t,12c-CLA isomer to 3.2 (1.6 + 1.6) % of energy (CLA mix group). (15)N uniformly labeled milk-protein was included in the diet to measure the incorporation of dietary protein into liver and muscle. Basal metabolic rate, thermogenic response to feeding and energy expenditure during spontaneous activity or during an exercise at approximately 60% of VO(2max) were measured. Carnitine palmitoyltransferase-I (CPT-I), leptin, insulin and triiodothyronine concentrations, as well as the in vivo overall adiposity changes were also determined. After 6 wk, the whole-body triglyceride content determined in vivo by NMR was significantly higher in the R group than in the control and CLA mix groups. The CLA mix group differed from the others in the lack of body triglyceride accumulation between d 21 and d 45 of the study, and the appearance of a slight insulin-resistance (homeostatic model assessment index, P < 0.05). Paradoxically, the lack of effect on whole-body lipid oxidation was associated with a greater CPT-I-specific activity in tissues of both CLA-fed groups (P < 0.05). No other major effects of CLA feeding were detected. In conclusion, CLA supplementation in hamsters did not affect adipose weight or the components of energy expenditure despite a theoretically higher capacity of red muscle to oxidize lipids. Only a CLA mixture prevented whole-body triglyceride accumulation over time.     

Coherent infrared emission from myoglobin crystals: an electric field measurement

We introduce coherent infrared emission interferometry as a chi(2) vibrational spectroscopy technique and apply it to studying the initial dynamics upon photoactivation of myoglobin (Mb). By impulsive excitation (using 11-fs pulses) of a Mb crystal, vibrations that couple to the optical excitation are set in motion coherently. Because of the order in the crystal lattice the coherent oscillations of the different proteins in the crystal that are associated with charge motions give rise to a macroscopic burst of directional multi-teraHertz radiation. This radiation can be detected in a phase-sensitive way by heterodyning with a broad-band reference field. In this way both amplitude and phase of the different vibrations can be obtained. We detected radiation in the 1,000-1,500 cm(-1) frequency region, which contains modes sensitive to the structure of the heme macrocycle, as well as peripheral protein modes. Both in carbonmonoxy-Mb and aquomet-Mb we observed emission from six modes, which were assigned to heme vibrations. The phase factors of the modes contributing to the protein electric field show a remarkable consistency, taking on values that indicate that the dipoles are created "emitting" at t = 0, as one would expect for impulsively activated modes. The few deviations from this behavior in Mb-CO we propose are the result of these modes being sensitive to the photodissociation process and severely disrupted by it.     

Utility of the tumor bed marker in patients with breast cancer receiving induction chemotherapy

Purpose: Induction or neoadjuvant chemotherapy is used in patients with locally advanced breast cancer to offer a higher rate of conservative surgery. The possibility of reduction in size, even in some cases complete clinical and mammographic regression, can make the localization of the tumor bed difficult at the time of surgery. The purpose of this study was to describe our experience about the utility of US-guided implantation of a metallic marker in patients with breast cancer before induction chemotherapy.Material and Methods: Forty-three patients with 44 masses were diagnosed with percutaneous biopsy of breast carcinoma. Before beginning of the induction chemotherapy all of them were referred for metallic marker placement. A metallic harpoon was placed under US guidance.Results: One patient died during the chemotherapy. Six underwent mastectomy, and 9 still had a palpable tumor at the time of surgery. In the remaining 27 patients (with 28 lesions) pre-operative wire localization of the tumor bed was carried out: in 11 cases the harpoon was necessary for the localization of the tumor bed, in 6 the harpoon was useful, and in 11 patients the localization of the tumor could have been done without the marker. No complications were observed and the marker remained stable in all patients.Conclusion: In patients who undergo induction chemotherapy, the placement of a metallic harpoon under US guidance is a safe, simple and inexpensive technique for localization of the tumor bed previous to conservative surgery.     

Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study.

Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28-30 wk; birth weight, 820-1610 g) receiving parenteral nutrition supplying 1.5 g x kg(-1) x d(-1) amino acids and approximately 60 nonprotein kcal x kg(-1) x d(-1) were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g x kg(-1) x d(-1); glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH(13)CO(3) to assess the recovery of (13)C in breath, immediately followed by a 3-h L-[1-(13)C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 +/- 94 versus 503 +/- 83 microM, mean +/- SD; p < 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (-16%, p < 0.05) and leucine oxidation (-35%, p < 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (-20%, p < 0.05), and 4) no change in protein balance (nonoxidative leucine disposal - leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants.     

Niosomes and Polymeric Chitosan Based Vesicles Bearing Transferrin and Glucose Ligands for Drug Targeting

Purpose. To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting. Methods. A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/ cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis. Results. TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60 ± 0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles). Conclusions. Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake.