Primary carnitine deficiency and sudden death: in vivo evidence of myocardial lipid peroxidation and sulfonylation of sarcoendoplasmic reticulum calcium ATPase 2.

OBJECTIVES: Primary carnitine deficiency is an autosomal recessive disorder caused by mutations in the SLC22A5 gene which results in impaired carnitine transport, cytosolic fatty acid accumulation and impaired beta oxidation. The disease is associated with cardiomyopathy and arrhythmias, but the mechanism is unknown. We hypothesized that carnitine deficiency results in increased myocardial oxidative stress. METHODS: We evaluated a 22-year-old woman with primary carnitine deficiency and ventricular fibrillation, as well as her first-degree relatives. RESULTS: Sequencing of SLC22A5 identified two deleterious mutations (A142S and R488H) and a novel mutation predicted to be a splice variant. Histology demonstrated increased myocardial lipid deposition and swollen mitochondria. Immunohistochemistry demonstrated accumulation of the reactive aldehyde 4-hydroxy-2-nonenal, indicative of increased lipid peroxidation, and sulfonylation of sarcoendoplasmic reticulum calcium ATPase 2 at cysteine 674. CONCLUSIONS: These findings suggest that increased oxidant stress may contribute to myocardial dysfunction and arrhythmogenesis in this disorder.

Acinic cell carcinoma-papillary cystic variant. Pitfalls of fine needle aspiration diagnosis: study of five cases and review of literature.

OBJECTIVES: Acinic cell carcinoma (ACC) accounts for 12-17% of primary salivary gland carcinomas and 3.4% of all salivary gland neoplasms. ACC-papillary cystic variant (PCV) is a distinct subtype with clear-cut and well-defined morphological features as revealed in tissue sections, but it is more difficult to diagnose accurately on fine needle aspiration (FNA). The aim of this article was to discuss the causes of the erroneous interpretation as well as to draw attention of practicing pathologists to this rare and unique variant of ACC. METHODS: A computerized search of surgical and cytopathology files identified five diagnoses of ACC-PCV that were preceded by an FNA performed in-house with available slides for review. Cytological features were compared to histomorphological features of excisional surgical pathology specimens. RESULTS: Cytomorphological findings from these ACC-PCV cases have varied features that can be broadly divided in two major subtypes: hypocellular cystic specimens containing histiocyte-like vacuolated cells (two cases) and more cellular specimens containing papillary clusters of cells with a polymorphous appearance including granular cells, vacuolated cells and nondescript small cuboidal cells (three cases). CONCLUSIONS: Hypocellular, cyst-like specimens pose a diagnostic problem when using FNA, as they can easily be misinterpreted as a benign cyst of the salivary gland. Our review of cases found certain 'red flags' that should prompt pathologists to further investigate the true acinic origin of hypocellular cystic specimens. On close morphological examination, these specimens revealed the presence of tight cellular clusters, distinct cytoplasmic borders, larger nuclei with distinct nucleoli and binucleated cells.

A study on the influence of emulsion droplet size on the skin penetration of tetracaine.

OBJECTIVES/AIMS: The influence of emulsion droplet size on the skin penetration of a model drug, tetracaine, was studied. For this purpose, in vitro dermal and transdermal delivery of tetracaine from 6 emulsions (3 macro-emulsions with droplet sizes >1 microm and 3 nano-emulsions with droplet sizes <100 nm) were tested. METHODS: Two approaches were used: in the first one, the composition of the emulsions was kept constant, while in the second one, the surfactant concentration in the aqueous phase was kept constant by varying the overall surfactant concentration. RESULTS: The results from emulsions differing only in droplet size did not provide statistically significant evidence for the anticipated increase in transdermal or dermal delivery (after 24 h) when reducing emulsion droplet size. The same results were obtained when the surfactant concentration in the aqueous phase was kept constant, indicating that there is no influence of emulsion droplet size on the skin penetration of tetracaine within the droplet size range studied. CONCLUSION: This is in contrast to what has been reported in various publications that claim penetration to increase with reducing droplet size. It should be noted that the results reported so far are based on emulsions that apart from droplet size also differed in composition and/or system components.

Cervical schistosomiasis, human papilloma virus (HPV), and human immunodeficiency virus (HIV): a dangerous coexistence or coincidence?

BACKGROUND: Female genitourinary schistosomiasis (FGS) is widespread in endemic areas causing significant morbidity and mortality. Recent data suggest that FGS of the cervix not only is considered a risk factor for contracting different sexually transmitted diseases (STD), but also plays a significant role in modifying the natural history and immunological response to those infections, in particular HIV and HPV. CASE REPORT: A 32-year-old female from Zambia, who was recently diagnosed with HIV and high-grade dysplasia with koilocytosis on cervical Pap smear, underwent cervical conization which confirmed moderate cervical dysplasia and also revealed the presence of viable and nonviable schistosoma eggs in cervical stroma. Four different HPV types were isolated by PCR, including one "low-risk" (type 6) and three "high-risk" types (types 45,56, and 58). CONCLUSION: The presence of HPV, HIV infection, and cervical schistosomiasis in our patient is likely more than coexistence of multiple agents in the same milieu as cervical schistosomiasis increase susceptibility for other STDs including HIV and HPV. Therefore, in patients with schistosomiasis, immediate treatment for schistosomiasis and additional testing for HIV and HPV is warranted.

Cellular dyscohesion in fine-needle aspiration of breast carcinoma. Prognostic indicator for axillary lymph node metastases?

The role of fine-needle aspiration (FNA) in the diagnosis of breast carcinoma is established. We evaluated whether the degree of cellular dyscohesion and the nuclear grade in FNA material of breast carcinomas are reliable prognostic predictors for ipsilateral axillary lymph node metastasis. FNA specimens from 98 women with infiltrating ductal and infiltrating lobular carcinomas were evaluated by 2 observers for degree of cellular dyscohesion and nuclear grade. Follow-up specimens from lumpectomy and/or mastectomy with axillary dissection were available for each patient. By univariate analysis, degree of cellular dyscohesion and nuclear grade were not predictive of axillary lymph node metastasis regardless of tumor size. High histologic grade, size greater than 2 cm, and patient age younger than 52 years were significant predictors of metastasis. By multivariate analysis, size greater than 2 cm and age younger than 52 years were statistically significant for lymph node metastasis. In contrast with a published study, the results of the present study fail to show cellular dyscohesion in FNA specimens as predictive of lymph node metastasis; however, the scoring method for determining the degree of cellular dyscohesion is reproducible between 2 independent observers.

Polymeric surfactants based on inulin, a polysaccharide extracted from chicory. 1. Synthesis and interfacial properties.

Inulin, the polydisperse reserve polysaccharide from chicory, has been modified by carbamoylation in organic solvents. The reaction of inulin with a range of alkyl isocyanates resulted, after crystalization, in a variety of carbamoylated inulins from which the interfacial properties were determined. The medium and long chain carbamoylated inulins showed a good to very good reduction of the interfacial tension which makes these biopolymers interesting in the field of biodegradable surface active agents.

Trauma- and sepsis-induced hepatic ischemia and reperfusion injury: role of angiotensin II.

HYPOTHESIS: We hypothesized that angiotensin II, a potent vasoconstrictor, is involved in the occurrence of hepatic ischemia after burn and sepsis, and that administration of angiotensin II antagonist DuP753 would ameliorate this process. DESIGN: Randomized animal study. SETTING: University laboratory, investigational intensive care unit, University of Texas Medical Branch, Galveston. MATERIALS: Female pigs (n = 18, weighing 20-25 kg). INTERVENTIONS: All animals were prepared with ultrasonic flow probes on the portal vein and the common hepatic artery. Catheters were inserted in the superior mesenteric and left hepatic veins. After 5 days all animals were anesthetized and 12 of them received 40% total body surface area third-degree burn. Escherichia coli lipopolysaccharide (100 microg/kg) was intravenously administered at 18 hours postburn DuP753 was administered intravenously in a dose of 1 microg/kg to 6 pigs immediately after the burn. All animals were studied for 42 hours. MAIN OUTCOME MEASURES: Systemic and hepatic hemodynamics were measured and blood samples were drawn for determinations of arterial, mixed venous, and portal blood gases at baseline and at 14 consecutive time points, starting 1 hour after the burn. RESULTS: Burn caused a 4.6-fold increase in hepatic arterial vascular resistance and a 49% decrease in hepatic arterial blood flow. Postburn administration of angiotensin II receptor blocker DuP753 yielded a significant improvement in the hepatic arterial hemodynamics (only 12% increase in hepatic arterial vascular resistance and 8% decrease in hepatic arterial blood flow, P<.05 vs nontreated group, analysis of variance [ANOVA]). Postlipopolysaccharide hepatic arterial blood flow was significantly reduced (12% of baseline, P<.05, ANOVA), in contrast to DuP753-treated animals (64% of baseline, P<.05 vs nontreated group, ANOVA). Postburn blocking of angiotensin II receptors yielded a significant improvement in postlipopolysaccharide portal venous blood flow (85% of baseline vs 48% of baseline in nontreated animals, P<.05, ANOVA ). Postburn endotoxemia resulted in a significant decrease of hepatic oxygen delivery (22% of baseline) and hepatic oxygen consumption (30% of baseline), while no marked changes were observed in the DuP753-treated group (P<.05 vs nontreated group, ANOVA). CONCLUSIONS: Angiotensin II seems to play a pivotal role in burn- and sepsis-induced hepatic ischemia and reperfusion injury. Blocking angiotensin II receptors by DuP753 seems to abrogate this adverse effect of thermal injuries and sepsis on hepatic perfusion and oxygenation.

Hepatic blood flow and oxygen consumption after burn and sepsis.

BACKGROUND: Alteration in the hepatic circulation after burn and in sepsis seems to be an essential component in the development of multiple organ failure. METHODS: Female pigs (n = 12, 20-25 kg) were instrumented with ultrasonic flow probes on the portal vein and the common hepatic artery. Catheters were inserted in the superior mesenteric and left hepatic veins. After 5 days, all animals were anesthetized and six of them received 40% total body surface area third-degree burn. A total of 100 microg/kg Escherichia coli LPS was intravenously administered at 18 hours after burn. All animals were studied for 42 hours. RESULTS: Thermal injury resulted in a 48% decrease in hepatic arterial blood flow despite maintenance of normal cardiac output, resulting in a fall in hepatic oxygen delivery rate. Portal venous blood flow showed a 32% increase at 4 hours after burn. Post-LPS portal blood flow was significantly reduced for a period of 8 hours (51% of baseline (bl), p < 0.05 analysis of variance [ANOVA]). The hepatic arterial blood supply was also significantly reduced (12-67% of bl, p < 0.05 ANOVA) during the first 4 hours after LPS, indicating loss of the hepatic arterial response. The following 12 hours, a hepatic reperfusion phase was observed with an elevation of the hepatic arterial blood flow to 152% of bl (p < 0.05 ANOVA). Postburn endotoxemia resulted in a significant decrease of hepatic oxygen delivery (88%) and hepatic oxygen consumption (79%). Although the burn injury did not affect the portal venous pressure, postburn endotoxemia caused a significant portal hypertension during a period of 8 hours (225% of bl, p < 0.05 ANOVA). CONCLUSION: Postburn sepsis amplifies the selective vasconstrictive impact of thermal injury on hepatic arterial blood flow, yielding a pronounced ischemia/ reperfusion injury, associated with a critical reduction of hepatic oxygen delivery and consumption. A postburn septic challenge induces portal hypertension, which may account for previously documented gut barrier dysfunction.

Angiotensin II inhibitor DuP753 attenuates burn- and endotoxin-induced gut ischemia, lipid peroxidation, mucosal permeability, and bacterial translocation.

OBJECTIVE: To investigate the role of angiotensin II as a mediator of burn- and sepsis-induced gut ischemia and reperfusion injury and to determine whether treatment with the angiotensin II inhibitor DuP753 can attenuate mucosal injury and bacterial translocation in a burn/endotoxemia porcine model. SUMMARY BACKGROUND DATA: Thermal injuries and endotoxemia have been shown to induce ischemia and reperfusion injury to the intestine, leading to increased mucosal permeability and bacterial translocation. Angiotensin II, the production of which has been reported to increase after burn, is thought to be one of the primary mediators of postburn mesenteric vasoconstriction. METHODS: An ultrasonic flow probe was inserted into the superior mesenteric artery and a catheter into the superior mesenteric vein in 21 female pigs. After 5 days, all animals were anesthetized, and 14 received 40% total body surface area third-degree burn. DuP753 was administered intravenously at 1 microg/kg to seven pigs immediately after burn. Eighteen hours after burn, 100 microg/kg Escherichia coli lipopolysaccharide (LPS) was intravenously administered. Systemic and splanchnic hemodynamics were measured and blood samples were drawn for blood gas analysis. Plasma conjugated dienes (PCDs), an index of lipid peroxidation, were measured every 6 hours. Intestinal permeability was assessed every 6 hours by measuring the lactulose/mannitol excretion ratio. At the end of the study (42 hours), tissue samples were harvested for bacteriologic cultures. RESULTS: Burn caused a significant decrease in mesenteric blood flow, to approximately 58% of baseline. Postburn endotoxemia significantly reduced the blood flow in the superior mesenteric artery to 53% of baseline. Treatment with DuP753 prevented postburn vasoconstriction and subsequently abrogated the impact of postburn endotoxemia on blood flow in the superior mesenteric artery. Mesenteric oxygen supply was significantly reduced after burn and endotoxin to 60% and 51% of baseline levels, respectively. DuP753 administration significantly improved mesenteric oxygen supply after both insults. Burn- and LPS-induced mesenteric hypoxia, as indicated by decreased mesenteric oxygen consumption, was also ameliorated by DuP753 treatment. PCD levels were significantly elevated 8 hours after burn. LPS caused a higher and prolonged increase in PCD levels. Treatment with DuP753 significantly reduced PCD levels after burn and after LPS. Intestinal permeability, as assessed by the lactulose/mannitol ratio, showed 6-fold and 12-fold increases after thermal injury and LPS, respectively. In contrast, the lactulose/mannitol ratio was only doubled in DuP753-treated animals. Bacterial translocation was significantly increased after burn and endotoxin. The incidence of bacterial translocation in the DuP753-treated animals was similar to that in the sham group. CONCLUSIONS: Angiotensin II appears to play a pivotal role in the burn- and endotoxin-induced intestinal ischemia and reperfusion injury, with subsequent increases in permeability and bacterial translocation. Postburn administration of the angiotensin II receptor antagonist DuP753 significantly reduces the extent of these events.

Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis.

The genus Scedosporium contains two medically significant species of emerging mycotic agents, S. apiospermum and S. prolificans, which have received scant attention. Scedosporium apiospermum is the anamorph, or asexual state, of the cosmopolitan fungus Pseudallescheria boydii, with both sharing the same risk factors for infection, clinical spectrum, and histopathologic features. Scedosporium prolificans is a recently recognized agent of bone, soft tissue, and joint infections that occurs with highest frequency in children and young adults. S. prolificans may also cause potentially fatal disseminated infections in immunocompromised persons. The drug sensitivities of both Scedosporium species are significantly different from those of most other fungi, and thus identification of these organisms is important. Unfortunately, the pathological features of Scedosporium infections may be easily confused with other mycotic agents, resulting in delayed or inappropriate medical therapy. Because many pathologists and clinicians are unfamiliar with the significance of Scedosporium spp. infection, this communication describes three persons with differing clinical and pathological presentations of S. apiospermum infection. In one patient with sickle cell disease and chronic mycotic sinusitis, fungal colonies of S. apiospermum removed from the sinuses showed a pattern of alternating zones of mycelial hypercellularity and hypocellularity associated with conidiation, similar to a previous report of P. boydii infection. The clinicopathologic features of an immunocompetent person with S. apiospermum osteomyelitis, and a patient with S. apiospermum infection of the brain after bone marrow transplantation, are also described.

Sarcomatoid carcinoma of the larynx with neck and distant subcutaneous metastases. A case report with fine needle aspiration cytology.

BACKGROUND: Sarcomatoid carcinoma of the upper aerodigestive tract is an unusual neoplasm with divergent cellular differentiation. Typically this carcinoma is a squamous cell carcinoma with spindle and giant cell components and may be misinterpreted as a sarcoma. CASE: A 56-year-old, diabetic male presented with a 2.5-cm, left-sided neck mass. Fine needle aspiration showed a mixture of malignant squamous and spindle cells. A third population of osteoclastlike giant cells was also present. Similar cells were aspirated from a subcutaneous left leg lesion months later. CONCLUSION: The diagnosis of a sarcomatoid carcinoma of the larynx should be considered when malignant epithelial, spindle and giant cells are present in aspirated smear material from the neck.

Influence of surface coverage with poly(ethylene oxide) on attachment of sterically stabilized microspheres to rat Kupffer cells in vitro.

The attachment to rat Kupffer cells of polymeric microspheres, sterically stabilized with different amounts of pendant poly(ethylene oxide) (PEO), was assessed in vitro. Four types of copolymer polystyrene (PS) microspheres were synthesized by variation of four possible monomer ratios that included styrene, methoxy-PEO-methacrylate (750 and 2000 mol. wt PEO) and allylurea. This produced poly(styrene-(methoxy-PEO)methacrylate) microspheres with hydrophilic side-groups of either urea (PS-U-PEO) and/or mixed molecular weight (750/2000 mol. wt) PEO (PS-U-M-PEO, PS-M-PEO), or single molecular weight (2000) PEO (PS-PEO) at their surfaces. The hypothesis was tested that increasing the total content of PEO comprising the steric barrier reduces attachment to cell surfaces. Attachment of PEO microspheres bearing the urea spacer and/or mixed molecular weight PEO was found to be intermediate between charge stabilized control PS and PEO (2000 mol. wt) bearing particles. Post-adsorption of different Poloxamer (PEO-poly(propylene oxide)-PEO) surfactants to the microspheres further decreased attachment. Significant negative linear correlations between surface PEO content, measured by electron spectroscopy for chemical analysis (ESCA), and attachment to Kupffer cells were demonstrated. Decreases in attachment also resulted with all graft PEO particles bearing adsorbed sodium dodecyl sulphate (SDS), whilst the attachment of SDS-treated PS control particles increased. It is proposed that trains of adsorbed graft PEO are displaced by the SDS to increase the effective fraction of graft PEO within the steric layer. Overall, increasing the amount of hydrophilic PEO in the steric layer, from graft and adsorbed sources, reduces the attachment of these particles to Kupffer cells in vitro.

Surface modification of poly(lactide-co-glycolide) nanospheres by biodegradable poly(lactide)-poly(ethylene glycol) copolymers.

The modification of surface properties of biodegradable poly(lactide-co- glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethylene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da. respectively) were studied. The results reveal the formation of a PLA:PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of experimental intestinal anastomoses.

OBJECTIVE: This study was done to investigate whether administration of interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on anastomotic healing. SUMMARY BACKGROUND DATA: Recently, the authors showed that blood transfusion severely impairs anastomotic repair and significantly increases the susceptibility to intra-abdominal septic complications in rats. It has been reported that blood transfusions suppress IL-2 production and that IL-2 may stimulate wound healing. METHODS: Lewis rats underwent resection and anastomosis of both the ileum and colon. Subsequently, they received either 3 mL of saline (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion and transfusion/IL-2 groups) intravenously. From the operation onward, the animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4 x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other groups received only the dextrose solution. The animals were killed 3 or 7 days after the operation and examined for septic complications and anastomotic repair. RESULTS: Transfusion led to an enhanced incidence of anastomotic abscesses, which was almost completely abrogated after IL-2 administration. The anastomotic strength was consistently and significantly reduced after transfusion. Seven days after surgery, the anastomotic strength was completely restored by IL-2 treatment. For instance, the average bursting pressure (+/- the standard deviation) of the ileal anastomoses in the control, transfusion, and transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol: see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7, respectively (where * = significant vs. control group and [symbol: see text] = significant vs. transfusion group). In addition, IL-2 administration elevated the anastomotic hydroxyproline content, which was significantly decreased by transfusion alone, to the level found in the control group. The administration of IL-2 to control animals resulted unexpectedly in a significant reduction in anastomotic strength. CONCLUSIONS: Exogenous IL-2 reverses the negative effects of blood transfusions on anastomotic repair, but it impairs healing under normal conditions.

Breast fine needle aspiration cytology. Utility as a screening tool for clinically palpable lesions.

We examined breast fine needle aspiration cytology's role as a screening tool in addition to mammography and clinical examination for palpable breast lesions, circumventing operative biopsy of benign lesions while identifying cancer for definitive treatment and significant ductal proliferations that need histologic evaluation, such as atypical ductal hyperplasia and marked ductal hyperplasia. Five hundred thirty-three consecutive palpable breast lesions in 498 patients referred to cytopathologists were aspirated and the cytologic findings reported as follows: (1) malignant, treat as any histologic diagnosis of breast cancer (85); (2) suspicious, intraoperative or biopsy confirmation before therapy (11); (3) atypical, biopsy recommended to exclude breast cancer or significant ductal proliferation (atypical ductal hyperplasia and marked ductal hyperplasia) (45); (4) benign, excision not necessary (334); and (5) nondiagnostic, no ductal cells, and biopsy recommended if indicated clinically (58). Excision of 57/85 malignant lesions confirmed cancer in all cases. Follow-up of the remaining 28 patients showed: 17 were undergoing treatment for cancer without surgery, 8 were dead of the disease, and 3 were lost to follow-up. Biopsy of 11/11 suspicious lesions confirmed cancer. Biopsy of 27/45 atypical lesions showed: 1 carcinoma, 12 significant ductal proliferations (1 atypical ductal hyperplasia and 11 marked ductal hyperplasia) and 14 benign, nonproliferative breasts; 18 atypical lesions from 14 patients were not biopsied. Biopsy of 61/334 benign lesions showed 51 benign nonproliferative breasts, 7 missed significant ductal proliferations (6 marked ductal hyperplasia and 1 atypical ductal hyperplasia) and 3 false negatives (3 carcinomas). The three false negatives and the atypical ductal hyperplasia had a biopsy because of an abnormal mammogram. Review of material from false-negative cases showed underinterpretation of cells present on cytology slides in two cases and carcinoma missed by the aspiration needle in one case. The atypical ductal hyperplasia was in a separate, nonpalpable area in the same breast. Biopsy was avoided in 273/334 benign lesions from 249 patients: 86 had no follow-up, 160 had stable lesions, and 3 reported a change in their lesions (mean follow-up, 13 months). One of these three had a biopsy that showed a benign, nonproliferative breast. Biopsy of 11/58 nondiagnostic lesions showed 9 benign nonproliferative breasts, 1 atypical ductal hyperplasia and 1 carcinoma. No biopsy was performed on 47/58 nondiagnostic lesions from 45 patients: 1 had a repeat aspiration that was malignant, 10 had no follow-up, 33 had stable lesions, and 1 had an increase in the size of her lesion (mean follow-up, 13 months).(ABSTRACT TRUNCATED AT 400 WORDS)

Blood transfusion impairs the healing of experimental intestinal anastomoses.

Blood transfusions are reported to impair the cell-mediated immune response. Because both T lymphocyte and macrophage function are important for wound repair, the authors investigated the effect of blood transfusions on anastomotic repair. Lewis rats underwent resection of both ileum and colon, followed by the construction of either an everted or an inverted end-to-end anastomosis. Immediately after operation, they received either 3 mL saline intravenously, or 3 mL heparinized blood from Lewis or Brown Norway donors. The animals were killed 3 or 7 days after operation, and anastomotic strength was assessed by measuring the bursting pressure. Anastomotic abscesses and generalized peritonitis were not found in the control group. Blood transfusions, particularly allogeneic, significantly increased the incidence of these septic complications. Three days after operation, anastomotic strength was significantly reduced in both Lewis and Brown Norway transfused groups. For instance, average bursting pressures (+/- standard deviation [SD]) of inverted ileal anastomoses were 79 +/- 13 mmHg in the control group and 46 +/- 14 and 21 +/- 12 mmHg in the Lewis and Brown Norway transfused groups, respectively. Seven days after operation, the rupture site was found significantly more often within the anastomotic line in the animals that had received blood transfusions. The authors conclude that blood transfusions impair the healing of experimental intestinal anastomoses and increase susceptibility to intra-abdominal sepsis.

Future developments in cosmetic formulations.

Synopsis In recent years, there have been a great deal of interest in applications of microemulsions, liposomes (vesicles) and multiple emulsions in cosmetic formulations. These systems will provide the cosmetic industry with new types of formulations which are easier to apply, better functional benefit and potentially safer formulations. Microemulsions are thermodynamically stable systems and hence shelf life is no problem. Many cosmetic ingredients can be adequately solubilized in the swollen micelles of the microemulsions. Such solubilized systems may enhance transport and diffusion through various barriers, eg., the skin, thus enhancing the efficacy of the formulations. However, microemulsions may cause skin irritation by disrupting the liquid crystalline structure of the stratum corneum. This problem may be overcome by formulating microemulsions, which on evaporation produce lamellar liquid crystalline structures. The problem of skin irritation is certainly reduced or eliminated using liposomes or vesicles, which offer an alternative to microemulsions. The principles for formation and stabilization of vesicles are discussed in this paper and research work is needed to produce nanocapsules from liposomes, using polymerizable surfactants. Multiple emulsions of the water/oil/water (w/o/w) or oil/water/oil (o/w/o) types are also valuable systems for formulating cosmetics. In the first place, they offer a means of sustained release of the various ingredients. Secondly, they allow one to separate the various ingredients in the formulation, thus preventing their possible interaction. The basic principles required for preparation of stable multiple emulsions are summarised. Developments of polymeric surfactants led to the formulation of stable multiple emulsions. An example of a recently formulated stable w/o/w multiple emulsion is given in this paper The stability of the system was investigated using optical microscopy. Creaming occurred on storage, particularly at high temperature (40 degrees C) and this was significantly reduced by addition of Kelzan (a polysaccharide with high molecular weight). The final formulation was studied rheological techniques.

Steric stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro.

Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 micron) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8 degrees C and 37 degrees C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone (P less than or equal to 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed.

Vaginocervical cytology in victims of sexual assault.

To investigate the role of vaginocervical smears in alleged victims of rape, we reviewed the findings in 4,220 consecutive rape victims between the years 1982 and 1989. These rape victims showed a slight increase in cellular abnormalities (1.18% vs. .93%) when compared to a group of 17,187 routine smears from an indigent population in 1989. While the differences in the spectrum of cellular abnormalities were not statistically significant, the increase in abnormal smears is remarkable because of the younger age distribution and lower risk factors for cervical cancer in this group of rape victims (41% of the victims were never seen at our institution before their evaluation for alleged rape and were most probably of higher socioeconomic status and at lower risk for cervical cancer than the indigent population served at our hospital). This finding may reflect the low incidence of vaginocervical cytology screening among the general population of which rape victims are a random sample. Fifty-seven percent of the rape victims with cellular abnormalities who were also regular patients at our hospital returned for follow-up by appropriate repeat smears or biopsies. This was lower than the 95% general follow-up rate of vaginocervical smear abnormalities among the rest of the population screened at our hospital. We detected spermatozoa in 56% of the smears from victims who were examined within three days of the alleged sexual assault. Cytology adds to the criminal investigation of rape cases as we detected spermatozoa in four of 16 semen-negative cases from a random sample of 53 cases evaluated by the state crime lab.